Regiochemical control of product 1,3-difluoroaromatics from difluorocarbene additions to asymmetric cyclobutenes

ORGN 470

Scott B. Lewis, Jenny L. Muth, and Nikole D. Morrow. Department of Chemistry, James Madison University, MSC 7701, Harrisonburg, VA 22807
Previous studies with symmetric 1,2-disubstituted cyclobutenes in reactions with difluorocarbene have shown that they will produce the 1,3-difluoroaromatic motif in one pot in up to 77% yields. The synthesis of asymmetric compounds such as 1-phenyl-2-methylcyclobutene (1) and 1-butylcyclobutene (2) were undertaken in order to further study this novel approach to 1,3-difluoroaromatics. Reactions involving compounds 1 and 2 using Ph-Hg-CF3 have shown remarkable regioselectivity giving isomer ratios as high as 84:16 in the product 1,3-difluoroaromatics. Further, the major isomer formed when Ph-Hg-CF3 is used appears to be formed from a radical cation like intermediate, not a fully cationic intermediate as previously believed. Reactions of compound 2 using sodium chlorodifluoroacetate as the difluorocarbene source produced a nearly 50:50 ratio of the two possible 1,3-difluoroaromatic products.