Scalable biocatalytic C-H oxyfunctionalization reactions

Abstract

Catalytic C-H oxyfunctionalization reactions have garnered significant attention in recent years with their ability to streamline synthetic routes toward complex molecules. Consequently, there have been significant strides in the design and development of catalysts that enable diversification through C-H functionalization reactions. Enzymatic C-H oxygenation reactions are often complementary to small molecule based synthetic approaches, providing a powerful tool when deployable on preparative-scale. This review highlights key advances in scalable biocatalytic C-H oxyfunctionalization reactions developed within the past decade.

Figure. 1.

P450-catalyzed benzylic C–H hydroxylations

Figure. 2.

Biocatalytic benzylic C–H oxyfunctionalizations using non-450 enzymes

Figure. 3.

Biocatalytic allylic C–H oxidations

Figure 4.

Biocatalytic aromatic C–H oxyfunctionalizations

Figure 5.

Biocatalytic C–H hydroxylation of amino acids. Note: ^aYields based on the boc protected derivative(s), ^bOverall yield starting from L-lysine, ^cYield obtained after Fmoc protection and cyclization to the lactone derivative. ^dPercent conversion provided.^eNMR yield. ^fMulti-step cascade is carried out prior to isolation.

Figure 6.

Biocatalytic C–H monohydroxylation of steroidal frameworks. ^aPercent conversion.^bPercent site-selectivity.

Figure 7.

Biocatalytic C–H hydroxylation in diverse terpene scaffolds.

Figure 8.

C–H hydroxylation in complex macrolide scaffolds.

Figure 9.

Biocatalytic carbonyl α-C–H oxygenation reactions.

Figure 10.

C–H oxygenation in unactivated systems. ^aProduct isolated after a cascade of reaction(s). ^bPercent site-selectivity. ^cPercent conversion.