Asymmetric [4 + 2], [6 + 2], and [6 + 4] Cycloadditions of Isomeric Formyl Cycloheptatrienes Catalyzed by a Chiral Diamine Catalyst

Mikk Kaasik; Pan-Pan Chen; Sebastijan Ričko; Karl Anker Jørgensen; K N Houk

doi:10.1021/jacs.3c09551

Asymmetric [4 + 2], [6 + 2], and [6 + 4] Cycloadditions of Isomeric Formyl Cycloheptatrienes Catalyzed by a Chiral Diamine Catalyst

J Am Chem Soc. 2023 Nov 1;145(43):23874-23890. doi: 10.1021/jacs.3c09551. Epub 2023 Oct 20.

Authors

Mikk Kaasik¹, Pan-Pan Chen², Sebastijan Ričko^{1

3}, Karl Anker Jørgensen¹, K N Houk²

Affiliations

¹ Department of Chemistry, Aarhus University, DK-80000 Aarhus C, Denmark.
² Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095, United States.
³ Aarhus Institute of Advanced Studies, Aarhus University, DK-8000 Aarhus C, Denmark.

PMID: 37862136
DOI: 10.1021/jacs.3c09551

Abstract

Novel asymmetric aminocatalytic cycloadditions are described between formyl cycloheptatrienes and 6,6-dimethylfulvene that lead to [4 + 2], [6 + 2], and [4 + 6] cycloadducts. The unprecedented reaction course is dependent on the position of the formyl functionality in the cycloheptatriene core, and each formyl cycloheptatriene isomer displays a distinct reactivity pattern. The formyl cycloheptatriene isomers are activated by a chiral primary diamine catalyst, and the activation mode is dependent on the position of the formyl functionality relative to the cycloheptatriene core. The [4 + 2] and [6 + 2] cycloadducts are formed via rare iminocatalytic inverse electron-demand cycloadditions, while the [4 + 6] cycloadduct is formed by a normal electron-demand cycloaddition. The reactivity displayed by the different formyl cycloheptatrienes was investigated by DFT calculations. These computational studies account for the different reaction paths for the three isomeric formyl cycloheptatrienes. The aminocatalytic [4 + 2], [6 + 2], and [4 + 6] cycloadditions proceed by stepwise processes, and the interplay between conjugation, substrate distortion, and dispersive interactions between the fulvene and aminocatalyst mainly defines the outcome of each cycloaddition.