Borylated Cyclopropanes as Spring-Loaded Entities: Access to Vicinal Tertiary and Quaternary Carbon Stereocenters in Acyclic Systems

Abstract

Herein, we present the formation of acyclic frameworks bearing two consecutive stereocenters of either tertiary or quaternary nature starting from easily accessible cyclopropenes. This holistic approach involves a regio-and diastereoselective hydroor carboborylation of substituted cyclopropenyl esters. Formation of boronate complexes of the latter via the addition of nucleophiles and subsequent stereospecific 1,2-migration with carbon−carbon bond cleavage delivered the title compounds.

1,2‐Boronate Rearrangement: An Efficient Tool for the Opening, Functionalization and Formation of Strained Cycles

“…In 2022, Marek's group disclosed the successful use of a 1,2metallate rearrangement applied for the opening of cyclopropyl boronic esters 112. [42] The reaction led to the formation of two vicinal tertiary or quaternary stereocenters with an excellent diastereoselectivity. Readily accessible cyclopropenyl esters 111 were used as starting materials and submitted to a coppercatalyzed hydro-or carboborylation followed by conversion of the esters to the corresponding phosphates 113.…”

“…In 2022, Marek's group disclosed the successful use of a 1,2‐metallate rearrangement applied for the opening of cyclopropyl boronic esters 112 [42] . The reaction led to the formation of two vicinal tertiary or quaternary stereocenters with an excellent diastereoselectivity.…”

Synthesis and Functionalization of Tertiary Propargylic Boronic Esters by Alkynyllithium-Mediated 1,2-Metalate Rearrangement of Borylated Cyclopropanes

“…Based on our previous studies, ethyl esters 1a−d were transformed to phosphates 2a−d by a two-step reduction/phosphorylation sequence. 7,8,14 In addition, we decided to explore the potentially more suitable, yet less stable, cyclopropyl methyl iodides 4a−g, which were synthesized ad hoc, prior to the ring opening, from the corresponding bench-stable carbinols 3a−g (see Supporting Information for details). 15 It is noteworthy that potential minor regio-and/or diastereomers resulting from the Cu-catalyzed carboboration addition are fully separable by simple purification by column chromatography at the stage of phosphates or carbinols and therefore compounds 2a−d and 4a−g were thus obtained as single isomers with the pinacol borane conveniently oriented trans to the leaving group.…”

“…Inspired by our recent work, we set out to synthesize a library of borylated cyclopropyl esters 1a – h using the previously developed Cu-catalyzed hydro- and carboborylation (Scheme ). The starting mono- and disubstituted cyclopropenyl esters were easily obtained by a well-described Rh-catalyzed decomposition of ethyl diazoacetate in the presence of the corresponding alkynes .…”

“…Following this approach, diversity of substituents could be achieved by employing different cyclopropenes (R 1 and R 2 ) as well as by changing the nature of the electrophile (R 3 = H or allyl). Based on our previous studies, ethyl esters 1a – d were transformed to phosphates 2a – d by a two-step reduction/phosphorylation sequence. ,, In addition, we decided to explore the potentially more suitable, yet less stable, cyclopropyl methyl iodides 4 a– g , which were synthesized ad hoc , prior to the ring opening, from the corresponding bench-stable carbinols 3a – g (see Supporting Information for details) …”