Methyl cyanoformate (Mander's reagent)

(A) Numerous syntheses of natural products and related compounds have featured the use of methyl cyanoformate to prepare β-keto esters. In the first total syntheses of (+)-lyconadin A and (-)-lyconadin B, Smith and co-workers¹⁰ employed Mander's reagent for precisely this purpose. (Chemical Equation Presented) (B) The title reagent was used to prepare an acetylenic ester that served as an early stage intermediate in the first asymmetric total synthesis of (-)-platensimycin reported by Nicolaou and co-workers. ¹¹ (Chemical Equation Presented) (C) Ethyl cyanoformate has been shown to engage in a copper(I)-catalyzed [3+2] dipolar cycloaddition with various organoazides, including benzylazide, to afford the corresponding 1,5-disubstituted tetrazoles.⁶ (Chemical Equation Presented) (D) Nájera and co-workers reported the one-step synthesis of various chiral cyanocarbonates from a range of aldehydes using the title reagent in the presence of chiral bifunctional catalysts such as (R)-or (S)-BINOLAM-AlCl. ^12,13 It is believed that the catalytic cycle involves enantioselective hydrocyanation promoted by BINOLAMAlCl, followed by the turnover-limiting O-alkoxycarbonylation step. (Chemical Equation Presented) (E) Hill and Zheng have reported that irradiation (λ > 280 nm) of mixtures of various alkanes and methyl cyanoformate in the presence of either W ₁₀O₃₂ ^4- or PW₁₂O₄₀ ^3- produces the corresponding nitrile or α-iminoester, respectively.⁵ Such reactions can be highly selective if proper temperature controls are applied. An iminyl radical intermediate is thought to be involved in these conversions. (Chemical Equation Presented) (F) Nishihara and co-workers have described the highly stereoselective and palladium-catalyzed addition of methyl cyanoformate across norbornene-type double bonds and so affording norbornanes bearing both cyano and ester groups.¹⁴ It is believed that the complex trans-Pd(CN)(CO₂Me)(Ph₃P) ₂ is an intermediate in the catalytic cycle associated with this cyanoesterification process.¹⁵ (Chemical Equation Presented) (G) Shimizu and Murakami have effected the selective formation of α-keto esters by the rhodium-catalyzed reaction of ethyl cyanoformate with arylboronic acids.⁷ The observed conversion arises through preferential addition of an intermediate rhodium(I) species to the cyano group rather than to the ester carbonyl group. This conversion stands in sharp contrast to the outcomes observed when ethyl cyanoformate reacts with either phenyllithium or phenylmagnesium bromide so as to afford ethyl benzoate.⁷ (Chemical Equation Presented).