Reaction scope of the anti-4 and syn-4 selective processes.
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| Entry | 1: R1, Rf | R2 | Anti-4 selective processa | Syn-4 selective processa | ||||||
| Anti-4 | Yieldb (%) | Anti/sync | eed (%) | Syn-4 | Yieldb (%) | Syn/anti c | eed (%) | |||
| 1 | 1d: C6H5, CF3 | Allyl | anti-4d | 83 | >20 : 1 | 99 | syn-4d | 72 | 7.5 : 1 | >99 |
| 2 | 1e: 4-BrC6H4, CF3 | Allyl | anti-4e | 93 | >20 : 1 | 98 | syn-4e | 72 | 3.6 : 1 | 99 |
| 3 | 1f: 4-ClC6H4, CF3 | Allyl | anti-4f | 90 | >20 : 1 | 99 | syn-4f | 77 | 4.4 : 1 | 99 |
| 4 | 1g: 3-MeC6H4, CF3 | Allyl | anti-4g | 96 | >20 : 1 | 98 | syn-4g | 84 | 8.5 : 1 | 99 |
| 5 | 1h: 4-FC6H4, CF3 | Allyl | anti-4h | 88 | >20 : 1 | 98 | syn-4he | 78 | 4.4 : 1 | 99 |
| 6 | 1i: 4-MeOC6H4, CF3 | Allyl | anti-4ie,g | 90 | >20 : 1 | 98 | syn-4ie,f | 60 | 3.7 : 1 | >99 |
| 7 | 1j: 3,5-F2C6H3, CF3 | Allyl | anti-4j | 85 | >20 : 1 | 99 | syn-4je | 87 | 4.0 : 1 | >99 |
| 8 | 1k: 2-thienyl, CF3 | Allyl | anti-4k | 78 | >20 : 1 | 97 | syn-4kg | 37 | 2.1 : 1 | 99 |
| 9 | 1l: N-Ts-indol-3-yl, CF3 | Allyl | anti-4l | 82 | >20 : 1 | 96 | syn-4lg | 53 | 2.3 : 1 | >99 |
| 10 | 1m: C6H5, CF3CF2CF2 | Allyl | anti-4m | 69 | >20 : 1 | 98 | syn-4mg,h | 50 | 2.0 : 1 | >99 |
| 11i | 1n: cyclohexyl, CF3 | Allyl | anti-4ne | 98 | 16.7 : 1 | 99 | syn-4ne,f | 65 | 3.6 : 1 | >99 |
| 12i | 1o: Et, CF3 | Allyl | anti-4o | 98 | 15.3 : 1 | 97 | syn-4oe | 78 | 2.6 : 1 | >99 |
| 13i | 1p: Me, CF3 | Allyl | anti-4p | 97 | 10.1 : 1 | 89 | syn-4pe | 85 | 1.3 : 1 | 99 |
| 14 | 1d: C6H5, CF3 | Me | anti-4q | 91 | >20 : 1 | 97 | syn-4q | 77 | 5.3 : 1 | >99 |
| 15 | 1d: C6H5, CF3 | Bn | anti-4r | 81 | 18 : 1 | 98 | syn-4re | 70 | 5.9 : 1 | 99 |
| 16 | 1d: C6H5, CF3 | i-Bu | anti-4see | 50 | >20 : 1 | 96 | syn-4se,g | 50 | 6.7 : 1 | 99 |
Conditions: 1 (0.15 mmol), HE (0.165 mmol, 1.1 equiv.), 2p (0.015 mmol, 10 mol%), CH2Cl2 (0.60 mL), −30 °C, 24–48 h, then CH2Cl2 (1.8 mL), dhQD-2 for anti-4 or dhQN-10 for syn-4 (0.0075 mmol, 5 mol%), R2OH (0.30 mmol, 2 equiv.), 0 °C, 2–8 d.
Isolated yield of combined diastereoisomers 4 after chromatography on silica gel.
Determined on the crude mixtures by 19F NMR spectroscopy.
Enantiomeric excess of major diastereoisomer, determined by CSP HPLC.
In the ring-opening step, after 2–5 d, additional catalyst dhQD-2 for anti-4 or dhQN-10 for syn-4 (0.0075 mmol) and R2OH (0.15 mmol, 1–2 equiv.), were added.
Ring-opening step warmed to RT after 2 d.
Two step reaction performed by isolating intermediate 3 by a rapid filtration on silica gel.
Reduction step performed at 0 °C.
Conditions: 1 (0.05 mmol), HE (0.055 mmol, 1.1 equiv.), 2p (0.01 mmol, 20 mol%), CH2Cl2 (0.300 mL), −20 or 0 °C, 24–48 h, then CH2Cl2 (0.60 mL), dhQD-2 for anti-4 or dhQN-10 for syn-4 (0.01 mmol, 10 mol%), allyl alcohol (0.1 mmol, 2 equiv.), 0 °C, 3–6 d.