Table 1.

Activity and selectivity of myoglobin variants and other catalysts for the C—H functionalization of indole with ethyl α-diazoacetate (EDA).^[a] See also SI Tables S1 and S2.

Catalyst		EDA equiv	Conv. [b]	TON	% C-H funct.
Hemin	-	1	<1%	1	n.a.
Rh2(OAc)4[c]	-	1	5%	5	45[c]
Mb	Protein	1	<1%	1	n.a.
Mb(H64V)	Protein	1	<1%	<1	n.a.
Mb(L29A,H64V)	Protein	1	5%	6	100
Mb(H64V,V68A)	Protein	1	50%	62	100
Mb(H64V,V68A)[d]	Protein	1	54%	68	100
Mb(H64V,V68A)[d]	Protein	2	85%	106	100
Mb(H64V,V68A)[e]	Protein	2	34%	168	100
Mb(H64V,V68A)	Cells[f]	2	70%	18[h]	100
Mb(H64V,V68A)	Cells[g]	2	>99%	82[h]	100

^[a]Reactions conditions: 20 μM Mb variant or hemin (0.8 mol%), 2.5 mM indole, 2.5 or 5 mM EDA, 10 mM dithionite, 16 h. Reported values are mean values from n ≥ 2 experiments (SE <15%).

^[b]GC yield using calibration curve with authentic 3.

^[c]Using 0.8 mol% catalyst in CH₂Cl₂; other products: N—H insertion (42%) and double insertion (13%).

^[d]pH 9.0.

^[e]Using 5 μM protein (0.2 mol%) and pH 9.0.

^[f]OD₆₀₀ = 40.

^[g]OD₆₀₀ = 20. n.a. = not available.

^[h]As determined based on the protein concentration in cell lysates using ε₄₁₀ = 156 mM⁻¹ cm⁻¹.