1-Cyclohexene carboxyl

A "simple" reaction of ammonia and an alkyl halide can sometimes give unusual results. Treatment of 7.62 with ammonia, followed by treatment with acid, led to a product with the amine group distal to the carboxyl group. The alkene moiety also "migrated" into conjugation with the acid (derived from hydrolysis of the cyano group). In this reaction, 7.62 was converted to 4-amino-1-cyclohexene carboxylic acid (7.63).31... 

Catalytic hydrogenation of p-amino ammonium salt 7.707 gave 4-aminocyclo-hexane carboxylic acid (7.102), as a 72 28 cis trans mixture.53 Similarly, reduction of the meta-derivative (7.103) gave 3-amino-1-cyclohexene carboxylate, 7.105. A... 

Substituted aromatic acids provide a route to other cyclohexyl derivatives. An example is the catalytic hydrogenation of the benzene ring in 7.107 to give 4-amino-methyl-1-cyclohexene carboxylic acid, 7.108. Partial reduction of abenzene ring... 

This method can also be used for the preparation of cyclohexene carboxylic acid derivatives. Reaction of 7.119 with ammonia gave ethyl 2-amino-1-cyclohexene carboxylate, 7.109. The conversion of 7.119 to 7.109 has been reported several... 

SCHEME 7. Kinetics of /-butyl cyclohexene carboxylate deprotonation51... 

Bromo-2-pyrone is not only a valuable precursor for the synthesis of various 3-substituted 2-pyrones,7 but it is also a reactive unsymmetrical diene.8 3-Bromo-2-pyrone undergoes Diels-Alder cycloadditions with a regioselectivity and stereoselectivity that is superior to that of 2-pyrone. Furthermore, 3-bromo-2-pyrone is a chameleon (i.e., ambiphilic) dienophile, undergoing cycloaddition to both electron deficient and electron rich dienophiles. The cycloadducts of bromopyrone with dienophiles are isolable and are useful in the synthesis of diastereomerically pure cyclohexene carboxylates (Scheme 2).8... 

Carboxylic acids, that bear an asymmetric center at C-2, lose all their optical activity in the Kolbe electrolysis. This racemization can be interpreted as the result of a free radical or a fast equilibrium during desorption and adsorption at the electrode. A more detailed picture has been obtained by looking at the diastereoselectivity of the coupling of the cyclohexane- and cyclohexene-carboxylic acids (5)- 9). The saturated acids (5) and (6) couple randomly, which indicated that the intermediate radicals in these cases are not significantly adsorbed. With the unsaturated acids (7)-(9) the ratio of dimers was not totally statistical, reflecting somewhat the different stabilities of the products. This result can be interpreted to be due to a more product-like transition state that indicates some adsorption of the unsaturated radical. 

The milbemycins are a family of 16 membered lactones produced by Streptomyces hygroscopicus. The structures are character zed By a b.b spiroketal unit, a side chain with eight carbon atoms, and a complex cyclohexene carboxylic acid. A synthetic route for the spiroketal and connecting chain, and an approach to a southern portion analog via Diels Alder Chemistry are described. 

Figure 10. Synthesis of the stereoisomers of trans-6-methyl-3-cyclohexene carboxylic acid...

As far as the stability of the glycidyl group in ACECs in the epoxidation conditions of the cyclohexene ring is concerned, it has been found that glycidyl cyclohexene carboxylate (XV) and cyclohexenemethyl glycidyl ether (XVI) do not... 

Juvenile hormone I, T"11.6 5-(9-Hydroxynonamethylenoxy)cyclohexene-carboxylic acid, A"28.7 C16H29NO... 

A highly specialized synthesis converted (-)-shikimic acid 7.169) to 7.170. Reaction with azide and catalytic hydrogenation gave 5-aminoshikimate 7.171, methyl 5-amino-3,4-dihydroxy-l-cyclohexene carboxylate) in 21% overall yield. Amino acid 7.171 is an inhibitor of EPSP synthetase, and can be used as an herbicide,... 

Tetrahydrophthalic anhydride (7.775) was converted directly to c -5-amino-3-cyclohexene carboxylic acid, 7.77 by reaction with ammonia and then NaOCl. 107.14 If 7.775 is first opened, isomerized, and converted to the trans-diester (7,775), formation of the trans-anhydride is possible (7.179). This anhydride was then converted to trons-5-amino-3-cyclohexene carboxylic acid, 7.180. A related route converted 7.175 to racemic cis-methyl 2-carboxylcyclohex-4-enoate, which was resolved with cinchonidine.lO The resolved (+) or (-)-half-esters were then converted to (-)-7.77 or (+)-7.77. 

The biotransformation of the nonsteroidal, postcoital oral contraceptive, 2-methyl-3-ethyl-4-phenyl-A -cyclohexene carboxylic acid (Vll), was examined in monkeys and rabbits. In both species, only a trace of unaltered drug was found in the urine. At least eight metabolites were separated from rabbit urine, one of which, as yet unidentified, had 1.5 to 2.0 times the estrogenic potency of the parent compound. The antifertility effect, in the rat of certain -substituted, but not of unsubstituted compounds, was not blocked by prior treatment of the animals with SKF-525A. Thus, the authors suggest that when hydrogen alone is in the para V j position, further alteration of the... 

Prior to the work on prostaglandins, Hayashi and coworkers found a new route to effectively produce the dipeptidyl peptidase IV-selective inhibitor ABT-341 (Scheme 14.6) [14]. The strategy also comprised a Michael addition and HWE reaction, but these were in this case used to generate disubstituted cyclohexene carboxylates instead. After a diphenylprolinol silyl ether (10 mol%)-promoted asymmetric Michael addition of acetaldehyde (2.0 equiv) to nitroalkene 38 (97% ee) in 1,4-dioxane in 5 h, another Michael addition was initiated by addition of vinyl phosphonate 40 (1.2 equiv) under basic conditions (CS2CO3, 2.0 equiv) at 0 °C in dichloromethane. The subsequent intramolecular HWE reaction in ethanol at room temperature afforded the cyclohexene in 15 min., which was isomerized in situ by the addition of DiPEA (10 equiv) to yield trans-43. 

Stork s synthesis (Scheme 3.36) began with the enantiomerically pure cyclohexene carboxylic acid 230 which was converted to the enone 234, the... 

Enamide and enamine photocyclizations (9, 13, 14, 113) are central to yet another strategy which has been successfully employed by Ninomiya (9, 13, 14, 61-71), Kametani (74), and Atta-ur-Rahman (72, 73) in the synthesis of yohimbine alkaloids. These approaches typically begin with harmalane (336) which contains the ABC unit of the pentacyclic yohimbine targets (Scheme 3.56). Condensation of harmalane with an appropriately substituted cyclohexene carboxylic acid or benzoyl chloride 337 affords seco D-ring intermediate 338. To effect D-ring closure, the enamide chromophore in 338 is photocyclized to form pentacyclic enamide 339. Alternatively, photoreaction... 

A highly successful route to stereoisomers of substituted 3-cyclohexene-l-carboxylates runs via Ireland-Claisen rearrangements of silyl enolates of oj-vinyl lactones. The rearrangement proceeds stereospeaifically through the only possible boat-like transition state, in which the connecting carbon atoms come close enough (S. Danishefsky, 1980 see also section 4.8.3, M. Nakatsuka, 1990). 

The stmcture of vitamin A [11103-57-4] and some of the important derivatives are shown in Figure 1. The parent stmcture is aH-Zra/ j -retinol [68-26-8] and its lUPAC name is (all-E)-3,7-dimethyl-9-(2,6,6-trimethyl-l-cyclohexen-l-yl)-2,4,6,8-nonatetraen-l-ol (1). The numbering system for vitamin A derivatives parallels the system used for the carotenoids. In older Hterature, vitamin A compounds are named as derivatives of trimethyl cyclohexene and the side chain is named as a substituent. For retinoic acid derivatives, the carboxyl group is denoted as C-1 and the trimethyl cyclohexane ring as a substituent on C-9. The stmctures of vitamin A and -carotene were elucidated by Karrer in 1930 and several derivatives of the vitamin were prepared by this group (5,6). In 1935, Wald isolated a substance found in the visual pigments of the eye and was able to show that this material was identical with Karrer s retinaldehyde [116-31-4] (5) (7). 

Cyclohexene-l-carboxylic acid, 2-Kthy1, methyl ester)... 

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