Synthesis of Chiral Spiro-Oxaphospholenes

The importance of chiral BINOL phosphate catalysts 1 in asymmetric transformations can hardly be underestimated. Although many chiral catalysts have been prepared and assessed for their enantioselective properties, only few... [ view full abstract ]

The importance of chiral BINOL phosphate catalysts 1 in asymmetric transformations can hardly be underestimated. Although many chiral catalysts have been prepared and assessed for their enantioselective properties, only few have been applied on a broad scope of substrates and BINOL derivatives certainly belong to the class of 'priviliged chiral inducers'. BINOL phosphoric acid derivatives have been deployed in asymmetric versions of numerous and important organic transformations such as Friedel-Crafts, Pictet-Spengler, Strecker, reductive amination and hydrophosphonylation reactions. The excellent properties of BINOL phosphates to control enantioselectivities originate from the phosphorus containing seven-membered ring and the chiral binaphtyl moiety, locking the conformation of the Brønsted acid. Inspired by our expertise in oxaphospholene chemistry¹ and the synthesis of phosphorus containing allenes² and heterocycles, we envisioned the synthesis of chiral spirocyclic oxaphospholenes xx, which may be of interest for the design of new chiral phosphonic acid catalysts. Even though the halocyclization of (3-cyclohexyl)allenylphosphonates to spirocyclic oxaphospholenes is known for a few decades, this is the first example of the design of such chiral spirocyclic compounds. The synthesis we envisioned consists of three successive transformations from readily available chiral starting materials. Addition of an organometallic acetylide to chiral pool ketoterpenes xx was followed by a [2,3]-sigmatropic rearrangement of the resulting propargylic alcohols xx with diethyl chlorophosphite. Subsequently, the obtained chiral allenenylphosphonates xx are finally subjected to a halocyclization with a Lewis acid to give the desired chiral spirocyclic oxaphospholenes xx.

1.Fourgeaud, P.; Midrier, C. V., J.-P.; Volle, J.-N.; Pirat, J.-L.; Virieux, D. Tetrahedron 2010, 66, 75

2.Berton, J. K. E. T.; Heugebaert, T. S. A.; Debrouwer, W.; Stevens, C. V. Org. Lett. 2016, 18, 208.