Baylis-Hillman reaction enantioselective compounds

The aza-Morita-Baylis-HiUman reaction is known to be a useful and atom-economical C-C bond-forming reaction of electron-deficient alkenes with imines usually catalyzed by Lewis bases [202]. It formally involves a sequence of reactions including a Michael addition, a Mannich reaction, a proton transfer, and a retro-Michael reaction ( -elimination). Although there are many reports in the field of the enantioselective aza-Morita-Baylis-Hilhnan reaction, only rare examples of asymmetric domino reactions initiated by this reaction have been reported. In 2010, Sasai et al. [203] developed the first organocatalyzed asymmetric domino aza-Morita-Baylis-Hillman/aza-Michael reaction of a,p-unsaturated carbonyl compounds with N-tosylimines, allowing an easy access to chiral cis-1,3-disubstituted isoindolines as single diastereomers. The process was induced by a Hg-BINOL-derived catalyst and provided these products in high yields and enantioselectivities, as shown in Scheme 10.18. 

The introduction of the activated allylic bromides and Morita-Baylis-Hillman acetates and carbonates pioneered the development of a number of phosphine-catalyzed reactions in subsequent years [45]. Interestingly, the asymmetric variant of this type of transformation only appeared in the literature seven years later. In 2010, Tang, Zhou, and coworkers disclosed a highly enantioselective intramolecular ylide [3-f2] annulation using spirobiindane-based phosphine catalyst 31 (Scheme 20.27). BINAP was found inactive in this reaction even at an elevated temperature (70°C). Notably, both optically active benzobicyclo[4.3.0] compounds 32 and 32 with three continuous stereogenic centers could be obtained as major products in high yields and stereoselectivities just by a choice of an additive [Ti(OPr )4], which can block the isomerization of the double bond [46]. 

---