JP5120962B2

JP5120962B2 - Method for producing homoallyl hydrazide and asymmetric catalyst used therefor

Info

Publication number: JP5120962B2
Application number: JP2009058632A
Authority: JP
Inventors: 修小林; シュナイダーウーベ; 英之小西; チャクラバルティアナーニャ
Original assignee: Japan Science and Technology Agency; National Institute of Japan Science and Technology Agency
Current assignee: Japan Science and Technology Agency; National Institute of Japan Science and Technology Agency
Priority date: 2008-03-11
Filing date: 2009-03-11
Publication date: 2013-01-16
Anticipated expiration: 2029-03-11
Also published as: JP5685570B2; JP2013078760A; JP2009242390A

Description

この発明は、アリル化剤によってN-アシルヒドラゾンをアリル化するホモアリルヒドラジドの製造方法及びそれに用いる不斉触媒に関する。 The present invention relates to a method for producing homoallyl hydrazide in which N-acylhydrazone is allylated with an allylating agent and an asymmetric catalyst used therefor.

イミン類のアリル化は重要な炭素-炭素結合生成物であり（非特許文献１）、生成物のホモアリルアミン類は生理活性物質等の有用な中間体となる（非特許文献２）。イミンのアリル化は、通常はハロゲン化アリルをBarbier型反応条件で調製したアリルインジウム試薬を用いるが（非特許文献３）、最近ではアリルパラジウム（非特許文献４）やアリル水銀（非特許文献５）から金属交換反応でアリルインジウムを調製する方法も報告されている。
しかしながら、他のアリル化反応方法では毒性の高いアリルスズ（非特許文献６）や腐食性のあるアリルケイ素試薬（非特許文献７）、又は活性化されたイミン誘導体（非特許文献８）を用いる必要がある。一方、アシルヒドラゾン類は対応するカルボニル化合物から調製され、イミンに比べて非常に安定性が高い（非特許文献９）。しかしながらアシルヒドラゾンを用いる触媒的アリル化反応は、ごく限られた基質でしか報告されていない（非特許文献１０）。 Allylation of imines is an important carbon-carbon bond product (Non-Patent Document 1), and the product homoallylamines are useful intermediates such as physiologically active substances (Non-Patent Document 2). Allylation of imine uses an allylindium reagent in which allyl halide is usually prepared under Barbier-type reaction conditions (Non-patent Document 3). Recently, allylpalladium (Non-patent Document 4) and allylmercury (Non-patent Document 5) are used. ) To prepare allylindium by a metal exchange reaction.
However, other allylation methods require the use of highly toxic allyltin (Non-patent document 6), corrosive allylsilicon reagent (Non-patent document 7), or an activated imine derivative (Non-patent document 8). There is. On the other hand, acyl hydrazones are prepared from the corresponding carbonyl compounds, and are very stable compared to imines (Non-patent Document 9). However, catalytic allylation reaction using acyl hydrazone has been reported only with a very limited substrate (Non-patent Document 10).

一方、1価インジウムは低毒性であり、ハライドの形で市販されているが、一般的な有機溶媒に対する溶解度は極端に低い。また、特に1価インジウムはルイス酸性およびルイス塩基性の両方の性質を備え、ルイス塩基性の強い溶媒中では不均化が進行することがあり、0価と3価のインジウムへと変換される。特に水中かつ酸存在下ではこの傾向が顕著である。このようなことから、1価インジウム種を有機合成に用いた例は少ない。
特に、炭素-炭素結合生成反応を触媒量の1価インジウムを用いて行った例はこれまでに知られていない。 On the other hand, monovalent indium has low toxicity and is commercially available in the form of a halide, but its solubility in common organic solvents is extremely low. In particular, monovalent indium has both Lewis acidic and Lewis basic properties, and disproportionation may proceed in solvents with strong Lewis basicity, which is converted into zero-valent and trivalent indium. . This tendency is particularly remarkable in water and in the presence of an acid. For this reason, there are few examples of using monovalent indium species for organic synthesis.
In particular, an example in which a carbon-carbon bond generation reaction is performed using a catalytic amount of monovalent indium has not been known so far.

Kobayashi, S.; Ishitani, H. Chem. Rev. 1999, 99, 1069Kobayashi, S .; Ishitani, H. Chem. Rev. 1999, 99, 1069 Ding, H.; Friestad, G. K. Synthesis 2005, 2815Ding, H .; Friestad, G. K. Synthesis 2005, 2815 Loh, T.-P.; Ho, D. S.-C.; Xu, K.-C.; Sim, K.-Y. Tetrahedron Lett. 1997, 38, 865Loh, T.-P .; Ho, D. S.-C .; Xu, K.-C .; Sim, K.-Y. Tetrahedron Lett. 1997, 38, 865 Cooper, I. R.; Grigg, R.; MacLachlan, W. S.; Sridharan, V.; Thornton-Pett, M. Tetrahedron Lett. 2003, 44, 403Cooper, I. R .; Grigg, R .; MacLachlan, W. S .; Sridharan, V .; Thornton-Pett, M. Tetrahedron Lett. 2003, 44, 403 Chan, T. H.; Yang, Y. J. Am. Chem. Soc. 1999, 121, 3228Chan, T. H .; Yang, Y. J. Am. Chem. Soc. 1999, 121, 3228 Nakamura, H.; Nakamura, K.; Yamamoto, Y. J. Am. Chem. Soc. 1998, 120, 4242Nakamura, H .; Nakamura, K .; Yamamoto, Y. J. Am. Chem. Soc. 1998, 120, 4242 Nakamura, K.; Nakamura, H.; Yamamoto, Y. J. Org. Chem. 1999, 64, 2614Nakamura, K .; Nakamura, H .; Yamamoto, Y. J. Org. Chem. 1999, 64, 2614 Ferraris, D.; Dudding, T.; Young, B.; Drury, W. J. III; Lectka, T. J. Org. Chem. 1999, 64, 2168Ferraris, D .; Dudding, T .; Young, B .; Drury, W. J. III; Lectka, T. J. Org. Chem. 1999, 64, 2168 Oyamada, H.; Kobayashi, S. Synlett 1998, 249Oyamada, H .; Kobayashi, S. Synlett 1998, 249 Cook, G. R.; Maity, B. C.; Kargbo, R. Org. Lett. 2004, 6, 1741Cook, G. R .; Maity, B. C .; Kargbo, R. Org. Lett. 2004, 6, 1741

従って、本発明は、一価インジウムを用いてN-アシルヒドラゾンをアリル化するホモアリルヒドラジドの製造方法、及びそれに用いる不斉触媒の提供を目的とする。 Accordingly, an object of the present invention is to provide a method for producing homoallyl hydrazide in which N-acylhydrazone is allylated using monovalent indium, and an asymmetric catalyst used therefor.

このような課題を解決するために、本発明者らは鋭意研究した結果、一価のインジウムでN-アシルヒドラゾンのアリル化反応が進行することを見出し、本発明を完成するに至った。 In order to solve such problems, the present inventors have intensively studied. As a result, they found that the allylation reaction of N-acylhydrazone proceeds with monovalent indium, and completed the present invention.

即ち、本発明のホモアリルヒドラジドの製造方法は、一価のインジウム塩存在下、式Ｉ

（式中、R¹は、脂肪族炭化水素基、置換基として2-メトキシ基、3-メトキシ基、4-メトキシ基、4-ジメチルアミノフェニル基、4-メチル基、4-フェニル基、4-ニトロ基、4-ヒドロキシ基、4-クロロ基を有していてもよい芳香族炭化水素基、複素環式芳香族基又はアルコキシカルボニル基；R²は、水素原子又はアルキル基；R³は、脂肪族炭化水素基、又は芳香族炭化水素基）で表されるN-アシルヒドラゾンと、式ＩＩ

（式中、R⁴はそれぞれ同じであっても異なっていてもよいアルキル基；R⁵は、水素原子、炭化水素基、ハロゲン基、又はアルコキシ基；R⁶〜R^８は、それぞれ同じであっても異なっていてもよい水素原子又はアルキル基）で表されるアリルボロネート又はα-置換アリルボロネートを反応させる、式ＩＩＩ

又はその鏡像体で表されるホモアリルヒドラジドの製造方法であって、さらに、式Ｖ

又は、式ＶＩ

（式中、R ^９は、水素原子又はアルキル基；R ¹⁰ 、R ¹² は、それぞれ同じであっても異なっていてもよく、脂肪族炭化水素基、又は芳香族炭化水素基；R ¹¹ 、R ¹⁴ は、水素原子、それぞれ同じであっても異なっていてもよく、脂肪族炭化水素基、又は芳香族炭化水素基；R ¹³ はシアノ基またはアミノ基）又はその鏡像体で表される不斉配位子の存在下で反応を行う。 That is, the method for producing homoallyl hydrazide according to the present invention comprises formula I in the presence of a monovalent indium salt.

(Wherein R ¹ is an aliphatic hydrocarbon group, 2-methoxy group, 3-methoxy group, 4-methoxy group, 4-dimethylaminophenyl group, 4-methyl group, 4-phenyl group, 4 as a substituent , -Aromatic group optionally having a nitro group, 4-hydroxy group, 4-chloro group , heterocyclic aromatic group or alkoxycarbonyl group; R ² is a hydrogen atom or alkyl group; R ³ is An N-acylhydrazone represented by the formula II, an aliphatic hydrocarbon group or an aromatic hydrocarbon group);

Wherein R ⁴ is the same or different alkyl group; R ⁵ is a hydrogen atom, a hydrocarbon group, a halogen group, or an alkoxy group; R ^{6 to} R ⁸ are the same. Allyl boronate or α-substituted allyl boronate represented by the formula III

Or a homoallyl hydrazide production method represented by an enantiomer thereof , further comprising the formula V

Or the formula VI

(Wherein R ⁹ is a hydrogen atom or an alkyl group; R ¹⁰ and R ¹² may be the same or different, and each is an aliphatic hydrocarbon group or an aromatic hydrocarbon group; R ¹¹ , R ¹⁴ is a hydrogen atom, which may be the same or different from each other, an aliphatic hydrocarbon group or an aromatic hydrocarbon group; R ¹³ is a cyano group or an amino group) or an enantiomer thereof The reaction is carried out in the presence of a ligand .

前記一価のインジウム塩の添加量が20 mol%以下であることが好ましい。 The addition amount of the monovalent indium salt is preferably 20 mol% or less.

前記アリルボロネート又はα-置換アリルボロネートは、式ＩＶ

で表されることが好ましい。 The allyl boronate or α-substituted allyl boronate has the formula IV

It is preferable to be represented by

前記α-置換アリルボロネートのR^５がメチル基で表されることが好ましい。
前記α-置換アリルボロネートのR^５がＣｌで表されることが好ましい。 R ⁵ of the α-substituted allyl boronate is preferably represented by a methyl group.
R ⁵ of the α-substituted allyl boronate is preferably represented by Cl.

本発明の不斉触媒は、一価のインジウムと、式Ｖ

又は、式ＶＩ

（式中、R^９は、水素原子又はアルキル基；R¹⁰、R¹²は、それぞれ同じであっても異なっていてもよく、置換基を有していてもよい脂肪族炭化水素基、又は置換基を有していてもよい芳香族炭化水素基；R¹¹、R¹⁴は、水素原子、それぞれ同じであっても異なっていてもよく、置換基を有していてもよい脂肪族炭化水素基、又は置換基を有していてもよい芳香族炭化水素基；R¹³はシアノ基またはアミノ基）又はその鏡像体で表される不斉配位子とからなる不斉触媒であって、N-アシルヒドラゾンのアリル化に用いられる。 The asymmetric catalyst of the present invention comprises monovalent indium and a compound of formula V

Or the formula VI

(Wherein R ⁹ is a hydrogen atom or an alkyl group; R ¹⁰ and R ¹² may be the same or different and each may be an aliphatic hydrocarbon group which may have a substituent, or a substituent; An aromatic hydrocarbon group which may have a group; R ¹¹ and R ¹⁴ may be the same or different from each other, and may be an aliphatic hydrocarbon group which may have a substituent; Or an aromatic hydrocarbon group which may have a substituent; R ¹³ is a cyano group or an amino group) or an asymmetric ligand represented by an enantiomer thereof, -Used for allylation of acyl hydrazone.

本発明によれば、一価インジウムを用いてN-アシルヒドラゾンをアリルボロネートによりアリル化することができる。 According to the present invention, N-acylhydrazone can be allylated with allyl boronate using monovalent indium.

本発明は、一価インジウムの存在下、N-アシルヒドラゾンをアリルボロネートによりアリル化するものである。 In the present invention, N-acylhydrazone is allylated with allylboronate in the presence of monovalent indium.

N-アシルヒドラゾンのアリル化の触媒として、N-アシルヒドラゾンに対し１〜５０mol%の１価のインジウムを用い、好ましくは１〜２０mol%、より好ましくは５〜２０mol%である。
１価のインジウムとしては、ヨウ化インジウム、臭化インジウム、塩化インジウム等のハロゲン化インジウム、またはインジウムトリフラートを好適に用いることができる。 As a catalyst for the allylation of N-acylhydrazone, 1 to 50 mol% of monovalent indium is used with respect to N-acylhydrazone, preferably 1 to 20 mol%, more preferably 5 to 20 mol%.
As monovalent indium, indium halides such as indium iodide, indium bromide, and indium chloride, or indium triflate can be suitably used.

本発明で用いるインジウムは、有機溶媒中に溶解又は分散させて用いることができ、有機溶媒としては、トルエンや塩化メチレンが特に望ましい。テトラヒドロフランを用いると、1価のインジウムが不均化して0価と3価のインジウム種が生じることがある。
又、反応系に、添加剤としてアルコールやフェノールを加えると、収率および選択性が向上する。このようなアルコールとしては、例えばメタノール、イソプロピルアルコールが挙げられる。 Indium used in the present invention can be used by dissolving or dispersing in an organic solvent, and toluene or methylene chloride is particularly desirable as the organic solvent. When tetrahydrofuran is used, monovalent indium may disproportionate and 0 and trivalent indium species may be generated.
Further, when alcohol or phenol is added as an additive to the reaction system, the yield and selectivity are improved. Examples of such alcohol include methanol and isopropyl alcohol.

N-アシルヒドラゾンは、式Ｉ

（式中、R¹は、置換基を有していてもよい脂肪族炭化水素基、置換基を有していてもよい芳香族炭化水素基、又はアルコキシカルボニル基；R²は、水素原子又はアルキル基；R³は、置換基を有していてもよい脂肪族炭化水素基、又は置換基を有していてもよい芳香族炭化水素基）で表される。 N-acylhydrazones have the formula I

Wherein R ¹ is an aliphatic hydrocarbon group which may have a substituent, an aromatic hydrocarbon group which may have a substituent, or an alkoxycarbonyl group; R ² is a hydrogen atom or An alkyl group; R ³ is an aliphatic hydrocarbon group which may have a substituent, or an aromatic hydrocarbon group which may have a substituent.

アリルボロネート又はα-置換アリルボロネートは、式ＩＩ

（式中、R⁴はそれぞれ同じであっても異なっていてもよいアルキル基；R⁵は、水素原子、炭化水素基、ハロゲン基、又はアルコキシ基；R⁶〜R^８は、それぞれ同じであっても異なっていてもよい水素原子又はアルキル基）で表される。
ここで、式II において、R⁵が水素原子の場合は（α-無置換の）アリルボロネートであり、R⁵が水素原子以外の場合はα-置換アリルボロネートである。（α-無置換の）アリルボロネートは、後述する不斉配位子を用いるエナンチオ選択的反応に主に利用されるので、後述する不斉配位子と併用するのが好ましい。α-置換アリルボロネートは、ジアステレオ選択的かつα位選択的なアリル化反応に主に利用される。 Allyl boronate or α-substituted allyl boronate is of formula II

Wherein R ⁴ is the same or different alkyl group; R ⁵ is a hydrogen atom, a hydrocarbon group, a halogen group, or an alkoxy group; R ^{6 to} R ⁸ are the same. Or a hydrogen atom or an alkyl group which may be different from each other.
Here, in the formula II, when R ⁵ is a hydrogen atom, it is an (α-unsubstituted) allyl boronate, and when R ⁵ is other than a hydrogen atom, it is an α-substituted allyl boronate. Since the (α-unsubstituted) allyl boronate is mainly used for enantioselective reaction using an asymmetric ligand described later, it is preferably used in combination with the asymmetric ligand described later. α-Substituted allyl boronates are mainly used for diastereoselective and α-selective allylation reactions.

前記アリルボロネート又はα-置換アリルボロネートとしては、式ＩＶ

で表されるものを用いることができる。 The allyl boronate or α-substituted allyl boronate includes the formula IV

Can be used.

さらに、式Ｖ

又は、式ＶＩ

（式中、R^９は、水素原子又はアルキル基；R¹⁰、R¹²は、それぞれ同じであっても異なっていてもよく、置換基を有していてもよい脂肪族炭化水素基、又は置換基を有していてもよい芳香族炭化水素基；R¹¹、R¹⁴は、水素原子、それぞれ同じであっても異なっていてもよく、置換基を有していてもよい脂肪族炭化水素基、又は置換基を有していてもよい芳香族炭化水素基；R¹³はシアノ基またはアミノ基）又はその鏡像体で表される不斉配位子の存在下で反応を行うことが好ましい。
上記アミノ基は一つまたは二つの炭化水素基を有するものが好ましく、さらに好ましくはメチルアミノ基、ジメチルアミノ基またはエチルアミノ基である。
R¹⁰〜R¹²としては、フェニル基が好ましい。R¹¹としては水素原子が望ましい。
上記式Ｖ、ＶＩの不斉配位子は、一価インジウムと不斉触媒を構成するため、生成物をエナンチオ選択的に得られる。 Furthermore, the formula V

Or the formula VI

(Wherein R ⁹ is a hydrogen atom or an alkyl group; R ¹⁰ and R ¹² may be the same or different and each may be an aliphatic hydrocarbon group which may have a substituent, or a substituent; An aromatic hydrocarbon group which may have a group; R ¹¹ and R ¹⁴ may be the same or different from each other, and may be an aliphatic hydrocarbon group which may have a substituent; Or an aromatic hydrocarbon group which may have a substituent; R ¹³ is a cyano group or an amino group) or an asymmetric ligand represented by an enantiomer thereof is preferably used.
The amino group preferably has one or two hydrocarbon groups, more preferably a methylamino group, a dimethylamino group or an ethylamino group.
R ^{10 to} R ¹² are preferably a phenyl group. R ¹¹ is preferably a hydrogen atom.
Since the asymmetric ligands of the above formulas V and VI constitute an asymmetric catalyst with monovalent indium, the product can be obtained enantioselectively.

特に、Ｒ^１３がシアノ基である式ＶＩの不斉配位子（セミコリン配位子）と用いると、式Ｖの不斉配位子（ビスオキサゾリン配位子等）と同様高い収率及びエナンチオ選択性が得られる。 In particular, when used with an asymmetric ligand of the formula VI (semicholine ligand) in which R ¹³ is a cyano group, the yield and enantiomer are as high as those of the asymmetric ligand of the formula V (such as a bisoxazoline ligand). Selectivity is obtained.

式ＩＩのα-置換アリルボロネートとして、R^５がメチル基で表されるものを用いると、収率、シアステレオ選択性（アンチ／シン選択性）、エナンチオ選択性がいずれも高いので好ましい。
また、式ＩＩのα-置換アリルボロネートとして、R^５がＣｌで表されるものを用いても、収率、エナンチオ選択性がいずれも高いので好ましい。なお、R^５がＣｌのα-置換アリルボロネートを用いると、医薬品開発の有用な中間体となる生成物が得られる。 As the α-substituted allyl boronate of the formula II, it is preferable to use a compound in which R ⁵ is represented by a methyl group, since all of yield, shear stereoselectivity (anti / syn selectivity) and enantioselectivity are high.
In addition, it is preferable to use an α-substituted allylboronate of the formula II in which R ⁵ is represented by Cl because both yield and enantioselectivity are high. When an α-substituted allyl boronate in which R ⁵ is Cl is used, a product that is a useful intermediate for drug development is obtained.

本発明において、反応系の溶媒中の各成分の濃度はそれぞれ0.01〜5mol/lであることが好ましい。
この反応の温度は、好ましくは-78〜60℃である。
この反応時間は、数分〜数１０時間程度である。
この反応系には上記成分のほか、適宜、触媒や界面活性剤等の公知の添加剤を添加してもよい。 In the present invention, the concentration of each component in the solvent of the reaction system is preferably 0.01 to 5 mol / l.
The temperature of this reaction is preferably -78 to 60 ° C.
This reaction time is about several minutes to several tens of hours.
In addition to the above components, known additives such as catalysts and surfactants may be added to this reaction system as appropriate.

本発明の製造方法によって、式ＩＩＩ

で表されるホモアリルヒドラジドが、ジアステレオ選択的（アンチ選択的）に得られる。又、上記した不斉触媒を用いた場合は、ホモアリルヒドラジドがエナンチオ選択的反応に得られる。
生成物は、抽出、カラムクロマトグラフィー、蒸留、再結晶等の一般的精製法を利用して回収できる。 According to the production method of the present invention, the compound of formula III

Is obtained diastereoselectively (anti-selectively). Further, when the above-mentioned asymmetric catalyst is used, homoallyl hydrazide can be obtained in an enantioselective reaction.
The product can be recovered using common purification methods such as extraction, column chromatography, distillation, recrystallization and the like.

以下、実施例にて本発明を例証するが本発明を限定することを意図するものではない。 The following examples illustrate the invention but are not intended to limit the invention.

なお、以下の各実施例において、１価のヨウ化インジウム(粉末, 99.999%、Aldrich社)は、アルゴン雰囲気下で保存し、精製せずに用いた。アリルボロネートである2-Allyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane （ Aldrich社）は蒸留して使用した。α-メチルアリルボロネートである2-(But-3-en-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane) 及びその他のアリルボロネートは報告例に基づいて合成した（以下の報告例１〜３）。添加剤は精製して用いた。他の試薬（東京化成社又はAldrich社）は精製せずに用いた。
報告例１；α-メチルアリルボロネート、α-アルコキシアリルボロネート：Hoffmann, R. W.; Wolff, J. J. Chem. Ber. 1991, 124, 563.
報告例２；α-クロロアリルボロネート：Hoffmann, R. W.; Landmann, B. Chem. Ber. 1986, 119, 1039.
報告例３；α-置換アリルボロネート合成の中間体：Matteson, D. S.:Majumdar, D. J. Am. Chem. Soc. 1980, 102, 7588. In each of the following examples, monovalent indium iodide (powder, 99.999%, Aldrich) was stored in an argon atmosphere and used without purification. The allyl boronate 2-Allyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (Aldrich) was used after distillation. α-Methylallylboronate 2- (But-3-en-2-yl) -4,4,5,5-tetramethyl-1,3,2-dioxaborolane) and other allylboronates are Based on these, the following report examples 1 to 3 were synthesized. The additive was used after purification. Other reagents (Tokyo Kasei Co. or Aldrich) were used without purification.
Report Example 1; α-methylallylboronate, α-alkoxyallylboronate: Hoffmann, RW; Wolff, JJ Chem. Ber. 1991, 124, 563.
Report Example 2: α-chloroallylboronate: Hoffmann, RW; Landmann, B. Chem. Ber. 1986, 119, 1039.
Report Example 3; Intermediate for α-Substituted Allylboronate Synthesis: Matteson, DS: Majumdar, DJ Am. Chem. Soc. 1980, 102, 7588.

＜１価のヨウ化インジウムによる、α-メチルアリルボロネートのN-アシルヒドラゾンへの付加反応の一般操作＞

アルゴン雰囲気下、１価のヨウ化インジウム(3.0 mg, 0.0125 mmol) 及び 3-フェニルプロパナール由来の N-ベンゾイルヒドラゾン(63.1 mg, 0.250 mmol) をフラスコに加えた。次にトルエン (0.50 mL) およびイソプロピルアルコール (96 μL, 1.25 mmol) を加えた。さらにα-メチルアリルボロネート(78 μL, 0.375 mmol) を加えて室温で４８時間撹拌した。1 M K₂CO₃ 水溶液(2.0 mL)を加えて反応を停止し、塩化メチレンで３回抽出した。有機層を合わせて飽和食塩水で洗浄し、無水硫酸ナトリウムで乾燥した。溶媒を留去した後、粗生成物を分取薄層クロマトグラフィー(ヘキサン/酢酸エチル = 2/1) で精製し、生成物であるN'-(4-methyl-1-phenylhex-5-en-3-yl)benzohydrazideを85%で与えた(65.5 mg, 0.213 mmol, α:γ = 97:3, syn:anti = 5:95)。生成物の分析データは、報告例（Kobayashi, S.; Hirabayashi, R. J. Am. Chem. Soc. 1999, 121, 6942.）のものと一致した。 <General operation of addition reaction of α-methylallylboronate to N-acylhydrazone with monovalent indium iodide>

Under an argon atmosphere, monovalent indium iodide (3.0 mg, 0.0125 mmol) and 3-phenylpropanal-derived N-benzoylhydrazone (63.1 mg, 0.250 mmol) were added to the flask. Then toluene (0.50 mL) and isopropyl alcohol (96 μL, 1.25 mmol) were added. Further, α-methylallylboronate (78 μL, 0.375 mmol) was added and stirred at room temperature for 48 hours. 1 MK ₂ CO ₃ aqueous solution (2.0 mL) was added to stop the reaction, and the mixture was extracted 3 times with methylene chloride. The organic layers were combined, washed with saturated brine, and dried over anhydrous sodium sulfate. After distilling off the solvent, the crude product was purified by preparative thin layer chromatography (hexane / ethyl acetate = 2/1), and the product N '-(4-methyl-1-phenylhex-5-en -3-yl) benzohydrazide was given at 85% (65.5 mg, 0.213 mmol, α: γ = 97: 3, syn: anti = 5:95). Analytical data for the product was consistent with that of the reported example (Kobayashi, S .; Hirabayashi, RJ Am. Chem. Soc. 1999, 121, 6942.).

上記式ＶＩＩにおいて、N-ベンゾイルヒドラゾンを種々に変えて同様に反応を行った（式ＸＶＩＩ）。
N-ベンゾイルヒドラゾンは、以下のいずれかの方法で調製した。
(1) N-ベンゾイルヒドラジンと小過剰量のアルデヒドのテトラヒドロフラン溶液に、濃塩酸を数滴加え、N-ベンゾイルヒドラジンが消失するまで室温で撹拌した。沈殿が生じた場合は、濾過し、洗浄した後に適当な溶媒（酢酸エチル、酢酸エチル／ヘキサン、塩化メチレン）から再結晶した。沈殿が生じなかった場合は、溶媒を減圧留去し、残さを再結晶かシリカゲルクロマトグラフィーで精製した。
(2) N-ベンゾイルヒドラジンと小過剰量のアルデヒドのジメチルホルムアミド溶液を数時間加熱還流した。室温に戻した後、（１）の方法で精製した。

得られた生成物を以下の（１）〜（８）に示す。 In the above formula VII, N-benzoylhydrazone was changed in various ways to carry out the same reaction (formula XVII).
N-benzoylhydrazone was prepared by one of the following methods.
(1) A few drops of concentrated hydrochloric acid were added to a tetrahydrofuran solution of N-benzoylhydrazine and a small excess of aldehyde, and the mixture was stirred at room temperature until N-benzoylhydrazine disappeared. When precipitation occurred, it was filtered, washed and recrystallized from an appropriate solvent (ethyl acetate, ethyl acetate / hexane, methylene chloride). When no precipitation occurred, the solvent was distilled off under reduced pressure, and the residue was purified by recrystallization or silica gel chromatography.
(2) A dimethylformamide solution of N-benzoylhydrazine and a small excess of aldehyde was heated to reflux for several hours. After returning to room temperature, it was purified by the method (1).

The obtained products are shown in the following (1) to (8).

（１）N'-(1-(4-methoxyphenyl)-2-methylbut-3-enyl)benzohydrazide:（式ＸＶＩＩでＲ^１が4-MeOC₆H₄；Ｒ^２がHのもの）
生成物の収率98%、α:γ = 99:1, syn:anti = 9:91であった。

Mp 87.4-88.2 C;¹H NMR (400 MHz, CDCl₃) δ0.76 (major, d, J = 6.8 Hz, 3H), 1.06 (minor, d, J = 6.8 Hz, 3H), 2.35-2.48 (major, m, 1H), 2.57-2.63 (minor, m, 1H), 3.75 (br d, J = 9.6 Hz, 1H), 3.80 (s, 3H), 4.97-5.05 (minor, br, 1H), 5.22 (dd, J = 10.0, 1.6 Hz, 1H), 5.28 (dd, J = 16.8, 1.6 Hz, 1H), 5.36-5.40 (major, br, 1H), 5.72-5.85 (minor, m, 1H), 5.86-5.99 (major, m, 1H), 6.87 (dd, J = 8.8, 2.4 Hz, 2H), 7.14-7.55 (m, 8H); ¹³C NMR(100 MHz, CDCl₃) δ15.6 (minor), 17.8 (major), 41.9 (minor), 44.1 (major), 55.2, 68.0 (major), 68.1 (minor), 113.5 (minor), 113.8 (major), 116.6, 126.7, 128.6, 129.5, 131.6, 132.6, 132.9, 140.1 (minor), 141.5 (major), 159.1, 166.8; IR (KBr) 3291, 3065, 3033, 2961, 2932, 2907, 2836, 2247, 1639, 1613, 1579, 1512, 1461, 1304, 1249, 1177, 1037, 910, 827, 810, 733, 693 cm^-1; HR-ESIMS: Calcd for C₁₉H₂₃N₂NaO₂ ([M+Na]⁺) 311.1754; Found: 311.1762. (1) N '-(1- (4-methoxyphenyl) -2-methylbut-3-enyl) benzohydrazide: (Formula XVII where R ¹ is 4-MeOC ₆ H ₄ ; R ² is H)
The yield of the product was 98%, α: γ = 99: 1, syn: anti = 9: 91.

Mp 87.4-88.2 C; ¹ H NMR (400 MHz, CDCl ₃ ) δ0.76 (major, d, J = 6.8 Hz, 3H), 1.06 (minor, d, J = 6.8 Hz, 3H), 2.35-2.48 ( major, m, 1H), 2.57-2.63 (minor, m, 1H), 3.75 (br d, J = 9.6 Hz, 1H), 3.80 (s, 3H), 4.97-5.05 (minor, br, 1H), 5.22 (dd, J = 10.0, 1.6 Hz, 1H), 5.28 (dd, J = 16.8, 1.6 Hz, 1H), 5.36-5.40 (major, br, 1H), 5.72-5.85 (minor, m, 1H), 5.86 -5.99 (major, m, 1H), 6.87 (dd, J = 8.8, 2.4 Hz, 2H), 7.14-7.55 (m, 8H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ15.6 (minor), 17.8 (major), 41.9 (minor), 44.1 (major), 55.2, 68.0 (major), 68.1 (minor), 113.5 (minor), 113.8 (major), 116.6, 126.7, 128.6, 129.5, 131.6, 132.6, 132.9 , 140.1 (minor), 141.5 (major), 159.1, 166.8; IR (KBr) 3291, 3065, 3033, 2961, 2932, 2907, 2836, 2247, 1639, 1613, 1579, 1512, 1461, 1304, 1249, 1177 , 1037, 910, 827, 810, 733, 693 cm ^-1 ; HR-ESIMS: Calcd for C ₁₉ H ₂₃ N ₂ NaO ₂ ([M + Na] ⁺ ) 311.1754; Found: 311.1762.

（２）N' -(1-(4-chlorophenyl)-2-methylbut-3-enyl)benzohydrazide: （式ＸＶＩＩでＲ^１が4-Cl C₆H₄；Ｒ^２がHのもの）
生成物の収率96%、α:γ = 99:1, syn:anti = 4:96であった。

Mp 121.9-123.0 C;¹H NMR (400 MHz, CDCl₃) δ0.78 (dd, J = 6.9, 2.1 Hz, 3H), 2.41 (dq, J = 8.9, 6.9 Hz, 1H), 3.82 (d, J = 9.6 Hz, 1H), 5.23 (d, J = 10.3 Hz, 1H), 5.28 (d, J = 17.4 Hz, 1H), 5.35 (br d, J = 6.8 Hz, 1H), 5.92 (ddd, J = 18.5, 8.9, 3.2 Hz, 1H), 7.28-7.32 (m, 5H), 7.36 (t, J = 7.6 Hz, 2H), 7.46 (t, J = 8.3 Hz, 1H), 7.53 (d, J = 7.6 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃) δ17.7, 44.0, 67.9, 116.9, 126.7, 128.6, 128.6, 129.8, 131.8, 132.7, 133.3, 139.4, 141.0, 167.2; IR (KBr) 3435, 3290, 3066, 2976, 2928, 2870, 2248, 1639, 1603, 1578, 1530, 1489, 1458, 1312, 1091, 1027, 1014, 997, 908, 821, 794, 733, 693, 648 cm^-1; HR-ESIMS: Calcd for C₁₈H₁₉N₂NaO ([M+Na]⁺) 337.1078; Found: 337.1074. (2) N ′-(1- (4-chlorophenyl) -2-methylbut-3-enyl) benzohydrazide: (Formula XVII where R ¹ is 4-Cl C ₆ H ₄ ; R ² is H)
The yield of the product was 96%, α: γ = 99: 1, syn: anti = 4: 96.

Mp 121.9-123.0 C; ¹ H NMR (400 MHz, CDCl ₃ ) δ0.78 (dd, J = 6.9, 2.1 Hz, 3H), 2.41 (dq, J = 8.9, 6.9 Hz, 1H), 3.82 (d, J = 9.6 Hz, 1H), 5.23 (d, J = 10.3 Hz, 1H), 5.28 (d, J = 17.4 Hz, 1H), 5.35 (br d, J = 6.8 Hz, 1H), 5.92 (ddd, J = 18.5, 8.9, 3.2 Hz, 1H), 7.28-7.32 (m, 5H), 7.36 (t, J = 7.6 Hz, 2H), 7.46 (t, J = 8.3 Hz, 1H), 7.53 (d, J = 7.6 Hz, 2H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ17.7, 44.0, 67.9, 116.9, 126.7, 128.6, 128.6, 129.8, 131.8, 132.7, 133.3, 139.4, 141.0, 167.2; IR (KBr) 3435, 3290, 3066, 2976, 2928, 2870, 2248, 1639, 1603, 1578, 1530, 1489, 1458, 1312, 1091, 1027, 1014, 997, 908, 821, 794, 733, 693, 648 cm ^-1 ; HR-ESIMS: Calcd for C ₁₈ H ₁₉ N ₂ NaO ([M + Na] ⁺ ) 337.1078; Found: 337.1074.

（３）N'-(1-(2-methoxyphenyl)-2-methylbut-3-enyl)benzohydrazide: （式ＸＶＩＩでＲ^１が2-MeO C₆H₄；Ｒ^２がHのもの）
生成物の収率75%、α:γ = 99:1, syn:anti = 6:94であった。

Mp 89.1-90.8 C;¹H NMR (400 MHz, CDCl₃) δ0.85 (major, d, J = 6.8 Hz, 3H), 1.07 (minor, d, J = 6.8 Hz, 3H), 2.53 (major, dd, J = 16.0, 9.2 Hz, 1H), 2.70-2.77 (minor, m, 1H), 3.72 (major, s, 3H), 3.76 (minor, s, 3H), 4.43 (major, br d, J = 10.0 Hz, 1H), 4.56 (minor, br d, J = 10.0 Hz, 1H), 5.21 (dd, J = 10.0, 2.0 Hz, 1H), 5.27 (dd, J = 17.2, 1.2 Hz, 1H), 5.42 (br d, J = 5.6 Hz, 1H), 5.97-6.06 (m, 1H), 6.87 (d, J = 8.0 Hz, 1H), 7.00 (dd, J = 8.0, 6.8 Hz, 1H), 7.20-7.58 (m, 8H); ¹³C NMR (100 MHz, CDCl₃) δ14.4 (minor), 17.5 (major), 40.4 (minor), 43.5 (major), 55.2 (minor), 55.4 (major), 61.0 (major), 61.6 (minor), 110.6 (minor), 110.7 (major), 114.7 (minor), 116.1 (major), 120.2 (minor), 120.8 (major), 126.7, 128.0, 128.2, 128.5, 129.0, 131.5, 133.1 (minor), 133.2 (major), 141.0 (minor), 141.8 (major), 157.8 (minor), 158.5 (major), 166.6 (minor), 166.7 (major); IR (KBr) 3445, 3292, 3065, 2962, 2932, 2837, 2249, 1652, 1612, 1579, 1512, 1457, 1442, 1420, 1304, 1249, 1176, 1068, 1037, 998, 909, 827, 734, 693, 648 cm^-1; HR-ESIMS: Calcd for C_19/H₂₃N₂O₂ ([M+H]⁺) 311.1754; Found: 311.1746. (3) N '-(1- (2-methoxyphenyl) -2-methylbut-3-enyl) benzohydrazide: (Formula XVII where R ¹ is 2-MeO C ₆ H ₄ ; R ² is H)
The yield of the product was 75%, α: γ = 99: 1, syn: anti = 6: 94.

Mp 89.1-90.8 C; ¹ H NMR (400 MHz, CDCl ₃ ) δ0.85 (major, d, J = 6.8 Hz, 3H), 1.07 (minor, d, J = 6.8 Hz, 3H), 2.53 (major, dd, J = 16.0, 9.2 Hz, 1H), 2.70-2.77 (minor, m, 1H), 3.72 (major, s, 3H), 3.76 (minor, s, 3H), 4.43 (major, br d, J = 10.0 Hz, 1H), 4.56 (minor, br d, J = 10.0 Hz, 1H), 5.21 (dd, J = 10.0, 2.0 Hz, 1H), 5.27 (dd, J = 17.2, 1.2 Hz, 1H), 5.42 (br d, J = 5.6 Hz, 1H), 5.97-6.06 (m, 1H), 6.87 (d, J = 8.0 Hz, 1H), 7.00 (dd, J = 8.0, 6.8 Hz, 1H), 7.20-7.58 (m, 8H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ14.4 (minor), 17.5 (major), 40.4 (minor), 43.5 (major), 55.2 (minor), 55.4 (major), 61.0 ( major), 61.6 (minor), 110.6 (minor), 110.7 (major), 114.7 (minor), 116.1 (major), 120.2 (minor), 120.8 (major), 126.7, 128.0, 128.2, 128.5, 129.0, 131.5, 133.1 (minor), 133.2 (major), 141.0 (minor), 141.8 (major), 157.8 (minor), 158.5 (major), 166.6 (minor), 166.7 (major); IR (KBr) 3445, 3292, 3065, 2962, 2932, 2837, 2249, 1652, 1612, 1579, 1512, 1457, 1442, 1420, 1304, 1249, 1176, 1068, 1037, 998, 909, 827, 734, 693, 648 cm ^-1 ; HR-ESIMS: Calcd for C _{19 /} H ₂₃ N ₂ O ₂ ([M + H] ⁺ ) 311.1754; Found: 311.1746.

（４）N'-(4-methyhexa-1,5-dien-3-yl)benzohydrazide: （式ＸＶＩＩでＲ^１がCH₂= CH；Ｒ^２がHのもの）
生成物の収率85%、α:γ = 99:1, syn:anti = 9:91であった。

¹H NMR (400 MHz, CDCl₃) δ1.00 (d, J = 6.8 Hz, 3H), 2.24 (dq, J = 8.6, 6.8 Hz, 1H), 3.25 (t, J = 8.8 Hz, 1H), 5.12-5.29 (m, 5H), 5.66 (ddd, J = 16.8, 10.0, 8.8 Hz, 1H), 5.84 (ddd, J = 16.8, 10.0, 8.8 Hz, 1H), 7.41 (t, J = 7.6 Hz, 2H), 7.50 (t, J = 7.6 Hz, 1H), 7.71 (d, J = 6.8 Hz, 2H), 7.77 (br s, 1H); ¹³C NMR (100 MHz, CDCl₃) δ17.3, 41.5, 67.9, 116.4, 119.5, 126.8, 128.7, 131.7, 133.0, 137.7, 160.9, 166.9; IR (neat) 3446, 3290, 3080, 2978, 2929, 2871, 2249, 1645, 1604, 1578, 1531, 1457, 1419, 1315, 1066, 1027, 996, 909, 734, 694, 648 cm^-1; HR-ESIMS: Calcd for C₁₄H₁₈N₂NaO ([M+Na]⁺) 253.1311; Found: 253.1299. (4) N ′-(4-methyhexa-1,5-dien-3-yl) benzohydrazide: (Formula XVII where R ¹ is CH ₂ = CH; R ² is H)
The yield of the product was 85%, α: γ = 99: 1, syn: anti = 9: 91.

¹ H NMR (400 MHz, CDCl ₃ ) δ1.00 (d, J = 6.8 Hz, 3H), 2.24 (dq, J = 8.6, 6.8 Hz, 1H), 3.25 (t, J = 8.8 Hz, 1H), 5.12-5.29 (m, 5H), 5.66 (ddd, J = 16.8, 10.0, 8.8 Hz, 1H), 5.84 (ddd, J = 16.8, 10.0, 8.8 Hz, 1H), 7.41 (t, J = 7.6 Hz, 2H), 7.50 (t, J = 7.6 Hz, 1H), 7.71 (d, J = 6.8 Hz, 2H), 7.77 (br s, 1H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ17.3, 41.5 , 67.9, 116.4, 119.5, 126.8, 128.7, 131.7, 133.0, 137.7, 160.9, 166.9; IR (neat) 3446, 3290, 3080, 2978, 2929, 2871, 2249, 1645, 1604, 1578, 1531, 1457, 1419 , 1315, 1066, 1027, 996, 909, 734, 694, 648 cm ^-1 ; HR-ESIMS: Calcd for C ₁₄ H ₁₈ N ₂ NaO ([M + Na] ⁺ ) 253.1311; Found: 253.1299.

（５）N'-(4-methyl-1-phenylhex-5-en-1-yn-3-yl)benzohydrazide:（式ＸＶＩＩでＲ^１がPhC≡C；Ｒ^２がHのもの）
生成物の収率99%、α:γ = 99:1, syn:anti = 5:95であった。

Mp 101.8-104.3 C;¹H NMR (400 MHz, CDCl₃) δ1.24 (dd, J = 6.9, 2.1 Hz, 3H), 2.53 (dq, J = 6.9, 6.2 Hz, 1H), 4.00 (dd, J = 6.8, 3.4 Hz, 1H), 5.15 (d, J = 10.3 Hz, 1H), 5.21 (d, J = 16.5 Hz, 1H), 5.25 (br s, 1H), 5.89 (ddd, J = 18.3, 8.3, 2.0 Hz, 1H), 7.26-7.41 (m, 7H), 7.49 (t, J = 6.9 Hz, 1H), 7.77 (d, J = 6.9 Hz, 2H), 8.18 (br d, J = 6.2 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃) δ16.7, 41.7, 57.8, 85.1, 87.3, 116.4, 122.7, 126.9, 128.2, 128.6, 131.7, 131.8, 132.7, 140.1, 167.1; IR (KBr) 3299, 3065, 3034, 2975, 2931, 2902, 2860, 2248, 1646, 1602, 1579, 1506, 1490, 1457, 1442, 1372, 1339, 1313, 1169, 1087, 1070, 1027, 1010, 995, 908, 862, 840, 798, 760, 733, 690, 650 cm^-1; HR-ESIMS: Calcd for C₂₀H₂₁N₂O₅ ([M+H]⁺) 305.1648; Found: 305.1645. (5) N '-(4-methyl-1-phenylhex-5-en-1-yn-3-yl) benzohydrazide: (Formula XVII where R ¹ is PhC≡C; R ² is H)
The yield of the product was 99%, α: γ = 99: 1, syn: anti = 5: 95.

Mp 101.8-104.3 C; ¹ H NMR (400 MHz, CDCl ₃ ) δ1.24 (dd, J = 6.9, 2.1 Hz, 3H), 2.53 (dq, J = 6.9, 6.2 Hz, 1H), 4.00 (dd, J = 6.8, 3.4 Hz, 1H), 5.15 (d, J = 10.3 Hz, 1H), 5.21 (d, J = 16.5 Hz, 1H), 5.25 (br s, 1H), 5.89 (ddd, J = 18.3, 8.3, 2.0 Hz, 1H), 7.26-7.41 (m, 7H), 7.49 (t, J = 6.9 Hz, 1H), 7.77 (d, J = 6.9 Hz, 2H), 8.18 (br d, J = 6.2 Hz , 1H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ16.7, 41.7, 57.8, 85.1, 87.3, 116.4, 122.7, 126.9, 128.2, 128.6, 131.7, 131.8, 132.7, 140.1, 167.1; IR (KBr) 3299, 3065, 3034, 2975, 2931, 2902, 2860, 2248, 1646, 1602, 1579, 1506, 1490, 1457, 1442, 1372, 1339, 1313, 1169, 1087, 1070, 1027, 1010, 995, 908, 862, 840, 798, 760, 733, 690, 650 cm ^-1 ; HR-ESIMS: Calcd for C ₂₀ H ₂₁ N ₂ O ₅ ([M + H] ⁺ ) 305.1648; Found: 305.1645.

（６）Methyl 2,3-dimethyl-2-(2-(phenylcarbonyl)hydrazinyl)pent-4-enoate: （式ＸＶＩＩでＲ^１がMeO₂C；Ｒ^２がMeのもの）
生成物の収率95%、α:γ = 91:9, syn:anti = 8:92であった。

Mp 61.8-63.7 C;¹H NMR (400 MHz, CDCl₃) δ1.11 (major, d, J = 6.8 Hz, 3H), 1.12 (minor, d, J = 6.8 Hz, 3H), 1.35 (major, s, 3H), 1.36 (minor, s, 3H), 2.65-2.77 (m, 1H), 3.75 (s, 3H), 5.10-5.20 (m, 3H), 5.80-5.92 (m, 1H), 7.43 (t, J = 7.6 Hz, 2H), 7.50 (t, J = 7.6 Hz, 1H), 7.71-7.85 (m, 3H); ¹³C NMR (100 MHz, CDCl₃) δ14.3 (minor), 14.8 (major), 18.1 (minor), 18.7 (major), 43.6 (minor), 44.0 (major), 52.1 (minor), 52.2 (major), 67.7 (major), 68.0 (minor), 116.6 (minor), 117.6 (major), 126.8, 128.6, 131.7, 132.8 (minor), 132.9 (major), 137.7 (major), 138.6 (minor), 166.4 (major), 166.6 (minor), 175.2 (minor), 175.3 (major); IR (KBr) 3282, 3067, 2981, 2950, 2877, 2840, 1733, 1644, 1603, 1579, 1541, 1457, 1381, 1312, 1261, 1191, 1130, 1071, 1027, 997, 922, 793, 694 cm^-1; HR-ESIMS: Calcd for C₁₅H₂₁N₂O₅ ([M+H]⁺) 277.1547; Found: 277.1540. (6) Methyl 2,3-dimethyl-2- (2- (phenylcarbonyl) hydrazinyl) pent-4-enoate: (Formula XVII where R ¹ is MeO ₂ C; R ² is Me)
The yield of the product was 95%, α: γ = 91: 9, syn: anti = 8: 92.

Mp 61.8-63.7 C; ¹ H NMR (400 MHz, CDCl ₃ ) δ1.11 (major, d, J = 6.8 Hz, 3H), 1.12 (minor, d, J = 6.8 Hz, 3H), 1.35 (major, s, 3H), 1.36 (minor, s, 3H), 2.65-2.77 (m, 1H), 3.75 (s, 3H), 5.10-5.20 (m, 3H), 5.80-5.92 (m, 1H), 7.43 ( t, J = 7.6 Hz, 2H), 7.50 (t, J = 7.6 Hz, 1H), 7.71-7.85 (m, 3H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ14.3 (minor), 14.8 ( major), 18.1 (minor), 18.7 (major), 43.6 (minor), 44.0 (major), 52.1 (minor), 52.2 (major), 67.7 (major), 68.0 (minor), 116.6 (minor), 117.6 ( major), 126.8, 128.6, 131.7, 132.8 (minor), 132.9 (major), 137.7 (major), 138.6 (minor), 166.4 (major), 166.6 (minor), 175.2 (minor), 175.3 (major); IR (KBr) 3282, 3067, 2981 , 2950, 2877, 2840, 1733, 1644, 1603, 1579, 1541, 1457, 1381, 1312, 1261, 1191, 1130, 1071, 1027, 997, 922, 793, 694 cm - ¹ ; HR-ESIMS: Calcd for C ₁₅ H ₂₁ N ₂ O ₅ ([M + H] ⁺ ) 277.1547; Found: 277.1540.

（７）N'-(2-chloro-1-phenylbut-3-enyl)benzohydrazide:（式ＸＶＩＩでＲ^１がPh；Ｒ^２がHのもの、但し、式ＸＶＩＩのボロネートの代わりに式ＩＶのボロネート（R⁵=Cl, R⁶=R⁷=R⁸=H）を用いた）
生成物の収率９２%、α:γ = 95:5, major:minor = >95:<5であった。

¹H NMR (400 MHz, CDCl₃) δ4.39 (d, J = 6.4 Hz, 1H), 4.57 (dd, J = 9.2, 6.4 Hz, 1H), 5.28 (d, J = 10.0 Hz, 1H), 5.33 (br s, 1H), 5.35 (d, J = 17.2 Hz, 1H), 6.00 (ddd, J = 17.2, 9.6, 9.6 Hz, 1H), 7.33-7.48 (m, 8H), 7.57-7.62 (m, 2H), 7.71 (br s, 1H); ¹³C NMR (100 MHz, CDCl₃) δ64.4, 68.4, 119.5, 126.9, 128.4, 128.4, 128.6, 128.8, 131.9, 132.5, 135.2, 137.6, 167.4; IR (neat) 3282, 3062, 3032, 1644, 1603, 1578, 1531, 1494, 1455, 1420, 1356, 1313, 1266, 1073, 1027, 989, 933, 801, 738, 699 cm^-1; HR-ESIMS: Calcd for C₁₇H₁₈ClN₂O ([M+H]⁺) 301.1102; Found:301.1110. (7) N '-(2-chloro-1-phenylbut-3-enyl) benzohydrazide: (Formula XVII where R ¹ is Ph; R ² is H, except that the boronate of formula IV (R ⁵ = Cl, R ⁶ = R ⁷ = R ⁸ = H) is used instead of the boronate of formula XVII)
The yield of the product was 92%, α: γ = 95: 5, major: minor => 95: <5.

¹ H NMR (400 MHz, CDCl ₃ ) δ4.39 (d, J = 6.4 Hz, 1H), 4.57 (dd, J = 9.2, 6.4 Hz, 1H), 5.28 (d, J = 10.0 Hz, 1H), 5.33 (br s, 1H), 5.35 (d, J = 17.2 Hz, 1H), 6.00 (ddd, J = 17.2, 9.6, 9.6 Hz, 1H), 7.33-7.48 (m, 8H), 7.57-7.62 (m , 2H), 7.71 (br s, 1H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ 64.4, 68.4, 119.5, 126.9, 128.4, 128.4, 128.6, 128.8, 131.9, 132.5, 135.2, 137.6, 167.4; IR (neat) 3282, 3062, 3032, 1644, 1603, 1578, 1531, 1494, 1455, 1420, 1356, 1313, 1266, 1073, 1027, 989, 933, 801, 738, 699 cm ^-1 ; HR-ESIMS : Calcd for C ₁₇ H ₁₈ ClN ₂ O ([M + H] ⁺ ) 301.1102; Found: 301.1110.

（８）N'-(2-(benzyloxy)-1-phenylbut-3-enyl)benzohydrazide:（式ＸＶＩＩでＲ^１がPh；Ｒ^２がHのもの、但し、式ＸＶＩＩのボロネートの代わりに式ＩＶのボロネート（R⁵=ベンジルオキシ, R⁶=R⁷=R⁸=H）を用いた）
生成物の収率＞９９%、α:γ =９７:３, major:minor = >94:<6であった。

¹H NMR (400 MHz, CDCl₃) δ3.97 (dd, J = 7.2, 6.4 Hz, 1H), 4.31 (d, J = 6.0 Hz, 1H), 4.38 (d, J = 11.6 Hz, 1H), 4.61 (d, J = 12.0 Hz, 1H), 5.25 (d, J = 17.2 Hz, 1H), 5.38 (d, J = 10.4 Hz, 1H), 5.43 (br d, J = 6.0 Hz, 1H), 5.93 (ddd, J = 19.6, 9.6, 8.0 Hz, 1H), 7.16-7.18 (m, 2H), 7.24-7.34 (m, 8H), 7.38-7.44 (m, 3H), 7.49 (d, J = 7.2 Hz, 2H), 7.54 (br d, J = 4.4 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃) δ67.3, 70.2, 82.8, 120.4, 126.7, 127.5, 127.7, 127.8, 128.2, 128.3, 128.5, 128.6, 131.6, 132.8, 135.0, 138.1, 138.5, 166.4; IR (neat) 3440, 3065, 3032, 2870, 2250, 1654, 1604, 1579, 1523, 1496, 1455, 1387, 1362, 1306, 1205, 1091, 1071, 1027, 994, 909, 792, 734, 701cm^-1; HR-ESIMS: Calcd for C₂₄H₂₅N₂O₂ ([M+H]⁺) 373.1911; Found: 373.1927. (8) N ′-(2- (benzyloxy) -1-phenylbut-3-enyl) benzohydrazide: (formula XVII, wherein R ¹ is Ph; R ² is H, provided that formula IV is replaced by formula IV instead of boronate of formula XVII Boronate (using R ⁵ = benzyloxy, R ⁶ = R ⁷ = R ⁸ = H)
The yield of the product was> 99%, α: γ = 97: 3, major: minor => 94: <6.

¹ H NMR (400 MHz, CDCl ₃ ) δ3.97 (dd, J = 7.2, 6.4 Hz, 1H), 4.31 (d, J = 6.0 Hz, 1H), 4.38 (d, J = 11.6 Hz, 1H), 4.61 (d, J = 12.0 Hz, 1H), 5.25 (d, J = 17.2 Hz, 1H), 5.38 (d, J = 10.4 Hz, 1H), 5.43 (br d, J = 6.0 Hz, 1H), 5.93 (ddd, J = 19.6, 9.6, 8.0 Hz, 1H), 7.16-7.18 (m, 2H), 7.24-7.34 (m, 8H), 7.38-7.44 (m, 3H), 7.49 (d, J = 7.2 Hz , 2H), 7.54 (br d, J = 4.4 Hz, 1H); ¹³ C NMR (100 MHz, CDCl ₃ ) δ67.3, 70.2, 82.8, 120.4, 126.7, 127.5, 127.7, 127.8, 128.2, 128.3, 128.5 , 128.6, 131.6, 132.8, 135.0, 138.1, 138.5, 166.4; IR (neat) 3440, 3065, 3032, 2870, 2250, 1654, 1604, 1579, 1523, 1496, 1455, 1387, 1362, 1306, 1205, 1091 , 1071, 1027, 994, 909, 792, 734, 701cm ^-1 ; HR-ESIMS: Calcd for C ₂₄ H ₂₅ N ₂ O ₂ ([M + H] ⁺ ) 373.1911; Found: 373.1927.

＜１価のヨウ化インジウムと不斉配位子（ビスオキサゾリン）からなる不斉触媒による、アリルボロネートのN-アシルヒドラゾンへの不斉付加反応の一般操作＞

アルゴン雰囲気下、１価のヨウ化インジウム(3.0 mg, 0.0125 mmol) 及びベンズアルデヒド由来の N-ベンゾイルヒドラゾン(56.1 mg, 0.250 mmol)および不斉配位子である2,2'-methylenebis[(4R,5S)-4,5-diphenyl-2-oxazoline] (Ph₂-Box, 5.7 mg, 0.0125 mmol)をフラスコに加えた。次にトルエン (0.50 mL) およびメタノール(10 μL, 0.25 mmol)を加え、反応容器を０度に冷却した。さらにアリルボロネート(70 μL, 0.375 mmol)をゆっくり加えて０度で４８時間撹拌した。1 M K₂CO₃ 水溶液(2.0 mL)を加えて反応を停止し、温度を室温まで上げ、塩化メチレンで３回抽出した。有機層を合わせて飽和食塩水で洗浄し、無水硫酸ナトリウムで乾燥した。溶媒を留去した後、粗生成物を分取薄層クロマトグラフィー(ヘキサン/酢酸エチル = 2/1) で精製し、生成物であるN'-(1-phenylbut-3-enyl)benzohydrazideを83%収率(55.4 mg、0.208 mmol)、94% eeで与えた。 <General operation of asymmetric addition reaction of allylboronate to N-acylhydrazone by asymmetric catalyst consisting of monovalent indium iodide and asymmetric ligand (bisoxazoline)>

Under an argon atmosphere, monovalent indium iodide (3.0 mg, 0.0125 mmol) and benzaldehyde-derived N-benzoylhydrazone (56.1 mg, 0.250 mmol) and the asymmetric ligand 2,2'-methylenebis [(4R, 5S) -4,5-diphenyl-2-oxazoline] (Ph ₂ -Box, 5.7 mg, 0.0125 mmol) was added to the flask. Toluene (0.50 mL) and methanol (10 μL, 0.25 mmol) were then added and the reaction vessel was cooled to 0 degrees. Further, allyl boronate (70 μL, 0.375 mmol) was slowly added and stirred at 0 degree for 48 hours. 1 MK ₂ CO ₃ aqueous solution (2.0 mL) was added to stop the reaction, the temperature was raised to room temperature, and the mixture was extracted with methylene chloride three times. The organic layers were combined, washed with saturated brine, and dried over anhydrous sodium sulfate. After distilling off the solvent, the crude product was purified by preparative thin layer chromatography (hexane / ethyl acetate = 2/1), and the product N ′-(1-phenylbut-3-enyl) benzohydrazide was purified by 83. % Yield (55.4 mg, 0.208 mmol), given in 94% ee.

＜１価のヨウ化インジウムと不斉配位子（セミコリン）からなる不斉触媒による、アリルボロネートのN-アシルヒドラゾンへの不斉付加反応の一般操作＞

アルゴン雰囲気下、加熱乾燥した5ml-スクリュー管瓶に、ヨウ化インジウム（Ｉ）（5 mol%）及び不斉配位子L^*3d（式ＸＶＩＩＩの構造式参照） (5 mol%)を秤量した。メタノール（3当量）を加えた後、トルエン溶媒中、室温で1時間攪拌して触媒調製を行った。ヒドラゾン1(0.2−0.3mmol;1.0等量)を加えた後、アルゴンで置換し、０℃まで冷却した。表１に示した種々のヒドラゾンアリルボロネート2（0.30-0.45mmol;1.5等量）を滴下して加え、それぞれ表１に示した時間攪拌を行った。反応終了後、ジクロロメタンで(by factor 10)希釈し、炭酸カリウム水溶液（１Ｍ）を加え、反応を停止し、室温に戻した。有機相を分離した後、ジクロロメタンで有機相を抽出する操作を３回繰り返し、無水硫酸ナトリウムを用いて乾燥した。ろ過後、減圧濃縮し、得られた粗製化合物を分取薄層クロマトグラフィーにより精製して（ヘキサン/酢酸エチル＝19:1-4:1）、目的のホモアリルヒドラジド4(それぞれ実験例１〜１６の4a〜4pに相当)を得た。
得られた結果を表１に示す。 <General operation of asymmetric addition reaction of allylboronate to N-acylhydrazone by asymmetric catalyst consisting of monovalent indium iodide and asymmetric ligand (semicholine)>

Indium iodide (I) (5 mol%) and asymmetric ligand L ^* 3d (see structural formula of formula XVIII) (5 mol%) were weighed into a 5 ml-screw tube bottle that had been dried under heating in an argon atmosphere. . After adding methanol (3 equivalents), the catalyst was prepared by stirring in a toluene solvent at room temperature for 1 hour. After adding hydrazone 1 (0.2-0.3 mmol; 1.0 equivalent), it was replaced with argon and cooled to 0 ° C. Various hydrazone allyl boronates 2 (0.30-0.45 mmol; 1.5 equivalents) shown in Table 1 were added dropwise, and stirring was performed for the times shown in Table 1, respectively. After completion of the reaction, the reaction mixture was diluted with dichloromethane (by factor 10), and an aqueous potassium carbonate solution (1M) was added to stop the reaction, and the temperature was returned to room temperature. After separating the organic phase, the operation of extracting the organic phase with dichloromethane was repeated three times and dried using anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the resulting crude compound was purified by preparative thin layer chromatography (hexane / ethyl acetate = 19: 1-4: 1) to obtain the desired homoallyl hydrazide 4 (each of Experimental Examples 1 to 4). 16 corresponding to 4a to 4p).
The obtained results are shown in Table 1.

実験例１〜１６の生成物4a〜4pのうち、4a, 4b, 4c, 4d, 4e, 4f, 4h, 4k, 4m, 4o, 4pは既知化合物であった。なお、生成物4a,4b,4c,4d,4h,4kの分析値は、それぞれ文献Ａ（R. Berger, P. M. A. Rabbat, J. L. Leighton, J. Am. Chem. Soc. 2003, 125, 9596-9597.）、文献Ｂ（U. Schneider, I-H. Chen, S. Kobayashi, Org. Lett. 2008, 10, 737-740.）、文献Ｃ（F. Garcia-Flores, L. S. Flores-Michel, E. Juaristi, Tetrahedron Lett. 2006, 47, 8235-8238.）、文献Ｄ（S. Kobayashi, C. Ogawa, H. Konishi, M. Sugiura, J. Am. Chem. Soc. 2003, 125, 6610-6611.）、文献Ｅ（D. Hui, G. K. Friestad, Synthesis 2004, 2216-2221.）、文献Ｆ（K. L. Tan, E. N. Jacobsen, Angew. Chem. Int. Ed. 2007, 46, 1315-1317.）の値と一致した。
また、生成物4e,4mの分析値は、上記非特許文献２の値と一致した。生成物4f,4pの分析値は、上記非特許文献４の値と一致した。生成物4oの分析値は、上記非特許文献６の値と一致した。 Among the products 4a to 4p of Experimental Examples 1 to 16, 4a, 4b, 4c, 4d, 4e, 4f, 4h, 4k, 4m, 4o, and 4p were known compounds. Analytical values of the products 4a, 4b, 4c, 4d, 4h, and 4k are shown in Reference A (R. Berger, PMA Rabbat, JL Leighton, J. Am. Chem. Soc. 2003, 125, 9596-9597. ), Reference B (U. Schneider, IH. Chen, S. Kobayashi, Org. Lett. 2008, 10, 737-740.), Reference C (F. Garcia-Flores, LS Flores-Michel, E. Juaristi, Tetrahedron). Lett. 2006, 47, 8235-8238.), Literature D (S. Kobayashi, C. Ogawa, H. Konishi, M. Sugiura, J. Am. Chem. Soc. 2003, 125, 6610-6611.), Literature E (D. Hui, GK Friestad, Synthesis 2004, 2216-2221.) And literature F (KL Tan, EN Jacobsen, Angew. Chem. Int. Ed. 2007, 46, 1315-1317.).
The analytical values of the products 4e and 4m coincided with the values of Non-Patent Document 2 above. The analytical values of the products 4f and 4p agreed with the values of Non-Patent Document 4 above. The analytical value of the product 4o coincided with the value of Non-Patent Document 6 above.

一方、生成物4g,4i,4j,4l,4nは、それぞれ新規の化合物であり、これらの化合物のデータを以下に示す。 On the other hand, the products 4g, 4i, 4j, 4l, and 4n are novel compounds, and data of these compounds are shown below.

生成物4g（N-[(R)-1-(4-phenylphenyl)but-3-enyl]benzohydrazide、式ＸＩＸ、実験例７）

生成物4gのデータ：白色固体(収率： 98%; er = 98:2); ¹H NMR (CDCl₃, 400 MHz): δ= 2.47-2.60 (m, 2H), 4.21 (t, J = 7.2 Hz, 1H), 5.11-5.30 (m, 3H), 5.80-5.92 (m, 1H), 7.31-7.46 (m, 8H), 7.55-7.70 (m, 7H); ¹³C NMR (CDCl₃, 100 MHz): δ= 40.3, 63.5, 118.1, 126.7 (2C), 126.9 (3C), 127.1 (2C), 127.2, 128.0 (2C), 128.5 (2C), 128.7 (2C), 131.7, 132.6, 134.3, 140.4, 140.6, 167.1; HPLC (DAICEL CHIRALPAK IC, ⁿhexane-ⁱPrOH = 9:1, 1.0 mL/min): t_R (min) = 13.0 (R), 16.6 (S). Product 4g (N-[(R) -1- (4-phenylphenyl) but-3-enyl] benzohydrazide, Formula XIX, Experimental Example 7)

Data for product 4g: white solid (yield: 98%; er = 98: 2); ¹ H NMR (CDCl ₃ , 400 MHz): δ = 2.47-2.60 (m, 2H), 4.21 (t, J = 7.2 Hz, 1H), 5.11-5.30 (m, 3H), 5.80-5.92 (m, 1H), 7.31-7.46 (m, 8H), 7.55-7.70 (m, 7H); ¹³ C NMR (CDCl ₃ , 100 MHz): δ = 40.3, 63.5, 118.1, 126.7 (2C), 126.9 (3C), 127.1 (2C), 127.2, 128.0 (2C), 128.5 (2C), 128.7 (2C), 131.7, 132.6, 134.3, 140.4 , 140.6, 167.1; HPLC (DAICEL CHIRALPAK IC, ⁿ hexane- ⁱ PrOH = 9: 1, 1.0 mL / min): t _R (min) = 13.0 (R), 16.6 (S).

生成物4j（N-[(R)-1-(naphthalene-2-yl)but-3-enyl]benzohydrazide、式ＸＸ、実験例１０）

生成物4jのデータ：薄黄色固体(収率： 90%; er = 98:2); ¹H NMR (CDCl₃, 500 MHz): δ= 2.51-2.63 (m, 2H), 4.32 (dd, J = 6.8 Hz, J = 7.3 Hz, 1H), 5.09-5.21 (m, 2H), 5.33 (br s, 1H), 5.79-5.89 (m, 1H), 7.27-7.32 (m, 2H), 7.39-7.49 (m, 3H), 7.51-7.57 (m, 4H), 7.78-7.85 (m, 4H); ¹³C NMR (CDCl₃, 125 MHz): δ= 40.3, 64.0, 118.1, 125.4, 125.8, 126.0, 126.7 (3C), 127.6, 127.8, 128.3, 128.5 (2C), 131.7, 132.6, 133.0, 133.3, 134.3, 139.0, 167.1; HPLC (DAICEL CHIRALPAK ADH, ⁿhexane-ⁱPrOH = 9:1, 1.0 mL/min): t_R (min) = 18.8 (R), 21.7 (S). Product 4j (N-[(R) -1- (naphthalene-2-yl) but-3-enyl] benzohydrazide, Formula XX, Experimental Example 10)

Data for product 4j: pale yellow solid (yield: 90%; er = 98: 2); ¹ H NMR (CDCl ₃ , 500 MHz): δ = 2.51-2.63 (m, 2H), 4.32 (dd, J = 6.8 Hz, J = 7.3 Hz, 1H), 5.09-5.21 (m, 2H), 5.33 (br s, 1H), 5.79-5.89 (m, 1H), 7.27-7.32 (m, 2H), 7.39-7.49 (m, 3H), 7.51-7.57 (m, 4H), 7.78-7.85 (m, 4H); ¹³ C NMR (CDCl ₃ , 125 MHz): δ = 40.3, 64.0, 118.1, 125.4, 125.8, 126.0, 126.7 (3C), 127.6, 127.8, 128.3, 128.5 (2C), 131.7, 132.6, 133.0, 133.3, 134.3, 139.0, 167.1; HPLC (DAICEL CHIRALPAK ADH, ⁿ hexane- ⁱ PrOH = 9: 1, 1.0 mL / min) : t _R (min) = 18.8 (R), 21.7 (S).

生成物4l（N-[(R)-1-(furan-3-yl)but-3-enyl]benzohydrazide、式ＸＸＩ、実験例１２）

生成物4lのデータ：白色固体(収率： 97%; er = 95:5); ¹H NMR (CDCl₃, 500 MHz): δ= 2.32-2.47 (m, 2H), 4.05 (t, J = 6.8 Hz, 1H), 4.95-5.15 (m, 3H), 5.68-5.78 (m, 1H), 6.35 (s, 1H), 7.28-7.34 (m, 4H), 7.38-7.43 (m, 1H), 7.56-7.60 (m, 2H), 7.74 (br s, 1H); ¹³C NMR (CDCl₃, 125 MHz): δ= 38.9, 55.4, 109.0, 117.9, 125.4, 126.7, 128.5 (2C), 131.8, 132.6, 134.3, 140.3 (2C), 143.2, 167.1; HPLC (DAICEL CHIRALPAK IC, ⁿhexane-ⁱPrOH = 9:1, 1.0 mL/min): t_R (min) = 10.6 (R), 12.5 (S). Product 4l (N-[(R) -1- (furan-3-yl) but-3-enyl] benzohydrazide, Formula XXI, Experimental Example 12)

Data for product 4l: white solid (yield: 97%; er = 95: 5); ¹ H NMR (CDCl ₃ , 500 MHz): δ = 2.32-2.47 (m, 2H), 4.05 (t, J = 6.8 Hz, 1H), 4.95-5.15 (m, 3H), 5.68-5.78 (m, 1H), 6.35 (s, 1H), 7.28-7.34 (m, 4H), 7.38-7.43 (m, 1H), 7.56 -7.60 (m, 2H), 7.74 (br s, 1H); ¹³ C NMR (CDCl ₃ , 125 MHz): δ = 38.9, 55.4, 109.0, 117.9, 125.4, 126.7, 128.5 (2C), 131.8, 132.6, 134.3, 140.3 (2C), 143.2, 167.1; HPLC (DAICEL CHIRALPAK IC, ⁿ hexane- ⁱ PrOH = 9: 1, 1.0 mL / min): t _R (min) = 10.6 (R), 12.5 (S).

生成物4n（N-[(R)-1-(pyridin-4-yl)but-3-enyl]benzohydrazide、式ＸＸＩＩ、実験例１４）

生成物4lのデータ：薄黄色固体(収率： 98%; er = 92:8); ¹H NMR (CDCl₃, 500 MHz): δ= 2.41-2.54 (m, 2H), 4.16 (dd, J = 6.8 Hz J = 7.3 Hz, 1H), 5.12-5.26 (m, 3H), 5.76-5.86 (m, 1H), 7.24-7.28 (m, 2H), 7.34-7.39 (m, 2H), 7.44-7.49 (m, 1H), 7.66-7.72 (m, 2H), 8.34-8.45 (m, 3H); ¹³C NMR (CDCl₃, 125 MHz): δ= 39.8, 63.0, 118.8, 122.9 (2C), 126.9 (2C), 128.5 (2C), 131.8, 132.5, 133.3, 149.6 (2C), 151.2, 167.6; HPLC (DAICEL CHIRALPAK ADH, ⁿhexane-ⁱPrOH = 9:1, 1.0 mL/min): t_R (min) = 25.5 (R), 29.7 (S). Product 4n (N-[(R) -1- (pyridin-4-yl) but-3-enyl] benzohydrazide, Formula XXII, Experimental Example 14)

Data for product 4l: pale yellow solid (yield: 98%; er = 92: 8); ¹ H NMR (CDCl ₃ , 500 MHz): δ = 2.41-2.54 (m, 2H), 4.16 (dd, J = 6.8 Hz J = 7.3 Hz, 1H), 5.12-5.26 (m, 3H), 5.76-5.86 (m, 1H), 7.24-7.28 (m, 2H), 7.34-7.39 (m, 2H), 7.44-7.49 (m, 1H), 7.66-7.72 (m, 2H), 8.34-8.45 (m, 3H); ¹³ C NMR (CDCl ₃ , 125 MHz): δ = 39.8, 63.0, 118.8, 122.9 (2C), 126.9 ( 2C), 128.5 (2C), 131.8, 132.5, 133.3, 149.6 (2C), 151.2, 167.6; HPLC (DAICEL CHIRALPAK ADH, ⁿ hexane- ⁱ PrOH = 9: 1, 1.0 mL / min): t _R (min) = 25.5 (R), 29.7 (S).

＜α位がメチル基のα-置換アリルボロネートを用いたN-アシルヒドラゾンへの不斉付加反応の一般操作＞

アルゴン雰囲気下、加熱乾燥した5ml-スクリュー管瓶に、ヨウ化インジウム（Ｉ）（10 mol%）及び不斉配位子L^*3d（式ＸＶＩＩＩの構造式参照） (10 mol%)を秤量した。それぞれ実験例２１〜３１に対応するよう、表２に示す溶媒を加えた後、室温で1時間攪拌して触媒調製を行った。ヒドラゾン1(0.2−0.3mmol;1.0等量)を加えた後、アルゴンで置換し、所定温度まで冷却した。表１に示した種々のヒドラゾンアリルボロネートrac-5（0.30-0.45mmol;1.5等量）を滴下して加え、０℃で8〜96時間（各実験例で異なる）攪拌を行った。反応終了後、ジクロロメタンで(by factor 10)希釈し、炭酸カリウム水溶液（１Ｍ）を加え、反応を停止し、室温に戻した。有機相を分離した後、ジクロロメタンで有機相を抽出する操作を３回繰り返し、無水硫酸ナトリウムを用いて乾燥した。ろ過後、減圧濃縮し、得られた粗製化合物を分取薄層クロマトグラフィーにより精製して（ヘキサン/酢酸エチル＝19:1-4:1）、目的のホモアリルヒドラジド6(それぞれ実験例２１〜３１の6a〜6rに相当)を得た。
得られた結果を表２に示す。 <General operation of asymmetric addition reaction to N-acylhydrazone using α-substituted allylboronate with α-methyl at the α-position>

In 5 ml-screw tube bottle dried under heat in an argon atmosphere, indium (I) iodide (10 mol%) and asymmetric ligand L ^* 3d (see structural formula of formula XVIII) (10 mol%) were weighed. . The solvents shown in Table 2 were added so as to correspond to Experimental Examples 21 to 31, respectively, and then the catalyst was prepared by stirring at room temperature for 1 hour. After adding hydrazone 1 (0.2-0.3 mmol; 1.0 equivalent), it was replaced with argon and cooled to a predetermined temperature. Various hydrazone allyl boronates rac-5 (0.30-0.45 mmol; 1.5 equivalents) shown in Table 1 were added dropwise, and the mixture was stirred at 0 ° C. for 8 to 96 hours (different in each experimental example). After completion of the reaction, the reaction mixture was diluted with dichloromethane (by factor 10), and an aqueous potassium carbonate solution (1M) was added to stop the reaction, and the temperature was returned to room temperature. After separating the organic phase, the operation of extracting the organic phase with dichloromethane was repeated three times and dried using anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the resulting crude compound was purified by preparative thin layer chromatography (hexane / ethyl acetate = 19: 1-4: 1) to give the desired homoallyl hydrazide 6 (each of Experimental Examples 21 to 21). 31 corresponding to 6a to 6r).
The obtained results are shown in Table 2.

生成物6a〜6rのジアステレオマー比（α-付加物のanti:syn比）の値、構造異性体比 (α：γ比比)の値、は¹H NMR 分析により決定した。
生成物6a〜6rのうち、6a,6dは既知化合物であり、それぞれ上記非特許文献１，４の値と一致した。
一方、生成物6c,6e,6f,6i,6j,6k,6l,6o,6pのエナンチオマーはそれぞれ新規の化合物である。各生成物の絶対配置は6a,6dの文献値との比較により決定した。これらの化合物のデータを以下に示す。 The values of diastereomeric ratio (anti-syn ratio of α-adduct) and structural isomer ratio (α: γ ratio) of products 6a to 6r were determined by ¹ H NMR analysis.
Of the products 6a to 6r, 6a and 6d are known compounds, which correspond to the values of Non-Patent Documents 1 and 4, respectively.
On the other hand, the enantiomers of the products 6c, 6e, 6f, 6i, 6j, 6k, 6l, 6o, and 6p are novel compounds. The absolute configuration of each product was determined by comparison with literature values of 6a and 6d. Data for these compounds is shown below.

生成物6c（N-[(1R,2R)-1-(3-methoxyphenyl)-2-methylbut-3-enyl]benzohydrazide、式ＸＸＩＶ、実験例２２）

生成物6cのデータ：薄黄色液体(収率： 90%;α:γ=>99:1;anti:syn=6.1:1(α-adduct); er = 94:6(anti-diastereisomer)); ¹H NMR (CDCl₃, 500 MHz): δ= 0.80 (anti; d, J = 6.8 Hz, 3H), 1.08 (syn; d, J = 6.8 Hz, 3H), 2.39-2.49 (anti; m, 1H), 2.63-2.68 (syn; m, 1H), 3.79 (anti; s, 3H), 3.81 (syn; s, 3H), 5.02-5.06 (syn; m, 4H), 5.21-5.32 (anti; m, 3H), 5.39 (anti; br s, 1H), 5.80-5.89 (syn; m, 1H), 5.90-5.99 (anti; m, 1H), 6.81-6.95 (m, 4H), 7.22-7.55 (m, 6H); HPLC (DAICEL CHIRALPAK ADH, ⁿhexane-ⁱPrOH = 19:1, 1.0 mL/min): t_R (min) = 14.5 (anti-R,R), 18.5 (anti-S,S), 22.7 (syn, major enantiomer), 27.4 (syn, minor enantiomer).
なお、実験例２２は反応時間24時間で行った。 Product 6c (N-[(1R, 2R) -1- (3-methoxyphenyl) -2-methylbut-3-enyl] benzohydrazide, Formula XXIV, Experimental Example 22)

Data for product 6c: light yellow liquid (yield: 90%; α: γ => 99: 1; anti: syn = 6.1: 1 (α-adduct); er = 94: 6 (anti-diastereisomer))); ¹ H NMR (CDCl ₃ , 500 MHz): δ = 0.80 (anti; d, J = 6.8 Hz, 3H), 1.08 (syn; d, J = 6.8 Hz, 3H), 2.39-2.49 (anti; m, 1H ), 2.63-2.68 (syn; m, 1H), 3.79 (anti; s, 3H), 3.81 (syn; s, 3H), 5.02-5.06 (syn; m, 4H), 5.21-5.32 (anti; m, 3H), 5.39 (anti; br s, 1H), 5.80-5.89 (syn; m, 1H), 5.90-5.99 (anti; m, 1H), 6.81-6.95 (m, 4H), 7.22-7.55 (m, 6H); HPLC (DAICEL CHIRALPAK ADH, ⁿ hexane- ⁱ PrOH = 19: 1, 1.0 mL / min): t _R (min) = 14.5 (anti-R, R), 18.5 (anti-S, S), 22.7 (syn, major enantiomer), 27.4 (syn, minor enantiomer).
In addition, Experimental Example 22 was performed with a reaction time of 24 hours.

生成物6e（N-{(1R,2R)-1-[4-(dimethylamino)phenyl]-2-methylbut-3-enyl}benzohydrazide、式ＸＸＶ、実験例２４）

生成物6eのデータ：薄黄色液体(収率： 72%;α:γ=>99:1;anti:syn=2.8:1(α-adduct); er = 94:6(anti-diastereisomer)); ¹H NMR (CDCl₃, 500 MHz): δ= 0.78 (anti; d, J = 6.8 Hz, 3H), 1.07 (syn; d, J = 6.8 Hz, 3H), 2.41-2.49 (anti; m, 1H), 2.59-2.65 (syn; m, 1H), 2.94 (anti; s, 6H), 2.95 (syn; s, 6H), 3.70 (anti; d, J = 9.6 Hz, 1H), 3.97 (syn; d, J = 5.6 Hz, 3H), 5.01-5.06 (syn; m, 2H), 5.19-5.32 (anti; m, 2H), 5.77-5.86 (syn; m, 1H), 5.90-6.00 (anti; m, 1H), 6.69-6.74 (m, 2H), 7.18-7.22 (m, 2H), 7.31-7.36 (m, 3H), 7.41-7.46 (m, 2H), 7.52-7.58 (m, 2H); ¹³C NMR (CDCl₃, 125 MHz): δ= 15.7 (syn), 17.9 (anti), 40.6 (2C), 41.9 (syn), 44.0 (anti), 68.1 (anti), 68.2 (syn), 112.2 (syn), 112.5 (anti), 114.8 (syn), 116.3 (anti), 126.7 (2C), 128.5 (2C), 129.2 (2C), 131.5, 132.9 (syn), 133.0 (anti), 140.3 (syn), 141.7 (anti), 149.7 (syn), 149.9 (anti), 166.6 (anti), 166.8 (syn); HPLC (DAICEL CHIRALPAK ADH, ⁿhexane-ⁱPrOH = 9:1, 1.0 mL/min): t_R (min) = 8.8 (anti-R,R), 10.8 (anti-S,S), 13.2 (syn, major enantiomer), 20.0 (syn, minor enantiomer).
なお、実験例２４は反応時間84時間で行った。 Product 6e (N-{(1R, 2R) -1- [4- (dimethylamino) phenyl] -2-methylbut-3-enyl} benzohydrazide, Formula XXV, Experimental Example 24)

Data for product 6e: light yellow liquid (yield: 72%; α: γ => 99: 1; anti: syn = 2.8: 1 (α-adduct); er = 94: 6 (anti-diastereisomer))); ¹ H NMR (CDCl ₃ , 500 MHz): δ = 0.78 (anti; d, J = 6.8 Hz, 3H), 1.07 (syn; d, J = 6.8 Hz, 3H), 2.41-2.49 (anti; m, 1H ), 2.59-2.65 (syn; m, 1H), 2.94 (anti; s, 6H), 2.95 (syn; s, 6H), 3.70 (anti; d, J = 9.6 Hz, 1H), 3.97 (syn; d , J = 5.6 Hz, 3H), 5.01-5.06 (syn; m, 2H), 5.19-5.32 (anti; m, 2H), 5.77-5.86 (syn; m, 1H), 5.90-6.00 (anti; m, 1H), 6.69-6.74 (m, 2H), 7.18-7.22 (m, 2H), 7.31-7.36 (m, 3H), 7.41-7.46 (m, 2H), 7.52-7.58 (m, 2H); ¹³ C NMR (CDCl ₃ , 125 MHz): δ = 15.7 (syn), 17.9 (anti), 40.6 (2C), 41.9 (syn), 44.0 (anti), 68.1 (anti), 68.2 (syn), 112.2 (syn) , 112.5 (anti), 114.8 (syn), 116.3 (anti), 126.7 (2C), 128.5 (2C), 129.2 (2C), 131.5, 132.9 (syn), 133.0 (anti), 140.3 (syn), 141.7 ( anti), 149.7 (syn), 149.9 (anti), 166.6 (anti), 166.8 (syn); HPLC (DAICEL CHIRALPAK ADH, ⁿ hexane- ⁱ PrOH = 9: 1, 1.0 mL / min): t _R (min) = 8.8 (anti-R, R), 10.8 (anti-S, S), 13.2 (syn, major enantiomer), 20.0 (syn, minor enantiomer).
In addition, Experimental Example 24 was performed with a reaction time of 84 hours.

生成物6f（N-[(1R,2R)-2-methyl-1-p-tolylbut-3-enyl]benzohydrazide、式ＸＸＶＩ、実験例２５）

生成物6fのデータ：薄黄色液体(収率:quant;α:γ=>99:1;anti:syn=5.2:1(α-adduct); er = 96:4(anti-diastereisomer)); ¹H NMR (CDCl₃, 500 MHz): δ= 0.78 (anti; d, J = 7.3 Hz, 3H), 1.07 (syn; d, J = 6.8 Hz, 3H), 2.33 (syn; s, 3H), 2.35 (anti; s, 3H), 2.43-2.47 (anti; m, 1H), 2.61-2.65 (syn; m, 1H), 3.78 (anti; d, J = 9.6 Hz, 1H), 4.04 (syn; d, J = 7.0 Hz, 1H), 4.99-5.05 (syn; m, 2H), 5.20-5.31 (anti; m, 2H), 5.38 (br d, J = 6.3 Hz, 1H), 5.77-5.86 (syn; m, 1H), 5.90-5.99 (anti; m, 1H), 7.11-7.57 (m, 9H); HPLC (DAICEL CHIRALPAK ADH, ⁿhexane-ⁱPrOH = 19:1, 1.0 mL/min): t_R (min) = 10.2 (anti-R,R), 11.7 (anti-S,S), 15.9 (syn, major enantiomer), 18.0 (syn, minor enantiomer).
なお、実験例２５は反応時間24時間で行った。 Product 6f (N-[(1R, 2R) -2-methyl-1-p-tolylbut-3-enyl] benzohydrazide, Formula XXVI, Experimental Example 25)

Data for product 6f: light yellow liquid (yield: quant; α: γ => 99: 1; anti: syn = 5.2: 1 (α-adduct); er = 96: 4 (anti-diastereisomer))); ¹ H NMR (CDCl ₃ , 500 MHz): δ = 0.78 (anti; d, J = 7.3 Hz, 3H), 1.07 (syn; d, J = 6.8 Hz, 3H), 2.33 (syn; s, 3H), 2.35 (anti; s, 3H), 2.43-2.47 (anti; m, 1H), 2.61-2.65 (syn; m, 1H), 3.78 (anti; d, J = 9.6 Hz, 1H), 4.04 (syn; d, J = 7.0 Hz, 1H), 4.99-5.05 (syn; m, 2H), 5.20-5.31 (anti; m, 2H), 5.38 (br d, J = 6.3 Hz, 1H), 5.77-5.86 (syn; m , 1H), 5.90-5.99 (anti; m, 1H), 7.11-7.57 (m, 9H); HPLC (DAICEL CHIRALPAK ADH, ⁿ hexane- ⁱ PrOH = 19: 1, 1.0 mL / min): t _R (min ) = 10.2 (anti-R, R), 11.7 (anti-S, S), 15.9 (syn, major enantiomer), 18.0 (syn, minor enantiomer).
In addition, Experimental Example 25 was performed with a reaction time of 24 hours.

生成物6i（N-[(1S,2S)-1-(4-hydroxyphenyl)-2-methylbut-3-enyl]benzohydrazide、式ＸＸＶＩＩ、実験例２６）

生成物6iのデータ：薄黄色液体(収率:98%;α:γ=>99:1;anti:syn=8.1:1(α-adduct); er = 93:7(anti-diastereisomer)); ¹H NMR (CDCl₃, 400 MHz): δ= 0.75 (anti; d, J = 6.7 Hz, 3H), 1.05 (syn; d, J = 6.7 Hz, 3H), 2.39-2.51 (anti; m, 1H), 2.57-2.65 (syn; m, 1H), 3.72 (anti; d, J = 10.0 Hz, 1H), 3.98 (syn; d, J = 5.6 Hz, 1H), 4.96-5.03 (syn; m, 2H), 5.17-5.31 (anti; m, 2H), 5.44 (br s, 1H), 5.70-5.78 (syn; m, 1H), 5.85-5.96 (anti; m, 1H), 6.75-6.82 (m, 2H), 7.14-7.56 (m, 7H); HPLC (DAICEL CHIRALPAK ADH, ⁿhexane-ⁱPrOH = 9:1, 1.0 mL/min): t_R (min) = 21.0 (anti, major), 30.8 (anti, minor), 40.1 (syn, major), 50.9 (syn, minor).
なお、実験例２６は反応時間8時間で行った。 Product 6i (N-[(1S, 2S) -1- (4-hydroxyphenyl) -2-methylbut-3-enyl] benzohydrazide, Formula XXVII, Experimental Example 26)

Data for product 6i: pale yellow liquid (yield: 98%; α: γ => 99: 1; anti: syn = 8.1: 1 (α-adduct); er = 93: 7 (anti-diastereisomer))); ¹ H NMR (CDCl ₃ , 400 MHz): δ = 0.75 (anti; d, J = 6.7 Hz, 3H), 1.05 (syn; d, J = 6.7 Hz, 3H), 2.39-2.51 (anti; m, 1H ), 2.57-2.65 (syn; m, 1H), 3.72 (anti; d, J = 10.0 Hz, 1H), 3.98 (syn; d, J = 5.6 Hz, 1H), 4.96-5.03 (syn; m, 2H ), 5.17-5.31 (anti; m, 2H), 5.44 (br s, 1H), 5.70-5.78 (syn; m, 1H), 5.85-5.96 (anti; m, 1H), 6.75-6.82 (m, 2H ), 7.14-7.56 (m, 7H); HPLC (DAICEL CHIRALPAK ADH, ⁿ hexane- ⁱ PrOH = 9: 1, 1.0 mL / min): t _R (min) = 21.0 (anti, major), 30.8 (anti, minor), 40.1 (syn, major), 50.9 (syn, minor).
In addition, Experimental Example 26 was performed with a reaction time of 8 hours.

生成物6j（N-[(1R,2R)-2-methyl-1-(naphthalen-2-yl)but-3-enyl]benzohydrazide、式ＸＸＶＩＩＩ、実験例２７）

生成物6jのデータ：薄黄色液体(収率:94%;α:γ=>32:1;anti:syn=11:1(α-adduct); er = 97:3(anti-diastereisomer)); ¹H NMR (CDCl₃, 400 MHz): δ= 0.80 (anti; d, J = 6.8 Hz, 3H), 1.10 (syn; d, J = 6.8 Hz, 3H), 2.51-2.60 (anti; m, 1H), 2.65-2.76 (syn; m, 1H), 4.99-5.06 (syn; m, 2H), 5.24-5.36 (anti; m, 2H), 5.48 (d, J = 6.8 Hz, 1H), 5.80-5.88 (syn; br s, 1H), 5.95-6.04 (anti; m, 1H), 7.25-7.57 (m, 8H), 7.77-7.87 (m, 4H); HPLC (DAICEL CHIRALPAK ADH, ⁿhexane-ⁱPrOH = 9:1, 0.8 mL/min): t_R (min) = 10.5 (anti-R,R), 11.9 (anti-S,S), 14.5 (syn, major enantiomer), 17.7 (syn, minor enantiomer).
なお、実験例２７は反応時間24時間で行った。 Product 6j (N-[(1R, 2R) -2-methyl-1- (naphthalen-2-yl) but-3-enyl] benzohydrazide, Formula XXVIII, Experimental Example 27)

Data for product 6j: light yellow liquid (yield: 94%; α: γ => 32: 1; anti: syn = 11: 1 (α-adduct); er = 97: 3 (anti-diastereisomer))); ¹ H NMR (CDCl ₃ , 400 MHz): δ = 0.80 (anti; d, J = 6.8 Hz, 3H), 1.10 (syn; d, J = 6.8 Hz, 3H), 2.51-2.60 (anti; m, 1H ), 2.65-2.76 (syn; m, 1H), 4.99-5.06 (syn; m, 2H), 5.24-5.36 (anti; m, 2H), 5.48 (d, J = 6.8 Hz, 1H), 5.80-5.88 (syn; br s, 1H), 5.95-6.04 (anti; m, 1H), 7.25-7.57 (m, 8H), 7.77-7.87 (m, 4H); HPLC (DAICEL CHIRALPAK ADH, ⁿ hexane- ⁱ PrOH = 9: 1, 0.8 mL / min): t _R (min) = 10.5 (anti-R, R), 11.9 (anti-S, S), 14.5 (syn, major enantiomer), 17.7 (syn, minor enantiomer).
In addition, Experimental Example 27 was performed with a reaction time of 24 hours.

生成物6k（N-[(1R,2R)-1-(furan-2-yl)-2-methylbut-3-enyl]benzohydrazide、式ＸＸＩＸ、実験例２８）

生成物6kのデータ：薄黄色固体(収率:85%;α:γ= 49:1;anti:syn=4.5:1(α-adduct); er = 96:4(anti-diastereisomer)); ¹H NMR (CDCl₃, 400 MHz): δ= 0.88 (anti; d, J = 6.8 Hz, 3H), 1.10 (syn; d, J = 6.8 Hz, 3H), 2.63-2.70 (anti; m, 1H), 2.72-2.80 (syn; m, 1H), 3.96 (anti; d, J = 6.8 Hz, 3H), 3.96 (anti; d, J = 6.8 Hz, 1H), 4.16 (syn; br, 1H), 5.04-5.15 (syn; m, 2H), 5.19-5.31 (anti; m, 2H), 5.84-5.96 (syn + anti; m, 1H), 6.25-6.35 (m, 2H), 7.25-7.64 (m, 8H); HPLC (DAICEL CHIRALPAK ODH, ⁿhexane-ⁱPrOH = 40:1, 0.8 mL/min): t_R (min) = 32.7 (anti-R,R), 41.0 (anti-S,S), 46.0 (syn, major enantiomer), 66.4 (syn, major enantiomer).
なお、実験例２８は反応時間96時間で行った。 Product 6k (N-[(1R, 2R) -1- (furan-2-yl) -2-methylbut-3-enyl] benzohydrazide, Formula XXIX, Experimental Example 28)

Data for product 6k: light yellow solid (yield: 85%; α: γ = 49: 1; anti: syn = 4.5: 1 (α-adduct); er = 96: 4 (anti-diastereisomer))); ¹ H NMR (CDCl ₃ , 400 MHz): δ = 0.88 (anti; d, J = 6.8 Hz, 3H), 1.10 (syn; d, J = 6.8 Hz, 3H), 2.63-2.70 (anti; m, 1H) , 2.72-2.80 (syn; m, 1H), 3.96 (anti; d, J = 6.8 Hz, 3H), 3.96 (anti; d, J = 6.8 Hz, 1H), 4.16 (syn; br, 1H), 5.04 -5.15 (syn; m, 2H), 5.19-5.31 (anti; m, 2H), 5.84-5.96 (syn + anti; m, 1H), 6.25-6.35 (m, 2H), 7.25-7.64 (m, 8H ); HPLC (DAICEL CHIRALPAK ODH, ⁿ hexane- ⁱ PrOH = 40: 1, 0.8 mL / min): t _R (min) = 32.7 (anti-R, R), 41.0 (anti-S, S), 46.0 ( syn, major enantiomer), 66.4 (syn, major enantiomer).
In addition, Experimental Example 28 was performed with a reaction time of 96 hours.

生成物6l（N-[(1R,2R)-1-(furan-3-yl)-2-methylbut-3-enyl]benzohydrazide、式ＸＸＸ、実験例２９）

生成物6lのデータ：無色液体(収率:quant;α:γ=>99:1;anti:syn=4.9:1(α-adduct); er = 96:4(anti-diastereisomer)); HPLC (DAICEL CHIRALPAK ODH, nhexane?iPrOH = 19:1, 1.0 mL/min): tR (min) = 12.8 (anti-S,S), 16.9 (anti-R,R), not visible (syn, minor enantiomer), 21.4 (syn, major enantiomer).
なお、実験例２９は反応時間24時間で行った。 Product 6l (N-[(1R, 2R) -1- (furan-3-yl) -2-methylbut-3-enyl] benzohydrazide, Formula XXX, Experimental Example 29)

Data for product 6l: colorless liquid (yield: quant; α: γ => 99: 1; anti: syn = 4.9: 1 (α-adduct); er = 96: 4 (anti-diastereisomer)); HPLC ( DAICEL CHIRALPAK ODH, nhexane? IPrOH = 19: 1, 1.0 mL / min): tR (min) = 12.8 (anti-S, S), 16.9 (anti-R, R), not visible (syn, minor enantiomer), 21.4 (syn, major enantiomer).
In addition, Experimental Example 29 was performed with a reaction time of 24 hours.

生成物6o（N-[(1R,2R)-2-methyl-1-(thiophen-2-yl)but-3-enyl]benzohydrazide、式ＸＸＸＩ、実験例３０）

生成物6oのデータ：薄黄色固体(収率:quant;α:γ=>99:1;anti:syn=11:1(α-adduct); er = 94:6(anti-diastereisomer)); ¹H NMR (CDCl₃, 400 MHz): δ= 0.89 (anti; d, J = 6.8 Hz, 3H), 1.12 (syn; d, J = 6.8 Hz, 3H), 2.42-2.49 (anti; m, 1H), 2.64-2.67 (syn; m, 1H), 4.17 (anti; d, J = 7.9 Hz, 1H), 4.41 (syn; d, J = 6.0 Hz, 1H), 5.11-5.18 (syn; m, 2H), 5.21-5.32 (anti; m, 2H), 5.43 (br, 1H), 5.89-5.96 (syn + anti; m, 1H), 6.96 (br, 2H), 7.25-7.60 (m, 6H); HPLC (DAICEL CHIRALPAK ODH, ⁿhexane-ⁱPrOH = 19:1, 1.0 mL/min): t_R (min) = 11.6 (anti-S,S), 15.6 (anti-R,R), 23.3 (syn, minor enantiomer), 25.8 (syn, major enantiomer).
なお、実験例３０は反応時間24時間で行った。 Product 6o (N-[(1R, 2R) -2-methyl-1- (thiophen-2-yl) but-3-enyl] benzohydrazide, Formula XXXI, Experimental Example 30)

Data for product 6o: light yellow solid (yield: quant; α: γ => 99: 1; anti: syn = 11: 1 (α-adduct); er = 94: 6 (anti-diastereisomer))); ¹ H NMR (CDCl ₃ , 400 MHz): δ = 0.89 (anti; d, J = 6.8 Hz, 3H), 1.12 (syn; d, J = 6.8 Hz, 3H), 2.42-2.49 (anti; m, 1H) , 2.64-2.67 (syn; m, 1H), 4.17 (anti; d, J = 7.9 Hz, 1H), 4.41 (syn; d, J = 6.0 Hz, 1H), 5.11-5.18 (syn; m, 2H) , 5.21-5.32 (anti; m, 2H), 5.43 (br, 1H), 5.89-5.96 (syn + anti; m, 1H), 6.96 (br, 2H), 7.25-7.60 (m, 6H); HPLC ( DAICEL CHIRALPAK ODH, ⁿ hexane- ⁱ PrOH = 19: 1, 1.0 mL / min): t _R (min) = 11.6 (anti-S, S), 15.6 (anti-R, R), 23.3 (syn, minor enantiomer ), 25.8 (syn, major enantiomer).
In addition, Experimental Example 30 was performed with a reaction time of 24 hours.

生成物6q（N-[(1R,2R)-1-(4-chlorophenyl)-2-methylbut-3-enyl]benzohydrazide、式ＸＸＸＩＩ、実験例３１）

生成物6qのデータ：薄黄色固体(収率:83%;α:γ=＞99:1;anti:syn=13:1(α-adduct); er = 92:8(anti-diastereisomer)); ¹³C NMR (CDCl₃, 125 MHz): δ= 15.7 (syn), 17.9 (anti), 40.6 (2C), 41.9 (syn), 44.0 (anti), 68.1 (anti), 68.2 (syn), 112.2 (syn), 112.5 (anti), 114.8 (syn), 116.3 (anti), 126.7 (2C), 128.5 (2C), 129.2 (2C), 131.5, 132.9 (syn), 133.0 (anti), 140.3 (syn), 141.7 (anti), 149.7 (syn), 149.9 (anti), 166.6 (anti), 166.8 (syn); HPLC (DAICEL CHIRALPAK ADH, ⁿhexane-ⁱPrOH = 9:1, 1.0 mL/min): t_R (min) = 8.8 (anti-R,R), 10.8 (anti-S,S), 13.2 (syn, major enantiomer), 20.0 (syn, minor enantiomer).
なお、実験例３１は反応時間84時間で行った。 Product 6q (N-[(1R, 2R) -1- (4-chlorophenyl) -2-methylbut-3-enyl] benzohydrazide, Formula XXXII, Experimental Example 31)

Data for product 6q: light yellow solid (yield: 83%; α: γ => 99: 1; anti: syn = 13: 1 (α-adduct); er = 92: 8 (anti-diastereisomer))); ¹³ C NMR (CDCl ₃ , 125 MHz): δ = 15.7 (syn), 17.9 (anti), 40.6 (2C), 41.9 (syn), 44.0 (anti), 68.1 (anti), 68.2 (syn), 112.2 ( syn), 112.5 (anti), 114.8 (syn), 116.3 (anti), 126.7 (2C), 128.5 (2C), 129.2 (2C), 131.5, 132.9 (syn), 133.0 (anti), 140.3 (syn), 141.7 (anti), 149.7 (syn), 149.9 (anti), 166.6 (anti), 166.8 (syn); HPLC (DAICEL CHIRALPAK ADH, ⁿ hexane- ⁱ PrOH = 9: 1, 1.0 mL / min): t _R ( min) = 8.8 (anti-R, R), 10.8 (anti-S, S), 13.2 (syn, major enantiomer), 20.0 (syn, minor enantiomer).
In addition, Experimental Example 31 was performed with a reaction time of 84 hours.

＜α位がＣｌのα-置換アリルボロネートを用いたN-アシルヒドラゾンへの不斉付加反応の一般操作＞

アルゴン雰囲気下、加熱乾燥した5ml-スクリュー管瓶に、ヨウ化インジウム（Ｉ）（10 mol%）及び不斉配位子L^*3d（式ＸＶＩＩＩの構造式参照） (10 mol%)を秤量した。溶媒としてジクロロメタンーエタノール (1:1) を加えた後、室温で1時間攪拌して触媒調製を行った。ヒドラゾン1a(0.2−0.3mmol;1.0等量)を加えた後、アルゴンで置換し、所定温度まで冷却した。アリルボロネートrac-7（0.30-0.45mmol;1.5等量）を滴下して加え、-20℃で96時間攪拌を行った。反応終了後、ジクロロメタンで(by factor 10)希釈し、炭酸カリウム水溶液（１Ｍ）を加え、反応を停止し、室温に戻した。有機相を分離した後、ジクロロメタンで有機相を抽出する操作を３回繰り返し、無水硫酸ナトリウムを用いて乾燥した。ろ過後、減圧濃縮し、得られた粗製化合物を分取薄層クロマトグラフィーにより精製して（ヘキサン/酢酸エチル＝19:1-4:1）、目的のホモアリルヒドラジド8aを得た。
生成物8aのジアステレオマー比（α-付加物のanti:syn比）の値、構造異性体比 (α：γ比)の値、は¹H NMR 分析により決定した。生成物8aの絶対配置は、N−boc保護基のホモアリルヒドラジドのX線解析によって決定した。
生成物8aは新規の化合物であり、そのデータを以下に示す。
生成物8a（N-[(1S,2R)-2-chloro-1-phenylbut-3-enyl]benzohydrazide）のデータ：薄黄色固体(収率:84%;α:γ=49:1;anti:syn=49:1(α-adduct); er = 92:8(anti-diastereisomer)); ¹H NMR (CDCl₃, 500 MHz): δ= 4.41 (d, J = 6.8 Hz, 1H), 4.57 (dd, J = 6.8 Hz, J = 9.1 Hz, 1H), 5.30-5.41 (m, 3H), 5.98-6.08 (m, 1H), 7.31-7.51 (m, 9H), 7.57 (d, J = 7.9 Hz, 2H); ¹³C NMR (CDCl₃, 500 MHz): ( = 64.3, 68.4, 119.6, 126.7 (2C), 128.4 (3C), 128.6 (2C), 128.7 (2C), 131.9, 132.4, 135.1, 137.6, 167.2; HPLC (DAICEL CHIRALPAK ODH, ⁿhexane-ⁱPrOH = 19:1, 1.0 mL/min): t_R (min) = 29.4 [minor enantiomer: anti-(R,S)], 35.9 [major enantiomer: anti-(S,R)], other signals were not detected. <General procedure for asymmetric addition reaction to N-acylhydrazone using α-substituted allylboronate with Cl at α-position>

In 5 ml-screw tube bottle dried under heat in an argon atmosphere, indium (I) iodide (10 mol%) and asymmetric ligand L ^* 3d (see structural formula of formula XVIII) (10 mol%) were weighed. . After adding dichloromethane-ethanol (1: 1) as a solvent, the catalyst was prepared by stirring for 1 hour at room temperature. After adding hydrazone 1a (0.2-0.3 mmol; 1.0 equivalent), it was replaced with argon and cooled to a predetermined temperature. Allyl boronate rac-7 (0.30-0.45 mmol; 1.5 equivalents) was added dropwise and stirred at −20 ° C. for 96 hours. After completion of the reaction, the reaction mixture was diluted with dichloromethane (by factor 10), and an aqueous potassium carbonate solution (1M) was added to stop the reaction, and the temperature was returned to room temperature. After separating the organic phase, the operation of extracting the organic phase with dichloromethane was repeated three times and dried using anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the resulting crude compound was purified by preparative thin layer chromatography (hexane / ethyl acetate = 19: 1-4: 1) to obtain the desired homoallyl hydrazide 8a.
The value of diastereomer ratio (anti-syn ratio of α-adduct) and structural isomer ratio (α: γ ratio) of product 8a were determined by ¹ H NMR analysis. The absolute configuration of product 8a was determined by X-ray analysis of the homoallyl hydrazide of the N-boc protecting group.
Product 8a is a novel compound and the data is shown below.
Data for product 8a (N-[(1S, 2R) -2-chloro-1-phenylbut-3-enyl] benzohydrazide): light yellow solid (yield: 84%; α: γ = 49: 1; anti: syn = 49: 1 (α-adduct); er = 92: 8 (anti-diastereisomer)); ¹ H NMR (CDCl ₃ , 500 MHz): δ = 4.41 (d, J = 6.8 Hz, 1H), 4.57 ( dd, J = 6.8 Hz, J = 9.1 Hz, 1H), 5.30-5.41 (m, 3H), 5.98-6.08 (m, 1H), 7.31-7.51 (m, 9H), 7.57 (d, J = 7.9 Hz , 2H); ¹³ C NMR (CDCl ₃ , 500 MHz): (= 64.3, 68.4, 119.6, 126.7 (2C), 128.4 (3C), 128.6 (2C), 128.7 (2C), 131.9, 132.4, 135.1, 137.6 , 167.2; HPLC (DAICEL CHIRALPAK ODH, ⁿ hexane- ⁱ PrOH = 19: 1, 1.0 mL / min): t _R (min) = 29.4 [minor enantiomer: anti- (R, S)], 35.9 [major enantiomer: anti- (S, R)], other signals were not detected.

Claims

In the presence of a monovalent indium salt, the formula I

Or the formula VI

(Wherein R ⁹ is a hydrogen atom or an alkyl group; R ¹⁰ and R ¹² may be the same or different, and each is an aliphatic hydrocarbon group or an aromatic hydrocarbon group; R ¹¹ , R ¹⁴ is a hydrogen atom, which may be the same or different from each other, an aliphatic hydrocarbon group or an aromatic hydrocarbon group; R ¹³ is a cyano group or an amino group) or an enantiomer thereof A method for producing homoallyl hydrazide, wherein the reaction is carried out in the presence of a ligand .

The method for producing homoallyl hydrazide according to claim 1, wherein the addition amount of the monovalent indium salt is 20 mol% or less.

The allyl boronate or α-substituted allyl boronate has the formula IV

The manufacturing method of the homoallyl hydrazide of Claim 1 or 2 represented by these.

The method for producing homoallyl hydrazide according to any one of claims 1 to 3 , wherein R ⁵ of the α-substituted allylboronate is represented by a methyl group.

The method for producing homoallyl hydrazide according to any one of claims 1 to 3 , wherein R ⁵ of the α-substituted allylboronate is represented by Cl.