I. Engaging Cationic Intermediates in Asymmetric Catalysis: Enantioselective Reactions of Carbenium Ions and N,N-Dialkyliminium Ions II. Enantioselective Catalysis of the Cope-Type Hydroamination by H-Bond Donors
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CitationBrown, Adam Ross. 2013. I. Engaging Cationic Intermediates in Asymmetric Catalysis: Enantioselective Reactions of Carbenium Ions and N,N-Dialkyliminium Ions II. Enantioselective Catalysis of the Cope-Type Hydroamination by H-Bond Donors. Doctoral dissertation, Harvard University.
AbstractThe research described here explores the ability of dual H-bond donor catalysts to induce asymmetry in a variety of synthetically useful transformations that proceed via diverse reactive intermediates. In Chapters 1-3, we investigate ureas and thioureas as anion-binding catalysts for asymmetric reactions that proceeed via cationic intermediates with little precedent as electrophiles in asymmetric catalysis. Chapter 4 details our application of H-bond donor catalysis to the Cope-type hydroamination. Chapter 1 describes the development of an asymmetric aldehyde alkylation catalyzed by a bifunctional primary aminothiourea. A variety of 2-aryl propionaldehydes are alkylated with benzhydryl bromides in moderate to good yields and good enantioselectivities. Catalyst structure-activity relationship studies of the alkylation pointed towards electrophile activation by the dual H-bond donor moiety. Experiments aimed at gaining a better understanding of the electophile activation mode and characterizing the activated electrophilic intermediate in the alkylation reaction are described in Chapter 2. The development of an enantioselective cyanide addition to N,N-dialkyliminium intermediates is the subject of Chapter 3. A variety of strategies for accessing N,N- dialkyliminium ions are established, and chiral thioureas are shown to promote the addition of cyanide to such intermediates with moderate enantioselectivities. Chapter 4 details our discovery that thioureas bearing polarizable and conformationally constrained aromatic groups catalyze highly enantioselective Cope-type hydroaminations. This powerful transformation provides a variety of chiral pyrrolidine products under mild reaction conditions.
Citable link to this pagehttp://nrs.harvard.edu/urn-3:HUL.InstRepos:11030585
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