Homologation Reaction of Ketones with Diazo Compounds

Abstract

This review covers the addition of diazo compounds to ketones to afford homologated ketones, either in the presence or in the absence of promoters or catalysts. Reactions with diazoalkanes, aryldiazomethanes, trimethylsilyldiazomethane, α-diazo esters, and disubstituted diazo compounds are covered, commenting on the complex regiochemistry of the reaction and the nature of the catalysts and promoters. The recent reports on the enantioselective version of ketone homologation reactions are gathered in one section, followed by reports on the use of cyclic ketones ring expansion in total synthesis. Although the first reports of this reaction appeared in the literature almost one century ago, the recent achievements, in particular, for the asymmetric version, forecast the development of new breakthroughs in the synthetically valuable field of diazo chemistry.

Synthesis of Amido Esters and Amido Phosphonates through Carbonylation of Diazo Compounds Followed by Nucleophilic Addition Reaction

“…[41,42] In general, organic carbonyl compounds decompose and generate CO above room temperature or in the presence of a strong base. [43][44][45] Thus, if we use an organic carbonyl compound as a nongaseous CO source, we will need a separate catalyst to activate the diazo compound and yield the carbene. [43][44][45] Thus, if we use an organic carbonyl compound as a nongaseous CO source, we will need a separate catalyst to activate the diazo compound and yield the carbene.…”

The ligand influence in stereoselective carbene transfer reactions promoted by chiral metal porphyrin catalysts

“…Diazo derivatives of the general formula N 2 C(R)(R 1 ) are sustainable and atom-efficient starting materials of these reactions because the formation of the carbene [(R)(R 1 )C:] functionality occurs with the contemporary extrusion of benign molecular nitrogen as the only by-products. 9,10 Diazo derivatives can be efficiently synthesised by introducing R/R 1 groups with different electronic behaviour (donor/donor, acceptor/donor or acceptor/acceptor) to fine-tune the reactivity of the carbene metal species with respect to the electrophilic/nucleophilic nature of the organic substrate. In addition, the steric nature of substituents onto the carbene carbon atom can affect the reaction stereoselectivity by driving the approach of the metal carbene complex to the organic substrate.…”

Catalyst‐Dependent Chemoselective Formal Insertion of Diazo Compounds into C−C or C−H Bonds of 1,3‐Dicarbonyl Compounds

“…In the case of the silvercatalyzed C( = O) À Cinsertion, 1,3-diketone 2 is first converted by AgOTf into silver enolate A,w hich engages with diazo compound 1 to give the electrophilic silver carbenoid B following loss of molecular nitrogen. In contrast to existing catalytic methods for the insertion of nucleophilic diazo compounds into ketones, [4] thetransient formation of an electrophilic silver carbenoid (B)a nd the subsequent cyclopropanation would represent an ovel mode of carbenoid reactivity.Notably,the formation of product 3ah (Scheme 1) would be consistent with such am echanism, where cyclopropanation occurs at the double bond of the predominant enol form (i.e., that of the methyl ketone), rather than ap athway that relies on migrating group ability,i nw hich migration of the C2 carbon atom would likely be disfavored. In contrast to existing catalytic methods for the insertion of nucleophilic diazo compounds into ketones, [4] thetransient formation of an electrophilic silver carbenoid (B)a nd the subsequent cyclopropanation would represent an ovel mode of carbenoid reactivity.Notably,the formation of product 3ah (Scheme 1) would be consistent with such am echanism, where cyclopropanation occurs at the double bond of the predominant enol form (i.e., that of the methyl ketone), rather than ap athway that relies on migrating group ability,i nw hich migration of the C2 carbon atom would likely be disfavored.…”