Table 1.
Optimization of reaction conditions for double annulations of cysteine.a
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| entry | solvent | t1 (h) | 3a (%)b | t2 (h) | T1(°C) | 5a (%)b |
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| 1 | EtOH | 3 | 86 | – | ||
| 2 | iPrOH | 6 | 95 | 12 | 105 | 81 |
| 3 | MeOH | 6 | 93 | 12 | 70 | 78 |
| 4 | EtOH | 6 | 95 | 12 | 90 | 81 |
| 5 | EtOH | 6 | 95 | 9 | 90 | 81 |
| 6c,e | EtOH | 6 | 95 (86) | 9 | 90 | 83 (73) |
| 7d,e | EtOH | 9 | 90 | 79 (70) | ||
| 8 d | EtOH | 6 | 90 | 67 | ||
| 9 d | EtOH | 18 | 90 | 75 | ||
| 10d | MeOH | 9 | 70 | 76 | ||
| 11d | iPrOH | 9 | 105 | 78 | ||
| 12d | MeCN | 9 | 90 | 67 | ||
aOne-pot reaction of 1.0:1.15 of 1a/2 for N,S-acetalation 3a followed by addition of 1.1:1.0 of 1a/4a for [3 + 2] cycloaddition.bDetected by LC–MS, isolated yield in parenthesis. cIntermediate 3a was isolated in the two-step reaction. dCascade reaction of 2.2:1.1:1.0 of 1a/2/4a. edr > 4:1, Determined by 1H NMR analysis of the crude products after the reaction mixture filtered through a pad of silica gel and removal of solvent.