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Synlett 2005(14): 2151-2154  
DOI: 10.1055/s-2005-872227
LETTER
© Georg Thieme Verlag Stuttgart · New York

1,2-syn-Selective and Enantioselective Michael Reactions of Acyclic Enones with a Propionate-Derived Nucleophile Catalyzed by Oxazaborolidinone

Toshiro Harada*, Toyonao Yamauchi, Shinya Adachi
Department of Chemistry and Materials Technology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan
Fax: +85(75)7247580; e-Mail: harada@chem.kit.ac.jp;
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Publication History

Received 17 June 2005
Publication Date:
20 July 2005 (online)

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Abstract

allo-Threonine-derived oxazaborolidinone 1b is demonstrated to be an effective catalyst for the stereoselective Michael reaction of simple acyclic enones with propionate-derived silyl ketene acetals. The reaction affords the corresponding Michael adducts with two contiguous asymmetric centers with high syn selectivity and enantioselectivity.

Key words

asymmetric - boron - catalysis - Lewis acids - Michael additions

9

In this reaction, a racemic enolsilane, EtO2CCH(Me)CH(Ph)CH=(OTBS)Me, was obtained as a major product in 49% yield.

10

Reaction of 3a with Me2C=C(OTMS)OEt under similar conditions gave the corresponding Michael adducts in only 6% ee (60% yield). These results suggest that the extent of the Si +-catalyzed pathway depends significantly on the structure of the nucleophiles.

11

Typical experimental procedure (Table 1, entry 8). To a solution of O-(4-biphenoyl)-N-tosyl-(l)-allo-threonine [7c] (136 mg, 0.30 mmol) in CH2Cl2 (3 mL) under an argon atmosphere at r.t. was added dichlorophenylborane (39 µL, 0.30 mmol). After being stirred for 30 min, the mixture was concentrated in vacuo. To a solution of the resulting OXB 1b, silyl ketene acetal (E)-4b (523 mg, 3.0 mmol), tert-butyl methyl ether (0.48 mL, 4.0 mmol) in CH2Cl2 (2 mL) at
-78 °C were added a CH2Cl2 (2 mL) solution of 3a (146 mg, 1.0 mmol) and 2,6-diisopropylphenol (535 mg, 3.0 mmol) over 6 h by syringe pump. After the completion of the addition, the mixture was quenched by the addition of a sat. aq soln of NaHCO3 and filtered. The filtrate was extracted three times with hexane, dried (MgSO4), and concentrated in vacuo. The residue was dissolved in 1 N HCl (2 mL) and THF (10 mL) and the resulting solution was stirred at r.t. for 30 min. The mixture was poured into aq NaHCO3 and extracted three times with Et2O. The organic layers were dried (MgSO4) and concentrated in vacuo. Purification of the residue by flash chromatography (SiO2, 4-20% EtOAc in hexane) gave 158 mg (64%) of adduct syn-5a (syn/anti = 16:1, 86% ee): 1H NMR (500 MHz, CDCl3): δ = 0.94 (3 H, d, J = 7.0 Hz), 1.27 (3 H, t, J = 7.1 Hz), 1.98 (3 H, s), 2.65 (1 H, qd, J = 7.0, 9.9 Hz), 2.75 (1 H, dd, J = 4.8, 16.2 Hz), 2.85 (1 H, dd, J = 9.6, 16.2 Hz), 3.38 (1 H, dt, J = 4.8, 9.7 Hz), 4.15 (2 H, q, J = 7.1 Hz), 7.16-7.30 (5 H, m) [minor anti isomer resonated at δ = 1.15 (3 H, d, J = 7.0 Hz), 1.05 (3 H, t, J = 7.1 Hz), 3.94 (2 H, m)]; 13C NMR (125.8 MHz, CDCl3): δ = 14.2, 15.8, 30.3, 44.1, 45.5, 48.4, 60.5, 126.9, 128.1, 128.6, 141.4, 175.6, 206.7. Anal. Calcd for C15H20O3: C, 72.55; H, 8.12. Found: C, 72.69; H, 8.34. HPLC, Daicel Chiralpak AD-H, 1.0 mL/min, 0.7% 2-PrOH in hexane (S) t R 26.8 min, (R) t R 19.9 min.

12

The low diastereoselectivity observed in the reaction using B-methyl OXB 1f (Table [1] , entry 10) might support this rationale.