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44286-AC1
Bio-Inspired Cobalt Catalysts for Carbene and Nitrene Transfer Reactions

X. Peter Zhang, University of South Florida

1. Design and Synthesis of New Chiral Porphyrins

New members of chiral porphyrins ([H₂(Por*)]) have been designed and synthesized via palladium-mediated quadruple amidation reactions of readily accessible bromoporphyrins with various chiral amide building blocks. Among this family of D₂-symmetric [H₂(Por*)], a group of six derivatives [H₂(P1)]–[H₂(P6)], possessing diverse electronic, steric, and chiral environments, has been demonstrated as effective chiral ligands in supporting Co-based carbene and nitrene transfer reactions. The structures of cobalt(II) complexes of [H₂(P1)]–[H₂(P6)] are shown in Figure 1, along with those of two analogous achiral porphyrins [H₂(P7)] and [H₂(P8)].

2. Asymmetric Cyclopropanation of Alkenes

The well-documented importance of cyclopropanes in numerous fundamental and practical applications has stimulated vast efforts for the synthesis of the smallest carbocycles. Metal-catalyzed asymmetric cyclopropanation of alkenes with diazo reagents constitutes the most direct and general method for stereoselective construction of the unique all-carbon triangular structures. A number of outstanding chiral catalysts have been reported to achieve high diastereo- and enantioselectivity for several classes of cyclopropanation reactions, most of which employed styrene derivatives and some electron-rich olefins with diazoacetates. Ongoing endeavors in the field aim at further expansion of its substrate scope to include different types of alkenes and with various kinds of carbene configurations.

2-1. Cobalt-Catalyzed Asymmetric Cyclopropanation of Electron-Deficient Olefins

Asymmetric cyclopropanation of electron-deficient olefins containing electron-withdrawing groups such as a,b-unsaturated carbonyl compounds and nitriles have proven to be a challenging problem presumably due to the electrophilic nature of the metal-carbene intermediates in the catalytic cycles. We have reported a general and efficient catalytic system for asymmetric cyclopropanation of electron-deficient olefins. [Co(P1)] (Figure 1) was shown to cyclopropanate a wide range of a,b-unsaturated carbonyl compounds and nitriles (Table 1), forming the corresponding electrophilic cyclopropane derivatives in high yields and selectivities. Furthermore, the [Co(P1)]-based catalytic process could be operated efficiently at room temperature in a one-pot fashion with olefins as limiting regents and would not require the slow-addition of diazo reagents.

2-2. Cobalt-Catalyzed Asymmetric Cyclopropanation with Diazosulfones

A number of asymmetric catalytic processes have been successfully developed to permit olefin cyclopropanation in high yields and high selectivities. While the vast majority of those catalytic systems employed diazocarbonyls, mostly diazoacetates, as carbene sources, metal-catalyzed asymmetric cyclopropanation reactions with other types of diazo reagents are underdeveloped. To further augment its substrate generality, we decided to explore the effectiveness of the [Co(Por*)]-based catalytic system for asymmetric cyclopropanation with diazo reagents, rather than diazoacetates. As a result of this effort, we have reported that [Co(P6)] is a highly effective catalyst for asymmetric cyclopropanation employing diazosulfones (Table 2).

3. Selective Aziridination of Alkenes

Metal-catalyzed olefin aziridination is a fundamentally and practically important chemical process that has received increasing research attention. The resulting aziridines, the smallest nitrogen-containing heterocyclic compounds, are key elements in many biologically and pharmaceutically interesting compounds and serve as a class of versatile synthons for preparation of functionalized amines. In view of the similarity to diazo reagents for carbene transfer processes, azides should have the potential to serve as a general class of nitrene sources for metal-mediated nitrene transfer reactions, including aziridination. In addition to their wide availability and ease of synthesis, azide-based nitrene transfers would generate chemically stable and environmentally benign nitrogen gas as the only by-product. Despite these attributes, only a few catalytic systems have been developed that can effectively catalyze the decomposition of azides for aziridination.

3-1. Cobalt-Catalyzed Effective Aziridination with Arylsulfonyl Azides

Previously, we reported that [Co(TPP)] can catalyze olefin aziridination with commercially available diphenylphosphoryl azide (DPPA) as a convenient new nitrene source, leading to the formation of N-phosphorylated aziridines. In an attempt to expand the catalytic process for other azides, it was found that [Co(TPP)] was ineffective for olefin aziridination with sulfonyl azides. As part of our efforts to develop new porphyrin ligands to enhance Co-based catalytic processes, we have reported the design and synthesis of a new porphyrin P7 (Figure 1) based on potential hydrogen bonding interaction in the assumed metal-nitrene intermediate. The Co(II) complex of P7 [Co(P7)] was shown to be a highly active catalyst for aziridination of different aromatic olefins with various arylsulfonyl azides, forming the corresponding aziridines in excellent yields under mild conditions (Table 3).

3-2. Cobalt-Catalyzed Asymmetric Aziridination with Diphenylphosphoryl Azides

To improve its catalytic efficiency as well as to develop its asymmetric variant, we have made considerable efforts to identify chiral porphyrins to support the Co/DPPA-based catalytic aziridination with hopes of enhancing its activity and selectivity. Recently, we reported the results from our systematic studies regarding the use of D₂-symmetric chiral porphyrins (Figure 1) for the Co-based asymmetric olefin aziridination using DPPA. In addition to improved yields under milder conditions, acceptable asymmetric induction has been achieved. This represents the first Co(II)-catalyzed asymmetric aziridination process (Table 4).