The synthesis of organic compounds possessing heteroatoms substituent has been considered as a key topic in organic chemistry. In particular, N,O-acetals have been conceived as a precursor of the iminium ion-mediated C-C bond formation.1 In most cases in this area, the stereochemical information of the N,O-acetal can be easily destroyed due to the instability of the N,O-acetals.
We developed the synthesis of chemically labile N,O-acetals and utility for the first time.2 The synthesis of stereodefined N,O-acetals was achieved by the Pd-catalyzed asymmetric hydroamination of alkoxyallene. Various tosyl-protected homoprpargylic amines were converted into corresponding N,O-acetalsin excellent yield with high rigio- and stereoselectivity. In addition, we combined the stereodefined N,O-acetal with Au-catalyzed cycloisomerization. 3 The diasteromeric N,O-acetals were converted into the corresponding cis- and trans-2,6-disubstituted piperidines. We expect that this unique strategy represents an important concept in synthetic organic chemistry.
(1) Warriner, S. Category 4: Compounds with Two Carbon-Heteroatom Bonds in Science of Synthesis: Houben-Weyl Methods of Molecular Transformations; Eds.;Georg Thieme Verlag: Stuttguart; 2007; Vol 30, p 7.
(2) Kim, H.; Rhee, Y. H. J. Am. Chem. Soc. Accepted for publication
(3) Kim, C.; Bae, H. J.; Lee, J. H.; Jeong, W.; Kim, H.; Sampath, V.; Rhee, Y. H. J. Am. Chem. Soc. 2009, 131, 14660.