Enantioselective Assembly of Alkylated Stereogenic Centers

Enantioselective reduction of trisubstituted alkenes is also a powerful method for establishing alkylated stereogenic centers. Juan C. Carretero of the Universidad Autonoma de Madrid has found (Angew. Chem. Int. Ed. 2007,46, 3329) that the enantioselective reduction of unsaturated pyridyl sulfones such as 4 was directed by the sulfone, so the other geometric isomer of 4 gave the opposite enantiomer of 5. The protected hydroxy sulfone 5 is a versatile chiral building block. 

Samuel H. GeUman of the University of Wisconsin has reported (/. Am. Chem. Soc. 2007, 129, 6050) an improved procedure for the aminomethylation of aldehydes. L-Prohne-catalyzed condensation with the matched a-methyl benzylamine derivavative 7 gave the aldehyde, which was immediately reduced to the alcohol 8 to avoid racemization. The amino alcohol 8 was easily separated in diastereomericaUy-pure form. 

In the past, aldehydes have been efficiently a-alkylated using two-electron chemistry. David W. C. Macmillan of Princeton University has developed (Science 2007, 316, 582 J. Am. Chem. Soc. 2007, 129, 7004) a one-electron alternative. The organocatalyst 9 formed an imine with the aldehyde. Qne-electron oxidation led to an a-radical, which was trapped by the allyl silane (or, not pictured, a sdyl enol ether) leading to the a-alkylated 

Secondary alkylated centers can also be prepared by 8, 2 alkylation of prochiral substrates such as 11. BenL. Feringaofthe University of Groningen has shown (-f Org. Chem. 2007, 72, 2558) that the displacement proceeded with high ee even with conventional Grignard reagents. The products so formed are versatile intermediates for further transformation. 

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