Progress in Enantioselective Phosphine Organocatalysis

Enantioselective organocatalysis.

Enantioselective organocatalysis has emerged as a powerful synthetic paradigm that is complementary to metal-catalysed transformations and has accelerated the development of new methods to make diverse chiral molecules. The operational simplicity, ready availability of catalysts and low toxicity associated with organocatalysis makes it an attractive method to synthesise complex structures. Here...

Comprehensive Enantioselective Organocatalysis

Enantioselective organocatalysis using SOMO activation.

The asymmetric alpha-addition of relatively nonpolar hydrocarbon substrates, such as allyl and aryl groups, to aldehydes and ketones remains a largely unsolved problem in organic synthesis, despite the wide potential utility of direct routes to such products. We reasoned that well-established chiral amine catalysis, which activates aldehydes toward electrophile addition by enamine formation, co...

Enantioselective aldehyde alpha-nitroalkylation via oxidative organocatalysis.

The first enantioselective organocatalytic alpha-nitroalkylation of aldehydes has been accomplished. The aforementioned process involves the oxidative coupling of an enamine intermediate, generated transiently via condensation of an amine catalyst with an aldehyde, with a silyl nitronate to produce a beta-nitroaldehyde. Two methods, one that furnishes the syn beta-nitroaldehyde and a second tha...

Preparation of (-)-Nutlin-3 using enantioselective organocatalysis at decagram scale.

Chiral nonracemic cis-4,5-bis(aryl)imidazolines have emerged as a powerful platform for the development of cancer chemotherapeutics, stimulated by the Hoffmann-La Roche discovery that Nutlin-3 can restore apoptosis in cells with wild-type p53. The lack of efficient methods for the enantioselective synthesis of cis-imidazolines, however, has limited their more general use. Our disclosure of the ...