Design and Synthesis of a Water-Tolerant Chiral Indium Complex: ­Application to One-Pot Three-Component Mannich-Type Reactions in Water

Abstract

A novel chiral indium(III) camphorsulfonate complex prepared from indium trichloride, allyltributylstannane and (1S)-(+)-10-camphorsulfonic acid has been developed as a water-tolerant Lewis acid to afford high yields (up to 99%) in one-pot three-component Mannich-type reactions in a true water environment.

Key words

chiral indium complex - one-pot three-component Mannich-type reaction - allyltributylstannane

References and Notes

• 1a Li C.-J. Chan T.-H. Organic Reactions in Aqueous Media   John Wiley & Sons; New York: 1997. 
• 1b Organic Synthesis in Water   Grieco PA. Blacky Academic and Professional; London, England: 1998. 
• 2 Loh T.-P. Chua G.-L. Chem. Commun.  2006,  2739 
• 3a Teo Y.-C. Tan K.-T. Loh T.-P. Chem. Commun.  2005,  1318 
• 3b Teo Y.-C. Goh J.-D. Loh T.-P. Org. Lett.  2005,  7:  2743 
• 3c Teo Y.-C. Loh T.-P. Org. Lett.  2005,  7:  2539 
• 3d Lu J. Ji S.-J. Teo Y.-C. Loh T.-P. Org. Lett.  2005,  7:  159 
• 3e Lu J. Hong M.-L. Ji S.-J. Loh T.-P. Chem. Commun.  2005,  1010 
• 3f Lu J. Ji S.-J. Teo Y.-C. Loh T.-P. Tetrahedron Lett.  2005,  46:  7435 
• 4 Teo Y.-C. Goh E.-L. Loh T.-P. Tetrahedron Lett.  2005,  46:  6209 
• 8a Loh T.-P. Liung SBKW. Tan K.-L. Wei L.-L. Tetrahedron  2000,  56:  3227 
• 8b Loh T.-P. Wei L.-L. Tetrahedron Lett.  1998,  39:  323 

5

Crystal Data: C₂₁H₃₉C₄InO₁₂S₂, M = 804.26, colorless prism. Crystal dimensions: 0.20 × 0.15 × 0.04 mm, monoclinic, space group P2(1), a = 6.9145(2) Å, b = 15.3916(6) Å, c = 15.5826 (6) Å, V = 1657.02(10) ų, Z = 2, D _c = 1.612 Mg/m³. Reflections collected: 34477; independent reflections: 7580 (R _int = 0.0432), final R[I > 2σ(I)] = 0.0428, R (all data) = 0.0535, R _w = 0.1327. Crystallographic data for this crystal has been deposited with the Cambridge Crystallographic Data Center as supplementary publication number CCDC 624125. Copies of the data can be obtained free of charge on application to CCDC, 12 Union Road Cambridge CB2, 1EZ, UK [fax: [phone]; e-mail: [e-mail]].

6

Reactions with aliphatic aldehydes or aliphatic amines afforded the products in low yields.

7

Typical Reaction Procedure: Anhydrous benzaldehyde (0.05 mL, 0.5 mmol) and indium complex 4 (20 mg, 0.025 mmol) were mixed and stirred at r.t. in H₂O (5 mL) for 10 min before the addition of anhyd aniline (0.06 mL, 0.6 mmol). The resulting mixture was stirred at r.t. for 30 min. 1-Methoxy-1-trimethylsilyloxypropene (0.2 mL, 1 mmol) was then added. The suspension was stirred at r.t. for 1 d and then extracted with EtOAc (3 × 25 mL). The organic layers were combined, washed with brine (5 mL), dried over anhyd MgSO₄, and concentrated under reduced pressure. The product was obtained in 69% yield after silica gel column chromatography as a yellowish wet solid; R _f 0.61 (hexane-EtOAc, 4:1). ¹H NMR (CDCl₃): δ = 7.23-7.31 (m, 5 H), 7.03-7.10 (m, 2 H), 6.50-6.65 (m, 3 H), 4.53 (s, 1 H), 3.67 (s, 3 H), 1.30 (s, 3 H), 1.20 (s, 3 H). ¹³C NMR (CDCl₃): δ = 176.97, 146.86, 139.17, 128.95, 128.21, 127.93, 127.38, 117.22, 113.34, 64.30, 52.01, 46.95, 24.48, 20.65. FTIR (thin film): 1715.8 cm^-1. HRMS: m/z calcd for C₁₈H₂₁NO₂: 283.1572; found: 283.1568.

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The drop in reactivity by the fourth or fifth cycle may be attributed to loss of catalyst due to organic extraction.