JPS60185791A - Beta-trialkylsilyl-beta,gamma-unsaturated aldehyde and preparation thereof - Google Patents

Abstract

NEW MATERIAL:A compound expressed by formula I (R<1> is H or lower alkyl; R<2> and R<3> are lower alkyl). EXAMPLE:2-Methyl-3-trimethylsilyl-3-octenal. USE:An intermediate for synthesizing stereoselectively various erythro and threo alcohols. PREPARATION:For example, an epoxy compound expressed by formula II (R<4> is a protecting group of the hydroxyl group) is condensed with a Grignard reagent expressed by formula III (X<1> is halogen) preferably at 2:1-1:3 ratio between the former and the latter in a solvent, e.g. diethyl ether, to prepare a condensate expressed by formula IV, which is then hydrolyzed in the presence of an acid substance, e.g. dichloroacetic acid, to remove the protecting group therefrom. The resultant diol expressed by formula V is then oxidized with periodic acid.

Description

[Detailed description of the invention]

The present invention relates to a β-trialkylsilyl-β,γ-unsaturated aldehyde represented by the general formula (wherein R1 represents a hydrogen atom or a lower alkyl group, and R2 and R3 represent a lower alkyl group) and a method for producing the same. . β-trialkylsilyl-β represented by general formula (1),
γ-unsaturated aldehyde [hereinafter, this will be abbreviated as compound (1). ] is a new compound), and various ELITE o (e
rythro) body and), L/, IJ-(thr
It is useful as an intermediate for the stereoselective synthesis of alcohols of the eo ) form. According to the present invention, compound (1) is an epoxy compound represented by the general formula % (in which R3 is as defined above and L" represents a hydroxyl group). is the general formula (wherein R1 and R2 are as defined above,
l represents a rogen atom. ) to obtain a condensate represented by the general formula (wherein R1, R2, Ra and R4 are as defined above), and by decapturing the condensate, - A method comprising using a diol represented by the general formula R3 (wherein R', 'R2 and 1ζ3 are as defined above) and oxidizing the diol with periodic acid [Method (1)] can be manufactured. 1, according to the present invention, a compound of the general formula (H) in which R1 is a lower alkyl group, that is, a compound of the general formula [wherein R3 is as defined above and R5 is R1 in the general formula (1)]
The same applies to R1 when is a lower alkyl group. ] The compound represented by the general formula % (in which R2 and R5 are the above-mentioned formula) is a trialkyl silylacetylene compound represented by the formula % (in which R2 and R5 are the same as the above-mentioned formula). Produced by a method [method (2)] comprising reacting α-bromoaldehyde with the general formula (in the formula, Hs represents a lower alkyl group) of the 51 product gold reacted with yum halide. You can also do it. Furthermore, according to the present invention, in general formula (I), R
Compounds in which 1 is a hydrogen atom and R3 is a methyl group, that is, 2-methyl-3-trialkylsilyl-3- represented by the general formula (wherein R2 is as defined above) Butene-1
-R is obtained by reacting 2-trialkylsilyl-1,3-butadiene represented by the general formula (wherein R2 is as defined above) with isoptylmagnesiumolide in the presence of a titanium compound. Then, the product is reacted with a formate having the general formula % (where M represents a lithium, sodium or potassium atom or MgX2, where X2 represents a -.logen atom). It can also be produced by a method [method (8)] consisting of: In each of the above general formulas, i<z, R2, R3 and 1
The lower argyl group represented by e5 includes methyl, ethyl, propyl, butyl, and the like. Also,
R4 may be any holding group that is effective for carrying out the above method (1), such as trimenalsilyl group, 1-ethoxyethyl group, -1 to n-butoxyethyl group, tetrahydropyranyl group, tert-butyl group. The halogen atom represented by , tri can be a chlorine, bromine or iodine atom. The reaction between the epoxy compound of formula (II) and the Grignard reagent of formula (I[j) in method (1) above is expressed by the following formula (
■) Based on the epoxy compound of 1 to 30 mol.
・A mixture of a cuprous halogenated catalyst and an equimolar to twice the molar amount of sialkylsulnide (e.g. dimethyl sulfide, diethyl sulfide, etc.) and a Grignard reagent of formula (Iff) at about -20°C to room temperature. After the reaction, the epoxy compound of formula (II) is preferably added dropwise to the reaction mixture. Examples of the reaction solvent that can be used include diethyl ether, dibutyl ether, and tetrahydro7ran. As the cupric halide catalyst, for example, cuprous iodide, cuprous chloride, etc. are used. The ratio of the Grignard reagent of formula (In) to the epoxy compound of formula (■) is preferably 1=2 to 3:1 (molar ratio). The condensate of formula (■) obtained by this reaction can be prepared by a conventional method, for example, dichloro

[Deprotection is achieved by hydrolysis in the presence of an acidic substance such as co-acetic acid or dilute hydrochloric acid, followed by oxidation using a periodate salt such as sodium periodate to give the compound (1). I can do it. The periodate oxidation reaction is carried out using sodium periodate in an equimolar amount to 3 times the molar amount of the diol of formula (V) obtained by hydrolyzing the condensate of formula (IV), and the reaction is carried out at about -10"C~ It is preferable to carry out the reaction in a room. Alcohols such as methanol, ethanol, propatool, etc. can be used as a solvent for this oxidation reaction. Note that method (1)
The epoxy compound of formula (n) used as a raw material is subjected to a known 5harpress oxidation reaction [for example, J, Am, Chem, Soc, 02,5
974 (see [980)], crotyl alcohol and an equimolar to twice molar amount of peroxide (e.g. cumene hydroperoxide, tert-butyl hydroperoxide, etc.) in the presence of a vanadium catalyst. It can be easily obtained by reacting to obtain 2,3-epoxyptanol and then retaining its hydroxyl group according to a conventional method. In method (2), the reaction between the acetylene compound of formula (■) and isobutylmagnesium halide is carried out at about -20 to 60°C, preferably -10 to 30°C in the presence of a titanium compound as a catalyst. Monkey. The time required for the reaction depends on the reaction temperature, but is usually about ~1
The reaction ends at 0 hours. As the isobutylmagnesium halide, isobutylmagnesium bromide, isobutylmagnesium chloride, etc. are used. As a titanium compound, Cp2Tiα
2(C1) represents a cyclopentadienyl group. ] is preferably used. The titanium compound is preferably used in a proportion of about 1 to 20 moles relative to the acetylene compound of formula (■), and the inbutylmagnesium halide is preferably used in a proportion of about 1 to 1.5 moles per mole of the acetylene compound of formula (2). . Diethyl ether, diethyl ether, etc. can be used as a reaction solvent. The reaction between the product obtained by the above reaction (hereinafter referred to as product A) and α-bromoaldehyde of formula (■) is
It can be carried out at a temperature within the range of 0°C to 40°C. Preferably, α-bromoaldehyde of formula (■) is added dropwise to a solution containing product A at a low temperature of -80 to -40°C, and after the completion of the dropwise addition, the temperature is raised to around room temperature to drive the reaction. The time required for the reaction depends on the scale of the reaction, but is usually about 5 hours. The α-bromaldehyde of formula (■) is the acetylene compound 1 of formula (■) used to produce product A.
It is preferably used in a proportion of about 1 to 2 moles per mole. Next, to explain the previous method (3), about 1 to 1.5 times the molar amount of isobutylmagnesium halide of the 2-) IJ alkylsilyl-1,3-butadiene of formula (X) and the formula (X) 2-trialkylsilyl-1,3
- In the presence of a titanium compound having a molar ratio of about 1 to 20 to butadiene, the reaction is carried out at about -20 to 60°C, preferably at room temperature, and to the resulting reaction solution is added a formate of formula (XI), and about -
By reacting at 10 to 50°C, 2-methyl-3-trialkylsilyl-3-buten-1-al of formula (DO) can be obtained. 2-trialkylsilyl-1 of formula (X) , 3-butadiene and isobutylmagnesium halide can usually be completed in about 1 to 10 hours.The same reaction solvent and titanium compound as in method (2) can be used for this reaction.Formula ( XI
) is used in a proportion of about 1 to 2 moles per mole of compound of formula (X). A part of the usefulness of the compound (1) provided by the present invention and which can be produced by each of the above methods will be shown below. (1) Bi) (cave) That is, the compound gl (D is the Grignard test mulberry of the gods R'
Reacts with MgX (where R6 is an organic group and X represents a -.rogen atom) to produce the corresponding erythro alcohol (
Selectively give only X[). After oxidizing the erythro-alcohol (Kari), it can be converted into threo-alcohol αff1) which has the opposite three-dimensional structure. Alcohols (Xll) and (Xlll) thus obtained
), for example, when treated with sodium hydride in a mixed solvent of tetrahydrofuran (Tf)/hexamethylphosphoramide (H+V1PA), only the silyl group is selectively eliminated, resulting in alcohols (XIV)> and J:
U (XV) K can lead. Also, 7 le: l-le (Xl
Epoxidation of l) and (X[II), for example with tert-butylno)hydrobaroxide in the presence of a vanadium catalyst, followed by treatment with trifluoroacetic acid in methanol gives the corresponding ketones (XV[) and (
You can also get a sake cup. As mentioned above, the compound (1) provided by the present invention is an extremely useful compound in that various erythro and threo alcohols 41 can be synthesized freely and stereoselectively depending on the purpose. be. Naturally, since the compound of formula (DO) can be made into an optically active form by 5harpress oxidation of crotyl alcohol, the compound (1) derived from the optically active metal compound of formula (IX) The carbon to which the R3- group is bonded is an optically active center, so the formula (Xll) ~ (X
The compound of vll) is also an optically active compound. Compounds of formulas (Xll) to (2) are known as the basic skeletons of various physiologically active natural products, and a simple method for synthesizing them has been desired. The conventional general method is an improved method of aldol reaction [for example, Moriyuki M, Pharmacia, Vol. 1.17, 82]
5 (1981)], the Grignard reaction of crotyl halide [eg C,H. Heathcock, ” Asy+nmetric
Organic Reactions''. VOl, 3 + J, D 6MOr r I S
On + K'd, + Ac aderrl I C
Pre es S + New York (1984) O and R, W, Hofmann. Angew, Chem, Int, Ed, Engl.
21, 555 (1982)] or variations thereof [e.g. C., HlHeathcock et al., Te
trabedron Lett, , 4765 (] 9
83)], but the unexploded uAa compound (1) is a multipurpose compound that makes it possible to freely and easily synthesize only the desired stereoisomer of the compound that has been synthesized by those known methods. It can be said that it is a raw material. Hereinafter, the present invention will be explained in more detail with reference to Examples. Example 1 Isobutylmagnesium bromide (
Approximately 60 kg of Cp2Tiα2 (5 mo1
%) and stirred at 0°C for 20 minutes. At 0℃
After adding 0 mmol), the mixture was reacted at room temperature (approximately 20 to 25°C) for 5 hours. Add diethyl ether 15+ to this solution.
After adding m, the mixture was cooled to -60°C. 1.29 (8.6 mmol) of α-bromopropionaldehyde was slowly added dropwise at the same temperature for 1 hour, and then at room temperature for 1 hour.
Allowed time to react. 20 m of 3N Hα was added, and the aqueous layer was extracted twice with diethyl ether. After drying the ether layer over anhydrous magnesium sulfate and distilling off the solvent under reduced pressure, the crude product was purified by column chromatography (silica gel) to obtain 454 μl of 2-methyl-3-trimethylsilyl-3-octenal. (yield 44.6%). The NMR spectrum measured for this product was as follows. "H-NMR (Cα4) δ0.10 (s, 9H,
3C1(3). 0.65-0.95 (rn+3H+CH3C
H2) + 1.05 (d, 3H+J=7H2I C
)I3CH), 1.10~1.60 (m, 4H
, (CH2)2CH:l). 1.90-2.35 (m+2H, CH=CH2)
+ 2.95 (q, I n + J = 71 ce, C”k
JC: Hs ), 5.81 (t + I H, J=
8 out, C excerpt). 9.34Cs, IH, CHO). Example 2 1-hexynyltrimethylsilane 1.4'7F, (
9,53 mmol), isobutylmagnesium 70mide 12nLe (12,4 mmol, 0.96 M dix
Ch/l/x-7-l solution), Cp2Tiα2 approx. 1
The same reaction as in Example 1 was carried out using 2.80 f (14.3 mmol) of 2omy (5 mol %) and 20% α-bromoheptylaldehyde to obtain 931q of 2-pentele-3-trimethylsilyl-3-octenal 3 (
Yield: 38 cm). The 'H-NMR spectrum of this product was 0''H-NMR (Cα4)δ0.
19 (S, 9'H, 3CHa). 0.80~2.38(m), 2.82~3.06(
m, 11-f, CI (CHz). 5.91 (t, IH, J=8Hz, CH=CH2). 9.37 (d, IH, J=2.5 output, C11O). Example 3 Isobutylmagnesium bromide 23 ml (1,6
, 1 mmol, 0.70M dixyl solution), Cp2TICZ2 approx. 2TICZ5mol1%
) and 1-propynyltrimethylsilay 1.37
A reaction was carried out in the same manner as in Example 1 using r (12.2 mmol) to give 2-methyl-3-trimethylsilyl-
740 ■ of 3-pentenal 5 was obtained (yield 35.6%)
. The H-NMR spectrum of this product was as follows: H-NMR (Cα4) δ0.20 (s, 9H, 3CH
s), 1.10(d, 3n, J=7Hz, CHaC
H), 1.81 (d, 3H, J=7Hz. CHsC=), j, ol (q, IH, J=7Hz, CH
CHs), 5.98(qtlH, J=7Hz, (l(=
C), 9.33 (s, IH, CHO). Example 4 2-trimethylsilyl-1,3-butadiene 2.039 (16.1 mm, ol) Ni7 under argon atmosphere
Butylmagnesium bromide (24,3rt11) 7
．． 7ml of 0.73M diethyl ether solution of TIO1) was added. Cp2Ti (12200
ml (5 mo 1%) was added and stirred for 4 hours to prepare an ether solution of Grignard reagent 7. Tetrahydrogen O7 run (hereinafter referred to as 'I'HF) (2sml) of 23.1 mmol under argon atmosphere
V) Ethylmagnesium bromide (31
, 3tnl, 26.0 mmol) (7) 0.83
MTHF 6 liquid was added dropwise over 40 minutes. Add Grignard reagent 7 (16,1 mmol) prepared above to this solution.
The ether solution of 1) was added dropwise at 0° C. over 20 minutes, followed by stirring at room temperature for 30 minutes. 2Ncy after reaction completion
The reaction solution was poured into 5 ml of aqueous solution, and the aqueous layer was extracted twice with diethyl ether. The collected organic layer was thoroughly washed with saturated brine and dried over anhydrous magnesium sulfate. After distilling off the solvent under reduced pressure, the crude product was purified by column chromatography (silica gel) to obtain 2-
Methyl-3-trimethylsilyl-3-butynal 8 is 1
．． 33f was obtained (yield 53.0%). The 'H-NMR spectrum of this product was as follows. "H-NMR δ0.10 (s, 9H, 3C) I3),
1.15 (d, 3H. J=7Hz, Cdan 5cH)? 3.10 (dq,
] u, J=2Hz. J'=7Hz, CHC)is), 5.57(s, 2H,
CH2=C). 9. KO Ll (d, IH, J=2Hz, CHO). Further, when a reaction similar to the above was carried out using lithium formate, sodium formate, or potassium formate in addition to HCOOMgBr, the yield of aldehyde 8 was between about 40 and 30%. Example 5 (1) 1 material 8 components A~0□-j view Kaa. 9 10 2.3-Epoxybutanol 400 kg (0,454 mm
ol ) in dimethylformamide (10, mJ), add 1.3 ml of triethylamine (9.3 mn1 ol
), trityl chloride 2.5y (0.90mmol
) and dimethylaminopyridine 60~(0,49mm
ol) was added thereto, and the mixture was stirred for 12 hours while being kept at 35-40°C. The mixture was diluted with 50 d of diethyl ether, and the precipitated triethylamine hydrochloride was separated using celite. F-liquid 11th
After washing with brine, it was dried over anhydrous magnesium sulfate. After removing the solvent, it was purified using a silica gel column (hexane/diethyl ether = 40/1 to 5/1) to obtain 1-trityloxy-2,3-epoxybutane 0.9141 (2,77 m
1nol) was obtained (yield 61.5%). N of this
The MR spectrum was as follows. 1H-NMR (CC14) δ1.29 (d, J
=4.5Hz, 3H. CH-CH CH3), 2.55-2.85 (m, 2H, Xo/). 3.03-3.28 (m, 2H, CH20). 7.02-7.45 (m, 15H, Ar). Copper iodide 230~(1,21 mmol) in the reactor
Take a total amount of dimethyl sulfide and add 0.70 m/(9,6
mmol) 2 times to completely dissolve. THF
After adding 20 ml, cooling to 0°C and stirring for 10 minutes, 1-trimethylsilylethynylmagnesium bromide 11 (18 ml, 0.61 M THF solution 1.11
mmol) was slowly added dropwise. 30 minutes later 1-trityloxy-2.3-1boxipta:yH) (1,
98? , 6.0 mmof) in diethyl ether (15 iJ) was slowly added dropwise. After stirring at 0° C. for 12 hours, a saturated ammonium chloride U aqueous solution was added. After returning to room temperature, the product was extracted three times with diethyl ether. The collected organic layer was washed with dilute hydrochloric acid, aqueous ammonia and saturated brine in this order, and dried over anhydrous magnesium sulfate. When the solvent was distilled off under reduced pressure, 4-hydroxy-3-methyl-2-trimethylsilyl-5-trityloxy-1-pentene 12 having the following NMR spectrum was obtained. This product was used in the next reaction without purification. 12”) i-NMI likelihood δ0.06 (s, 9 i
' r 3 C1-ls) T 1.03 (d+31
i, J=7Hz, C)ls), 2.00~2.1
7 (br s, IH. OR), 2.42 (qui, J=7H2,]
H, CHCHa). 2.70-3.20 (m, 2H, CH20),
3.80 (dt, J=3.5Hz. 7f1z, LH, Cf(Of(), r, j5~r, C
3<rn, 1sH, hr). 4-Hydroxy-3-methyl-2-trimethylsilyl-
5 to 12 trityloxy-1-pentenes were placed in a flask, cooled to 0°C, and then added with an approximately 60% dichloroacetic acid aqueous solution (15 ml), followed by vigorous stirring at room temperature for 1 hour. After cooling to 0°C, the mixture was neutralized with a 10% aqueous sodium hydroxide solution. The product was extracted three times with methylene chloride, and the collected extracts were washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified using a silica gel column (benzene/diethyl ether=]/1→diethyl ether), resulting in 3-methyl-4-trimethylsilyl-4-pentene-1,2-diol υ of 0. 95
0? (5.05 mmol) was obtained (yield: 84.2% for 10 shells). The NMR spectrum of this product was as follows. 1HNMR(Cα4) δo, o 9 (S , 9
Ht3CHs), 1.03(d+J-8H
z 'r 3 H+ CHa ) + 2.23 (q
u i+ J-8Hz +I H, CHCHa) +
3-06 to 3-70 (ITI + 3 H+ CH
(OH)C! ! 20H). 4.03~4.25(br s, 2f(,OH),
5.38 (d, J=3Hz. IH9danCH=C), 5.61 (d, J=3Hz, IH
,HCH=C)0υ 3-methyl-4-trimethylsilyl-4-pentene-1
,2-diol 0.310 ? (1,65 mmol
) ethanol solution (5tttl) was cooled to 0°C, and then added to this was an aqueous sodium periodate solution (12d, 0.3M aqueous solution, 3.6 mmol) cooled to 0°C.
added. The mixture was stirred at 0° C. for 1 hour and 18 hours of water was added. Extraction was performed four times with pentane, and the collected organic layers were dried over anhydrous magnesium sulfate. When all the solvent was distilled off under reduced pressure and purified using a silica gel column (pentane/diethyl ether-5/), 2-methyl-3-trimethylsilyl-3-butynal 14 was obtained with a concentration of 0.231? (1,48 mmol) was obtained (yield 89.9%). The NMR spectrum of this product was as shown below. 'H-NiviRδ0.10 (S, 9H, 3CH3),
1.15 (d, 3H. J=7Hz, CHa), 3.10 (dq, 1
1LJ=2Hz, 7Hz. CHCHa), 5.57(s, 2H,CH2
=C), 9.31 (d, IH. J-2 exit, Cl-10). Reference Example 1] A 1.72M diethyl ether solution of 5.9 mmol of ethylmagnesium bromide was added to a diethyl ether solution (1 od) of 5 2-methyl-3-trimethylsilyl-3-butenal 3o 7my (1,97 mmol) at -78°C. (3.4 ml) was slowly added, and the mixture was allowed to react at ambient temperature for 3 hours. 3N hydrochloric acid was added, and the aqueous layer was extracted twice with diethyl ether. The ether was dried over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure, and the crude product was purified by column chromatography (silica gel) to obtain the erythro form 3-methyl-2-) IJ methylsilyl-1
338 ~hexen-4-ol 15 was obtained (yield 92.3%). The NMR spectrum of this alcohol 15 was as shown below.
CHa), 0.91 (t, 3H, J = 6Hz, 3CH
2) 90.97 (d r 3 H+J=6.3Hz
, CHsCH), 1.15-1.70 (m,
2H, CH2CH3) 1.83 (br s, IH,
0II), 2.3o (qui, IH, J=6.
3H2. CHCH3) 93.30 (d t + I H+
J-7Hz, J'-5,5H2, CHO) 5.39
(d, if(, J==aHz, I(CH=C),
5.57 (d, IH. J=3Hz, HCH=C). 13cm NMR (CDα3) δ-1,1, 10,6,1
4, 2, 27, 7. 43.1, 74.8, 124.7, 155.9
. Reference Examples 2 to 4 The following reactions were carried out in the same manner as in Reference Example 1, and the results shown in Table 1 were obtained. Table 1 ■ Note: 1-Pr is inglovir group, Et is ethyl group, Ph
represents a phenyl group, and n-J3ti represents a normal butyl group. The same shall apply hereinafter in this specification. The NMR spectrum of the alcohol produced was as shown below. 6-(CH3)20H), 0.97 (d, 3B,
J=7Hz, CH3C)i). 1.53 (br S , If(,0f() , 1
．． 60 (sep, IH. J=6,3fLz, CH(CH,q)2), 2.57(
qui, IH. , J=6) Iz , CHCHs ), 3.08 (
dd, 1f(, J=4.5Hz. J'=7I(z, C1(0), 5.43(d, iH, J
=3Hz. HCH=C), 5.65 (d, IH, J=3Hz
, HCH=C). 13C-NMR (CDα3)δ-0,8,] 2.9
, ] 8.7. 19.5, 30.6, 40.7.77.6, 125.3
, 156.1. 5.47 (d, IH, J=34.(z, HCH
=C), 5.70(t, 1H, J=3Hz, HCH=
C), 7.14 (s, 5H. C6 slow 5). 13C-NIV[R(CDα3)δ-1,2,] 3.
7, 44.9. 75.1, 125.6, 126.2, 126.9, 12
8.0°143.3, 155.3. 1) I-NM1 only Cα4) δ 0.14(s, 91(,
3CHs). 18 CHCl(3,C1(2cH=c), 3.2
6 (dt, J=6.5Hz. J=5.54(z, If(,CHOH), 5.92(t
, J=8Hz. 1M, CI (=C). 13C-NMI conversion (CD(,xa)δ0.7, ]
0.6, ] 3.5, ] 4.0. 22.5, 27.4, 32.0, 32.5, 4
2.4, 74.6. ] 42.5, 142.9. Reference example 5 Erythro body 3-,, 'chiru 2-)! A methylene chloride solution (5 m) of pyridinium chlorochromate [hereinafter referred to as FCC] 0,
50? (2.4 mmol) was added and stirred at room temperature for 3 hours. 5 d of a mixed solvent of hexane and diethyl ether (volume ratio 5:1) was added for extraction. After distilling off the organic layer under reduced pressure, column chromatography was performed to obtain 3.
-nonal-2-trimethylsilyl-1-hexene-4-
215 to 100% of 1" were obtained (yield: 9G.9%). The NMR spectrum of this ketone 19 was as follows. 1H-NMR (Cα4) δ0.1 2 (S + 9
H + 3 (-H3), 0.9 2 (t,
3H, J=71 (z, Cdan3CH2), 1.
05 (d, 3H, J-7Hz, CH3CH),
1.90-2.63 (m, 2H, CH2CH3)
. 3, 2'2 (Q s I H, J=7Hz, C
HCua), 5.38 (d, IH. J=3Hz, FCH-C), 5.5] (d, IH,
J=3Hz, HCI(=C). Reference Examples 6 to 8 The following reactions were carried out in the same manner as in Reference Example 5, and the results shown in Table 2 were obtained.Table 2 The NMR spectra of the produced ketones were as follows.屓-NMLya (CC14) 6 0.1 2 (s,
9H, 3CH3). 5, 38 (d, IH, J=3Hz, lHcH=c)
. 5,47(d,])l,J=3Hz,HCH-==C)
. 22 2, 5 14z, HCfi-li. 5.56 (
d, H (, J=2.5Hz. HCH-c), 7.1 3-7.9 3 (m, s
J-i, CeHs). 22 3, 1 0 (q, J=7I(z, 114, C
HC(,)), 5.80 (t. J=8Hz, lH, CR=C). Reference example 9 Ketone 19 (426~, 2.3 rr+mo I
) methanol solution (4d) was cooled to -10°C. Add NaBH4 (4 6mfl 1.2 1n) to this solution.
il101) was added, and the mixture was allowed to react at the same temperature for 30 minutes. Add vinegar v0.30ml (4.8 mmol),
The mixture was stirred at room temperature for 30 minutes. The solution was made basic by adding saturated aqueous Na)f003 solution and extracted three times with diethyl ether. The ether layer was dried over anhydrous magnesium sulfate,
After distilling off the solvent under reduced pressure, the threo-3-methyl-2-trimethylsilyl-1-hexen-4-ol 23 was purified by column chromatography (silica gel) to give 358
Tq was obtained (yield 84.0%). This alcohol 23
The NMR spectrum of was as follows. 'H-NMR (Cα4) δ0.11 (s, 9H, 3C
Ha), 0.88(t, 3H, J=71(z, CH
sCfi2), 0.94 (d, 3H, J=7
1 (z. Ji 3CH), 1.20-1.85 (rrl, 3
H,Cf(zCHa,OH). 2.30(qui, IH, J-7H2, CHCI(3
), 3.37 (dt, IH. J=3Hz, J'=7Hz, CHO), 5.4
5 (d, IH, J=3Hz. HCH=C), 5.65 (d, IH, J=3Hz, DanC
H=C). 13C-NMR (CDα3) δ-0,9,9,9,17
, 8, 26, 5, 45, 7. 75.5, 125.6, 155.9° Reference Examples 10 to 12 The following reactions were carried out in the same manner as in Reference Example 9, and the results shown in Table 3 were obtained. The NMR spectrum of the produced alcohol was as follows. ”) i-NMR (Cα4) 60.12 (S, 9H13C
H3). J'=7)1z, CHCHs), 3.28 (
d, In, J=9Hz. CHO), 5.47 (d, IH, J=3H2
, HCH-C). 5.69 (d, IH, J=3Hz, HCH=C). 13C-NMR (CDα3) δ-0,7,14,0,1
8,4. 20.9, 29.2, 43.8, 78.2, 1
26. G, 156.4. IH, J=3111CH=C), 7.17(8,5)1
．． C5Hs). 13C-NMR (CDα3) δ-0,9,1B,5,
48.0. 77.9, 126.0, 127.0, 127.5, 12
8.1°142.7, 155.6. 7H, (C82)2. C'H2CH3,OH), 1
．． 95-2.41(m+ aHr Cdan2CH=CCH
), 3.30 (d t , J=3)1z. J=8Hz, IH, CHO), 6.02 (t
, J=8Hz. IH, CH=C). 13C-NMR (CDα3) δ0.7, 10.0,
] 4.0. 18.2, 22.4, 26.6, 31.9, 3
2.3, 45.2. 76.0, 142.2, ] 43.7. Reference Example 13 Under argon atmosphere, erythro alcohol (64 m4
, 0.34 mmol) in THF solution (1.5 d)
was heated to 30°C. This solution is designated as Na1-1 (50% in oil, 0.016F, 0.34 mmol) IMPA (hereinafter referred to as IMPA). )1 m/ was added, and the reaction was continued at the same temperature for 3 hours. After adding 3N hydrochloric acid and stirring at room temperature for 30 minutes, the aqueous layer was extracted twice with a mixed solvent of hexane and diethyl ether (volume ratio 1:1). The organic layer was dried over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure, and then purified by column chromatography (silica gel) to obtain erythro form β-methyl homoallyl alcohol 27 from 31 (yield 86%). )0 The NMR spectrum of this alcohol was as follows. 'H-NMR (CQ'4) δ0.92 (t, 3H
, J=7Hz, CHsCIh). 0.99 (d, 3H, J=7Hz, CH2O)
1. ), 1.20-1.80 (m,.3H,OH,CH=CH2), 198-2.4] (m
, IN, C)iCHs )+3.27 (dt, IH
, J=4.5f(z, J=8Hz, CHO), 4
．． 83-5.20 (m, 2H, CI!+=C),
5.72 (ddd, IH, J=7Hz. J'=9Hz, J"=161-1z, CH2=C
H). Reference Examples 14 to 20 The following reactions were carried out in the same manner as in Reference Example 13, and the results shown in Table 4 were obtained. Table 4 The NMR spectrum of the produced alcohol was as follows. ” 1(-NIVIR(CO! 4) δ0.91 (
t, 3H, J = 71 (Z. OHCH3CH2), 0.98 (d, 3H, J = 7Hz
, CMsC4(). Self” 1.33-1.80 (l■1,2H,CH=C
H2), 1.90-282・30(m・1′(・0dan0
1')・3・21(dt・11・k6Hz, J'=7.
5) 1z, CHO) + 4.87-5.21 (m. 2H, CH2=C), 5.68 (m, IH, C
H=CH2). "H-NIARCCα4) δ0.89 (d, 6H,
J=7Hz. Suga] M, J = 6Hz, C'HO) + 4.
85-5.14 (m+ 2 H+CH+-C),
5.39-5.89 (m, 1 horse CH=C). 1) i-NMR (Cα4) δ0.87, U, 93
, 1.00 (3d.,, C, 1l(Eli)2in, 2.flnizi-2;
47 (m, ■, C1,1, Cl-13). 2.0ri (t, IJl,, L-611z, CIL)
), 4.8SL-5,18 (ITI, 2H, CHz
=C), 5-485-93 (ITI, IH+CL
-1=cH2). 1H-NMR (Cα4) δ0.93 (d, 3H, J=7
ratio. 31CH2=C), 5.39-5.85 (m,
IH, CH=CH2). 7.13 (8,'5)i, Cs 5) IH-NMR (
Cα4) δ0.86 (d, 3H, J=7Hz. IIi-NMR(CD(J3.) δ0.90(t
, J=7H1,3H. Q J=7Hz, 2H, CH2CH=CH), 2.25
(sex. JI-1711z + 1", C view C mountain +), 3
．． :l 7 (tl, t, J・1llllz. J=511Z, in, coon,), 5.38 (
dd, J = 711z. t+=] 5Hz, IH,Cdan-CHCH+)
, 5.50 (dj +J= 15Hz, J=
7Hz, IH, CH-CHCH). "H-NMR (CDQja) δ0.89 (t, J
=6H2, 314°OHCH3), 0.96(t, J=
7H2,31(,CH3),0.991H,CI(01
-1), 5.33 (dd, J=8Hz, J=16H
z. ] IH+C)! -CHCH2) + 5-53 (
d't, J-16Hz 16.5 Hz, IH
,,CH2CH3H) ,'Reference side 21 Erythro form 4-methyl-5-trimethylsilyl-5-decen-3-ol 18 (342rny, 1.41
mmol) in methylene chloride solution (5 ml).
Add 2.8 mmol of butyl hydroboxide (hereinafter referred to as TBHP) and cool to 0°C. Catalytic amount of vanadium acetylacetonate) [VO(acac
)2] was added and stirred overnight. After adding diethyl ether and transferring onto the aqueous NaHCOs solution,
The organic layer and the aqueous layer were separated, and the aqueous layer was further extracted with diethyl ether. The collected organic layer was dried over anhydrous magnesium sulfate, the solvent box was removed using a rotary evaporator, and the obtained crude product was purified by silica gel column chromatography to obtain the erythro form 4-methyl-5-trimethylsilyl-
325 pieces of 5,6-epoxydecan-3-ol 35 were obtained (yield: 89.j).The NM of this alcohol 35 was
The R spectrum was as follows. "H-NMR (C (J4) δ0.10 (S, 9H,
3CHa ), 0.87 (t + J = 6.5Hz
, 6H, 2CH3), 0.87 (d, J
=6.5Hz, 3H. CHaCH), 1.13-1.87 (m,,9'
H, (CH2)3, CH. CH2CH3), 2.30-2.45(m, IH
,0)4),2.77-3.07"H-NMR(C
Q'4 D20) aO, 10, 0, 87, 0, 87°1
．． 13-1.87, 2.77-3.07, 3.46
(dt, J=3.5H2'+j=61-1z,
IH, CHOH). When threo-4-methyl-5-trimethylsilyl-5-decen-3-ol is oxidized with t-butyl hydroperoxide in the same manner as above, the threo-4-methyl-5-trimethylsilyl-5,6 shows the following NMR spectrum.
-Epoxydecan-3-ol 36 was obtained in a yield of 87%. "H-NMR (CQ!4) δ0.16 (s, 9H, 3
CHs). Reference Example 22 Erythrobody A#: 7-R35 (318~, 1.23r
nmol) and pyridine (398 ml, 4.
92mlTIO1) diethyl ether solution (7mJ)
263 ml (3,69 mmo) of acetyl chloride at 0°C
1) was slowly added dropwise. ] Stir for 14 hours while gradually increasing the temperature to 3℃. The reaction solution was poured into brine and the product was extracted three times with diethyl ether. After drying the collected surface layer over anhydrous magnesium sulfate, the solvent was distilled off using a rotary evaporator, and the resulting residue was purified using silica gel chromatography to obtain the erythro form 3-acetoxy-4-methyl-5-trimethylsilyl-5゜6. -Epoxydecane 37 was obtained in 332 cm (yield: 89.8 cm).The NMR spectrum of this acetate 37 was as follows.
Ha), 0.81 (t. J-7klz, 3H, CHa) + 0.86
(d, J-71 (z + 3 H, CH3) +0.
88(t, J=71iz, 3H, Cl-l3
), x, 14-1.87 (m. 9H, CI(, (CH2)3, CH2CH3),
1.92 (S,3H,'CHsCO). 2.56 2.81 (m + I H, CH via) +
4.57 (dt, J-J, 5 Hz. J=8 Hz, IH, CHOAc). Threo-4-methyl-5-trimethylsilyl-5,6-
Epoxydecan-3-ol 36 was prepared in the same manner as above (
When reacted with acetyl chloride, the corresponding threo acetate 38 was obtained in a yield of 97%. 'l(-NMR(Cα4)δ0.09 (s, 9H
, 3Cf (a) + Reference Example 23 in methanol solution (2d) with 72 m of trifluoroacetic acid.
1 (1.01 mmol) and stirred for 13 hours while maintaining the temperature at about 23°C. Diethyl ether was added to the solution, then the ether solution was poured into brine, and the product was extracted five times with diethyl ether. After drying the collected organic layer over anhydrous magnesium sulfate, the solvent was distilled off using a rotary evaporator to obtain the threo compound 3-
Acetoxy-4-methyldecan-5-one 39 and threo-3-hydroxy-4-one were obtained. This mixture was dissolved in diethyl ether (4 m/), followed by the addition of 136 tnl (1.69 mmol) of pyridine. Cool this solution to ]0°C and add acetyl chloride 96 d
(1,35mrriol) i knee) < jJI
]eJ. After stirring at room temperature for 5 hours, the mixture was poured into brine. The product was extracted three times with diethyl erucyl, the collected organic layer was dried over anhydrous magnesium sulfate, the solvent was distilled off, and the residual liquid was purified by silica gel column chromatography to obtain the threo form β-
Ashichitoxigaton 39 is 67m? (yield 87.
3%). The NMR spectrum of this β-acetoxyketone 39 was as follows. "H-NMR (CCl4) δ0.85 (t, J=7Hz
, 3H, CHa). 0.88 (t, J=6Hz, 3H, CHs)
, 0.99 (d, J=7Hz, 3H. CHaCH), 1.13-1.71 (m, 8H,
(CH2)3, CH2CH3). 1.93 (S, 3H,, CHsCO), 2.37 (
t, J=7Hz, 2H. CH2C0), 2.73 (quj, J=7Hz, IH,
CHCHa), 4.89(dt, J=5 H2,
J=7H1,IH,CHOAc). Reference Example 24 Erythro form 3-hydroxy-4-methyldecan-5-one 40 (37 r/J, 20 mmol) and pyridine 64. ml (0.80 mmol) of diethyl ether (3 rug) at 0°C.
3 ml (0.60 mmol) was slowly added. After stirring overnight at room temperature, diethyl ether was added and the mixture was poured into brine. The product was extracted three times with diethyl ether, the combined organic layers were dried over anhydrous magnesium sulfate, and the solution a+-
After distilling off, the obtained crude product was purified by column chromatography to obtain 35 m
'! (yield 77%). This acetate 41 N
The MR spectrum was as follows. 1H-NMR (Cα4) 60.87 (t + J-7
Hz + 3 H, CHs). 0.89(t, J=6H2,3H, CI(3), 1.
00 (d, J=7Hz. 3H, CHsCH), 1.11-1.86 (m,,
8H, (CH2)3. 3H, CHCHs, CH2C0), 4.98(q,
J=6H2, IH. CHOAc). In addition, when erythro form 3-acetoxy-4-methyl-5-trimethylsilyl-5,6-epoxydecane 37 is treated with trifluoroacetic acid in methanol (approximately 28°C, 9 hours) in the same manner as in Reference Example 23, the above-mentioned result is obtained. Erythro acetate 41 was obtained in a yield of 90 cm. Patent applicant: RiRashi Co., Ltd. Agent: Ken Honda, patent attorney

Claims (1)

[Claims] 1. β-trialkylsilyl-β, γ represented by the general formula % (wherein R1 represents a hydrogen atom or a lower alkyl group, and R2 and R3 represent a lower alkyl group) -Unsaturated aldehydes. 2. An epoxy compound represented by the general formula (wherein R3 represents a lower alkyl group and R4 represents a hydroxyl group protecting group) is prepared by the general formula (wherein R1 represents a hydrogen atom or a lower alkyl group and R2 represents a lower alkyl group). (XI represents a halogen atom) to obtain a condensate represented by the general formula (wherein R1, R2, R3 and R4 are as defined above), The condensate is deprotected to obtain rersiol having the general formula (wherein R1, R2 and R3 are as defined above), and the diol is oxidized with periodic acid. , R', R2 and R3 are as defined above.) A method for producing a β-trialkylsilyl-β,γ-unsaturated aldehyde. 3. After reacting a trialkylsilyl acetylene compound represented by the general formula % formula % (in the formula, R2 and R5 represent lower alkyl groups) with inobutylmagnesium halide in the presence of a titanium compound, the product ν is reacted with α-bromoaldehyde represented by the general formula % (wherein R3 represents a lower alkyl group) (wherein R2, ) A method for producing a β-trialkylsilyl-β,γ-unsaturated aldehyde. 4. After reacting 2-trialkylsilyl-1,3-butadiene represented by the general formula % formula % (wherein R2 represents a lower alkyl group) with inbutylmagnesium halide in the presence of a titanium compound, A general formula characterized in that the product is reacted with a formate of the general formula (wherein M represents a lithium, sodium or potassium atom, or MgX'', and X2 represents a halogen atom) 2-methyl-3-trialkylsilyl-3-butene-1 represented by the formula % (wherein R2 is as defined above)
-Production method of Earl.