Isoxazoles as precursors to functionalized carbocycles and oxacycles

ORGN 946

Martin G. Kociolek, mgk5@psu.edu1, Nicholas G. Straub1, Jolene V. Schuster, Jolene.V.Schuster@Dartmouth.edu2, and Matthew D Jackel1. (1) Science, Penn State Erie, The Behrend College, 31 Hammermill Building, 5091 Station Road, Erie, PA 16563-0107, (2) Chemistry Department, Dartmouth College, HB 6128, Hanover, NH 03755
Isoxazoles have long been recognized as versatile synthetic intermediates for the construction of 1,3-difunctionalized compounds. Previously, we demonstrated that 3-bromoisoxazoles and 3-carboxyisoxazoles can undergo ring opening to yield 2-ketonitriles. The enolates derived from these ketonitriles have been shown to undergo a variety of condensation reactions with carbonyl compounds. Recently, we have shown that with the appropriate substrate, an isoxazole with a tethered carbonyl group, these two reactions can be used in tandem, in a one-pot ring opening/cyclization sequence. Herein, we wish to report on the successful application of this methodology using both 3-bromoisoxazoles and 3-carboxyisoxazoles as precursors for the synthesis of a series of functionalized 5, 6 and 7-membered carbocycles. In addition, we will report on the application of these isoxazoles to the synthesis of oxacycles, with particular emphasis on a series of substituted benzoxepins, whose parent ring structure is found in number of biologically active natural products.