Zinc-Mediated Chain Extension of β-Keto Phosphonates

Abstract

A variety of beta-keto phosphonates can be converted to gamma-keto phosphonates through reaction with ethyl(iodomethyl)zinc. The presence of alpha-alkyl substituents, Lewis basic functionality, and modestly acidic NH-protons are accommodated in substrates of this reaction. Chain extension of beta-keto phosphonates that contained olefinic functionality proceeded more quickly than cyclopropanation; however, it was not possible to effect the chain extension to the exclusion of cyclopropane formation. A primary reason for this imperfect chemoselectivity appears to be the slow chain extension of beta-keto phosphonates. Nevertheless, the simplicity, the scope, and efficiency of this method serve to make it an attractive alternative to the established methods for gamma-keto phosphonate formation.

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

“…On the basis of these results and related precedents, [7,23] ap lausible mechanism for the chemoselective one-carbon insertion of diazo compounds into acyclic 1,3-dicarbonyl species is proposed (Scheme 4). 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.…”

“…[5] Whereas diazo compounds have also been widely explored as asource of carbenoids in transition-metal catalysis, [6] the insertion of diazo-derived metal carbenoids into acyclic C À Cb onds is unknown. [7] To the best of our knowledge,o nly one report by Wang and co-workers has described af ormal insertion of rhodium carbenoids derived from diazo compounds into the CÀCb onds of strained benzocyclobutenols to form quaternary carbon centers through sequential C À Cb ond cleavage,c arbene migratory insertion, and intramolecular aldol reaction. [8] We targeted an ew method to achieve the insertion of diazo-derived carbenoids into acyclic CÀCbonds.…”

Formation of γ‐Keto Esters From β‐Keto Esters: Methyl 5,5‐Dimethyl‐4‐Oxohexanoate

“…In fact, the method described above has been applied successfully to β-keto amides 9 and β-keto phosphonates. 10 Unsubstituted β-keto esters, amides and phosphonates have been chain-extended in yields that ranged from 58% to 98% (Table I). The primary limitation to this method is the inefficiency with which αsubstituted esters and amides undergo methylene insertion.…”

A Mechanistic Investigation into the Zinc Carbenoid-Mediated Homologation Reaction by DFT Methods: Is a Classical Donor−Acceptor Cyclopropane Intermediate Involved?

“…5 Application of this powerful methodology has found utility in the construction of complex ring systems. 6 Additional investigations have expanded the field of substrates to include β -keto phosphonates 7 and amides. 8 Substantial variation of this reaction is possible through the application of tandem reaction processes, for example, the introduction of residues at the α-position (such as hydroxyalkyl, 9 alkyl, 8 and iodomethyl 10 ) or at the β -position with modified alkyl carbenoids.…”