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. Author manuscript; available in PMC: 2012 Jan 1.
Published in final edited form as: Chem Sci. 2011;4(2):573–589. doi: 10.1039/C0SC00394H

Table 2. Single and double asymmetric homoallylic alcohol–imine coupling reactions en route to chiral piperidines.

graphic file with name nihms269836u2.jpg
entry homoallylic alcohol imine 1,5-aminoalcohola yield (%) dr piperidineb(yield)
1 graphic file with name nihms269836t13.jpg graphic file with name nihms269836t14.jpg graphic file with name nihms269836t15.jpg 83 24:1 graphic file with name nihms269836t16.jpg
2 graphic file with name nihms269836t17.jpg 124 graphic file with name nihms269836t18.jpg 75 20:1 graphic file with name nihms269836t19.jpg
3 graphic file with name nihms269836t20.jpg 124 127 61 25:4:1
4 graphic file with name nihms269836t21.jpg ent-124 graphic file with name nihms269836t22.jpg 76 ≥50:1 graphic file with name nihms269836t23.jpg
5 graphic file with name nihms269836t24.jpg 124 graphic file with name nihms269836t25.jpg 88 35:4:1 graphic file with name nihms269836t26.jpg
a

Reaction conditions for cross coupling: imine (1 eq), Ti(Oi-Pr)4 (1.5 eq), c-C5H9MgCl (3.0 eq), Et2O (−60 to −30 °C), then add alkoxide (1.5 eq) (−40 to 0 °C or rt).

b

Reaction conditions for cyclization: For 126 - 2-NsCl, Et3N, DMAP, CH2Cl2, rt. For 128 -MsCl, Et3N, CH2Cl2, rt. R = CH(Ph)CH2OMe. For 131 and 134 - 1) H2 (1 atm), Pd(OH)2, AcOH/MeOH (1:10 v/v), rt, 2) 2-NsCl, Et3N, DMAP, CH2Cl2, 0 °C to rt, 3) PPh3, DIAD, THF, rt.