title: Enantioselective rhodium-catalyzed [2 + 2 + 2] cycloadditions of terminal alkynes and alkenyl isocyanates: mechanistic insights lead to a unified model that rationalizes product selectivity.
abstract: This manuscript describes the development and scope of the asymmetric rhodium-catalyzed [2 + 2 + 2] cycloaddition of terminal alkynes and alkenyl isocyanates leading to the formation of indolizidine and quinolizidine scaffolds. The use of phosphoramidite ligands proved crucial for avoiding competitive terminal alkyne dimerization. Both aliphatic and aromatic terminal alkynes participate well, with product selectivity a function of both the steric and electronic character of the alkyne. Manipulation of the phosphoramidite ligand leads to tuning of enantio- and product selectivity, with a complete turnover in product selectivity seen with aliphatic alkynes when moving from Taddol-based to biphenol-based phosphoramidites. Terminal and 1,1-disubstituted olefins are tolerated with nearly equal efficacy. Examination of a series of competition experiments in combination with analysis of reaction outcome shed considerable light on the operative catalytic cycle. Through a detailed study of a series of X-ray structures of rhodium(cod)chloride/phosphoramidite complexes, we have formulated a mechanistic hypothesis that rationalizes the observed product selectivity.
authors.affiliation: Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523, USA.
authors.forename: Derek M
authors.initials: DM
authors.lastname: Dalton
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Oberg
authors.forename: Robert T
authors.initials: RT
authors.lastname: Yu
authors.forename: Ernest E
authors.initials: EE
authors.lastname: Lee
authors.forename: Stéphane
authors.initials: S
authors.lastname: Perreault
authors.forename: Mark Emil
authors.initials: ME
authors.lastname: Oinen
authors.forename: Melissa L
authors.initials: ML
authors.lastname: Pease
authors.forename: Guillaume
authors.initials: G
authors.lastname: Malik
authors.forename: Tomislav
authors.initials: T
authors.lastname: Rovis
mesh_terms: D000480:Alkynes / Q000737:chemistry*; D002384:Catalysis; D017953:Isocyanates / Q000737:chemistry*; D012238:Rhodium / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000480:Alkynes; D017953:Isocyanates; D012238:Rhodium