A (2+2) photocycloaddition-fragmentation approach for cis-fused lycorine-type natural product synthesis

Members of the Amaryllidaceae alkaloid family exhibit a unique cis-junction between the B and C ring being challenging targets for enantioselective total synthesis. By considering cyclobutanes not as products but rather as reactive intermediates, a [2+2] photocycloaddition-fragmentation sequence was successfully developed to enable a conceptually new entry to cis-fused lycorine-type alkaloids of the Amaryllidaceae family. Hence, the cis-selective annulation of six-membered rings on isoquinolones was successfully accomplished by employing cyclobutenes as olefin components and a variety of substitution patterns was accessible by this simple two step procedure. During our investigation we found the high ring strain of bicyclo[2.2.0]hexanes and a donor-acceptor substitution pattern to be crucial for successful transformation.