Highly Enantioselective [3+2] Annulation of Cyclic Enol Silyl Ethers with Donor-Acceptor Cyciopropaness Accessing 3α-Hydroxy [n.3.0]Carbobicycles

摘要

[n.3.0]Carbobicycles containing a tertiary alcohol moiety located at the ring junction are found as a key structure in a large number of biologically active and naturally occurring molecules such as botrydials, africanols, palustrols, lucinones, furoscrobiculins, etc. (Figure 1). In the past decades, considerable effort has been focused on the synthesis of these [n.3.0]bicycles, and many methods have been documented, such as nBu3Sn- or SmI2-initiated radical cyclization, ring-closing metathesis, and [n + 2] annulations based on cyclic enol ethers. So far, however, very few direct and catalytic asymmetric versions have been developed. As the [3+2] annulation of cyclic enol ethers with cyclo-propanes can efficiently establish the bicyclic skeleton, the tertiary alcohol unit, and at least two contiguous chiral centers in one step, it provides an appealing and concise approach to synthesize the 3α-hydroxy [n.3.0]carbobicyclic structure. Unfortunately, this efficient cycloaddition method often results in low diastereoselectivity and the formation of the ring-opened side products.