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Synlett 2011(4): 481-484  
DOI: 10.1055/s-0030-1259524
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© Georg Thieme Verlag Stuttgart ˙ New York

Organocatalytic Enantioselective Direct Aldol Reaction in Aqueous Media Catalyzed by a Bifunctional Diamine Catalyst

Vishnumaya Bisaia, Vinod K. Singh*a,b
a Department of Chemistry, Indian Institute of Technology Kanpur, Kanpur, Uttar Pradesh 208016, India
b Department of Chemistry, Indian Institute of Science Education and Research Bhopal, ITI (Gas Rahat) Building, Govindpura, Bhopal, Madhya Pradesh 462023, India
Fax: +91(512)2597436; e-Mail: vinodks@iitk.ac.in;
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Publication History

Received 26 October 2010
Publication Date:
02 February 2011 (online)

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Abstract

Organocatalytic direct asymmetric anti-aldol reaction was developed in aqueous medium using a BINOL-derived diamine/protic acid bifunctional catalyst. The catalytic protocol could offer the opportunity to access anti-aldol products with high level of enantioselectivities with moderate diastereoselectivities.

Key words

aldol reaction - aqueous medium - organocatalyst - diamine - protic acid - enantioselectivity

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General Procedure for the Direct Aldol Reaction with the Catalyst 3 in Brine: An aldehyde (0.5 mmol) was added to a mixture of ketone (2 mmol) and an organocatalyst 3 (10 mol%) with DNBSA (10 mol%) in brine (0.5 mL) at r.t. The reaction mixture was stirred and the progress of the reaction was monitored by TLC. After reaction was over (as indicated by TLC), the reaction mixture was diluted with EtOAc (2 mL). The organic layer was separated and dried over anhyd Na2SO4. It was purified over silica gel by column chromatography. The enantiomeric excess(ee) of the aldol product was determined by chiral HPLC analysis. The relative and absolute configurations of the products were determined by comparison with the known ¹H NMR, chiral HPLC analysis, and optical rotation values.

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Compound characterization data for selected compounds:
(2S,1′ R )-2-[Furan-2-yl(hydroxy)methyl]cyclohexan-1-one (4f): It was obtained in a maximum of 80% yield and 96% ee. The optical purity was determined by HPLC on chiralpak AD-H column (hexane-2-propanol, 90:10); flow rate 0.5 mL/min, 220 nm; t R ( major) = 26.8 min, t R ( minor) = 31.2 min; [α]²5 D +21 (c = 1.0, CHCl3). ¹H NMR (500 MHz, CDCl3): δ = 1.23-1.35 (m, 1 H), 1.61-1.71 (m, 3 H), 1.83-1.85 (m, 1 H), 2.10-2.37 (m, 1 H), 2.38-2.49 (m, 2 H), 2.89-2.95 (m, 1 H), 3.89 (br s, 1 H), 4.83 (d, J = 8.6 Hz, 1 H), 6.27-6.34 (m, 2 H), 7.36-7.38 (m, 1 H). Anal. Calcd for C11H14O3: C, 68.02; H, 7.27. Found: C, 68.09; H, 7.25.
(2S,1′ R )-2-[Hydroxy(naphthalene-2-yl)methyl]-cyclohexan-1-one (4g): It was obtained in a maximum of 88% yield and 96% ee. The optical purity was determined by HPLC on chiralpak AS-H column (hexane-2-propanol, 90:10); flow rate 0.5 mL/min; t R ( major) = 26.6 min, t R ( minor) = 30.8 min; [α]²5 D +5.8 (c = 1.3, CHCl3). ¹H NMR (400 MHz, CDCl3): δ = 1.25-1.35 (m, 2 H), 1.48-1.76 (m, 3 H), 2.04-2.09 (m, 1 H), 2.36-2.51 (m, 2 H), 2.69-2.75 (m, 1 H), 4.08 (br s, 1 H), 4.96 (d, J = 8.8 Hz, 1 H), 7.45-7.49 (m, 2 H), 7.71-7.89 (m, 5 H). Anal. Calcd for C17H18O2: C, 80.28; H, 7.13. Found: C, 80.18; H, 7.11.
(2S,1′ R ) 3-[Hydroxy(phenyl)methyl]tetrahydrothio-pyran-4-one (5b): It was obtained in a maximum of 77% yield and 98% ee. The optical purity was determined by HPLC on chiralpak OD-H column (hexane-2-propanol, 98:2); flow rate 0.5 mL/min, t R ( major) = 60.6 min, t R ( minor) = 87.1 min; [α]²5 D +17.1 (c = 1.4, CHCl3). ¹H NMR (400 MHz, CDCl3): δ = 2.48-2.60 (m, 2 H), 2.75-2.81 (m, 1 H), 2.83-2.88 (m, 1 H), 2.92-3.04 (m, 3 H), 3.42 (br s, 1 H), 4.97
(d, J = 8.8 Hz, 1 H), 7.26-7.39 (m, 5 H). Anal. Calcd for C12H14O2S: C, 64.83; H, 6.35. Found: C, 64.89; H, 6.33.