Table 1. Cyclopropanation of Alkenes of Differing Steric and Electronic Properties with Ethyl Diazoacetatea.
| CYP119(+)b |
CYP119(−)c |
free
Ir(Me)-PIX |
||||
|---|---|---|---|---|---|---|
| alkene | ee (%) | dr (cis:trans) | ee (%) | dr (cis:trans) | ee (%) | dr (cis:trans) |
| styrene | 73 | 2:1 | –74 | 5:1 | 0 | 1:4 |
| α-Me-styrene | 82 | 11:1 | –86 | 3:1 | 0 | 1:2 |
| cis-β-Me-styrene | 75 | 27:1* | –18 | 40:1* | 0 | 10:1* |
| trans-β-Me-styrene | 86 | 13:1** | –32 | 4:1** | 0 | 1:>25** |
| hexen-5-one | 79 | 4:1 | –88 | 8:1 | 0 | 1:4 |
| cyclopentene 12 | 2:1:t:t*** | 228:1:t:1*** | 3:1:1:3*** | |||
| 1-octene | 66 | 4:1 | –78 | 6:1 | 0 | 1:4 |
| cis-2-octene | 39 | 8:1** | –60 | 1:1** | 0 | 5:1** |
a
Tabulated data describes the outcome of the reactions using two mutants of CYP119 identified in the initial phase of directed evolution in comparison to the same reactions catalyzed by the free Ir(Me)-PIX cofactor. c = cis, t = trans. *Major diastereomer is 2-c,3-c:2-t,3-t, ref = COOEt; **Major diastereomer is 2-c,3-c:2-t,3-t, ref = COOEt; ***minor products not determined, major product shown as compound 13, t = trace. For details, see Table S5.
b
CYP119 (+): Ir(Me)-PIX CYP119 with the mutations C317G, V254A.
c
CYP119 (−): Ir(Me)-PIX CYP119 with the mutations C317G, L69F, T213V.