Catalytic Asymmetric Alkyne Addition to Aldehydes and Applications of Propargylic Alcohols in Synthesis A toolbox of catalytic systems for the asymmetric alkynylzinc addition to aldehydes has been constructed to provide high enantioselectivities for a diverse range of alkynes. A new H 8 BINOL-based bifunctional catalytic system for the highly enantioselective addition of alkyl propiolates to aliphatic aldehydes was developed to address a remaining limitation in asymmetric alkyne additions. This

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... system was also found to be highly enantioselective for additions to aromatic and , -unsaturated aldehydes. With effective methods to access a variety of optically active propargylic alcohols, the utility of propargylic alcohol based enynes in the diastereoselective intramolecular Pauson-Khand Reaction was demonstrated. High diastereoselectivities could be obtained (up to 99:1), with the diastereoselectivity of the cycloaddition being influenced by the size of the alkyne substituent. From this foundation a flexible strategy for the asymmetric synthesis of the 5,5,7and 5,5,8-polycyclic ring systems common in a variety of natural products was developed. Key to this strategy was the development of a highly enantioselective BINOL-ZnEt 2 -Ti(O i Pr) 4 -Cy 2 NH catalytic system for the addition of 1,3-diynes to enals, a chemoselective and diastereoselective Pauson-Khand-type reaction of dienediyne substrates, and enyne metathesis to form the 7-and 8-membered ring systems. These polycyclic ring systems contain an embedded 1,3-diene that has been shown to be a suitable reaction partner for a highly stereoselective [4+2] cycloaddition reaction to furnish the 5,5,7,6-ring system as a single stereoisomer. iii