Elimination cyclic systems

In a freely rotating system it was relatively easy to achieve the orbital overlap requirements of the E2 elimination. Cyclic systems are rotationally constrained, so in the cyclohexane system, the coplanar overlap requirement is satisfied only if both C-H and C-L bonds are both axial. This fra/ti-diaxial restriction affects the product distribution. 

In addition to the synthetic applications related to the stereoselective or stereospecific syntheses of various systems, especially natural products, described in the previous subsection, a number of general synthetic uses of the reversible [2,3]-sigmatropic rearrangement of allylic sulfoxides are presented below. Several investigators110-113 have employed the allylic sulfenate-to-sulfoxide equilibrium in combination with the syn elimination of the latter as a method for the synthesis of conjugated dienes. For example, Reich and coworkers110,111 have reported a detailed study on the conversion of allylic alcohols to 1,3-dienes by sequential sulfenate sulfoxide rearrangement and syn elimination of the sulfoxide. This method of mild and efficient 1,4-dehydration of allylic alcohols has also been shown to proceed with overall cis stereochemistry in cyclic systems, as illustrated by equation 25. The reaction of trans-46 proceeds almost instantaneously at room temperature, while that of the cis-alcohol is much slower. This method has been subsequently applied for the synthesis of several natural products, such as the stereoselective transformation of the allylic alcohol 48 into the sex pheromone of the Red Bollworm Moth (49)112 and the conversion of isocodeine (50) into 6-demethoxythebaine (51)113. 

The steps are the same as in the addition-elimination mechanism, but in reverse order. Evidence for this sequence is as follows (1) The reaction does not proceed without ethoxide ion, and the rate is dependent on the concentration of this ion and not on that of ArS. (2) Under the same reaction conditions, chloroacetylene gave 83 and 80. (3) Compound 83, treated with ArS, gave no reaction but, when EtO was added, 80 was obtained. It is interesting that the elimination-addition mechanism has even been shown to occur in five- and six-membered cyclic systems, where triple bonds are greatly strained. Note that both the addition-elimination and elimination-addition sequences, as shown above, lead to overall retention of configuration, since in each case both addition and elimination are anti. 

In open-chain compounds, the molecule can usually adopt that conformation in which H and X are anti periplanar. However, in cyclic systems this is not always the case. There are nine stereoisomers of 1,2,3,4,5,6-hexachlorocy-clohexane seven meso forms and a dl pair (see p. 161). Four of the meso compounds and the dl pair (all that were then known) were subjected to elimination of HCl. Only one of these (1) has no Cl trans to an H. Of the other isomers, the fastest elimination rate was about three times as fast as the... 

Hofmann elimination reactions from hi- and tri-cyclic systems can, however, be used to create internal unsaturation without loss of a trialkyl amine as shown in Scheme 1.14 for the synthesis of the hexahydrothieno [ZjJazecine. 

Like amine oxide elimination, selenoxide eliminations normally favor formation of the E-isomer in acyclic structures. In cyclic systems the stereochemical requirements of the cyclic TS govern the product composition. Section B of Scheme 6.21 gives some examples of selenoxide eliminations. 

In cyclic systems, the usual simple requirements of Saytzev or Hofmann rules may be overridden by other special requirements of the system, e.g. the preference for elimination from the truns-diaxial conformation in cyclohexane derivatives (cf. p. 255). Another such limitation is that it is not normally possible to effect an elimination so as to introduce a double bond on a bridgehead carbon atom in a fused ring system (Bredt s rule), e.g. (47) (48) ... 

This elimination fails with diacetates of enediols and involves an overall cis-elimination in cyclic systems. 

Hymenocardine (58), (32, 40) has a p-hydroxy-w-aminoacetophenone unit (81), instead of the usual styrylamine, in its cyclic system which can be recognized in addition to N,N-dimethylisoleucylvaline and tryptophan in its acid hydrolysate. Mild alkaline hydrolysis results in ring opening via /3 elimination on the hydroxyamino acid and severance of the phenolate to a tetrapeptide 82 whose structure was determined by mass spectrometry and further hydrolysis. It is the only peptide alkaloid in which /3-hydroxy valine is involved in the aryl ether bridge. 

The halogen-metal exchange of one of a geminal pair of bromine atoms is readily achieved -a carbenoid is formed which may have sufficient stability to react as an organolithium before decomposing to a carbene by a-elimination.. m in cyclic systems, diastereoselectivity in this process has long been known,114116 though the outcome of reactions such as that of 137 is under a mixture of kinetic and thermodynamic control.117... 

Until recently the commonly held view has been that any system having the possibility of free choice will prefer the anti over the syn elimination path. However, where steric constraints make anti elimination unfavourable as in cyclic systems, the normally difficult syn eliminations can occur. 

We are now in a position to interpret the reactions of steroid amines, particularly with respect to the dominant retention of configuration in substitution and the considerable or exclusive elimination of axial amino groups. Shoppee has pointed out [3] that the ratio, elimination/substitution, for a series of axial amines follows the order expected on the basis of steric hindrance to the formation of the axial alcohol. In simple mono- and bi-cyclic systems, as well as in acycUc amines, the proportion of olefinic products is far lower (often ca. 30% than for many steroids. This agrees with the concept that very high yields of olefins result from steric frustration of cis substitution. A semi-quantitative correlation of olefin yield with the number and nature of the sy -diaxial interactions at the reaction centre is even possible (Table 27). 

Silyl enol ethers, which are readily generated regiospecifically from ketones, can also be reduced to al-kenes, particularly by hydroboration. " Hydroboration of silyl enol ethers results in the addition of boron to the 3-c on of the double bond to afford fra/is-3-trimethylsilyloxy organoboranes, which in cyclic systems undergo anti elimination in the presence of acid to give the alkenic product (Scheme 42). A number of acids have been tested successfully, including carboxylic acids, BF3-Et20 and... 

A / -elimination reaction also occurs with linear and cyclic glycol mono-alkyl ether radicals. In this case the nucleofugal leaving group is the alkoxy function, RO, as shown in Scheme 7 for base catalysis and a cyclic system in which alkoxide elimination leads to ring-opening [63] ... 

In a cyclic system [38] the process involved is consistent with a stepwise mechanism, with equilibration between ring-opened and ring-closed Grignard reagents intermediates, followed by a fast elimination step, since the rate of formation of the cyclopropane 72 is independent of the stereochemistry at C-7, in intermediates 70 and 71 [Eq. (22)]. 

The situation is more complicated in cyclic systems such as the indoloquinolizidine iV-oxide (27a,b), where one of the a-carbon centers is activated by the presence of an aromatic (indole) substituent, as compound (28) is obtained from both the cis and trans isomers of (27 Scheme 5). Since the relative rates and yields of the two reactions are comparable, it appears that anti elimination is not an absolute requirement for this and related Polonovski reactions. 

Another case is the elimination reaction in cyclic systems. In such systems the conformation is determined by the flexibility or rigidity of the ring. The following correlation between ring size and degree of selectivity is observed (Table 3). ... 

For xanthogenate and acetate elimination from cyclic systems, the regioselectivity is dependent upon the accessibility of the alternative syn elimination transition states. The c/i-2-phenyl acetate (123 X = OAc) and xanthogenate (123 X = OCSSMe) both eliminate exclusively away from the phenyl substituent to give 3-phenylcyclohexene (124 equation 55), whereas the corresponding /ran5-2-phenyl com-... 

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