In the investigation of efficient chemical transformations, the carbon-carbon bond-forming reactions play an outstanding role. In this context, organocatalytic processes have achieved considerable attention. 1 Beside their facile reaction course, selectivity, and environmental friendliness, new synthetic strategies are made possible. Particularly, the inversion of the classical reactivity (Umpolung) opens up new synthetic pathways. 2 In nature, the coenzyme thiamine (vitamin B1), a natural thiazolium salt, utilizes a catalytic variant of this concept in biochemical processes as nucleophilic acylations. 3 The catalytically active species is a nucleophilic carbene. 4

Organocatalysis by N-Heterocyclic Carbenes

Practical methodologies for the synthesis of indoles.

Organocatalytic Reactions Enabled by N-Heterocyclic Carbenes.

Large-scale applications of transition metal-catalyzed couplings for the synthesis of pharmaceuticals.

Modern synthetic methods have revolutionized polymer chemistry through the development of new and powerful strategies for the controlled synthesis of complex polymer architectures. 1-5 Many of these developments were spawned by new classes of transition metal catalysts for the synthesis of new polyolefin microstructures, 5 the design of highly efficient families of “living” polymerization strategies for the synthesis of block, graft, and star polymers, 6-12 controlled methods for the synthesis of dendritic macromolecules, 3,13,14

Organocatalytic ring-opening polymerization.

A highly enantioselective and practical synthesis of the HIV-1 reverse transcriptase inhibitor efavirenz (1) is described. The synthesis proceeds in 62% overall yield in seven steps from 4-chloroaniline (6) to give efavirenz (1) in excellent chemical and optical purity. A novel, enantioselective addition of Li-cyclopropyl acetylide (4a) to p-methoxybenzyl-protected ketoaniline 3a mediated by (1R,2S)-N-pyrrolidinylnorephedrine lithium alkoxide (5a) establishes the stereogenic center in the target with a remarkable level of stereocontrol.

Practical asymmetric synthesis of Efavirenz (DMP 266), an HIV-1 reverse transcriptase inhibitor

A direct asymmetric hydrogenation of unprotected enamino esters and amides is described. Catalyzed by Rh complexes with Josiphos-type chiral ligands, this method gives β-amino esters and amides in high yield and high ee (93−97% ee). No acyl protection/deprotection is required.

Highly Efficient Synthesis of β-Amino Acid Derivatives via Asymmetric Hydrogenation of Unprotected Enamines

Kilogram-scale synthesis of the HIV reverse transcriptase inhibitor efavirenz was achieved by means of a highly enantioselective alkynylation of prochiral ketones 1 with alkynyllithium or alkynylmagnesium reagents in the presence of chiral zinc aminoalkoxides as mediators. With the achiral auxiliary 2,2,2-trifluoroethanol (R3=CF3CH2), the efavirenz precursor 2 (R1=H, R2=cyclopropyl) was obtained with an ee of 99.2%.

A Novel, Highly Enantioselective Ketone Alkynylation Reaction Mediated by Chiral Zinc Aminoalkoxides

Synthesis of alpha-amido ketones via organic catalysis: thiazolium-catalyzed cross-coupling of aldehydes with acylimines.

http://ccc.chem.pitt.edu/wipf/Current%20Literature/Mike_2.pdf

Richard D. Tillyer

Papers

Practical asymmetric synthesis of Efavirenz (DMP 266), an HIV-1 reverse transcriptase inhibitor

Highly Efficient Synthesis of β-Amino Acid Derivatives via Asymmetric Hydrogenation of Unprotected Enamines

A Novel, Highly Enantioselective Ketone Alkynylation Reaction Mediated by Chiral Zinc Aminoalkoxides

Synthesis of alpha-amido ketones via organic catalysis: thiazolium-catalyzed cross-coupling of aldehydes with acylimines.

Synthesis of substituted imidazoles via organocatalysis.