Intramolecular cycloaddition reactions of electron-rich alkynes: new methods for the synthesis of optically active building blocks for organic synthesis

Ynol ethers and alkynamines are functional groups that possess significant potential in organic chemistry for the formation of carbon-carbon bonds. Due to their linear geometry, electron-rich alkynes are relatively unhindered to approach by functional groups present in the same or different molecules, and can prospectively form up to three new bonds in a single reaction. Recently discovered sigmatropic processes involving alkynyl ethers give rise to aldo- and ketoketene intermediates, which can be trapped in an inter- or intramolecular fashion to provide diverse ?,d-unsaturated carboxylic acid derivatives, 2-indanones, and fused cyclobutanones under remarkably mild reaction conditions. In all cases, molecular complexity is significantly enhanced in these reactions, and the materials produced contain multiple new carbon-carbon bonds and contiguous stereogenic centers. However, the utility of these reactions in organic synthesis to date has been limited due to the inavailability of enantioselective variants of these processes. In the proposed research we will investigate the preparation of optically active polycyclic products from chiral lkynylamines bearing tethered alkene or alkyne functional groups. The alkynylamine starting materials, readily prepared from abundant petrochemicals and chiral secondary amines, are rapidly transformed into keteneiminium ions by reaction with a variety of electrophiles; subsequent facile intramolecular cycloaddition reactions with pendant functionality will give rise to complex chiral building blocks useful for organic synthesis. Taking advantage of the unique reactivity of alkynylamines, these tandem inter- and intramolecular reactions will avoid the use of elevated reaction temperatures and transition-metal catalysis, thus providing a mild and environmentally friendly methodology for complex molecule synthesis.