Palladium-Catalyzed Formal Insertion of Carbenoids into Aminals via C–N Bond Activation

Abstract

A new strategy for selective insertion of metal carbenes into C-N bond has been developed via Pd-catalyzed C-N bond activation. A series of aminals and α-diazoesters with different substituents were successfully incorporated even in 0.1 mol % of catalyst under mild conditions, affording a wide range of α,β-diamino acid esters with quarternary carbon-centers. Preliminary mechanistic studies uncovered that the unique electrophilic cyclopalladated species could easily react with diazoacetates to generate a Pd-carbenoid intermediate which was involved in the catalytic cycle.

Iron‐Catalyzed Aminomethyloxygenative Cyclization of Hydroxy‐α‐diazoesters with N,O‐Aminals

“…These results inspired us to consider whether the construction of oxacycles‐α,α‐disubstituted β‐amino esters can be achieved by reacting hydroxyl tethered α‐diazoesters with N , O ‐aminals under suitable conditions. In continuation with our ongoing interest in the aminal chemistry, [10,11a,12] we herein report an iron‐catalyzed intramolecular aminomethyloxygenative cyclization reaction between hydroxyl‐ tethered α‐diazoesters and N , O ‐aminals, which provides a new and rapid approach to oxacycle‐containing α,α‐disubstituted β‐amino esters (Scheme ).…”

“…For instance, transition‐metal‐catalyzed insertion of metal carbenes or carbenoids generated in situ from α‐diazoesters into N—H bonds has been developed to the preparation of α‐amino acid derivatives, [8d,8e,8g‐8j] and transition‐metal‐catalyzed multicomponent reactions involving diazo compounds with alcohols and imines (iminiums) were documented for the construction of α‐hydroxy‐β‐amino esters . In 2015, we developed a synthetic methodology for the efficient construction of a,β‐diamino acid esters bearing a quaternary carbon‐center by palladium‐catalyzed formal insertion of carbenoids into aminals via C—N bond activation . More recently, we and several other groups have demonstrated that N , O ‐aminals are also valuable aminomethylation reagents to react with diazo compounds to deliver the α‐hydroxy‐β‐ amino esters (Scheme ) .…”

Gold‐Catalyzed Formal [4+1]/[4+3] Cycloadditions of Diazo Esters with Triazines

“…[10] Recently,K rische and co-workers developed as eries of novel ruthenium-catalyzed hydroaminomethylations by using hexahydro-1,3,5-triazines as precursors of N-aryl formaldimines (Scheme 1a). [12] Inspired by these pioneering reports,a nd in continuation of our ongoing research interests in gold-carbene-mediated transformations, [13] we report herein the unprecedented formal [4+ +1]/[4+ +3] cyclo-additions between diazo esters and hexahydro-1,3,5-triazines (Scheme 1b). [12] Inspired by these pioneering reports,a nd in continuation of our ongoing research interests in gold-carbene-mediated transformations, [13] we report herein the unprecedented formal [4+ +1]/[4+ +3] cyclo-additions between diazo esters and hexahydro-1,3,5-triazines (Scheme 1b).…”

Copper-catalyzed cyanothiolation to incorporate a sulfur-substituted quaternary carbon center

“…We speculate that the generation of the product might be via two paths. In path a, the interaction of thiocyanate 2 and the copper carbene species B leads to the formation of the copper III carbene species C , 12 followed by migratory insertion 18a,19 to give the intermediate D . The reductive elimination of D provides the major product 3 and regenerates Cu I .…”

“…In this respect, the chemical bond cleavage of heteroatom-containing reactants and installation of both cleaved carbon and heteroatom fragments onto carbenoid species via transition metal catalysis is one of the most attractive and promising methods to incorporate a heteroatom-containing quaternary carbon center. Currently, examples of inserting nitrogen 12 and oxygen, 13 which have small atomic radii, are limited. In addition, introducing the large steric hindrance of a sulfur atom into the metal–carbene through cleavage of the S–C bond to construct a sulfur-substituted quaternary carbon is generally done via the rearrangement of sulfonium ylide, 14 where the employment of a noble metal catalyst is demanded.…”