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Synlett 2010(5): 712-714  
DOI: 10.1055/s-0029-1219379
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

(1R,5R)-1-(1′-Dimethylaminoethyl)-2-isopropylidene-5-methylcyclohexanol as a Chiral Ligand in the Enantioselective Addition of Diethylzinc to Aldehydes

Ashok K. Yadav*, Manoj Kumar, Tripti Yadav, Renuka Jain
Department of Chemistry, University of Rajasthan, Jaipur 302055, India
Fax: +91(141)2700364; e-Mail: drakyada@yahoo.co.in;
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Publication History

Received 13 August 2009
Publication Date:
08 February 2010 (online)

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Abstract

An efficient chiral ligand, (1R,5R)-1-(1′-dimethylaminoethyl)-2-isopropylidene-5-methylcyclohexanol, has been developed for the enantioselective addition of diethylzinc to some prochiral aldehydes to afford S-alcohols. The overall conversion rate was 80-98% with excellent enantiomeric excess (79-98%).

Key words

ionic liquid - intermolecular reductive coupling - prochiral aldehydes - chiral ligand - enantioselectivity

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Typical Experimental Procedure for Preparative-Scale Electrosynthesis
The electrolysis was carried out in a double-walled cell (Metrohm, 100 ml) equipped with cover glass inlet and outlet, thermometer, and magnetic stirrer. This cell was divided by a medium-porosity glass frit into two separate compartments. The catholyte was a 10 mL mixture of [BMIM]BF4-i-PrOH (9:1) containing 0.03 M (R)-(+)-pulegone and 0.04 M of MeCN. The anolyte was 5 mL of [BMIM]BF4-i-PrOH (9:1). A smooth copper foil (1 × 1 cm) was used as a cathode and a platinum foil (1 × 1 cm) was used as an anode. Nitrogen gas was bubbled for 10 min and the electroreductive coupling was carried out by passing current 0.1 A for the time corresponding to charge-transfer equivalent to 1.1 F/mol.
The catholyte was extracted with EtOAc (3 × 10 mL), the extract dried over anhyd MgSO4, filtered, and the solvent was removed by distillation under reduced pressure. The product so obtained was purified by chromatography on a swollen triacetyl cellulose(microcrystalline) column, and elution was performed by EtOH to afford 1a in pure form in 70% yield. R f = 0.55 (hexane-EtOAc, 10:1). IR (neat): ν = 3460, 1700, 1640, 880 cm-¹. ¹H NMR (300 MHz, CDCl3):
δ = 1.05 (d, 3 H, J = 6.5 Hz, CH3) 1.28 (m, 2 H, CH2), 1.60 (m, 1 H, CH), 1.65 (m, 2 H, CH2), 1.70 (s, 6 H, 2 × CH3), 1.95 (m, 2 H, CH2), 2.10 (s, 3 H, COCH3), 3.80 (s, 1 H, OH). ¹³C NMR (75 MHz, CDCl3): δ = 14.60, 19.20, 20.50, 21.60, 25.60, 38.40, 42.40, 92.50, 125.30, 142.70, 207.10. Anal. Calcd for C12H20O2: C, 73.41; H, 10.27. Found: C, 73.62; H, 10.12.

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Compound 1a was heated to reflux with O-methyloxime hydrochloride in the presence of 0.03 M Et3N in EtOH. Removal of the solvent gave the oximated product which, upon lithium aluminium hydride reduction, afforded compound 1d in 90% yield. Compound 1d, when refluxed with 2 mol of MeI resulted in the desired chiral ligand 1e in 95% yield; bp 150-153 ˚C (67 mbar); R f = 0.4 (hexane-EtOAc, 1:1). IR (neat): ν = 3855, 2780, 1645, 886 cm-¹. ¹H NMR (300 MHz, CDCl3): δ = 1.05 (d, 3 H, J = 6.5 Hz, CH3), 1.12 (d, 3 H, J = 7.1 Hz, CH3), 1.30-1.42 (m, 4 H, 2 × CH2), 1.62 (m, 1 H, CH), 1.75 (m, 6 H, 2 × CH3), 1.95 (m, 2 H, CH2), 2.30 (s, 6 H, 2 × CH3), 2.95 [q, 1 H, J = 7.1 Hz, CHN(CH3)2], 3.85 (s, 1 H, OH). ¹³C NMR (75 MHz, CDCl3): δ = 12.10, 19.20, 20.60, 22.40, 26.20, 37.25, 39.50, 44.15, 66.50, 78.30, 125.20, 142.70. Anal. Calcd for C14H27ON: C, 74.59; H, 12.08; N, 6.21. Found: C, 74.43; H, 11.84; N, 5.96.

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Representative Spectroscopic Data( S )-1-phenylpropan-1-ol (4a)
Bp 94-95 (13.3 mbar); R f = 0.35 (hexane-EtOAc, 8:2). IR (neat): ν = 3400, 3020, 2990, 1600, 1100 cm-¹. ¹H NMR (300 MHz, CDCl3): δ = 0.90 (t, J = 6.0 Hz, 3 H, CH3), 1.40-1.55 (m, 2 H, CH2CH3), 3.60 (br s, 1 H, OH), 4.50 (t, J = 7.0 Hz, 1 H, CHOH), 7.10-7.40 (m, 5 H, ArH). ¹³C NMR (75 MHz, CDCl3): δ = 11.10, 33.10, 78.20, 124.60, 128.40, 128.80, 139.20. Anal. Calcd for C9H12O: C, 79.36; H, 8.88. Found: C, 79.55; H, 8.70.
( S )-3-Nonanol (4e)
Bp 192-194 ˚C; R f = 0.40 (hexane-EtOAc, 8:2). IR (neat):
ν = 3600, 2970, 1350, 1100 cm-¹. ¹H NMR (300 MHz, CDCl3): δ = 0.90 (t, J = 6.0 Hz, 3 H, CH3), 0.95 (t, J = 6.0 Hz, 3 H, CH3), 1.20-1.62 (m, 12 H, 6 × CH2), 2.20 (br s, 1 H, OH), 3.25 (t, J = 7.0 Hz, 1 H, CHOH). ¹³C NMR (75 MHz, CDCl3): δ = 11.00, 15.30, 22.40, 25.20, 29.80, 30.60, 33.10, 38.40, 75.50. Anal. Calcd for C9H20O: C, 74.92; H, 13.98. Found: C, 74.75; H, 13.80.