Research

Overview

Our general interest is in the area of synthetic organic chemistry, particularly the development of novel methodologies and their application in the synthesis of natural products exhibiting unique chemical complexity and significant biological activity.  One of our recent focuses has been functionalization of olefins with an emphasis on chemo-, regio-, enantio-, and diastereoselectivity.  The following projects highlight some of our group's recent endeavors (Figure 1).

Figure 1

 

Epoxidation

Optically active epoxides are highly versatile synthetic intermediates and present in various natural products and biologically active molecules.  In addition, epoxides have been proposed to be biosynthetic intermediates for the rapid construction of complex polycyclic natural products such as brevetoxin B (Figure 2).  Asymmetric epoxidation of olefins provides a powerful approach to the synthesis of such epoxides.  To this end, we have developed an efficient asymmetric epoxidation method for a variety of trans- and trisubstitued olefins using fructose-derived ketone 1 as catalyst and Oxone or hydrogen peroxide as oxidants (Figure 3).  Similar results have also been obtained for more electron deficient olefins using diacetate ketone 2 (Figure 3).  Furtherfore, we have found that glucose-derived ketone 3 can give high enantioselectivities for the epoxidation of cis- and terminal olefins (Figure 4).   The epoxidation likely proceeds via a chiral dioxirane intermediate as shown in Figure 5.  The asymmetric epoxidation method has been widely utilized in the synthesis of various complex molecules and biologically active compounds.

       For our recent reviews on epoxidation: Chem. Rev. 2014, 114, 8199−8256. Click here to see article.

                                                                   Chem Rev. 2008, 3958-3987. Click here to see article.

                                                                   Acc. Chem. Res. 2004, 37, 488-496. Click here to see article.

                                                                  Synthesis 2000, 1979-2000. Click here to see article.

 

Figure 2

Figure 3

Figure 4

Figure 5

Back To Top

Diamination

Vicinal diamines are present in many biologically active compounds (Figure 6).  Diamination of olefins presents an attractive strategy for the selective synthesis of vicinal diamines.  We have developed Pd(0)- and Cu(I)-catalyzed regio- and stereoselective diaminations of olefins using di-tert-butyldiaziridinone or its analogues as the nitrogen source (Figure 7). It is particularly interesting that terminal olefins can be effectively diaminated at allylic and homoallylic carbons in good yields with high stereoselectivities via C-H activation (Figure 8). Furthermore, it has been shown that conjugated dienes can be regioselectively diaminated at either the terminal or internal C=C double bond by judicious choice of Cu(I) catalyst (Figure 9).

        For our recent review on diamination:  Acc. Chem. Res. 2014, 47, 3665−3678. Click here to see article.

                                                                   Chem. Soc. Rev. 2012, 41, 931-942. Click here to see article.

Figure 6

Figure 7

Figure 8

Figure 9

Back To Top

Cyclopropanation

Cyclopropanes are contained in many biologically and medicinally important molecules (Figure 10). Moreover, their ring strain allows for interesting synthetic transformations. The Simmons-Smith reaction is a widely utilized method for cyclopropantion of olefins.  We have
developed a novel class of reagents (RXZnCH₂I) that are highly reactive toward various olefins which had previously been unreactive (Figures 11 and 12).  We further developed a catalytic asymmetric version of the Simmons-Smith cyclopropanation for unfunctionalized olefins, which has been a long-standing synthetic challenge (Figure 13).

       For our recent review on cyclopropanation:  Org. Biomol. Chem. 2012, 10, 5498-5513. Click here to see article.

Figure 10

Figure 11

Figure 12

Figure 13

Back To Top

Aziridination

In our continuing efforts towards small ring synthesis originating from carbon-carbon double bonds, we have developed amine catalyzed aziridinations of electron-deficient olefins to form unprotected aziridines (Figure 14).  Our goals include designing more effective amine catalysts, development of an asymmetric process, expansion of substrate scope, and investigation of synthetic applications.

Figure 14

Back To Top