6_Asymmetric_Allylation

Chemistry 215 Handouts 中的一部分

Myers Brown Allylation and Crotylation Reactions Reviews:

Asymmetric Allylation Reactions Enantioselective Allylboration O R H+ (–)-Ipc2B R yield (%) 74 71 72 88 81–78 Et2O 23°C; R NaOH, H2O2 ee (%)a 93 86 87 83 96 ee (%)b 99 96 99 96 OH

Chem 215

Srebnik, M.; Ramachandran, P. V. Aldrichimica Acta 1987, 20, 9. Roush, W. R. In Comprehensive Organic Synthesis, Trost, B. M.; Fleming, I., Eds., Pergamon Press: New York, 1991, Vol. 2, pp. 1-53. Synthesis of B-Allyldiisopinocampheylborane

CH3 n-C3H7 n-C4H9 t-C4H9 C 6H 5

H 3C

CH3 CH3=

CH3 H3B S(CH3)2 THF, 0°C 72 h,72%

CH3 BH 2

(1R)-(+)- -Pinene 91.3% ee

(–)-Ipc2BH 98.9% ee CH3OH, 1 h 0°C, 100%

carried out without filtration of Mg salts. bAllylboration carried out at–100°C under Mg-salt free conditions. The reaction is quite general; the stereochemistry of the addition is the same in all cases examined. Lower reaction temperatures (0–78–100°C) lead to increased enantioselectivity.

aAllylboration

CH3 B 2

CH3 MgBr–78 25°C 25°C, 1 h BOCH3 2

Only Mg-salt free reagent can be used at–100°C because the reactive borane is sequestered by ate complex formation with CH3OMgBr at this temperature. Allylboration of aldehydes is essentially instantaneous at–78 or–100°C in the absence of Mg salts. H 3C

98.9% ee

98.9% ee

Prolonged incubation at 0°C affords enantiomerically enriched Ipc2BH. This is due to equilibration of tetraisopinocampheyldiborane with -pinene and triisopinocampheyldiborane; the symmetrical dimer crystallizes preferentially. Both enantiomers of -pinene are commercially available and inexpensive (Aldrich: (1R)-(+)- -pinene, 91% ee,$100/500mL; (1S)-(–)- -pinene, 87% ee,$42/100mL). B-Allyldiisopinocampheylborane can be prepared and used in situ after filtration of the magnesium salts produced during its formation.

H 3C H H H H R H H CH3 H B O H3C H CH3 CH3

Allylation of aldehydes proceeds through a chair-like TS where R occupies an equatorial position and the aldehyde facial selectivity derives from minimization of steric interactions between the axial Ipc ligand and the allyl group.

Brown, H. C.; Desai, M. C.; Jadhav, P. K. J. Org. Chem. 1982, 47, 5065-5069. Brown, H. C.; Singaram, B. J. Org. Chem. 1984, 49, 945-947. Jadhav, P. K.; Bhat, K. S.; Perumal, P. T.; Brown, H. C. J. Org. Chem. 1986, 51, 432-439.

Brown, H. C.; Jadhav, P. K. J. Am. Chem. Soc. 1983, 105, 2092-2093. Brown, H. C.; Bhat, K. S. J. Am. Chem. Soc. 1986, 108, 5919-5923. Racherla, U. S.; Brown, H. C. J. Org. Chem. 1991, 56, 401-404. M. Movassaghi