The vaulted biaryl ligands VANOL and VAPOL form a unique polyborate anion with a boroxinate core and is beginning to be recognized as a very unique and versatile platform for asymmetric catalysis. As an ion-pair with a protonated imine, this chiral anion will effect the aziridination of imines with diazo compounds with very high yields, diastereoselectivity and enanatioselectivity. Mechanistic investigations including natural abundance kinetic isotope studies will be undertaken to understand how the boroxinate catalyst is formed and how it functions in a variety of reactions including aziridination reactions. The boroxinate core is anionic and has seven oxygens which all bear some of the negative charge and it is possible that it serves as a template in which more than one substrate can H-bond with the boroxinate core at the same time and this helps to determine the transition state. Computations will be persued in an effort to understand how the substrates interact with the boroxinate core in the transition state of the aziridination and other reactions. In addition to the unique structure of this boroxinate catalyst, its utility is greatly enhanced by the fact that it can be assembled by the substrate from the ligand, a boron source, two equivalents of an alcohol or phenol and three equivalents of water. The diverse array of catalysts that can be generated by this process is thus virtually limitless. Investigations will also be carried out to determine the effectiveness of this boroxinate catalyst in other reactions including the Darzens reaction, [3+2] cycloadditions, aminoallylation of aldehydes, and the Ugi reaction.

Public Health Relevance

We have discovered the structure of the catalyst-substrate complex for the catalytic asymmetric aziridination reaction of imines (AZ reaction). With the information gained from this structure, the goals of this proposal are to study the mechanism by which these catalyst react, design new catalyst structures for enhanced reactivities and selectivities and to apply them to other organic reactions.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM094478-02
Application #
8244446
Study Section
Synthetic and Biological Chemistry B Study Section (SBCB)
Program Officer
Lees, Robert G
Project Start
2011-04-01
Project End
2015-03-31
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
2
Fiscal Year
2012
Total Cost
$266,054
Indirect Cost
$76,054
Name
Michigan State University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
193247145
City
East Lansing
State
MI
Country
United States
Zip Code
48824
Guan, Yong; López-Alberca, Maria P; Lu, Zhenjie et al. (2014) Catalytic asymmetric synthesis of alkynyl aziridines: both enantiomers of cis-aziridines from one enantiomer of the catalyst. Chemistry 20:13894-900
Bandar, Jeffrey S; Sauer, Gregory S; Wulff, William D et al. (2014) Transition state analysis of enantioselective Brønsted base catalysis by chiral cyclopropenimines. J Am Chem Soc 136:10700-7
Zhang, Xin; Staples, Richard J; Rheingold, Arnold L et al. (2014) Catalytic asymmetric ?-Iminol rearrangement: new chiral platforms. J Am Chem Soc 136:13971-4
Zhao, Wenjun; Huang, Li; Guan, Yong et al. (2014) Three-component asymmetric catalytic Ugi reaction--concinnity from diversity by substrate-mediated catalyst assembly. Angew Chem Int Ed Engl 53:3436-41
Han, Jianguang; Li, Xia; Guan, Yong et al. (2014) Enantioselective biomimetic total syntheses of kuwanons I and J and brosimones A and B. Angew Chem Int Ed Engl 53:9257-61
Ren, Hong; Wulff, William D (2013) Total synthesis of sedum alkaloids via catalyst controlled aza-Cope rearrangement and hydroformylation with formaldehyde. Org Lett 15:242-5
Vetticatt, Mathew J; Desai, Aman A; Wulff, William D (2013) Isotope effects and mechanism of the asymmetric BOROX Bronsted acid catalyzed aziridination reaction. J Org Chem 78:5142-52
Huang, Li; Zhang, Yu; Staples, Richard J et al. (2012) Double stereodifferentiation in the catalytic asymmetric aziridination of imines prepared from ?-chiral amines. Chemistry 18:5302-13
Majumdar, Nilanjana; Korthals, Keith A; Wulff, William D (2012) Simultaneous synthesis of both rings of chromenes via a benzannulation/o-quinone methide formation/electrocyclization cascade. J Am Chem Soc 134:1357-62
Gupta, Anil K; Mukherjee, Munmun; Wulff, William D (2011) Multicomponent catalytic asymmetric aziridination of aldehydes. Org Lett 13:5866-9