Catalytic reactions stereoselective deprotonations

Significant improvements to the Henry reaction have been achieved by using silyl nitronates and catalytic amounts of fluoride ion or, alternatively, a,a doubly deprotonated primary nitroalkanes. Both of these procedures, discovered by the Seebach group, have proved to be useful for the stereoselective preparation of vicinal amino alcohols. 

The Studer group presented a new cascade for the highly enantioselec-tive synthesis of substituted indane derivatives. Three stereocenters are formed in the NHC-catalyzed cascade reaction of enals with various p-dike-tones to give the corresponding indane derivatives with excellent stereoselectivity (up to 74% yield, 99% ee). It is predicted that the reaction occurs via a catalytic cycle using oxidative NHC catalysis. Reaction of the enal with NHC in the presence of an oxidant generates an o,p-unsaturated acylazolium ion. Conjugate addition of the likely deprotonated 1,3-dicarbonyl compound... 

NHC-catalyzed organocascades allowing the creation of both a C-C and a C-X bonds are rare. The group of Rovis has recently proposed a domino Michael/Stetter reaction for the preparation of optically active benzofuranones from salicylaldehydes and dimethyl acetylenedicarboxylate (DMAD) under dual catalytic conditions (Scheme 16.45) [94]. The reaction sequence involves a Lewis base-promoted oxa-Michael addition to produce a prochiral intermediate that then undergoes an NHC-catalyzed enantiodiscriminative Stetter reaction. Remarkably, the Lewis base not only triggers the initial oxa-Michael addition, but also serves as a Brpnsted base for deprotonation of the NHC precatalyst. The reaction scope could be extended to unsymmetrical alkynes and allenes with moderate to good stereoselectivities. 

The reaction of alkenyl epoxides with organometallic species (lithium, magnesium, copper, and boron) affords allylic alcohols, following an Sn and/or Sn mechanism. These processes can accommodate only little organic functionality and exhibit low regio- and/or stereoselectivity. Under smooth conditions, C—C bond formation proceeds by nucleophilic alkylation of vinyl epoxides in the presence of catalytic amounts of zerovalent palladium. Regio- and stereoselectivity can be achieved via the formation of a Tr-allylpal-ladium complex. Trost and Molander and Tsuji and co-workers simultaneously reported the first studies in 1981. Since then, numerous papers have dealt with this subject. Essentially, after chelation and oxidative addition of the palladium onto the vinyl epoxide, the zwitterionic 7r-allylpalladium complex deprotonates the nucleophile, which can in principle attack either carbon 2 (proximal attack) or 4 (distal attack) (Scheme 1). 

Three catalytic cycles differing in the mode of the substrate activation were computed (Scheme 3.11). In all three scenarios, the reaction was considered to proceed through initial a-deprotonation of the substrate and the subsequent stereoselective and rate-determining y-protonation. Computations showed that the routes I and III are competitive, whereas the overall activation-free barrier in Scenario II is at least 6 kcal/mol higher. 

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