Chiral auxiliaries, diastereoselectivity, asymmetric alkenes

Stereosectivity is a broad term. The stereoselectivity in cyclopropanation which has been discussed in the above subsection, in fact, can also be referred to as diastereoselectivity. In this section, for convenience, the description of diastereoselectivity will be reserved for selectivity in cyclopropanation of diazo compounds or alkenes that are bound to a chiral auxiliary. Chiral diazoesters or chiral Ar-(diazoacetyl)oxazolidinone have been applied in metal catalysed cyclopropanation. However, these chiral diazo precursors and styrene yield cyclopropane products whose diastereomeric excess are less than 15% (equation 129)183,184. The use of several a-hydroxy esters as chiral auxiliaries for asymmetric inter-molecular cyclopropanation with rhodium(II)-stabilized vinylcarbenoids have been reported by Davies and coworkers. With (R)-pantolactone as the chiral auxiliary, cyclopropanation of diazoester 144 with a range of alkenes provided c yield with diastereomeric excess at levels of 90% (equation 130)1... 

When TMM equivalents are tethered to alkenes, intramolecular cyclization generates bicyclic methylene-cyclopentane derivatives. Cyclization of 394, for example, led to a 51% yield of 395 along with 18% of the uncyclized triene, 396. 35 jhe cyclization reaction proceeded with excellent diastereoselectivity, as shown. Trost has also examined the attachment of chiral auxiliaries to the alkene partner to give asymmetric induction in reactions with TMM equivalents.231... 

A number of techniques are now available allowing the preparation of enantiomerically pure (or at least enriched) compounds via asymmetric nucleophilic addition to electron-deficient alkenes. Some of these transformations have already been successfully applied in total synthesis. In most cases, the methods are based on diastereoselective reactions, employing chirally modified substrates or nucleophiles. There are only very few useful enantioselective procedures accessible so far. The search for efficient en-antioselective methods, especially for those which are catalytic and do not require the use of stoichiometric amounts of chiral auxiliaries, remains a challenging task for the future. 

Under PKR conditions, two enantiomeric substrates are simultaneously converted into two structurally and configurationally different chiral products by reaction with chiral reagents or catalysts. It has been shown that to achieve the same selectivity, the selectivity factor s can be significantly lower for PKR than for a traditional kinetic resolution. As yet, there has been only one report of an asymmetric HWE reaction under PKR conditions [88], in which one equivalent of racemic aldehyde 143 was converted into alkene products 144 and 145 by reaction with half an equivalent each of two chiral phosphonates 28 and 20 bearing different chiral auxiliaries (Scheme 7.24). These alkene products, 144 and 145, were readily separable as a result of the difference in polarity between the two auxiliaries. It was clearly shown that the diastereoselectivities of the alkene products were dramatically improved compared to those obtained in the respective individual kinetic resolutions, especially in the case of alkene 145. 

---