? The goal of this proposal is the expansion of the utility of palladium-catalyzed C-O bond-forming cross-coupling reactions through fluorophobic acceleration. Novel protocols for the general and mild formation of aryl and diaryl ethers are advanced in which the intrinsic fluorophobicity of aryl, alkenyl, and alkyl units is exploited to expedite product formation through fluorophobic packing in the transition state of reductive elimination. On account of the ubiquity of aryl ethers in biologically-active molecules, it is an important challenge to develop a general catalytic method to produce this structural motif. The formation of diaryl, aryl-allyl, and aryl-alkyl ethers is addressed. In the case of aryl-allyl ether formation, it is proposed that a Claisen rearrangement, which is also accelerated in fluorous solvents, will quickly follow reductive elimination. Any chirality that is pre-installed into the allylic alcohol unit will be transferred into the product of the Claisen rearrangement, leading to the potential formation of a chiral quaternary center. Thus, a simple and cheap entry into complicated chiral building blocks for potential use in pharmaceutical synthesis is also advanced. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM075685-03
Application #
7281739
Study Section
Special Emphasis Panel (ZRG1-F04A (20))
Program Officer
Marino, Pamela
Project Start
2005-09-14
Project End
2008-09-12
Budget Start
2007-09-14
Budget End
2008-09-12
Support Year
3
Fiscal Year
2007
Total Cost
$48,680
Indirect Cost
Name
Massachusetts Institute of Technology
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
001425594
City
Cambridge
State
MA
Country
United States
Zip Code
02139
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