Enantioselective Construction of Cyclobutanes: A New and Concise Approach to the Total Synthesis of (+)-Piperarborenine B

Abstract

A highly diastereoselective and enantioselective Cu(II)/SaBOX-catalyzed [2 + 2] cycloaddition of methylidenemalonate and multisubstituted alkenes was developed to furnish optically active cyclobutanes in high yields with >99/1 dr and up to >99% ee. By application of the newly developed method, the total synthesis of (+)-piperarborenine B was completed in eight steps from methylidenemalonate and olefin in 17% overall yield with >99/1 dr and 99% ee.

Highly Stereoselective Direct Construction of Diaryl‐Substituted Cyclobutanes†

“…Furthermore, by the same strategy of Baran, the second aryl group was assembled by C—H bond functionalization via introducing and removing a directing group (Scheme 1b). To the best of our knowledge, efficient synthetic methods in the direct construction of the important diaryl‐substituted cyclobutane unit, are still barely been demonstrated. Recently, we have realized the copper catalyzed stereoselective [2+2] cyclizations of arylmethylidenemalonates with substituted styrenes, furnishing a series of multi‐ substituted cyclobutanes bearing two aryl groups on the 2,4‐positions in good to high yields with up to >95/5 dr (Scheme 1c).…”

Recent Applications of Rh‐ and Pd‐Catalyzed C(sp3)–H Functionalization in Natural Product Total Synthesis

“…Following the earlier reports, a number of groups have recently exploited cyclobutane C(sp 3 )–H arylation and alkenylation strategies in their total synthesis endeavors . Fox and co‐workers recently completed the total synthesis of (+)‐piperarborenine B [(+)‐ 62 ] through an amide‐directed C–H arylation (Scheme ) .…”

Stereoretention in Styrene Heterodimerisation Promoted by One-Electron Oxidants

“…[7][8][9][10][11][12] Cyclobutanation can now also be readily achieved via organocatalysis, [13][14][15] organometallic catalysis, 7,[16][17][18] as well as electrocatalysis [19][20][21][22] (Scheme 1). Until recently when the synthesis of substituted cyclobutanes could be realised via selective C-H functionalisation of unsubstituted cyclobutanes, [23][24][25][26] formal [2+2] cycloaddition remains the main strategy for the synthesis of complex, tetra-substituted cyclobutyl rings. [27][28][29][30] For the latter strategy, the formation of an unsymmetrical, tetra-substituted cyclobutane can arise from intermolecular heterodimerisation of two substituted alkenes.…”