Enantioselective homoaldol reactions

Scheme 13.25. Diastereoselective and enantioselective homoaldol reactions using titanated allyl carbamates.

When the protocol is applied to allylcarbamates 170, the deprotonation in the presence of (—)-sparteine does not occur with kinetic preference. Indeed, a dynamic resolntion by crystallization takes place. The epimeric allylfithinm componnds 171 and 172 are eqni-librating, whereby one of them crystallizes predominantly. Under optimized conditions, when n-butyllithium is used for the deprotonation and cyclohexane serves as a cosolvent, the preference of the diastereomer 172 leads to snbstimtion products in 90-94% gg393-395 enantioselective homoaldol reaction has been developed based on this protocol Transmetalation of the organolithium into the titaninm compound occnrring nnder inversion of the configuration (172 173) and subseqnent addition to aldehydes leads to... 

SCHEME 24. (-)-Sparteine-induced deprotonation of allyl carbamate 170. Dynamic resolution by crystallization and enantioselective homoaldol reaction... 

Lithium-metal exchange in the lithium-)—)-sparteine complexes 399 or 402, respectively, by diethylaluminium chloride or triisopropoxytitanium chloride proceeds with inversion providing useful reagents for enantioselective homoaldol reactions... 

Enantioselective homoaldol reaction induced by sparteine and Ti catalyzed, also asymmetric deprotonation of allyl carbamates. 

Hoppe, D, Tarara, G, Wikens, M, Jones, P G, Schmidt, D, Stezowski, J J, Enantioselective synthesis of methyl furanosides of unnatural 3,6-dideoxy-3-methylaldohexoses form lactates hy homoaldol reactions, Angew. Chem. Int. Ed. Engl., 26, 1034-1035, 1987. 

It is especially remarkable that optically active homoaldol adducts can be obtained when enantiomeri-cally pure 2-alkenyl carbamates (47 R = alkyl) are employed. Apparently the deprotonation occurs with retention of configuration and leads to configurationally stable lithium derivatives, which, after metal exchange with Ti(OPr )4, again with retention, add to aldehydes with efficient 1,3-chirality transfer coupled with enantiofacial differentiation at the carbonyl group, indicating a rigid six-membered transition state. Recently even an asymmetric homoaldol reaction by enantioselective lithiation of prochiral primary alkenyl carbamates in the presence of (-)-sparteine was reported. ... 

To expand of the scope of electrophiles in the lithiation-substitution reaction, aldehydes were employed and a highly diastereoselective homoaldol methodology was developed [104]. After generation of lithiated 141 under the standard conditions, transmetallation with EtjAlCl or TiCl(Oi-Pr)3, and substitution with various aldehydes provided the homoaldol products with both high diastereo-and enantioselectivities (Scheme 48). 

A highly enantioselective kinetic resolution of protected homoaldols via a catalytic asymmetric transacetalization reaction could be achieved with a novel phosphoric acid STRIP (6) (Table 1) [25]. A catalyst loading of 1 mol% could be routinely used at 20°C, and even 0.1 mol% of the catalyst can give very similar enantiomeric ratios. The method is applicable to the resolution of a wide range of secondary and, most remarkably, of tertiary homoaldols. In most cases, both acyclic homoaldols 7 and cyclic homoaldols 8 could be obtained in enantiomeric ratios exceeding 95 5. Although chemical kinetic resolutions of secondary alcohols by other methods are well developed [26], these are not readily applicable to kinetic resolutions of tertiary alcohols [27-34]. 

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