Cyclohexene stereoisomers

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 addition of bromotrichloromethane to cyclohexene gives a nearly 1 1 mixture of the two possible stereoisomers ... 

One of the most useful features of the Diels-Alder reaction is that it isstaeo-specific, meaning that a single product stereoisomer is formed. Furthermore, the stereochemistry of the reactant is maintained. If we carry out the cycloaddition with a cis dienophile, such as methyl ds-2-butenoate, only the cis-substituted cyclohexene product is formed. With methyl tmtts-2-butenoate, only thetrans-substituted cyclohexene product is formed. 

Another reaction unique to conjugated dienes is the Diels-Alder cycloaddition. Conjugated dienes react with electron-poor aikenes (dienophiles) in a single step through a cyclic transition slate to yield a cyclohexene product. The reaction is stereospecific, meaning that only a single product stereoisomer is formed, and can occur only if the diene is able to adopt an s-cis conformation. 

Vinyl radicals can also participate in 6-exo cyclizations. In pioneering work, Stork and his group at Columbia University showed that stereoisomeric vinyl bromides 20 and 21 (see Scheme 3) can be converted to cyclohexene 22.7 The significance of this finding is twofold first, the stereochemistry of the vinyl bromide is inconsequential since both stereoisomers converge upon the same product and second, the radical cyclization process tolerates electrophilic methoxycarbonyl groups. The observation that the stereochemistry of the vinyl bromide is inconsequential is not surprising because the barrier for inversion of most vinyl radicals is very low.8 This important feature of vinyl radical cyclization chemistry is also exemplified in the conversion of vinyl bromide 23 to tricycle 24, the key step in Stork s synthesis of norseychellanone (25) (see Scheme 4).9 As in... 

Juvabione is a terpene-derived ketoester that has been isolated from various plant sources. There are two stereoisomers, both of which occur naturally with R-configuration at C(4) of the cyclohexene ring and are referred to as erythro- and f/trao-juvabione. The 7(.S )-cnan(iomcr is sometimes called epijuvabione. Juvabione exhibits juvenile hormone activity in insects that is, it can modify the process of metamorphosis.18... 

Reactions of 1 with epoxides involve some cycloaddition products, and thus will be treated here. Such reactions are quite complicated and have been studied in some depth.84,92 With cyclohexene oxide, 1 yields the disilaoxirane 48, cyclohexene, and the silyl enol ether 56 (Eq. 29). With ( )- and (Z)-stilbene oxides (Eq. 30) the products include 48, ( > and (Z)-stilbenes, the E- and Z-isomers of silyl enol ether 57, and only one (trans) stereoisomer of the five-membered ring compound 58. The products have been rationalized in terms of the mechanism detailed in Scheme 14, involving a ring-opened zwitterionic intermediate, allowing for carbon-carbon bond rotation and the observed stereochemistry. 

Two amino acid stereoisomers protected by benzyloxycarbonyl groups were deprotected in different ways. One isomer was hydrogenolyzed on 5% Pd/C (0.05 mol Pd/mol) in AcOEt-MeOH for 16 hours at ambient pressure and temperature. The other isomer was dissolved in MeOH, and cyclohexene (10 mol/mol) was added under nitrogen followed by 5% Pd/C (0.18 mol Pd/mol). The temperature was immediately raised to reflux, and stirring was continued for 7 minutes (Scheme 4.60).266... 

Diastereofacial differentiation occurs upon cyclopropanation of the substituted oyclohexene 43 with methyl diazoacetate. Only the two stereoisomers endo-44 and exo-44 were found, both with a 5-anti methyl group 60). In contrast, the ring substituents in l-trimethylsiloxy-cyclohexenes 45 and 46 are not efficient for such a differentiation, so that the four possible diastereomers are actually formed. 

A study of the catalytic oxidation of six stereoisomers of 5-cyclohexene-l,2,3,4-tetrol revealed448 that, in all cases, an allylic hydroxyl group is selectively attacked, and a consideration of their favored conformations suggested that quasi-axial groups are selectively dehydrogenated before those that are quasi-equatorial. 

Azadienes of this sort were studied simultaneously by Mariano et al., who reacted mixtures of (1 ,3 ) and (1E, 3Z)-l-phenyl-2-aza-l,3-pentadiene 275 with several electron-rich alkenes, e.g., enamines and enol ethers (85JOC5678) (Scheme 61). They found the (l ,3 )-stereoisomer to be reactive in this process affording stereoselectively endo 276 or exo 277 piperidine cycloadducts in 5-39% yield, after reductive work-up with sodium borohydride. The stereochemistry of the resulting adducts is in agreement with an endo transition state in the case of dienophiles lacking a cis alkyl substituent at the /8-carbon (n-butyl vinyl ether, benzyl vinyl ether, and 1-morpholino cyclopentene), whereas an exo transition state was involved when dihydropyrane or c/s-propenyl benzyl ether were used. Finally, the authors reported that cyclohexene and dimethyl acetylenedi-carboxylate failed to react with these unactivated 2-azadienes. 

This procedure for stereoselective 1,4-functionalization of 1,3-dienes is based on 1,4-acetoxychlorination,2 and allows the preparation of 1,4-disubstituted 2 cyclohexenes with full stereocontrol of the carbon-carbon bond formation in the 4-position. It is also highly regioselective. Other procedures3 4 for obtaining 4-alkyl-substituted 3-cyclohexenol derivatives use 1,3-cyclohexadiene monoepoxide as starting material. None of the previous methods allow the selective preparation of both stereoisomers as shown here. 

The cyclohexene substructure resulting from Diels-Alder addition of acyclic dienes to fullerenes can adopt two boat conformations.50,387-389 If a new stereogenic center is generated during the cycloaddition, the boat-to-boat interconversion leads to conformational diastereoisomerism in each configurational stereoisomer.389,390 Such a case was studied by Zhang and Foote who performed VT (variable temperature) XH NMR and NOE measurements on... 

Treatment of cyclohexene with C6H5CHI2 and Zn(Cu) forms two stereoisomers of molecular formula C13H16. Draw their structures and explain why two compounds are formed. 

A comparison of the proportion of the saturated stereoisomers, formed under the same conditions (Pt02, AcOH) from the isomeric xylenes and the derived dimethylcyclohexenes, leads to the proposal that the reaction proceeds through the desorbed cyclohexenes. Low concentrations of the intermediate cyclohexenes were detected later. The effect of the metal on the stereoselectivity of hydrogenating o-xylene follows closely the effect of the metal on the hydrogenation of 1,2- and 1,6-dimethylcyclo-hexene. The highest selectivity for the conversion of o-xylene to the cis isomer is given by iridium... 

When an unsymmetrical diene adds to an unsymmetrical dienophUe, regioiso-meric products (not counting stereoisomers) are possible. Rearrangements have been encountered in some cases. In simple cases, 1-substituted dienes give cyclohexenes with a 1,2- and a 1,3- substitution pattern. 2-Substituted dienes... 

In Sec. 17.10 a mechanism is proposed for the conversion of ethylene bromo-hydrin into ethylene oxide in the presence of base, (a) To what general class does this reaction belong (b) Using models, show the likely steric course of this reaction, (c) Can you suggest a reason why sodium hydroxide readily converts /r<7/i5-2-chlorocyclohexanol into cyclohexene oxide, but converts the c/5-isomer into entirely different products (d) Account for the fact that addition of chlorine and water to oleic acid (c(5-9-octadece-noic acid) followed by treatment with base gives the same epoxide (same stereoisomer) as does treatment of oleic acid with a peroxy acid. 

Methylation of the lithium enolates derived from cyclohexen-2-one and l,l-bis(methylseleno)ethylli-thium t es place regioselectively but requires the use of more than one equivalent of HI A (S equiv., 0 C, 1 h). The product consists quite exclusively of the trans stereoisomer (99%) with a trace (1%) of the cis (Scheme 140, d and e). The latter can be obtained as a single stereoisomer on hydrolysis of the adduct resulting from the reaction of the same organometallics with 2-methylcyclohexen-2-one... 

As a closing example of the value of asymmetric synthesis in the area of insect chemistry, we describe the synthesis of the stereoisomers of trimedlure, a material discovered by empirical screening and used to monitor for "Medfly" (Figure 9). The commercial preparation of this attractant mixture involves a non-selective addition of HC1 to a substituted cyclohexene. The several products are shown in abbreviated form (Figure 9) the t-butyl esters of this mixture of acids has been employed for many years as a bait for the medfly (19). Each component,... 

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

Arylcarbenes are formed from benzaldehyde and some of its derivatives if the Clemmensen reduction is performed using boron trifluoride or another Lewis acid instead of hydrochloric acid. If the reaction is carried out in the presence of an alkene, which is often used as solvent, addition to the C-C double bond takes place and cyclopropane formation results in low to fair yields. The arylcyclopropanes are always formed as mixtures of stereoisomers and, in all cases but two, the endo-isomcr is significantly predominant. Thus, when a mixture of 4-methoxybenzaldehyde, boron trifluoride-diethyl ether complex and a considerable excess of cyclohexene was allowed to react with amalgamated zinc, 7-(4-methoxyphenyl)bicy-clo[4.1.0]heptane (1) was obtained in 60% yield. 

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