Fused‐Ring Formation by an Intramolecular “Cut‐and‐Sew” Reaction between Cyclobutanones and Alkynes

Abstract

The development of a catalytic intramolecular "cut-and-sew" transformation between cyclobutanones and alkynes to construct cyclohexenone-fused rings is described herein. The challenge arises from the need for selective coupling at the more sterically hindered proximal position, and can be addressed by using an electron-rich, but less bulky, phosphine ligand. The control experiment and C-labelling study suggest that the reaction may start with cleavage of the less hindered distal C-C bond of cyclobutanones, followed by decarbonylation and CO reinsertion to enable Rh insertion at the more hindered proximal position.

Theoretical Study of Rhodium‐Catalyzed C−C Activation of Cyclobutanones: Origin of Ligand‐Controlled Product Selectivity

“…The energy barrier for I‐TS3A′ was calculated to be relatively high, 24.4 kcal/mol relative to I‐2A , which is 6.6 kcal/mol higher than that for I‐TS3A ; this suggests that the pathway to the cyclopropane product 3a is ultimately suppressed. The theoretical results for the product selectivity are therefore consistent with experimental observations …”

“…For the PPh 3 , dppb and dppe ligands (Figures a–3c), which were shown experimentally to be less reactive, the barriers for the C−C reductive elimination step (20.4, 16.3 and 22.3 kcal/mol) are higher than that for CO reinsertion (15.8, 14.4 and 14.9 kcal/mol), respectively. These results are consistent with the experimental observations that when PPh 3 , dppb, and dppe ligands were used, the main products were cyclohexenone‐fused rings . For the bulky monodentate phosphine ligands XPhos and SPhos, which have been used in C−C activation of C3‐substituted cyclobutanones, CO reinsertion and C−C reductive elimination occur with coordination of a single phosphine to the Rh center because of the large steric repulsion of the ligands (Figures d and 3e).…”

“…Cyclobutanone C−C activation with a Rh(I) catalyst has great potential for the synthesis of fused‐ and bridged‐ring systems. However, this synthetic application is greatly limited because of direct CO extrusion from cyclobutanone, which leads to formation of cyclopropane as a byproduct .…”

“…The choice of ligand is critical for this transformation. PMe 2 Ph ligand prevents cyclopropane formation in the synthesis of cyclohexenone‐fused rings, whereas XPhos ligand prevents cyclopropane formation in bridged cyclopentane synthesis (Scheme ) . The theoretical studies have been conducted to unravel the selection of ligands in catalysis by Kamer, Jover, Sigman and Doyle .…”

“…Ring-opening reactions of cyclobutanone derivatives and subsequent insertion of π-unsaturated units give efficient access to enhanced molecular complexity in organic syntheses. [4] Cyclobutanone CÀ C activation with a Rh(I) catalyst has great potential for the synthesis of fused- [5] and bridged-ring [6] systems. However, this synthetic application is greatly limited because of direct CO extrusion from cyclobutanone, which leads to formation of cyclopropane as a byproduct.…”