Exploration of donor /acceptor carbenoids in the asymmetric synthesis of cyclopropanes utilizing rhodium(II) catalysis

• Main Author: Denton, Justin Ryan
• Format: Dissertation
• Language: English
• Published: ProQuest Dissertations & Theses 01-01-2008
• Subjects: Organic chemistry
• ISBN: 0549990550; 9780549990550

In the Davies group there are three research areas: methodology development, the total synthesis of natural products, and catalyst design & development. Donor/acceptor substituted rhodium carbenoids have been shown by the Davies’ group to have exceptional chemoselectivity, regioselectivity, and stereoselectivity in intermolecular cyclopropanation reactions. The first major section of this thesis was devoted to explore the scope and limitations of the acceptor (the electron withdrawing group) part of the donor/acceptor substituted diazo compounds in asymmetric intermolecular cyclopropanation by Rh (II) catalysis. In the context of these projects, Rh2(S-PTAD) 4 was found to be an exceptional chiral catalyst for intermolecular cyclopropanation when the acceptor group was either a trifluoromethyl, nitrile, or ketone group. The highly strained cyclopropanes could be synthesized in good yields, with high diastereoselectivity, and with high enantioselectivity, when Rh2(S-PTAD)4 was employed. The second major section (Chapter three) describes a collaborative investigation between the Davies and the Williams groups toward the first asymmetric synthesis of vibsanin E and related natural products. An asymmetric method to the key tricyclic core utilizing the Davies’ [4+3] cyclopropanation/Cope methodology, which contains 3 of the 5 continues stereocenters of vibsanin E, was developed utilizing Rh2(S-PTAD)4. The Williams group then used the enantiomerically pure tricycle to finish the synthesis of vibsanin E and is currently working on several other similar natural products in the vibsanin family. The last major section (Chapter four) of this thesis focuses on catalyst design & development. A new route to Rh2(S-PTAD) 4 was developed via a asymmetric Strecker approach, which provided gram quantities of this catalyst. Also within the chapter is described the synthesis of several hydrocarbon-soluble catalysts based on the Rh2( S-PTAD)4 scaffold. These catalysts are fully soluble in hexanes and/or 2,2-dimethylbutane to -78 °C and are active in the decomposition of donor/acceptor diazo compounds.