VERSATILE HETEROCYCLE SYNTHESIS VIA PALLADIUM-CATALYZED CYCLOADDITION AND ENANTIOSELECTIVE AMINATION OF 1,2-DIOLS THROUGH BORROWING HYDROGEN

Abstract

Construction of medium-sized rings represents a great challenge in organic chemistry, especially by intermolecular cycloaddition. We have developed the first catalytic [5+4] cycloaddition to prepare nine-membered heterocycles using palladium catalysis; the enantioselective variant has also been achieved. Highly diastereoselective functionalization of the nine-membered heterocycles through peripheral attack or transannular addition has led to structurally diverse polycyclic compounds in high efficiency with excellent stereoselectivity. We also discover an unexpected Pd-catalyzed synthesis of spirocyclic structures. The Lewis acid co-catalyst induces divergent reactivity for [3+2] or [4+2] cycloaddition through reversed regioselectivity. Both reactions proceed with excellent yield and diastereoselectivity. Borrowing hydrogen represents an economical and sustainable approach in organic synthesis. We have developed a highly enantioselective synthesis of 1,2-amino alcohols from readily available racemic 1,2-diols through borrowing hydrogen. An intriguing acid effect for this Ru-catalyzed amination reaction has been discovered, which leads to a significant improvement of the stereoselectivity of the process.