Substrate scope for Mb-mediated trans-(1R,2S) selective olefin cyclopropanation with dimethyl (diazomethyl)phosphonatea.
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|---|---|---|---|---|---|
| Entry | Mutations (vs. RR4) | Product | Yieldb | % de | % ee |
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| 1 | RR4 | R1 = H (4a) | 96% | 99% | >99% |
| 2 | RR4 | R1 = 4-F (4b) | 72% | 99% | 91% |
| 3 | RR4 | R1 = 4-Cl (4c) | 38% | 99% | 82% |
| T29C,V64A | 64% | 99% | 92% | ||
| 4 | RR4 | R1 = 4-Br (4d) | 38% | 99% | 65% |
| T29C,V64A | 63% | 99% | 84% | ||
| 5 | RR4 | R1 = 4-CF3 (4e) | 9% | 99% | 33% |
| T29C,V64A | 24% | 99% | 56% | ||
| 6 | RR4 | R1 = 4-OMe (4f) | 99% | 99% | 59% |
| 7 | RR4 | R1 = 4-Me (4g) | 22% | 99% | 57% |
| T29C,V64A | 41% | 99% | 76% | ||
| 8 | RR4 | R1 = 3-Me (4h) | 40% | 27% | 72% |
| T29V | 71% | 91% | 76% | ||
| 9 | RR4 | R1 = 2-Me (4i) | 99% | 99% | >99% |
| 10 | RR4 | R1 = 3-Br (4j) | 40% | 46% | 88% |
| T29V | 99% | 94% | 89% | ||
| 11 | RR4 |
 (4k) |
12% | 99% | 45% |
| T29V,V64A | 24% | 99% | 81% | ||
| 12 | RR4 |
 (4l) |
14% | 99% | 71% |
| T29C,V64A | 45% | 86% | 94% | ||
a
Reaction conditions: 5 mM olefin, 10 mM dimethyl (diazomethyl)phosphonate (1), Mb-expressing E. coli (OD600 = 100) in KPi buffer (50 mM, pH 7), 1 mL-scale, RT, 16 h.
b
Product conversion as determined by GC. Errors are within 10%.