This proposal focuses on the application of pericyclic reactions in new methodology for the synthesis of several important classes of organic compounds. General, stereocontrolled routes to functionalized cyclopropane derivatives will be developed based on the chemistry of cyclopropylboranes. Anion-accelered [1,3] sigmatropic rearrangements will be employed in stereocontrolled annulation approaches to five-membered carbocyclic compounds. A regiocontrolled annulation route to highly substituted aromatic compounds will be developed and applied to the total synthesis of the biologically important natural products bhogatin, ascochlorin, cristatin, barbatusol, and mycophenolic acid

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
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Medicinal Chemistry Study Section (MCHA)
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Massachusetts Institute of Technology
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Willumstad, Thomas P; Boudreau, Paul D; Danheiser, Rick L (2015) Synthesis of Highly Substituted Quinolines via a Tandem Ynamide Benzannulation/Iodocyclization Strategy. J Org Chem 80:11794-805
Lam, Tin Yiu; Wang, Yu-Pu; Danheiser, Rick L (2013) Benzannulation via the reaction of ynamides and vinylketenes. application to the synthesis of highly substituted indoles. J Org Chem 78:9396-414
Willumstad, Thomas P; Haze, Olesya; Mak, Xiao Yin et al. (2013) Batch and flow photochemical benzannulations based on the reaction of ynamides and diazo ketones. Application to the synthesis of polycyclic aromatic and heteroaromatic compounds. J Org Chem 78:11450-69
Lan, Yu; Danheiser, Rick L; Houk, K N (2012) Why nature eschews the concerted [2 + 2 + 2] cycloaddition of a nonconjugated cyanodiyne. Computational study of a pyridine synthesis involving an ene-Diels-Alder-bimolecular hydrogen-transfer mechanism. J Org Chem 77:1533-8
Wang, Yu-Pu; Danheiser, Rick L (2011) Synthesis of 2-iodoynamides and regioselective [2+2] cycloadditions with ketene. Tetrahedron Lett 52:2111-2114
Benda, Konstantin; Knoth, Tanja; Danheiser, Rick L et al. (2011) A New Route to Silyl-substituted Cyclobutenones and Silylketenes. Tetrahedron Lett 52:46-48
Robinson, Julia M; Tlais, Sami F; Fong, Jennie et al. (2011) A [4 + 4] annulation strategy for the synthesis of eight-membered carbocycles based on intramolecular cycloadditions of conjugated enynes. Tetrahedron 67:9890-9898
Mak, Xiao Yin; Crombie, Aimee L; Danheiser, Rick L (2011) Synthesis of polycyclic benzofused nitrogen heterocycles via a tandem ynamide benzannulation/ring-closing metathesis strategy. Application in a formal total synthesis of (+)-FR900482. J Org Chem 76:1852-73
Robinson, Julia M; Sakai, Takeo; Okano, Katsuhiko et al. (2010) Formal [2 + 2 + 2] cycloaddition strategy based on an intramolecular propargylic ene reaction/Diels-Alder cycloaddition cascade. J Am Chem Soc 132:11039-41
Sakai, Takeo; Danheiser, Rick L (2010) Cyano Diels-Alder and cyano ene reactions. Applications in a formal [2 + 2 + 2] cycloaddition strategy for the synthesis of pyridines. J Am Chem Soc 132:13203-5

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