Regiodivergent (3 + 2) annulation reactions of oxyallyl cations.

We report a new method for the regiodivergent dearomative (3 + 2) reaction between 3-substituted indoles and oxyallyl cations. Access to both regioisomeric products is possible and is contingent on the presence or absence of a bromine atom on the substituted oxyallyl cation. In this way, we are able to prepare molecules that contain highly-hindered, stereodefined, vicinal, quaternary centers.

Mechanistic Investigation of Site-specific DNA Methylating Agents Targeting Breast Cancer Cells.

We previously described the development of a DNA-alkylating compound that showed selective toxicity in breast cancer cells. This compound contained an estrogen receptor α (ERα)-binding ligand and a DNA-binding/methylating component that could selectively methylate the N3-position of adenines at adenine-thymine rich regions of DNA. Herein, we describe mechanistic investigations that demonstrate that this class of compounds facilitate the translocation of the ERα-compound complex to the nucleus and induce the expression of ERα target genes.

Diversification of Nucleophile-Intercepted Beckmann Fragmentation Products and Related Density Functional Theory Studies.

The nucleophile-intercepted Beckmann fragmentation (NuBFr) has the potential to be broadly applicable to the synthesis of indoline alkaloid-based natural products. However, the reaction has not been widely adopted, in part, because of limitations associated with the availability of appropriate promoter- reagents. We have devised a stereospecific Ag(I)-promoted reaction for functionalizing NuBFr products to give novel compositions of matter that may be useful in synthesis and medicinal chemistry.

Nucleophile-intercepted Beckmann fragmentation reactions.

We describe the first examples of nucleophile-intercepted Beckmann fragmentations of indoline oximes. This reaction uses MsCl as a promoter to give cyano chlorides and is believed to proceed through an aziridinium intermediate a double stereoinvertive process. Mechanistic insights have led to the further discovery that oxygen, nitrogen, and bromide nucleophiles can be employed for this fragmentation by the use of other promoters.