Methyl 3-cyclohexene-l-carboxylate

The method employed by Law, et al. to obtain N, 6-disubstituted ISQs [87] was a modification of the approaches of Henbest [88], Huffman [89] and Nelson [90] (Scheme 8). Epoxidation of commercially available methyl-3-cyclohexene-l-carboxylate (80) with m-CPBA yielded a mixture of epoxides (81a and 81b), which were then opened with various amines producing the isomeric amino alcohols (82a and 82b). Only isomer 82a is capable of undergoing cyclization to the... 

Treatment of trflns-3-methoxycyclohexanecarboxylic add with thionyl chloride produces the corresponding acid chloride. Treatment of cis-3-methoxycyclo-hexanecarboxylic acid with thionyl chloride leads to the formation of methyl frans-3-chlorocyclohexanecarboxylate and methyl 3-cyclohexene-l-carboxyl-ate in a ratio of 3 5. Propose a mechanism to account for the formation of all of the products, and explain the difference in products observed for the ds and trans isomers. 

Benzene-sensitized photolysis of methyl 3-cyclohexene-l-carboxylate in acetic acid leads to addition of acetic acid to the double bond. Only the /ranf-adducts are formed. What factor(s) is/are responsible for the reaction stereochemistry ... 

The purity of the product was determined by the checkers by GLC analysis using the following column and conditions 3-nm by 1.8-m column, 5% free fatty acid phase (FFAP) on acid-washed chromosorb W (60-80 mesh) treated with dimethyldichlorosilane, 90 C (1 min) then 90 to 200 C (15°C per rain). The chromatogram showed a major peak for methyl 2-methyl-l-cyclohexene-l-carboxylate preceded by two minor peaks for methyl 1-cyclohexene-l-carboxylate and l-acetyl-2-methylcyclohexene. The areas of the two impurity peaks were 5-6% and 0.5-2% that of the major peak. The purity of the product seems to depend upon careful temperature control during the reaction. The total amount of the two impurities was 14-21% in runs conducted at about -15 to -20°C or at temperatures below -23°C. 

N1 - 3-CYCLOHEXENE-l-CARBOXYLIC ACID 5-ETHYL-4-(p-HYDROXYPHENYLI-6-METHYL- ACETATE Ust r>... 

Methyl 5-Diethylamino-3-cyclohexene-l-carboxylate (9) General Procedure9 ... 

Direct allylie animationS8,89 is achieved by reaction of 3-cyclohexene-l-carboxylic esters or amides 1 with bis(A -4-toluenesulfonyl)sulfodiimide in an ene reaction, followed by a sigmatropic rearrangement. The regioselectivity of the first step, i.e., the ene reaction, is governed by steric factors of the ester or amide group. The methyl ester gives a 3 2 ratio (80% yield) and the ter -butyl ester a 3 1 ratio (70%), but the bulky TV.A -dicyclohexylamide furnishes a 20 1 ratio of the 5-tosylamino 3 and 2-tosylamino isomers 2 (32% yield). 

Palladium-catalyzed cyclization of 1,6-enynes is also applicable to cyclopentannulation if carbocycles are introduced with the substrate. This is demonstrated by a stereoselective palladium-catalyzed tandem alkylation/Alder ene cyclization starting from methyl ew-5-acetoxy-3-cyclohexene-l-carboxylate and dimethyl 2-(2-propynyl)malonate to give a single product with a cu-fused hydrindane skeleton in up to 85 % yield30. Similar conversions of preformed enynes or dienes have been reported95,90. 

Enones A, ethyl 6-methyl-2-oxo-3-cyclohexene-l-carboxylate B, 3-penten-2-one ... 

Tetrahydrobenzyl alcohol (( )3-cyclohexenene-l-methanol) and 30% aqueous hydrogen peroxide were purchased from Fluka, AG. 3-Cyclohexene-1-carboxylic acid and cis-4-cyclohexene-l,2-dicarboxylic acid were used as purchased from Lancaster Chemical Co. Methyl iodide, acetic anhydride, Oxone (potassium peroxymonosulfate), Aliquot 336 (methyl tri-n-octylammonium chloride), sodium tungstate dihydrate and N,N-dimethylaminopyridine (DMAP) were purchased from Aldrich Chemical Co. and used as received. 3,4-Epoxycyclohexylmethyl 3, 4 -epoxycyclohexane carboxylate (ERL 4221) and 4-vinylcyclohexene dioxide were used as purchased from the Union Carbide Corp. (4-n-Octyloxyphenyl)phenyliodonium hexafluoroantimonate used as a photoinitiator was prepared by a procedure described previously (4). 

Methyl 2-methyl-l-cyclohexene-l-carboxylate 1-Cyclohexene-l-carboxylic acid, 2-methyl-, methyl ester (9) (25662-38-3)... 

C13H20O, Mr 192.30, < ,q 1.008-1.016, ng5 1.444-1.448, not found to occur in nature, is a colorless to pale yellow liquid with green, fruity, floral odor reminiscent of galbanum. One of several cited syntheses involves as a key step a double vinyl magnesium chloride addition to methyl 3,3-dimethyl-6-cyclohexene-l-carboxylate to give the title compound [128]. 

Diastereomeric excesses as high as 84% were achieved for the photocycloaddition of methyl 3-oxo-l-cyclohexene-l-carboxylate to 2,/i-unsaturated homochiral ketals lla-c76. As the size of the ester alkyl group in the tartrate auxiliary increases from methyl to isopropyl a stepwise increase in the de values is obtained. 

Finally, the Diels-Alder reaction of dihydropyridine 7.214 and methyl acrylate gave cycloadduct 7.215. 74 Subsequent treatment with base led to 7.216. Osmyl-ation gave a mixture of diastereomers of methyl 3,4-dihydroxy-5-(N-Boe amino-methyl)-l-cyclohexene-l-carboxylate, 7.217 and 7.218. 

A soln. of frans,frans-l,4-diacetoxy-l,3-butadiene and methyl acrylate stabilized with hydroquinone heated slowly to reflux in xylene, and the product isolated after 37 hrs. methyl 2j, 5) -diacetoxy-3-cyclohexene-la-carboxylate. Y 93%. E. E. Smissman et al., Am. Soc. 84, 1040 (1962). 

Methyl 5-fluoro-4-(trifluoromethylsulfonyloxy)-2,3-dihydro-l-methyl-7-0X0-1//,7//-pyrido[3,2,l-iy]cinnoline-8-carboxylate(68,R = Me,R = R = H, R = F, R = Me, R = CF3SO2O) was reacted with 3-tributylstannyl-2-cyclohexen-l-one in the presence of lithium chloride and bis(triphenyl-phosphine)palladium(II) chloride in tetrahydrofuran for 3 days to give a 4-(3-oxo-l-cyclohexen-l-yl)derivative (92EUP470578). 

Diazoacetaldehyde dimethylacetal (12) has been used as a substitute for diazoacetaldehyde in 1,3-dipolar cycloadditions with l-benzopyran-2(//)-ones (40), styrene, methyl methacrylate, 1-cyanocyclopentene, and methyl cyclohexene-1-carboxylate (41). The resulting A -pyrazolines were readily transformed in two steps into cyclopropanecarbaldehydes [e.g., 13 —> 14 (Scheme 8.4)]. In a similar manner, 3-phenylcyclopropane-l,2-dicarbaldehyde was obtained from the reaction of 12 with dimethyleneketal of cinnamic aldehyde. 

Cyclohexene, l-methyl-4-( 1 -methyl-ethenyl)- [138-86-3], 56, 106 2-Cyclohexene-1-carboxylic acid, 2-... 

Dihydro-2-isopropyl-3.6-dimethoxypyrazine, a bis(lactim)ether, is converted into the 5-di-azo compound 1 by lithiation and diazo group transfer. The intermediate diazo compound reacts at room temperature with olefins such as cyclohexene to produce the cyclopropane derivatives with excellent diastereoselectivity . The derivative from cyclohexene is hydrolyzed by acid treatment to give methyl 7-cv(cfo-aminobicyclo[4.1.0]hcptane-7-carboxylate. The bis(lac-tim)ether diazo compound 1 is also involved in an exceptional asymmetric [2 + 1J cycloaddition producing cnantiomerically pure cyclopropenc derivatives4. Thus, reactions of the diazo compound with monosubstituted alkynes afford the spiro compounds as one diastereomer. Hydrolytic removal of the auxiliary and protection of the amino group provides enantiomerically pure methyl l-amino-2-arylcyclopropene-l-carboxylates in moderate overall yield. 

Juvabione, the compound responsible for this activity, was isolated from the balsam fir, Abies balsamea (L.) Miller, and identified as the methyl ester of todomatuic acid, (+)-4(i )-[ 1 R)-S -dimethyl-3 -oxohexyl]-1-cyclohexene-1-carboxylic acid [87]. This compound is a sesquiterpenoid (Fig. (6)) with a cyclohexene group and an a,(3-unsaturated methyl ester group the chemical data for this compound are summarized in Appendix II, Table 1. The IR spectrum suggests that there is a carbonyl ester group present in conjunction with a double bond (1722 and 1645 cm 1) and also an isolated carbonyl group (1712 cm 1) [87]. Mass spectroscopy confirms... 

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