Homoenolate is a reactive intermediate that possesses an anionic or nucleophilic carbon β to a carbonyl group or its synthetic equivalent. The recent discovery that homoenolates can be generated from α,β-unsaturated aldehydesviaN-Heterocyclic Carbene (NHC) catalysis has led to the development of a number of new reactions. A majority of such reactions include the use of carbon-based electrophiles, such as aldehydes, imines, enones, dienones etc. resulting in the formation of a variety of annulated as well as acyclic products. The easy availability of chiral NHCs has allowed the development of very efficient enantioselective variants of these reactions also. The tolerance showed by NHCs towards magnesium and titanium based Lewis acids has been exploited in the invention of cooperative catalytic processes. This tutorial review focuses on these and other types of homoenolate reactions reported recently, and in the process, updates the previous account published in 2008 in this journal.

Employing homoenolates generated by NHC catalysis in carbon–carbon bond-forming reactions: state of the art

Enzymes are a continuing source of inspiration for the design of new chemical reactions that proceed with efficiency, high selectivity and minimal waste. In many biochemical processes, different catalytic species, such as Lewis acids and bases, are involved in precisely orchestrated interactions to activate reactants simultaneously or sequentially. This type of 'cooperative catalysis', in which two or more catalytic cycles operate concurrently to achieve one overall transformation, has great potential in enhancing known reactivity and driving the development of new chemical reactions with high value. In this disclosure, a cooperative N-heterocyclic carbene/Lewis acid catalytic system promotes the addition of homoenolate equivalents to hydrazones, generating highly substituted gamma-lactams in moderate to good yields and with high levels of diastereo- and enantioselectivity.

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Cooperative catalysis by carbenes and Lewis acids in a highly stereoselective route to γ-lactams

Enantioselective synthesis through enzymatic asymmetrization

The invention is directed to methods to inhibit TGF-β and/or p38-α kinase using compounds of formula (1) or the pharmaceutically acceptable salts thereof wherein R3 is a noninterfering substituent; each Z is CR2 or N, wherein no more than two Z positions in ring A are N, and wherein two adjacent Z positions in ring A cannot be N; each R2 is independently a noninterfering substituent; L is a linker; n is 0 or 1; and Ar' is the residue of a cyclic aliphatic, cyclic heteroaliphatic, aromatic or heteroaromatic moiety optionally substituted with 1-3 noninterfering substituents.

Quinazoline derivatives as medicaments

The γ-lactam moiety is present in a large number of natural and non-natural biologically active compounds. The range of biological activities covered by these compounds is very broad. Functionalized γ-lactams are thus of high interest and have great potential in medicinal chemistry. This review provides a description of the title compounds by focusing on their synthesis, natural sources and biological activities.

Biologically active γ-lactams: synthesis and natural sources.

Diastereoselective and enantioselective total synthesis of the hepatoprotective agent clausenamide

Synthesis of a new carbapenem with a 6-methyl hydroxyacetate side chain

A process for the preparation of a 4-[3-carboxy-3-diazo-2-oxopropyl]azetidin-2-one of the formula ##STR1## comprising reacting a 4-acetoxy-2-azetininone of the formula ##STR2## with a compound of the formula ##STR3## in an inert solvent, in the presence of a base and of a silylating agent, in a one-pot process. Many of the products are new. The products are useful in the synthesis of carbapenem antibiotics.

Process for the preparation of carbapenem intermediates

Synthesis of an optically active 4-acetoxyazetidinone intermediate for penems and carbapenems

The invention relates to pyrazinylthiocarbapenems of the general formula (I) in which R , R , R and R have the meaning indicated in the description, processes for their preparation, and their use as medicaments.

Wolfgang Hartwig

Papers

Diastereoselective and enantioselective total synthesis of the hepatoprotective agent clausenamide

Synthesis of a new carbapenem with a 6-methyl hydroxyacetate side chain

Process for the preparation of carbapenem intermediates

Synthesis of an optically active 4-acetoxyazetidinone intermediate for penems and carbapenems

Pyrazinylthiocarbapenems, processes for their preparation, and their use