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David E. Minter

Professor, Synthetic Organic Chemistry

Research Interests

In general, Dr. Minter’s research is aimed at developing new synthetic methods which can be incorporated into syntheses of natural products and compounds of theoretical interest, particularly alkaloids and their analogs. The most recent research includes studies of boron-activated enamines and the reactions of gem-dihalocyclopropylcarbinyl systems.

Boron-activated Enamines. Although many of the difficulties associated with enamine alkylations and acylations (low reactivity, polyaklylation, etc.) can be prevented by using the corresponding imine anion, the problem of regioselectivity remains unsolved. Boron-activated enamines, which are formally the products from reactions of imine anions with boranes, exhibit high nucleophilicity and react with electrophiles only at carbon. A general method for synthesizing these molecules from ketones has not yet been developed, but these species can be generated for study from heteroaromatic amine boranes. Isoquinoline-N-borane undergoes nucleophilic attack at C-1 with alkyl-lithiums and alkoxides to give an intermediate enamine. This species can react further as a strong nucleophile to give substitution at C-4. It can also behave as a powerful hydride reducing agent. The reactions of enamines derived from isoquinoline have been used in this research to synthesize some of the simple tetrahydroisoquinoline alkaloids as well as a variety of 4-substituted isoquinolines and tetrahydroisoquinolines. Quinoline-N-boranes can react with nucleophiles at either C-2 or C-4 depending on reaction conditions and the specific nucleophile. Attack at C-4 under thermodynamic conditions leads to an isomeric enamine similar in reactivity to that derived from isoquinoline. This intermediate is potentially useful for introducing substituents at C-3 which are otherwise difficult to place at that position. Pyridine-N-borane undergoes nucleophilic attack at C-2 to generate a dienamine. Further reactions with electrophiles occur at the second carbon of the diene system rather than at the terminal carbon. This work has only just begun, but shows promise in the syntheses of 2,5-disubstituted-1,2,5,6-tetrahydropyridines and related compounds. Extensions of this work are under active investigation and will soon focus on the development of a general method to convert ketones into boron-activated enamines.

gem-Dihalocyclopropylcarbinyl Systems. The chemistry of the cyclopropylcarbinyl cation is well established and has been used in the syntheses of functionalized alkenes and dienes. However, when these cations are modified by the presence of electron withdrawing substituents, their chemistry changes dramatically. For example, gem-dichlorocyclopropylcarbinyl cations, generated from the alcohol or the olefin by protonation, react slowly with nucleophiles and exhibit a reversal in the expected regiochemistry of the nucleophilic ring opening reaction. Studies of the mechanistic aspects of this and related reactions are underway. Of particular interest are the geometry of the newly created double bond and the potential use of the reaction to generate highly functionalized olefins containing geometry-specific trisubstituted double bonds.

Diterpene synthesis. A new synthetic strategy for constructing functionalized bicyclo[5.3.0]-decane systems is in progress. This work will explore the application of the Skattebol rearrangement to natural product synthesis, particularly diterpenes which have antiviral and other biological activities.