Formation of Olefins by Eliminative Dimerization and Eliminative Cross‐Coupling of Carbenoids: A Stereochemical Exercise

Abstract

Two carbenoids combine to generate an olefin by a mechanism involving formation of an ate complex, 1,2-metalate rearrangement, and β-elimination. As each stage of this eliminative coupling is stereospecific, the overall stereochemical outcome can be understood and, in principle fully controlled, providing that the absolute stereochemical configurations of the reacting carbenoid species are defined. In contrast to traditional alkene syntheses, the eliminative cross-coupling of carbenoids offers a connective approach to olefins capable of precisely targeting a given isomer regardless of the nature of the features distinguishing the isomers. The formation of olefins by the eliminative dimerization and eliminative cross-coupling of carbenoids is reviewed with a range of illustrative examples, including the reactions of α-lithiated haloalkanes, epoxides, and carbamates. An emphasis is placed on stereochemical analysis and methods to generate sp -hybridized carbenoids in stereodefined form are surveyed.

Allylic alcohols and amines by carbenoid eliminative cross-coupling using epoxides or aziridines

“…Where 1,2-disubstituted alkenes are generated the E / Z stereoselectivity is modest, and preliminary results suggest the size of the leaving group does not play a significant role. However, the geometry of alkene formation might be controllable by using enantiomerically pure coupling partners [ 2 ]. Such terminal epoxides and aziridines are readily available [ 3 , 5 ], while the corresponding α-lithio ethers can be accessed from enantioenriched α-stannyl ethers [ 25 ].…”

“…Methods for the convergent generation of alkenes can be of significant utility in organic synthesis [ 1 ]. A relatively under-examined approach is through the interaction of two carbenoids [ 2 ]. Dimerisation of carbenoids may compete with a desired carbenoid transformation although its value has been demonstrated in, for example, our studies on lithium 2,2,6,6-tetramethylpiperidide ( 1 , LTMP)-induced syntheses of 2-ene-1,4-diols and 2-ene-1,4-diamines from terminal epoxides [ 3 ] and aziridines [ 4 – 5 ], respectively ( Scheme 1 ).…”

“…Dimerisation of carbenoids may compete with a desired carbenoid transformation although its value has been demonstrated in, for example, our studies on lithium 2,2,6,6-tetramethylpiperidide ( 1 , LTMP)-induced syntheses of 2-ene-1,4-diols and 2-ene-1,4-diamines from terminal epoxides [ 3 ] and aziridines [ 4 – 5 ], respectively ( Scheme 1 ). The eliminative cross-coupling of carbenoids can provide a way to unsymmetrical alkenes, provided the differential reactivity of the two carbenoids is suitably matched [ 2 ]. In the current letter, we report preliminary results on the latter strategy to form alkenes which possess an allylic heteroatom (hydroxy, amino) functionality ( Scheme 2 ).…”

A practical guide for using lithium halocarbenoids in homologation reactions

“…The concomitant presence of an electron-donating and electron-withdrawing substituent at the carbon center determines the so-called ambiphilicity of these reagents [ 5 , 10 ]. Thus, carbenoids display a dual reactivity ranging from nucleophilic to electrophilic [ 6 , 11 , 12 ]. Depending on the experimental conditions, they may selectively exhibit only one of these two properties [ 13 – 17 ]: it is normally accepted that the nucleophilic behavior is shown at low temperatures, while their electrophilicity comes into play at higher temperatures (Scheme 1 ) [ 6 , 18 , 19 ].…”

Consecutive and Selective Double Methylene Insertion of Lithium Carbenoids to Isothiocyanates: A Direct Assembly of Four‐Membered Sulfur‐Containing Cycles

“…[2] Regardless the essence of the adopted regime (nucleophilic, electrophilic or radical), the carbon skeleton elongation is limited to one methylene unit per homologation cycle, thus making multiple-homologations highly elusive processes in synthesis (Scheme 1-path a). [3] Although the intrinsic limited instability of reagents used for the purposefor example, metal carbenoids [4] -may account for this reluctant behaviour, the installation of valuable linchpins on the chain results an effective solution to the problem. In this sense, the introduction by Matteson of boronic esters (I) as privileged electrophilic manifolds to conduct homologation with lithium carbenoids, [5] underpinned the elaboration of the elegant concept of iterative homologations illustrated more recently by Aggarwal [6] and Blakemore (Scheme 1-path b).…”