JPH0491046A - Synthesis of cyclobutanols - Google Patents

Abstract

PURPOSE:To synthesize a cyclobutanol useful as an intermediate for medicines, agricultural chemicals, etc., with efficiently and high selectivity in position and stereostructure by reducing an optical [2+2] additive of a 1, 3-dioxin-4-one with a specific unsaturated compound. CONSTITUTION:(i) Compounds shown by formula IV to formula V, optical [2+2] additives of a compound shown by formula I [R<1> and R<2> are 1-6C alkyl or (CH)2)1; (l) is 4, 5 or 6]with compounds shown by formula II to formula III (R<3> is H or 1-8C alkyl) are reduced to efficiently give the objective compounds shown by formula VI to VII (R<4> is H or acyl) useful as an intermediate for oxetanocin (antiviral agent) while maintaining stereostructure. (ii) An ester structure part containing an unsaturated terminal of alcohol part is introduced to a reaction group at the 2-position of the compound shown by formula I and orientation of addition is controlled in one direction by intramolecular addition reaction to give a substituted cyclobutanol selectively in position and stereostructure.

Description

[Detailed Description of the Invention] [Industrial Application Field] The present invention provides a method for producing synthetic intermediates for pharmaceuticals, agriculture, etc.
This article relates to a new method for synthesizing cyclobutanols.

[Conventional technology]

Cyclobutanols are useful as intermediates for pharmaceuticals, agricultural chemicals, and the like. That is, the cyclobutanol derivative (7) is the following oxetanosine (8), which is known as an antiviral agent.
) is also useful as a synthetic intermediate for congener (a).

Furthermore, as shown below, cyclobutanol derivative (7) is converted into formyl compound by ring opening, and (5) and (6) by oxidation.
), all of which are intermediates of physiologically active substances.

On the other hand, in the following reactions, it was difficult to control the addition surface to dioxinone.

In other words, not only the (=1 adduct) of cyclopentene from the a side, but also the adduct from the b side were generated, and it was difficult to selectively obtain only the useful a side adduct. The development of efficient regio- and stereoselective synthetic methods for butanol derivatives is desired.

[Problem to be solved by the invention]

SUMMARY OF THE INVENTION In view of the above-mentioned problems, the present invention provides a novel method for synthesizing cyclobutanols, and more particularly, it provides an efficient regio- and stereoselective method for synthesizing cyclobutanols.

[Means to solve the problem]

The first method for synthesizing cyclobutanols of the present invention is a photoC2+2) adduct of 1,3-dioxin-4-ones represented by the general formula %) and an unsaturated compound represented by the general formula It is characterized in that cyclobutanols represented by the general formula are obtained by reducing the photo(2+2) adduct with the unsaturated compound represented by the general formula.

Another method of the first synthesis method of the present invention is characterized by obtaining 1,3-dioxin-4-ones represented by the general formula (1) and cyclobutanols represented by the general formula .

(Here, R and R2 each represent an alkyl group having 1 to 6 carbon atoms or -(CH2)-T-, and R3 represents hydrogen or an alkyl group having 1 to 8 carbon atoms. ρ is 4 to 6. R4 represents hydrogen or an acyl group.) The second method for synthesizing cyclobutanols of the present invention is as follows: 1.3
- An ester structure moiety (hereinafter referred to as
It is characterized by introducing a terminal unsaturation (terminal unsaturation) and synthesizing substituted cyclobutanol regio- and stereoselectively by intramolecular photo(2+2) addition reaction.

The method for synthesizing cyclobutanols of the present invention will be explained in more detail.

The first synthesis method is expressed, for example, by the following formula.

That is, the adduct (13) of 1,3-dioxin-4-one (1) and ethylene was added to tetrahydrofuran (TH
Reduction in F) gives cis-2-hydroxymethyl-1-cyclobutanol (14). In addition, the adduct (
After hydrolyzing 13), it is silylated with a silylating agent such as tert-butyldimethyltrichloride (hereinafter referred to as TBDSCN) to obtain a silyl ester (15).

The second synthesis method is to introduce a terminal unsaturation on the 2-position substituent of 1,3-dioxin-4-ones, which is represented by the general formula, to form a dioxinone body, which is represented by the general formula. In the second synthetic method of the present invention, the intramolecular adduct represented by the general formula is produced by a photo(2+2) addition reaction, and the adduct is reduced to form a cyclobutanol compound.
Methods for introducing a terminal unsaturation onto the 2-position substituent of 4-ones include the following methods A and B.

Method A: When an ester (20) obtained by a conventional method from a ketocarboxylic acid and an unsaturated alcohol is heated with formylated Meldrum's acid (21), a corresponding 2,2-disubstituted dioxinone (23) is obtained.

is obtained.

(In 2\, R and R are each an alkyl group having 1 to 6 carbon atoms, and m+n≧2.) As another method of the second synthesis method of the present invention, the intramolecular adduct is hydrolyzed. There is a method of obtaining a carboxylic acid represented by the below-mentioned formula (32).

As a specific compound of the compound represented by formula (23), allyl 4-(2-methyl-4-oxo-1,3dioxin-2-yl)butyrate (23a)(m-2,R-
CH,CH-CH2] (see Example 3), vinyl 4-(2-methyl-4-oxo-1,3-dioxin-2-yl)butyrate (23b)Cm = 2
．． R-CH-CH2] (see Example 7), and
Instead of Meldrum's acid (21), 2,2-dimethyl-1,3-dioxin-4 represented by the following formula % formula %)
- Can be used on or off.

Method B: A benzyl ester of a ketocarboxylic acid is induced into a dioxinone (A) according to Method A, and then depensylated by catalytic reduction to give a carboxylic acid (B), and an unsaturated alcohol is added to this with a suitable binder, e.g. 2. Condensation with zinc chloride diimide (DCC) or the like;
A 2-disubstituted dioxinone compound (23) is obtained.

(B) (Here, R is CH-CH-(CH2) n or CH-CH-CH-(CH2).-, and m+n≧1
It is. ) 2.2-Disubstituted dioquinone body (23) has R body and 8
However, both symmetries are optically active carboxylic acids (B
) can be synthesized.

One of the simple methods for preparing the optically active carboxylic acids is through resolution of their benzyl esters (A) using a chiral column. For example, benzyl ester (A)
is ChjraSpher (manufactured by Merck & Co.), CHIR
It can be separated into both symmetrical bodies using ALCEL OJ (manufactured by Daicel). Therefore, the optically active form of the carboxylic acid (B) can be synthesized by optically resolving the benzyl ester form (A) and then catalytically reducing it.

Specific compounds of dioxinone (A) include benzyl 2-methyl-4-oxo-1,3-dioxin-2-carboxylate (24) [:m-0] (see Example 5), benzyl 4- ( 2-Methyl-4-oxo-1゜3-dioxin-2-yl)-butyre) (25) (m-2)
(See Example 6), As a specific compound of carboxylic acid (B), 2-methyl-
4-oxo-1,3-dioxin-2-carboxylic acid (2
6) [m-0) (see Example 5(b)), 4-(2-methyl-4-oxo-1,3-dioxin-2-yl)acetic acid (27) (rn-2) (Example 6(b
), as a specific example of the 2.2-disubstituted dioxinone (23), 3-buten-1-yl 2-methyl-4oxo 1.3-dioxin-2-carboxylate (23c) (m-
0,R-CH2-CH-(CH2)2-) (Example 5
(C)), crotyl 4-(2-methyl-4-oxo-1°3-dioxin-2-yl)butyrate (23
d) Cm-2, R-M e CH-CHCH2] (
(See Example 6(C)).

The intramolecular photo[2+2] addition reaction in the second synthesis method of the present invention will be explained.

Intramolecular light (2+23 addition reaction involves ethyl acetate, hexane,
The process proceeds by irradiating light with a wavelength of around 300 nm in a solvent such as acetonitrile, and an intramolecular adduct is obtained.

In the dioxanone of formula (10), when the sum of m and n is 1, no adduct is obtained. When the sum of m and n was 2 or 3, parallel adduct (28) was obtained in good yield.

In this case, a very small amount of cross-type adduct (29) was observed as a by-product.

(23C) (28C) (29C) (23b) (28b) The intramolecular photoadduct is converted to cyclobutanol in the same way as the intermolecular photoadduct. For example, when the compound (28a) is reduced with lithium aluminum hydride, a cyclobutanol compound (3o) is obtained, which is ethylated (
31) was obtained, which was also hydrolyzed to give carboxylic acid (32
) and then silylated to obtain ester (33).

These conversion reactions are similarly applied to each of the compounds (28b) to (28d) described above.

(23a) (28a) (29a) In the reduction operation J of the synthesis method of the present invention, a relatively strong reducing agent can be used (, lithium aluminum hydride, 1-notium boron hydride, hydrogen Examples include boron chloride.

As a silylating agent, any silylating agent with spatial flexibility can be used. I can use it.

As the condensing agent, any dehydrating condensing agent that can be easily separated after the reaction can be used, but 2-cyclohexylcarbadiimide (DCC) is convenient.

Any light source can be used in the photoaddition reaction as long as it contains light with a wavelength of around 300 nm, but it is effective to use a mercury lamp.

Example 1 (a) 2-oxo-3,5-dioxabicyclo[4.
2.0] Octane-4-spirocyclohexane (13)
Synthesis of 1.3-dioxin-2-spirocyclohexane-4-
A solution of 168 mg of On (1') (IIIn+ol) in ethyl acetate (20 ml) was irradiated with light having a wavelength of 300 nm while flowing ethylene gas. After 5 hours, the solvent was distilled off, and the residue was treated with column chromatography (silica gel, 8 g) to give hexane-ethyl acetate (1
0:1) to obtain 143+ng of crystals (yield 73%).

This was recrystallized from pentane-ether with a melting point of 51-52℃.
Obtained a prism.

From the following physical property values of the obtained prism, the title compound (
13).

1R (CHCI3): 1730 cm'H-NMR (CDC13) δ: 1, 1.0-2. 00 (10H, m, cycle
ohexyl), 2.00-2.77 (4H, m,
C7-, C8H), 2, 95 3-45 (
I H1m, CIH), 4, 47 4-85 (
IH, m, CeH).

Elemental analysis 201, H1603 Calculated value (C, 67, 32; H, 8° 22o) Actual δFl value (C, 67, 32; H, 8, 25,) (b) Cis-
2-Hydroxyoxymethylcyclobutan-1-ol (
14) Synthesis of lithium aluminum hydride 152+ng (4mlI
2-oxo-3,5-dioxabicyclo[4.2.O]octane-4-spirocyclohexane (13) obtained in (a) above (364 + ng A THF (2n+1) solution of 2mIlol) was added dropwise thereto, and then the mixture was returned to room temperature and stirred for 6 hours. A 50% aqueous sodium hydroxide solution was added dropwise to this reaction solution until precipitation occurred.

The reaction solution was filtered through Celite, and the solution was dried and concentrated.

The residue was subjected to column chromatography (silica gel, 35 g
) treatment, eluting with hexane-ether (2:7) gave 1.96 mg (yield 96%) of an oil.

The physical properties of the obtained oil are as follows.
2-hydroxymethylcyclobutan-1-ol (14
).

IR(CHCl): 3445cn-'500M
llz HN M R (CD CI 3) 6:
1.490-1.561 (IH, m), 1.680-
1.766 (LH, m), 2.030-2.119
(], H, m), 2.284-2.362 (IH, m
), 2.448.2.564 (each ], H.

br S, OH), 2.649-2.730 (I
H, m), 3.825 (IH, br dd, J-
Ko 1. 0. 4. 5t(z, C-
H), 4. 038 (IH, br dd
, J=11. 0.8.9Hz.

C,'-H), 4.538 (IH,br q
S J-7, Ol1zSCI H).

High-resolution mass spectrum (hereinafter abbreviated as MS), mlz
:M Calculated value C3H1oO2:102.0680
．． Actual value 9102.0702 Example 2 (a) tert-butyldimethylsilyl 2
Synthesis Example 1 of (tert-butylmethylsiloxy)cyclobutane-1-carboxylic acid ester (15) (
In the same manner as in a), 100 mg (0.55 mmol) of 2-oxo-3゜5-dioxabicyclo[4.2.0]octane 4-subironclohexane (1B) in water-THF
A 3 ml (2:1) solution was stirred at room temperature for 5 hours.

The solvent was distilled off, and the residue was diluted with methylformamide (5 ml).
) was added. To this, 415 mg (2,75 mmol) of tert-butyldimethylsilyl chloride and 374 mg (5,5 mmol) of imidazole were added,
Stirred at room temperature for 2 days. 50 ml of water was added to the reaction solution, and the mixture was extracted three times with 10 ml of ether. The organic layer was washed with water, dried, and then the solvent was distilled off. The residue was treated with column chromatography (silica gel, 8 g) eluting with hexane-ethyl acetate (20:1), yielding 190 + ng of oil.
(1,00%) was obtained.

From the following physical property values of the obtained oil, it was confirmed that it was tert-butyldimethylsilyl 2-(tertbutyldimethylsiloxane)cyclobutane-1-carboxylic acid ester.

1 R (CHCIs): 1703cm500M
IIz "HNMR (CD C13) δ: 0.015
(6H, S, SiMe2), 0°280.
0.299 (each 3H,S.

S rMe2) , 2.013 2.080 (2Hm
), 2.193-2.258 (], H, m), 2.
300-2.394 (LH, m), 2.250 (I
H, ddd, J-1, 1,, 0°8, 屹3.0llz,
Ct H), 4.476 (1H1q, J-8,01
17, C2H).

MS mlz:M” Calculated value CHOSi: 344.220] Actual value: 3
44.2125° Example 3 (a) Allyl 4-(2-methyl-4-oxoco, 3
-Synthesis of dioquin-2-yl)butyrate (23a) Allyl 4-oxopentanoate was used as the ketoester, and 1.00 g of boiling toluene (20 mmol) was used as the ketoester.
rnl solution, formyl Meldrum's acid], , 7
2 g (], Ommol) was added over 15 minutes, followed by further refluxing for 90 minutes, the solvent and excess ketoester were distilled off, and the residue was purified by column chromatography (silica gel, 30 g) to give hexane-ethyl acetate ( 5:1) to give a colorless oil in 62% yield.

From the physical properties of the obtained oil, it was confirmed that it was allyl 4(2-methyl-4-oxo-1,3-dioxin-2-yl)butyrate.

IR(CHCI)+1740.1625cm-'1
H-NMR (CDC13) δ.

1, 70 (3H, S, Me), 2. 31
2.83 (4H, m, C-~C3H), 4, 62
(2Hld, J-5,01lz, CH2CH=
CH2), 5, 08 6, 33 (3H
, m-CH-CH2), 5.43 (IH, d, J-6
, 01lz, C-H), 7. 1 5
(] H, d.

J=6. 0llz, C-H).

MS mlz:M+ Calculated value C11H1405(b)
Synthesis of compound represented by formula (28a) 200 mg (0.88 mmol) of butyrate obtained in the above (a)
was irradiated with light at a wavelength of 300 nm for 3 hours at room temperature while flowing argon into a solution of ethyl acetate (200 ml). Thereafter, the solvent was distilled off, and the residue was treated with column chromatography (silica gel, 25 g) to obtain hexane-ether (3:
2) to obtain 160 mg (yield 80%) of crystal A and 829 mg (yield 15%) of crystal A. Crystal A has a melting point of 93-95 when recrystallized with ether-dichloromethane solvent.
Obtained a prism of °C. In addition, crystal B has a melting point of 14 B -1,44°C when recrystallized with ether-dichloromethane.
scaly crystals were obtained.

Crystal A was confirmed to be a compound represented by formula (28a) from the following physical property values.

IR(CHC'l) 2 1731cm-
'500 Mllz HN M R (CD CI g
) δ: 1.53 (3H, S, Me), 2.075
2, 120 (2H, m, C2H), 2. 3
44 (ko H, d t, J = 1 2.
0, 3. 811z, CaH), 2
．． 485 (IH, dt, J-12, 0°6.01lz
, C13-H), 2.56.2-2.630 (I H
, m, C7H) , 2゜6842.760 (2H, m
, C3-, C13-H), 3.231 (IH, ddd
d, J-11,0°8.0,5.5,1-0112.
C9H), 3.763 (IH, br d, J-12
,511z.

C6-H), 5.059 (IH,t, J-8,0
11z, C8H), 5, 268 (IH
, d d , J = 13, 屹 3 , -511z, C
eH).

MS mlz: M” rl calculated value c11H14
o5 '226.0840. Actual 11 value: 226.089
The 8° crystal B was confirmed to be a compound represented by formula (29a) from the following physical property values.

1R (CHCI3): 1731c■ 500 Mjlz' HN M R (CD C1a
) δ: 1.549 (3H, s, Me), 2.04
9 (IH; ddd, J-13,5,2,5,1,
011z.

C3-H), 2.160-2.342 (3H, MC-
, C3-H), 2.609 (IH, ddd.

J-13, 5, 10, 屹5. ○llz, Cs H), 2
．． 700 2.790 (IH=m, C3H), 3.
172 3.241 (LH, m, C7H), 3.33
7 (1H, br dd, J=10.0°4, 5H
z, Cto H), 3-91.5 (I H, d
d.

J-12, Sail 6, 011z, Ce H), 4.52
8 (IH, ddd, J-5, 0, 4, 52, 5Hz,
C9H), 5. 065 (1,H,dJ-12
, O11z, C6H).

Elemental analysis: Calculated value C1□H1405 (C, 58, 40; H, 6, 24), actual value (C,
58, 26; H, 6, 22).

(c) Synthesis of 2-acetoxy-1,3-diacetoxymethylcyclobutane (31) Lithium aluminum hydride 52 mg (1,,39Hn
The formula obtained in (b) above was added to a suspension of anhydrous tetrahydrofuran (5 ml) of ol) in an argon stream and under water cooling.
28a) Compound 111ff1g (46nun
A solution of 3 ml of terahydrofuran was added dropwise to the mixture. After 5 minutes, the mixture was returned to room temperature and stirred for 6 hours.

Approximately 10 drops of 50% aqueous sodium hydroxide solution was added and filtered through Celite. Anhydrous magnesium sulfate was added to the furnace solution to dry it, and the solvent was distilled off. ml of acetic anhydride] and 5 drops of pyridine were added to the residue, and the mixture was allowed to stand at room temperature overnight, and the acetic anhydride was distilled off under reduced pressure. The residue was subjected to column chromatography (silica gel, 8 g) eluting with hexane-ethyl acetate to obtain 25+ ng (yield 22%) of an oil.

The obtained oil was determined to be 2-acetoxy-
It was confirmed that it was 1,3-diacetoxymethylcyclobutane.

1 R(CHCl3): 1740 clQ500
Mllz HN M R (CD Cl 3) δ1.
680 (IH, dt J-1, 2, 屹8.011z, C
3-Ha), 2.031 (6H,S,2XOAc)
, 2. 071 (3H, S, 0Ac).

2, 1.72 (], H, da t, J-1
2,09, 0,3, OIlz, C3Hβ), 2.8
60 (2H, m, C2-, C9-H), 4.090 (2
Hld d, J-12,0,6,0llz, C1-H
), 4. 205 (2H, dd, J-12
,0゜9, 01lz, C-H), 5. 40
0 (IH.

dt, J-7,0,3, OIlz, CIH).

MS mlz:M”-0Ac H value C1oH15
0.], 99.0969. Actual value: 199.097]
.

Example 4 tert-butyldimethylsilyl (IR*2R3S*)
-2-tert-butyldimethybensiloxy-3~ (4-oxopentanoyloxy)
-Synthesis of cyclobutane-1-carboxylate (33) Allyl 4-(2-methyl-4-oxo-1,3-dioxin-2-yl)butyrate (23a) 0113 mg
(0,5s+gol) of water-THF (3: 1°4m
1) After adding p-toluenesulfonic acid (5 mg) to the solution and leaving it at room temperature for 4 days, the solvent was distilled off, and dimethylformamide (10 ml) was added to the residue.

To this, tert-butyldimethylsilyl chloride 378
mg (2,51ol), imidazole 340 @g
(5,0*ff1ol) was added and stirred at room temperature for 24 hours.

Add 100 ml of water to the reaction solution, add ether (20 ml
) and the organic layer was washed with water and dried, and then the solvent was removed. Column chromatography (silica gel,) of the residue
, Og) treatment, hexane-ethyl acetate (5:1.
) to obtain 170 mg (yield 96%) of an oily substance.

From the following physical property values of the obtained oil, the title compound (3
3) was confirmed.

IR(CHCl); 1720em-'500
Mllllz HN M R (CD CI 3)
δ: 0.052 (6H, S, S I Me2), 0
．． 259, 0. 288 (each 3H,S
.

S fMe), 0. 880, 0. 930
(each9H,S, tert-butyl)
, 1. 998 (IH.

dat, J-12,0,8,5,2,011z-Cs-
Hβ), 2. 182 (IH,br dt,
J-12, 0-7, 81Jz-C3Ha),
2. 186 (3H, S, Me), 2. 4
82-2. 598 (2H, m, OCCH2)
, 2.645-2, 770 (3H1m,
C4H1M e C0-CH2), 3.260 (I
H, Q, J-8,01lz.

C2-H), 4.218 (IH, dd, J-11,
0,6,811z, C-H), 3. 313
(IH, dd, J-11, 屹s, OJlz, Cr
H), 4. 660 (IH, d t, J
-7,2°2.0°, 01~H).

MSm/z: M+ Calculated value C17H280e S 1
:356.165B, n1 constant value: 356.1659° Example 5 (a) Benzyl 2-methyl-4-oxo-1°3-
Synthesis of dioxine-2-carboxylate (24) Benzyl pyruvate was used as the ketoester, and the other procedures were the same as in Example (a). Acicular crystals with a melting point of 48 to 49°C were obtained in a yield of 80%. .

The obtained crystals were confirmed to be benzyl 2-methyl-4-oxo-1,3-dioxin 2-carboxylate based on the physical property values shown below.

IR (CHC13): 1762, 1625° 1610c
m''H-NMR (CDC13) δ: ], 83 (3H, S, C6M e ), 5.24
(2H, S, -Cdan, Ph), 5.40 (IH.

d, J = 6.01lz, C3H), 7.18 (I
H.

d, J"" 6-01121C2H), 7.
33 (5Hs, ph).

Elemental analysis; calculated value C13H1205 (C162,9
0, H, 4, 87), actual value (C.

62, 94, H, 4, 94).

(b) Synthesis of 2-methyl-4-oxo-1,3-dioxin-2-carboxylic acid (26) Benzyl 2-methyl-4=oxo-1,3-oxine- obtained in (a) above
2-carboxyleto (24) 9 9 2mg
(4 ml Ilol) to 10% Pd-C (20
0mg) in methanol (20ml) at room temperature and pressure. The solvent was distilled off to give crystal 6B2+ag.
(yield 100%). Recrystallization was performed using an ether-pentane mixed solvent to obtain a prism having a melting point of 98 to 102°C.

According to the following physical property values of the obtained prism, 2-methyl-
It was confirmed that 4-oxo-1,3-dioxin-2=carboxylic acid.

IR (CHCI3): 3400-2400°1760
．． 1620.1610cm-''H-NMR (CDC1
3) δ: 1.91 (3H,S,CeMe), 5-48
(IHld, J-6-011z, C3H), 7, 33
(I H, d, J-6, 011z, C2H), 10
, 2 (I H, b r S, CO2H).

Elemental analysis; calculated value C6H605: (C, 45,58; H, 3,85), actual value (C,
45, 32, H, 3, 87).

(C) 3-buten-1-yl 2-methyl-4oxo-
1,3-dioxin-2-carboxy 1) (23c)
Synthesis of the carboxylic acid (2gaol) obtained in (b) above and 3-
A solution of buten-1-ol (2.4 mmol) in dichloromethane (10 ml) was cooled on ice and stirred until N,N'
-Dicyclohexylcarbodiimide (DCC) 49
5 ml (2.4 mmol) and 24 mg (0.2 smol) of 4-dimethylaminopyridine were added. 3
After 0 minutes, the mixture was brought to room temperature and stirred for an additional 3 hours. After filtering off the crystals, the crystals were concentrated and subjected to column chromatography (silica gel, 2
5g) treatment gave a colorless oil in 73% yield, eluting with hexane-ethyl acetate (5:1).

From the following physical properties of the obtained oil, 3-buten-1-yl 2-methyl-4-oxo-1,3-dioxin-2-
It was confirmed that it was a carboxylate.

IR (CHCI3): 1760, 1622°1609
cm-' IH-NMR (CDC13) δ: 1, 84 (3H, S, Me), 2. 43
(2H.

q, J-6,411z, Cdan. -CH-CH2
), 4-30 (2Hlt, J-6-411z,
C02CH2), 4. 87 6. 17 (3
H, mCH-CH2), 5.46 (IH, d, J-
6, 011z, C2-old, 7.23 (IH, d,
J=6, 011z, C3H).

MS m/z: M” Calculated value: C1oH120
5:212.0684, actual value: 212.0679° (
d) Synthesis of the compound represented by formula (28c)
) 200 m of 3-buten-1-yl 2methyl-4-oxo-1,3-dioxin-2-carboxylate
g (0.94 mmon) in the same manner as in Example 3(b) to obtain 145 mg of crystal A' (73% yield) and 20 mg of crystal B' (10% yield). Crystal A' was ether-dichloromethane. Melting point: 96 when recrystallized with solvent
A prism of ˜97° C. was obtained. Crystal B' was recrystallized with ether-pentane to obtain prisms with a melting point of 121-122°C.

Crystal A' was confirmed to be a compound represented by formula (28c) from the following physical property values.

=1 1 R (CHC13): 1759cm500M
llz HN M R (CD CI 3 ) δ
:1.693 1-760 (iHlm, C5H)
, 1.746 (3H,S,Me), 3.3852.
480 (2H, m, Cl2-H), 2,535 (L
H, d t , J-13, 0,10,011z,
Ce-H), 3.034 (LH, dddd, J-3
,7,3゜6.3.4,3.1llz, Cy H)
, 3.445 (IH, dddd, J-10, 5°9.
0,4-5,1.0112. C9H), 5.245
(IH, ddd, J-13, 0゜11.5, 4.01
lz, Ce H), 4. 905 (IH, d
dd, J-11,5,6,0,1,0Hz, Ce
H)-15,342(IH,t,J-9-011z
, Cs H).

MSm/z:M+ Old value C1oH12C5:212.
0684, actual value +212.0686° Crystal B' was confirmed to be a compound represented by formula (29c) from the following physical property values.

■ I R (CHC) 3): 1742 am500
Mllz HN M R (CD CI 3) δ.

1.622 (IH, ddd, J-16,06, 5,3
, 5 degrees, C3-H), 1. ．． 772 (3H, S, M
e), 2.172-2.247 (], Hm, Cy
H), 2.357 (]-]H,ddddJ-16
．． 0,145,6.5. ], 01lz.

C5-H), 2.522 (IH, dddd, J-1
6. 10. Sail 8. Leopard 1. , O11z, C7 old,
3, 1.423, 225 (I H, m, C6
H), 3.753 (IH, br t, J -8,0
11z, C9H), 4-674 (I Hd
dJ ”' 12. 0, 6. 0IIZ, C4
H), 4.803 (IH, d t, J-s, o,
5.01lz.

C3-H), 4.902 (IH, ddd, J-12
,0,11,0,4,0IIZ, C4H).

Elemental analysis: Calculated value C1oH1205 (C,56,6
0; H, 5, 70), actual value (C, 56, 55; H
5,63) Example 6 (a) Benzyl 4-(2-methyl-4-oxo-
1,3-dioxin-2-yl)-butyrate (25)
Synthesis was carried out in the same manner as in Example 3 except that benzyl 4-oxopentanoate was used as the ketoester, and a colorless oil was obtained in a yield of 80%.

Based on the following physical properties of the obtained oil, benzyl 4-
(2-methyl-4-oxo-1,3-dioxin-2-
It was confirmed that the

1 R(CHC13) =1739.16238a'
H-NMR (CDC13) δ: 1.67 (3H, S, Me), 2.13-2.81
(4H, m, C-~C3H), 5.13 (2H,
Both S and -C, ph), 5.36 (1, H, d, J~6
．． 0llz, C-H), 6.83 (IH, d,
J-6,0 肚, C2H), 7. 35 (5H,
S, Ph).

MS m/z: M+-C3H202 Calculated value CHO: 206.0942° Actual value: 206.0956° (b) 4-(2-Methyl-4-oxo-1,3=dioxin-2-yl)acetic acid (27 ) Synthesis Example 4 (a
) was reduced according to Example 3(b) to give 3721 g of crystals (yield: 10
0%) was obtained. Recrystallize with etherpentane mixed solvent,
Acicular crystals with a melting point of 69-72°C were obtained.

The obtained needle-like crystals were confirmed to be 4-(2-methyl-4-oxo-1,3-dioxin-2-yl)acetic acid based on the following physical property values.

IR (CHC13): 3450-2400°1730
．． 1622 cm''H-NMR (CDC13) δ.

1.72 (3H,S,Me), 2.052-82
(4Hlm, C-~Cs H), 5, 42
(I H, d, J = 6.01lz, CaH)
,7. 1.3 (IH, d, J=6.0
1lz.

02'-old, 10.13 (IH, br S.

CO2).

MS m/z M+-C3H202 Calculated value C3H803:116.0473, real? IFI
Value: ]i, 6.0459° (C) Crotyl-4(2-methyl-4-oxo-1
,3-dioxin-2-yl)butyrate (23d) A colorless oil was obtained in a yield of 75% from the carboxylic acid of (b) and crotyl alcohol in the same manner as in Example 5(C).

From the following physical properties of the obtained oil, crotyl-4-(
It was confirmed that it was 2-methyl-4-1,3-dioxin-2-yl)butyrate.

1R (CHCI3): 1730, 1622clI'H
-NMR (CDC13) δ: 1.68 (3H, S, Ce Me), 1.75 (
3H,d, J-5,011z, CH-CH2Me
), 2.10 2.80 (4H, m, C2-C3-
Old, 4.54 (2H, br d, J-5, 0ll
z, Co-Cdan2-), 5.42 (IH.

d, J-6,011z, C'-H),
5. 52-5, 97 (2H, m, CH-C
H), 7. 10 (IH, d, J-6,01
lz, C'-H).

MS: M - C3H202 = 1 calculated value CHO: 170.0942. Fruit 1 value: 17
0.0947°(d) Synthesis of the compound represented by formula (28d)
Crotyl-4-(2-methyl-4-oxo-13-dioxin-2-yl)butyrate (2,3
d) 300II1g (1.25mmol) in Example 3
In the same manner as in (b), 210 mg of crystal A* (yield 70%)
), 36 mg of crystal B* (yield 12%) was obtained.

Crystal A* is recrystallized with ether and has a melting point of 124-125.
Obtained a prism of °C.

Crystal B* is recrystallized with ether and has a melting point of 106-107.
Needle-shaped crystals were obtained.

From the following physical property values of the prism of crystal A*, formula (28d)
It was confirmed that the compound was

1 R (CHCIs): 1732e■500M
l1z'HNMR (CD C13) δ: 1.356
(3H, d, J-7,011z, C13M e )
, 1, 495 (3H, S, CI M
e), 2, 045 2-155 (3H,
m, C2C7-H), 2.332 (IH, d
t, J-12-0,4,01lz, C3H), 2.
634 (L H, d t , J = 12.0,5.
01lz, CaH), 2. 794 (IH
,ddd, J-8,0°5, 0,1. OH2
, C9H), 2. 893 (LH,br dq,
J=7.0, 6.01lz, C13H), 3. 7
84 (IH, dd, J-12, 0°1, 0Hz
, c6H), 5.045 (I H,t.

J=8. 01lz, Cs H), 5.
220 (IH.

d d, J-12-0, 3-011z, Ce H)
.

Elemental analysis: Calculated value Cl2H1605 (C,59,99;H6,71), Actual value: (
C, 59, 78, H6, 78).

From the following physical property values of the needle-like crystal of crystal B*, formula (29d)
It was confirmed that the compound was

1R (CuCl2): 1740, 1728c■500
Mllz HN M R (CD Cl s )
δ: 1.198 (3Hld, C8M e ), 1-
536 (3H, S, CIMe), 2-
150 2-330 (3H1m, C2Cs
H), 2, 330 2, 390 (I H
, mCg H), 2, 660 2, 757
(2H, m.

CC7H), 3.355 (IH, brdd, J-
10,0,4,01lz,C,o-H),3,907
(LH, dd, J-12,0,6,0Hz1C
e H), 4.115 (IH, dd, J -4,
0,2,011zSC9H),5. 076 (IH
ld, J-12,0'1lz-Ce H).

MS m/z: M +1 Calculated value CHO: 241.1075° Actual 1IFI value: 241.1119° Example 7 (a) Vinyl 4- (2-methyl-4-oxo-1
Synthesis of ,3-dioxin-2-yl)butyrate (23b) The same procedure as in Example 3 was repeated except that vinyl 4-oxopentanoate was used as the ketoester, and a colorless oil was obtained in a yield of 63%.

The physical properties of the obtained oil are as shown below.
It was confirmed that it was vinyl 4-12-methyl-4-oxo-1,3-dioxin-2-yl)butyrate.

IR (CuCl2): 1749, 1650° 1621c
-1'H-NMR (CDC+3) δ: 1.82 (3HS, Me), 2.132, 85
(4H,m, C-~CsH), 4.60
(IH, dd, J-6,0,2,0llz.

-CH-Cdan2), 4.90 (IH, dd, J-1
4,0,2,01lz, -CH-Cdan2), 5, 4
2 (I H, d, J -6,01lz-C5H)
,7. 12 (LH, d, J-6,01lz
c2-H), 7.28 (IH, dd, J-14, 0,
6,01lz, -CH-CH2).

MSm/z:M+ Calculated value C1oH120521,2
, 0684 Actual measurement value: 212.0722° (b) Formula (
Synthesis of compound represented by 28a) 200 mg (0.94 mol) of the butyrate (23b) obtained in (a) above was treated in the same manner as in Example 3(b) to obtain 1.82+ng of crystals (
A yield of 91%) was obtained.

Recrystallized from nityl dichloromethane, melting point 149~
A prism of 150°C (113°C-dec) was obtained.

The obtained prism can be calculated using the formula (28a) from the following physical property values.
It was confirmed that the compound was

IIR(CHCIg): 1741. cm500
Mllz HN M R (CD Cl 3) δ
1, 568 (3HS Me), 2.
2402.458 (5H, m, C2-C3-Cl2H
), 2. 764 (IH, d t, J
-1,1,, 0°7, 211zSCs H),
3. 193 (IH.

dddd, J-8,5,7,9,3,0,2,0H
z, Cg H), 4, 705 (I
H, dd d, J-8,0,2,0,1,0H
z, C7H), 5, 322 (IH, d t,
J-4,5,3,211z.

C6-H).

〔Effect of the invention〕

A feature of the synthesis method of the present invention is that when the photo[2+2] adduct is reduced, cyclobutanol is obtained while maintaining the steric structure of the adduct. The second is that the direction of addition can be controlled to one side by using an intramolecular reaction, and the third is that it is an effective asymmetric synthesis method. That is, by making the 2-substituted dioxinone optically active, the addition surface can be controlled 100%.

Claims (1)

[Claims] 1. General formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (1) 1,3-dioxin-4-ones shown by the general formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ A light [2+2] adduct with an unsaturated compound represented by ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (2) A general formula characterized by reducing ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (3) A method for synthesizing cyclobutanols shown in (Here, R^1 and R^2 each represent an alkyl group having 1 to 6 carbon atoms or -(CH_2)_l-, and R^
3 represents hydrogen or an alkyl group having 1 to 8 carbon atoms. R
^4 represents hydrogen or an acyl group. 1 represents 4-6. ) 2. 1,3-dioxin-4-ones shown by the general formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (1) and unsaturated compounds shown by the general formula ▲ There are mathematical formulas, chemical formulas, tables, etc. Light [2+2] adduct with a compound ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ General formula characterized by reducing (2') ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (3') , a method for synthesizing cyclobutanols. Here, R^1 and R^2 each represent an alkyl group having 1 to 6 carbon atoms or -(CH_2)_l-, and R^3
represents hydrogen or an alkyl group having 1 to 8 carbon atoms. R^
4 represents hydrogen or an acyl group. 1 represents 4-6. ) An ester structure moiety in which the terminal of the alcohol moiety is unsaturated is introduced onto the substituent at the 2-position of 3,1,3-dioxin-4-ones, and substituted cyclobutanol is produced by an intramolecular photo[2+2] addition reaction. Regio- and stereoselective synthesis of.