On the scope of a Prins-type cyclization of oxonium ions

The Prins cyclization of an aldehyde 1 with a homoallylic alcohol 2, affording tetrahydro-2H-pyrans 4 via the oxonium ion 3 as central intermediate, was conceptually transferred to (alk-3-enyloxy)acrylates 6, which form a related oxonium ion 7 upon treatment with acids (Scheme 1). The scope and utility of this modification of the Prins-type cyclization of oxonium ions is discussed exemplarily by means of the syntheses of ten tetrahydro-2H-pyran and tetrahydrofuran derivatives, featuring diverse substitution patterns as well as different degrees of molecular complexity. These target structures include (+/-)-ethyl (2RS)-2-[(2RS,4SR,6RS)- and (2SR,4RS,6SR)-2-tetahydro-4-hydroxy-6-methylpyran-2-yl]propanoate (23), (+/-)-ethyl [(2RS, 3RS)-tetrahydro-3-isopropenylfuran-2-yl]acetate (32), (+/-)-ethyl (2Z)-3-(tetrahydro-2,2-dimethylfuran-3-yl)acrylate (37), (+/-)-(3aRS,6RS, 7aRS)-octahydro-7a-methylbenzofuran-6-yl formate (42), (+/-)-ethyl (2RS,3RS,4aRS,8SR,8aRS)-hexahydro-2,5,5,8-tetramethyl-7-oxo-2H,5H-pyrano[4,3-b]pyran-3-carboxylate (48), and (+/-)-ethyl (2RS,3RS,6SR)-tetrahydro-6-(2-methoxy-2-oxoethyl)-3-methyl-2H-pyran-2-carboxylate (53) (see Schemes 3 and 5-8). Besides the stereochemistry and mechanistic details of this versatile oxonium-ion cyclization, the synthesis of suitable starting materials is also described.