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Synlett 2007(12): 1889-1892  
DOI: 10.1055/s-2007-984526
LETTER
© Georg Thieme Verlag Stuttgart · New York

Stereoselective Synthesis of 1,2,2-Trisubstituted Indane Derivatives Using a Tandem SN2-Michael Addition Sequence

Santosh J. Gharpure*, S. Raja Bhushan Reddy, Udishnu Sanyal
Department of Chemistry, Indian Institute of Technology Madras, Chennai 600036, India
Fax: +91(44)22574202; e-Mail: sjgharpure@iitm.ac.in;
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Publikationsverlauf

Received 19 April 2007
Publikationsdatum:
25. Juni 2007 (online)

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Abstract

An efficient strategy is developed for the synthesis of 1,2,2-trisubstituted indane derivatives employing a tandem SN2-Michael reaction sequence. The method is extended towards the synthesis of spiroindanes and indanopiperidines.

Key words

indane derivatives - tandem reactions - Michael additions - alkylation reactions - indanopiperidines

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All compounds exhibited spectral data consistent with their structures. Melting point, IR, NMR (1H and 13C) and HRMS spectral data for some of the compounds follow.
Triester 10a: IR (neat): 2954, 1731, 1434, 1247, 1157, 1074, 756, 735 cm-1. 1H NMR (400 MHz, CDCl3): δ = 7.12-7.19 (m, 4 H), 4.45 (dd, J = 5.3, 9.2 Hz, 1 H), 3.74 (s, 3 H), 3.71 (s, 6 H), 3.71 (AB, J = 16.4 Hz, 1 H), 3.42 (AB, J = 16.4 Hz, 1 H), 2.74 (ABX, J = 5.3, 16.0 Hz, 1 H), 2.51 (ABX, J = 9.2, 16.0 Hz, 1 H). 13C NMR (100 MHz, CDCl3, DEPT): δ = 172.19 (C), 171.44 (C), 170.34 (C), 142.88 (CH), 138.96 (C), 127.56 (CH), 127.21 (CH), 124.25 (CH), 123.79 (CH), 64.31 (C), 52.96 (Me), 52.63 (Me), 51.74 (Me), 46.42 (CH), 39.28 (CH2), 36.24 (CH2). HRMS (ESI): m/z [M + Na+] calcd for C16H18O6Na: 329.1001; found: 329.0996.
Ketoester 11d: mp 114-117 °C. IR (neat): 2986, 1742, 1686, 1597, 1233, 750 cm-1. 1H NMR (400 MHz, CDCl3): δ = 8.05 (dd, J = 1.2, 8.4 Hz, 2 H), 7.61 (t, J = 7.6 Hz, 1 H), 7.50 (t, J = 7.6 Hz, 2 H), 7.22-7.26 (m, 3 H), 7.12-7.15 (m, 1 H), 4.56 (t, J = 6.8 Hz, 1 H), 4.36 (q, J = 7.2 Hz, 2 H), 3.77 (AB, J = 16.0 Hz, 1 H), 3.71 (d, J = 6.8 Hz, 2 H), 3.58 (AB, J = 16.0 Hz, 1 H), 1.33 (t, J = 7.2 Hz, 3 H). 13C NMR (100 MHz, CDCl3, DEPT): δ = 197.37 (C), 168.52 (C), 141.01 (C), 137.95 (C), 136.34 (C), 133.62 (CH), 128.77 (CH), 128.22 (CH), 128.19 (CH), 127.90 (CH), 124.58 (CH), 123.60 (CH), 118.90 (C), 63.18 (CH2), 55.03 (C), 47.84 (CH), 42.92 (CH2), 40.83 (CH2), 13.96 (Me). HRMS (ESI): m/z [M + Na+] calcd for C21H19NO3Na: 356.1263; found: 356.1258.
Sulfone 11e: mp 125-127 °C. IR (neat): 3067, 2952, 1733, 1684, 1596, 1581, 1447, 1308, 1145, 749, 689 cm-1. 1H NMR (400 MHz, CDCl3): δ = 7.84-7.89 (m, 4 H), 7.54-7.58 (m, 2 H), 7.42-7.47 (m, 4 H), 7.03-7.09 (m, 3 H), 6.94-6.97 (m, 1 H), 4.86 (dd, J = 2.8, 8.8 Hz, 1 H), 3.89 (AB, J = 17.0 Hz, 1 H), 3.78 (AB, J = 17.0 Hz, 1 H), 3.70 (s, 3 H), 3.47 (ABX, J = 2.8, 17.6 Hz, 1 H), 3.33 (ABX, J = 8.8, 17.6 Hz, 1 H). 13C NMR (100 MHz, CDCl3, DEPT): δ = 197.44 (C), 167.78 (C), 142.21 (C), 138.58 (C), 136.81 (C), 136.70 (C), 134.26 (CH), 133.48 (CH), 130.48 (CH), 128.78 (CH), 128.76 (CH), 128.18 (CH), 127.82 (CH), 127.42 (CH), 123.96 (CH), 82.49 (C), 53.30 (Me), 45.35 (CH), 41.18 (CH2), 37.99 (CH2). HRMS (ESI): m/z [M + Na+] calcd for C25H22O5NaS: 457.1080; found: 457.1074.
Spirodione 13: mp 95-98 °C. IR (neat): 2923, 1734, 1704, 1595, 1277, 1238, 751, 732 cm-1. 1H NMR (400 MHz, CDCl3): δ = 8.02-8.06 (m, 1 H), 7.95-7.98 (m, 1 H), 7.82-7.89 (m, 2 H), 7.14-7.27 (m, 4 H), 4.22 (dd, J = 6.2, 9.3 Hz, 1 H), 3.35 (AB, J = 16.2 Hz, 1 H), 3.34 (s, 3 H), 3.28 (AB, J = 16.2 Hz, 1 H), 2.89-2.92 (m, 2 H). 13C NMR (100 MHz, CDCl3, DEPT): δ = 202.56 (C), 201.71 (C), 172.54 (C), 143.12 (CH), 141.86 (C), 141.73 (C), 139.58 (CH), 135.78 (CH), 135.65 (CH), 127.95 (CH), 127.60 (CH), 124.40 (CH), 123.60 (CH2), 123.47 (CH), 123.32 (CH), 61.81 (C), 51.58 (CH), 47.24 (CH2), 41.44 (CH2), 35.18 (CH2). HRMS (ESI): m/z [M + Na+] calcd for C20H16O4Na: 343.0946; found: 343.0954.
Lactam 16: mp 117-120 °C. IR (neat): 3235, 2982, 1721, 1651, 1485, 1367, 1265, 1224, 1015, 860, 732, 701 cm-1. 1H NMR (400 MHz, CDCl3): δ = 7.15-7.27 (m, 4 H), 6.04 (br s, 1 H), 4.18-4.24 (m, 1 H), 4.21 (q, J = 6.8 Hz, 2 H), 3.74 (ABX, J = 4.8, 13.2 Hz, 1 H), 3.43 (AB, J = 17.0 Hz, 1 H), 3.24 (ABX, J = 3.2, 13.2 Hz, 1 H), 3.02 (AB, J = 17.0 Hz, 1 H), 2.94 (ABX, J = 7.8, 15.6 Hz, 1 H), 2.53 (ABX, J = 6.4, 15.6 Hz, 1 H), 1.27 (t, J = 6.8 Hz, 3 H). 13C NMR (100 MHz, CDCl3, DEPT): δ = 174.97 (C), 173.55 (C), 143.72 (C), 139.52 (C), 127.58 (CH), 127.55 (CH), 124.46 (CH), 123.94 (CH), 61.53 (CH2), 53.15 (C), 46.84 (CH2), 45.54 (CH), 41.62 (CH2), 36.00 (CH2), 14.13 (Me). HRMS (ESI): m/z [M + Na+] calcd for C15H18NO3: 256.1287; found: 260.1291.

9

Representative Experimental Procedure: To a stirred solution of chloroester 1 (100.0 mg, 0.475 mmol) in DMF, were added dimethyl malonate (9a; 125.4 mg, 0.950 mmol) and Cs2CO3 (464.3 mg, 1.425 mmol) and the mixture was allowed to stir at r.t. for 3 h (TLC control). The reaction mixture was then diluted with Et2O, washed with H2O followed by brine and dried over Na2SO4. Subsequent filtration, evaporation of the solvent and purification of the residue by silica gel column chromatography using EtOAc-hexane (1:19) as eluent yielded the triester 10a [8] (118.0 mg, 81%) as a viscous oil.

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Crystal data for 11d: formula: C21H19NO3; unit cell parameters: a = 7.2791 (2), b = 12.4566 (4), c = 18.9233 (6) Å, β = 95.4010 (10)°; space group P2(1)/c; CCDC number 638873. Crystal data for 11e: formula: C25H22O5S; unit cell parameters: a = 12.8473 (3), b = 9.1054 (2), c = 18.5010 (4) Å, α = 90.00°, β = 95.8910 (10)°, γ = 90.00°; space group P2 (1)/c; CCDC number 638872. CCDC 638873 and CCDC 638872 contain the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.