Stereochemical drift

This accounts for the considerable discrepancy between the alkene Z/E ratio found on work-up and the initial oxaphosphetan ais/trans ratio. By approaching the problem from the starting point of the diastereomeric phosphonium salts (19) and (20), deprotonation studies and crossover experiments showed that the retro-Wittig reaction was only detectable with the erythreo isomer (19) via the cis-oxaphosphetan (17). Furthermore, it was shown that under lithium-salt-free conditions, mixtures of (19) and (20) exhibited stereochemical drift because of a synergistic effect (of undefined mechanism) between the oxaphosphetans (17) and (18) during their decomposition to alkenes. 

The initially obtained cw-oxaphosphetane can subsequently isomerize irreversibly to a /rarw-oxaphosphetane with the rate constant kAift x [ktmm (ktram + As)] (Figure 11.3). This isomerization is referred to as stereochemical drift. 

Fig. 11.3. Mechanism of the Wittig reaction. kcjs is the rate constant for the formation of the cis-oxaphosphetane, kmns is the rate constant for the formation of the trans-oxaphosphetane, and kdrjft is the rate constant for the isomerization of cis- to turns-configured oxaphosphetane, which is called "stereochemical drift."...

Under salt-free conditions, the cw-oxaphosphetanes formed from nonstabilized ylides can be kept from participating in the stereochemical drift and left intact until they decompose to give the alkene in the terminating step. This alkene is then a pure ci.s-isomer. In other words, salt-free Wittig reactions of nonstabilized ylides represent a stereoselective synthesis of cis-alkenes. 

On the other hand, stabilized ylides react with aldehydes almost exclusively via trans-oxaphosphetanes. Initially, a small portion of the cw-isomer may still be produced. However, all the heterocyclic material isomerizes very rapidly to the trans-configured, four-membered ring through an especially pronounced stereochemical drift. Only after this point does the... 

On the other hand, stabilized ylides react with aldehydes almost exclusively via trans-oxaphosphetanes. Initially, a small portion of the cw-isomer may still be produced. However, all the heterocyclic material isomerizes very rapidly to the fnms-configured, four-membered ring through an especially pronounced stereochemical drift. Only after this point does the [2+2]-cycloreversion start. It leads to triphenylphosphine oxide and an acceptor-substituted fnms-configured olefin. This frara-selectivity can be used, for example, in the C2 extension of aldehydes to /ran.v-con figured aj8-unsaturated esters (Figure 9.11) or in the fnms-selective synthesis of polyenes such as /1-carotene (Figure 9.12). 

There are two steps to the reaction that define the stereochemical outcome. The first is the intial addition of ylide and carbonyl, with inherent preferences for the fonnation of cis- and tran.r-oxaphosphetane intennediates (104) and (105), and the second is the ability of the intermediates to equilibrate. Maryanoff has studied numerous examples in which the final iE)/ Z) ratio of the alkene (102) produced does not correspond to the initial ratios of oxaphosphetanes (104) and (105) and has termed this phenomenon stereochemical drift .The intermediate oxaphosphetanes are thought to interconvert reversal to reactants (98) and (99), followed by recombination. In this case the final ratio of alkene can be substantially different from the initial addition ratio. 

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