JPS61257933A - Production of stereoselective alcohol from ketone - Google Patents
Production of stereoselective alcohol from ketoneInfo
- Publication number
- JPS61257933A JPS61257933A JP9864585A JP9864585A JPS61257933A JP S61257933 A JPS61257933 A JP S61257933A JP 9864585 A JP9864585 A JP 9864585A JP 9864585 A JP9864585 A JP 9864585A JP S61257933 A JPS61257933 A JP S61257933A
- Authority
- JP
- Japan
- Prior art keywords
- ketone
- reaction
- carried out
- alcohol
- stereoselective
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
【発明の詳細な説明】
〔産業上の利用分野〕
本発明は、次の一般式を有する反応剤
(但しR′はアルキル基ま几はハロゲン、R#はアルキ
ル基または水素)とケトンを作用させ、次いで炭素求核
剤主としてアルキル化剤を0℃以下で作用させることt
−特徴とする立体選択的アルコールの製造法に関する。Detailed Description of the Invention [Industrial Application Field] The present invention is directed to reacting a ketone with a reactant having the following general formula (where R' is an alkyl group or a halogen, and R# is an alkyl group or hydrogen). and then act with a carbon nucleophile mainly an alkylating agent at a temperature below 0°C.
-Regarding a method for producing a characteristic stereoselective alcohol.
本発明はこのような反応を行わせてエフアト11アルア
ルコールを選択的に生成させる方法であって、主として
医薬、農薬等所謂精密化学分野に於て有用な方法である
。The present invention is a method for selectively producing efuato-11 alcohol by carrying out such a reaction, and is a method useful mainly in the so-called fine chemistry fields such as pharmaceuticals and agricultural chemicals.
ケトンのアルキル化反応は長い間研究されており、有機
合成において基礎的反応の一つである。The alkylation reaction of ketones has been studied for a long time and is one of the fundamental reactions in organic synthesis.
最近、シクロヘキサノンからアキシアルアル=r −A
/ (axial alcOhol)をうるのに立体選
択的アルキル化剤の発達にかなりの努力がはられれてい
るが、エフアト11アルアルコール(equa−tor
ial alcohol)の選択的合成に対しては良い
方法が確立していない。Recently, from cyclohexanone to axialalal = r -A
Considerable efforts have been made to develop stereoselective alkylating agents to obtain equa-tor 11-alcohols (equa-tor
No good method has been established for the selective synthesis of ial alcohols.
峯
そこで、索発明者らは反応剤として次の立体的かさ高い
有機アルミニウム化合物であるメチルアルミニウムビス
(2,6−ジ−ターシャリ−ブチル−4−メチル−フェ
ノキサイド(me−thylaluminum bis
(2,6−di−tart −buthl−4−met
hylphenoxide ) C以下MADと略称す
る〕に注目し、この反応剤を使用してケトンの立体選択
的アルキル化反応について種々検討した。Therefore, the inventors used methylaluminum bis(2,6-di-tert-butyl-4-methyl-phenoxide), which is a sterically bulky organoaluminum compound, as a reactant.
(2,6-di-tart-buthl-4-met
Focusing on hylphenoxide (hereinafter abbreviated as MAD), various studies were conducted on stereoselective alkylation reactions of ketones using this reactant.
以下本発明法の一例を示して説明すると次の通りである
。An example of the method of the present invention will be described below.
1 (99:1) 2
(但しt−13uijターシャリ−ブチル基% Meは
メチル基である。〕
この内、MADhトnメチルアルミニウムと2.6−ジ
−ターシャ11−ブチル−4−メチルフェノール(モル
比l:2)ftトルエン中、xiで1時間反応させるこ
とにより調製する。1 (99:1) 2 (However, Me is a methyl group. molar ratio l:2) ft. Prepared by reacting for 1 hour at xi in toluene.
上式において、トルエン中で4−ターシャ+1−ブチル
−シクロへキサノンと3当量のMADとの処理に次いで
一78℃でメチルl]チウム(MeLi)のエーテル溶
液で処理すると84%の収率でメチルカルビノールの異
性体の混合物が得られ、その内99チはエフアト11ア
ルアルコール(eqと略称する)1.1%はアクシアル
アルコール(AXと略称する)2であることが分つ几。In the above formula, treatment of 4-tertiary + 1-butyl-cyclohexanone with 3 equivalents of MAD in toluene followed by treatment with an ethereal solution of methyl l]thium (MeLi) at -78°C gives a yield of 84%. A mixture of isomers of methyl carbinol was obtained, of which 99% was found to be efuato-11 alcohol (abbreviated as eq) and 1.1% was axial alcohol (abbreviated as AX).
MeLi単独ではax2とeqxとの比が79=21に
なると報告されている。(マクドナシト1テイ、エル、
ステイル、ダブり二一、シー、ジズ
ヤーナル、傘ブザアメ11カン、ケミカル、ソサイエテ
イ にuec>onald、T、L、; 5till。It has been reported that when MeLi is used alone, the ratio of ax2 to eqx is 79=21. (McDonalds 1 Tei, Elle,
Still, Double 21, Sea, This Yarnal, Kasabuzaame 11 Kan, Chemical, Society ni uec>onald, T, L,; 5till.
W、C,J、Am、Chem、 Soc、 1975
、9755280) 、え、。い、<一方
MADが有効なことは、ゞ反応剤を色々変えて同様な条
件下で詳細に検討した結果から明らかである。W, C, J, Am, Chem, Soc, 1975
,9755280) ,Eh. On the other hand, the effectiveness of MAD is clear from the results of detailed studies using various reactants under similar conditions.
即ち各種の有機アルミニウム反応剤の存在下で4−ター
シャリ−ブチル−シクロヘキサノンとMeLiとの反応
は、以下のようにax2とeqlを作り、その生成比率
にMe雪Azoph (phはフェニール基〕で[72
:28、ジメチルアルミニウム 2,4.6−ドリメチ
ルフエノキサイド(dimethyl aluminu
m 2 、4 、6− trimethylpheno
襦ide )では69:31、ジメチルアルミで5:9
5の生成割合である。That is, the reaction of 4-tert-butyl-cyclohexanone with MeLi in the presence of various organoaluminum reactants produces ax2 and eql as shown below, and the production ratio is changed by Me snow Azoph (ph is phenyl group) [ 72
:28, dimethyl aluminum 2,4.6-dimethyl phenoxide
m 2 , 4 , 6-trimethylpheno
69:31 for 襦ide), 5:9 for dimethyl aluminum
The production rate is 5.
t7tMADの量的関係を試験した結果、MeLiとM
ADを夫々3当量以上用いても顕著な収率の向上は見ら
れなかった。As a result of testing the quantitative relationship between t7tMAD, MeLi and M
Even when AD was used in an amount of 3 equivalents or more, no significant improvement in yield was observed.
MADとMeLi各2当量ではax:aq=1:99で
あるが59%の収率であり、反応剤が共に1当量ではa
x:eq=2:98であるが31%と低収率であった。When MAD and MeLi each have 2 equivalents, ax:aq=1:99, but the yield is 59%, and when both reactants have 1 equivalent, a
Although x:eq=2:98, the yield was low at 31%.
原料物質は上記の説明では4−ターシャ+7−−ブチル
−シクロへキサノンを使用したが、これに限定されるこ
とはなく、ケトンならば何でもよい。Although 4-tasha+7-butyl-cyclohexanone was used as the raw material in the above explanation, it is not limited thereto, and any ketone may be used.
また反応剤はMADに限定されることはなく、上式にお
いて Reはアルキル基またはハロゲン、R″はアルキ
ル基ま友は水素であればよい。Further, the reactant is not limited to MAD, and in the above formula, Re may be an alkyl group or a halogen, R'' may be an alkyl group, and hydrogen may be used.
炭素求核剤扛ここでUMeLi、グIJ ニヤール試薬
を具体的にあげて説明し友が、炭素求核剤ならば何でも
よい。Carbon nucleophile: UMeLi and Guineal reagents are specifically mentioned here, but any carbon nucleophile may be used as a carbon nucleophile.
反応の順序はケトンとMeLiを初めに反応させて後に
MADを作用させるのでは好ましくなく、また実施例2
.NIL4、実施例3.随5で示すように低温でMeL
iとMADの混合物とケトンとの反応t!MeLiの単
なる付加となり好ましくない。It is not preferable to react the ketone and MeLi first and then react with MAD, and Example 2
.. NIL4, Example 3. MeL at low temperature as shown in Appendix 5
Reaction of a mixture of i and MAD with a ketone t! MeLi is simply added, which is not preferable.
以下実施例で説明するが、これに限定されるものではな
い。Examples will be described below, but the invention is not limited thereto.
実施例1
トルエン1〇−中に1.322f(6ミリモル)の2.
6−ジ−ターシャリ−ブチル−4−メチルフェノールを
入れ、その溶液に2モルのヘキサンに溶解した3ミツ1
モルのトリメチルアルミニウムを加えた。その後室温で
1時間攪拌し友。Example 1 1.322 f (6 mmol) of 2.
6-di-tert-butyl-4-methylphenol was added to the solution, and 3 seeds dissolved in 2 mol of hexane were added to the solution.
mol of trimethylaluminum was added. After that, stir at room temperature for 1 hour.
その混合液t−−78℃に冷却し、1541’f(1ミ
リモル)の4−ターシャII−ブチルーシクロへキサノ
ンを入れ、次いで3ミリモルのMeLiの1.54モル
のエーテル溶液を一78℃で加え友。The mixture was cooled to -78°C, 1541'f (1 mmol) of 4-tertiary II-butylcyclohexanone was added, and then 3 mmol of MeLi in 1.54 mol of ether solution was added at -78°C. friend.
その後該液は2時間その温度で保持し友。その反応液は
l規定の塩酸溶液に注ぎ、その有機層を塩水で洗浄し比
。その後エーテルで抽出し濃縮液1と2の混合液をシ1
1カゲル充填のカラム、クロマトグラフィによって精製
し、14311Pを得t0
収率は84%、であり、ガス、クロマトグラフィで分析
した結果、1:2=99:1であった。The solution was then kept at that temperature for 2 hours. The reaction solution was poured into 1 normal hydrochloric acid solution, and the organic layer was washed with salt water and concentrated. After that, extract with ether and sift the mixture of concentrates 1 and 2 into 1 sieve.
The product was purified by chromatography using a column packed with 1 gel, and 14311P was obtained with a t0 yield of 84%. Analysis by gas and chromatography showed that the ratio was 1:2=99:1.
実施例2 以下の反応を第1表の如き条件で実施した。Example 2 The following reactions were carried out under the conditions shown in Table 1.
反応の条件は実施例1と同様である。The reaction conditions are the same as in Example 1.
(ax) (eq)
l(比較例2−1)2−1) 無 −79:2
12(# 2−2) I DAD 81
5:953(実施例1) # MA
D84 1:994(比較例2−3)2−3)+MA
D” 78 84:165(12−4) EtMg
Br 無9548:526(実施例2−1)
I MAD 91 1:997(比較例2
5)BuMgBr 無 58 56:448(
実施例2−2 ) I MAD 67
1:999(比較例2−6 ) AllylMgB
r 無 86 48:5210(実施例2−3)
I MAD 90 9:91液に加え
た。(ax) (eq) l (Comparative Example 2-1) 2-1) None -79:2
12 (# 2-2) I DAD 81
5:953 (Example 1) #MA
D84 1:994 (Comparative Example 2-3) 2-3) + MA
D” 78 84:165 (12-4) EtMg
Br No9548:526 (Example 2-1)
I MAD 91 1:997 (Comparative Example 2
5) BuMgBr None 58 56:448 (
Example 2-2) I MAD 67
1:999 (Comparative Example 2-6) AllylMgB
r None 86 48:5210 (Example 2-3)
I MAD 90 9:91 solution.
(b)−−−−−−エーテル溶液として使用実施例3゜ 実施例1と同様の条件で次の反応を行った。(b) ------Used as an ether solution Example 3゜ The following reaction was carried out under the same conditions as in Example 1.
番 号 炭素求核剤(b)kW、’−JR率 19
比酸 チ (aX/e q )
1(比較例a−1)MeLi 無 −92:
82(比較例3−2) # DAD
80 58:425(比較例3−3) MeLi+
MAD(&’ 81 91: 9但しくd)・・・
・・・反応は一95℃で3時間行なった。No. Carbon nucleophile (b) kW,'-JR rate 19
Specific acid (aX/eq) 1 (Comparative example a-1) No MeLi -92:
82 (Comparative Example 3-2) #DAD
80 58:425 (Comparative Example 3-3) MeLi+
MAD (&' 81 91: 9 but d)...
...The reaction was carried out at -95°C for 3 hours.
実施例4゜ 実施例1と同様の条件で次の反応を行なった。Example 4゜ The following reaction was carried out under the same conditions as in Example 1.
第3表
1(比較例4−1) MeLi 無 go
83:172(14−2) # DAD
77 48:523(実m例4−1 ) #
MAD 69 9:91(e’4(比較例4−
3 ) BuMgBr 無 86 79:21
5(実施例4−2) # MAD 75
1:996(比較例4−4 ) AllylMg
Br 無 95 56:447(実施例4−3)
I MAD 72 24ニア6但しくe)
・・・・・・反応は一95℃で3時間行なった。Table 3 1 (Comparative Example 4-1) MeLi No go
83:172 (14-2) #DAD
77 48:523 (Example 4-1) #
MAD 69 9:91 (e'4 (Comparative Example 4-
3) BuMgBr None 86 79:21
5 (Example 4-2) # MAD 75
1:996 (Comparative Example 4-4) AllylMg
Br None 95 56:447 (Example 4-3)
I MAD 72 24 near 6 however e)
...The reaction was carried out at -95°C for 3 hours.
実施例5゜ 実施例1と同様の条件で次の反応を行なった。Example 5゜ The following reaction was carried out under the same conditions as in Example 1.
、、、、、人 4.、、+ 箕’ >p 清
°−゛\1手続?甫正書(自発)
補 正 の 内 容
1、明細書第4頁2行目に
[−buthl Jとあるを
「−butyl Jと訂正。,,,,,people 4. ,,+ 箕' >p Qing
°−゛\1 procedure? Contents of the amendment (spontaneous) 1. In the second line of page 4 of the specification, [-buthl J] was corrected to ``-butyl J.
2、明細書第5頁15行目に
「Muc [)onald Jとあるを[Mac
[)onald Jと訂正。2. On page 5, line 15 of the specification, it says “Muc[)onald J”.
[)Corrected by onald J.
3、明細書簡6頁4行目に 「生成比率に」とあるを 「生成比率は」と訂正。3. On page 6, line 4 of the detailed letter It says "to the generation ratio" Corrected "The generation ratio is."
4、明細書簡8頁14行目に 「l細波」とあるを 「濃縮後」と訂正。4. On page 8, line 14 of the detailed letter It says "l honinami" Corrected to "after concentration."
Claims (6)
ル基または水素)とケトンを作用させ、次いで炭素求核
剤を0℃以下で作用させることを特徴とする立体選択的
アルコールの製造法。(1) Reactant having the following general formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (where R' is an alkyl group or halogen, R' is an alkyl group or hydrogen) is reacted with a ketone, and then a carbon nucleophile 1. A method for producing a stereoselective alcohol, which comprises reacting at a temperature of 0°C or lower.
−ブチル−シクロヘキサノンである特許請求の範囲第1
項記載の方法。(2) Claim 1 in which the ketone is cyclohexanone or 4-tert-butyl-cyclohexanone
The method described in section.
る)である特許請求の範囲第1項又は第2項記載の方法
。(3) The method according to claim 1 or 2, wherein the reactant is represented by a numerical formula, chemical formula, table, etc. (provided that R'' is a methyl group or a tertiary-butyl group).
グリニヤール試薬である特許請求の範囲第1項から第3
項までのいずれか1項記載の方法。(4) Claims 1 to 3, wherein the carbon nucleophile is an organolithium compound and/or a Grignard reagent.
The method described in any one of the preceding paragraphs.
から第4項までのいずれか1項記載の方法。(5) The method according to any one of claims 1 to 4, which is carried out in the presence of an organic solvent.
から第5項までのいずれか1項記載の方法。(6) The method according to any one of claims 1 to 5, wherein the reaction is carried out at -78°C.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP9864585A JPS61257933A (en) | 1985-05-09 | 1985-05-09 | Production of stereoselective alcohol from ketone |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP9864585A JPS61257933A (en) | 1985-05-09 | 1985-05-09 | Production of stereoselective alcohol from ketone |
Publications (2)
Publication Number | Publication Date |
---|---|
JPS61257933A true JPS61257933A (en) | 1986-11-15 |
JPS6332339B2 JPS6332339B2 (en) | 1988-06-29 |
Family
ID=14225236
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP9864585A Granted JPS61257933A (en) | 1985-05-09 | 1985-05-09 | Production of stereoselective alcohol from ketone |
Country Status (1)
Country | Link |
---|---|
JP (1) | JPS61257933A (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110809622A (en) * | 2017-06-19 | 2020-02-18 | 西姆莱斯有限公司 | Novel ambergris and/or indole aromatic composition |
-
1985
- 1985-05-09 JP JP9864585A patent/JPS61257933A/en active Granted
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110809622A (en) * | 2017-06-19 | 2020-02-18 | 西姆莱斯有限公司 | Novel ambergris and/or indole aromatic composition |
CN110809622B (en) * | 2017-06-19 | 2024-05-24 | 西姆莱斯有限公司 | Novel ambergris and/or indole fragrance compositions |
Also Published As
Publication number | Publication date |
---|---|
JPS6332339B2 (en) | 1988-06-29 |
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