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. 2014 Feb 1;5(2):598-601.
doi: 10.1039/C3SC52535J.

Cytochrome P450-Catalyzed Insertion of Carbenoids into N-H Bonds

Z Jane Wang  1 , Nicole E Peck  1 , Hans Renata  1 , Frances H Arnold  1
Affiliations

Cytochrome P450-Catalyzed Insertion of Carbenoids into N-H Bonds

Z Jane Wang et al. Chem Sci. .

Abstract

Expanding nature's catalytic repertoire to include reactions important in synthetic chemistry will open new opportunities for 'green' chemistry and biosynthesis. We demonstrate enzyme-catalyzed insertion of carbenoids into N-H bonds. This type of bond disconnection, which has no counterpart in nature, can be mediated by variants of the cytochrome P450 from Bacillus megaterium. The N-H insertion reaction takes place in water, provides the desired products in 26-83% yield, forms the single addition product exclusively, and does not require slow addition of the diazo component.

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Figures

Figure 1
Figure 1
Proposed carbenoid N-H insertion reaction by cytochrome P450.
Figure 2
Figure 2
Substrate scope for cytochrome P450-catalyzed N-H insertion.
Figure 3
Figure 3
(a) Competition reaction of styrene and aniline for cyclopropanation and N-H insertion, respectively, with EDA. (b) Reaction of bifunctional substrate 9 with EDA.
Figure 4
Figure 4
Product ratio of N-H insertion catalyzed by hemin versus P450 variant H2-5-F10.
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