Highly stereoselective synthesis of cyclopentanes bearing four stereocentres by a rhodium carbene-initiated domino sequence

Abstract

Stereoselective synthesis of a cyclopentane nucleus by convergent annulations constitutes a significant challenge for synthetic chemists. Though a number of biologically relevant cyclopentane natural products are known, more often than not, the cyclopentane core is assembled in a stepwise fashion due to lack of efficient annulation strategies. Herein, we report the rhodium-catalyzed reactions of vinyldiazoacetates with (E)-1,3-disubstituted 2-butenols generate cyclopentanes, containing four new stereogenic centers with very high levels of stereoselectivity (99% ee, >97 : 3 dr). The reaction proceeds by a carbene–initiated domino sequence consisting of five distinct steps: rhodium–bound oxonium ylide formation, [2,3]-sigmatropic rearrangement, oxy-Cope rearrangement, enol–keto tautomerization, and finally an intramolecular carbonyl ene reaction. A systematic study is presented detailing how to control chirality transfer in each of the four stereo-defining steps of the cascade, consummating in the development of a highly stereoselective process.

Gold(I)-catalyzed intramolecular cyclization/intermolecular cycloaddition cascade as a fast track to polycarbocycles and mechanistic insights

“…But a [3 + 2]-cycloaddition could be enabled in the presence of gold catalyst with identical starting materials 17 . Meanwhile, a variety of [3 + n ]-cycloadditions of vinyl/enol metal carbene species with corresponding dipolarophiles have been disclosed independently by Doyle 18 , Davies 19 , and Yoo 20 (Fig. 1b ).…”

Polyhydroxylated cyclopentane β-amino acids derived from D-mannose and D-galactose: synthesis and protocol for incorporation into peptides

“…The development of methodologies for the stereo-and regioselective synthesis of polysubstituted cyclopentane rings continues to be a challenge in synthetic chemistry. [26][27][28][29] A specific goal of this significant area of research is to increase the limited number of known polyhydroxylated cyclopentane β-amino acids, 3,30,31 that would enable access to a larger variety of hydro-or liposoluble cyclopentane-based β-peptides. This latter goal can be achieved by protection or deprotection of the hydroxyl substituents in polyhydroxylated cyclopentane rings.…”

Gold(I)-Catalyzed Intramolecular Cyclization/Intermolecular Cycloaddition Cascade: Fast Track to Polycarbocycles and Mechanistic Insights

“…But a [3+2]-cycloaddition could be enabled in the presence of gold-catalyst with identical starting materials 17 . Later, a variety of [3+n]-cycloadditions of vinyl/enol metal carbene species with corresponding dipolarophiles have been disclosed independently by Doyle 18,19 , Davies 20,21 , and Yoo 22 , assembling ve-to eight-membered carbocyclic and heterocyclic frameworks (Fig. 1b).…”