Applications of novel boron-nitrogen containing heterocycles : design and synthesis o planar-chiral Lewis acids for stereoselective organic synthesis
Author(s)Liu, Shih-Yuan, 1975-
Massachusetts Institute of Technology. Dept. of Chemistry.
Gregory C. Fu.
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Because Lewis acids are very versatile mediators of a variety of stereoselective organic transformations, a great deal of effort has been devoted toward the development of chiral Lewis acids. This thesis describes the design, synthesis, and applications of 1,2-azaborolyl complexes as a novel family of planar-chiral Lewis acids that can perform a wide range of stereoselective transformations. The 1,2-azaborolyl ligand is a five-membered B-N bearing heterocycle that is isoelectronic and isostructural with the ubiquitous cyclopentadienyl ligand. In Part I of this dissertation, the feasibility of using boron-substituted 1,2-azaborolyls as tunable cyclopentadienyl surrogates is established. Thus, X-ray structural and spectroscopic studies demonstrate that 1,2-azaborolyls can serve as six-electron [pi]-ligands to a variety of transition metals and that the electronic nature of the boron substituent can modulate the properties of the resulting complexes. Building on the foundations of 1,2-azaborolyl ligand chemistry described in Part I, we establish in Part II that 1,2-azaborolyl complexes bearing good leaving groups on boron can serve indeed as planar-chiral Lewis acids. As a result, we have successfully synthesized a number of enantiomerically pure planar-chiral Lewis acids, and we show through structural and stereochemical correlation studies that these Lewis acids can activate substrates such as aldehydes and imines toward stereoselective nucleophilic attack in a predictable fashion. Specifically, we have investigated planar-chiral Lewis acid mediated nucleophilic attack of Grignard reagents to imines and Lewis acid mediated Mukaiyama aldol reaction of aldehydes with silyl ketene acetals.(cont.) Our studies indicate that unfavorable peri-interactions between the imine substrate and the Lewis acid may be the conformation-controlling element for nucleophilic additions to imines. On the other hand, detailed mechanistic studies of the Mukaiyama aldol reaction suggest a reaction pathway involving an intermediate with a coplanar aldehyde-Lewis acid conformation. These studies demonstrate the broad scope and the high efficiency with which the chiral information is transferred from the planar-chiral Lewis acid to its substrates. Consequently, the turnover step (regeneration of the active Lewis acid) represents the last hurdle to be addressed for achieving asymmetric Lewis acid catalysis. Part III of this thesis describes miscellaneous applications that have been discovered during the course of the development of 1,2-azaborolyl-based planar-chiral Lewis acids. In Chapter 7, we present a surprisingly mild and versatile method for palladium-catalyzed Suzuki cross-couplings of aryl chlorides in the presence of a triarylphosphine. With this catalytic system, both sterically demanding and electronically deactivated aryl chlorides can be efficiently coupled with a range of boronic acids in good yields, and coupling of activated aryl chlorides can be accomplished at room temperature. In Chapter 8, we report the synthesis and characterization of novel 1,2-azaborines and their potential as benzene surrogates.
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, February 2004.Vita.Includes bibliographical references.
DepartmentMassachusetts Institute of Technology. Dept. of Chemistry.
Massachusetts Institute of Technology