Enantioselective Trifunctionalization of Terminal Alkynes
Langxuan Yang1, M Cole Detels1, Gojko Lalic1
1Department of Chemistry, University of Washington, Seattle, Washington 98195, United States.
None:
The stereoselective synthesis of alkenes has been one of the central objectives in organic chemistry. Significant advances in synthetic methodology have made mono- and disubstituted alkenes widely accessible from a variety of readily available precursors. However, increased steric hindrance in more highly substituted alkenes limits the effectiveness of these methods, and as a result, the efficient and selective synthesis of highly substituted alkenes remains a formidable challenge. Here, we demonstrate palladium-catalyzed trifunctionalization of terminal alkynes using organoboranes and allylic carbonates as coupling partners. This transformation provides tetrasubstituted alkenes with excellent regioselectivity and diastereoselectivity. Moreover, regiodivergent, diastereo- and enantioselective incorporation of the allylic fragment provides access to a wide range of complex 1,4-diene products. We present evidence that the palladium catalyst controls the selectivity of tetrasubstituted alkene formation and the selectivity of allylic substitution.
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One of the convenient methods for the preparation of aldehydes and ketones is via hydration of alkynes. Hydroboration-oxidation of alkynes is an indirect hydration reaction in which an alkyne is treated with borane followed by oxidation with alkaline peroxide to form an enol that rapidly converts into an aldehyde or a ketone. Terminal alkynes form aldehydes, whereas internal alkynes give ketones as the final product.
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Halogenation is another class of electrophilic addition reactions where a halogen molecule gets added across a π bond. In alkynes, the presence of two π bonds allows for the addition of two equivalents of halogens (bromine or chlorine). The addition of the first halogen molecule forms a trans-dihaloalkene as the major product and the cis isomer as the minor product. Subsequent addition of the second equivalent yields the tetrahalide.
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