Table 1.
Optimization studies for the key intramolecular allylic spiro-dearomatization.
| Entry | Catalyst | Ligand | T (°C) | Time (h) | Yield of 32 + 33 (%) | 32:33 |
|---|---|---|---|---|---|---|
| 1 | [Ir(COD)Cl]2 | P(OPh)3 | 25 | 36 | 0 | |
| 2* | [Ir(COD)Cl]2 | P(OPh)3 | 25 | 36 | 10 | 1:1 |
| 3 | Pd(dba)2 | PPh3 | 25 | 36 | 30 | 3.5:1 |
| 4 | Pd(dba)2 | P(o-tol)3 | 25 | 36 | 0 | |
| 5 | Pd(dba)2 | P(2-furyl)3 | 25 | 12 | 69 | 2.5:1 |
| 6 | Pd(dba)2 | P(OEt)3 | 25 | 12 | 75 | 2.5:1 |
| 7 | Pd(dba) | P(OPh)3 | 25 | 24 | 76 | 1.9:1 |
| 8† | Pd(dba)2 | P(OPh)3 | 25 | 12 | 84 (92% b.r.s.m.) | 2.0:1 |
| 9‡ | Pd(dba)2 | PPh3 | 50 | 24 | <1 | |
| 10 | Pd2(dba)3 | P(OPh)3 | 25 | 24 | 51 (76% b.r.s.m.) | 1.4:1 |
Typical reaction conditions: substrate (15 mg) was stirred with catalyst (20 mol%) and ligand (48 mol%) in CH2Cl2 under argon.
*
Cs2CO3 (2 equiv.) was used as an additive.
†
Performed on 100 mg scale.
‡
Ti(OPr-i)4 (2 equiv.) was used as an additive.
COD, 1,5-cyclooctadiene; dba, dibenzylideneacetone; b.r.s.m., based on recovered starting material.