Synlett 2008(7): 1045-1049  
DOI: 10.1055/s-2008-1072652
LETTER
© Georg Thieme Verlag Stuttgart · New York

Iodine-Catalyzed Nucleophilic Substitution Reactions of Benzylic Alcohols

Pabbaraja Srihari*, Dinesh C. Bhunia, Pamu Sreedhar, Jhillu S. Yadav
Organic Division-I, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Fax: +91(40)27160512; e-Mail: srihari@iict.res.in;
Further Information

Publication History

Received 31 October 2007
Publication Date:
28 March 2008 (online)

Abstract

Molecular iodine efficiently catalyzes the direct nucleophilic substitution of the hydroxy group of benzylic alcohols with carbon and oxygen nucleophiles.

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General Experimental Procedure
To a solution of the benzylic alcohol (1 mmol) and nucleophile (1.2 mmol) in MeCN (3 mL) was added I2 (5 mol%) and the mixture was stirred at 0 °C to r.t. After completion of the reaction (monitored by TLC), the reaction mixture was washed with sat. aq Na2S2O3 solution and extracted with EtOAc. The organic layer was separated and washed with brine, dried over anhyd Na2SO4, and the solvent was evaporated under vacuum. The resulting crude product was purified by silica gel column chromatography (EtOAc-hexane as the eluents).
Spectroscopic Data of Representative Examples
Compound 4c: yellow liquid. IR (neat): 3061, 3029, 2924, 2859, 1952, 1601, 1493, 1452, 1094, 1028, 739, 698 cm-1. 1H NMR (300 MHz, CDCl3): δ = 1.91 (p, J = 6.1 Hz, 2 H), 3.53 (t, J = 6.1 Hz, 2 H), 3.58 (t, J = 6.2 Hz, 2 H), 4.44 (s, 2 H), 5.26 (s, 1 H), 7.13-7.30 (m, 15 H). 13C NMR (100 MHz, CDCl3): δ = 142.0, 138.1, 127.8, 127.1, 127.0, 126.8, 126.7, 126.5, 83.2, 72.5, 66.9, 65.5, 29.8. MS (EI): m/z = 355 [M+ + Na]. HRMS: m/z calcd for C23H24O2Na: 355.1673; found: 355.1683.
Compound 5a: solid; mp 110-112 °C.16a IR (KBr): 3491, 3057, 2924, 1616, 1593, 1490, 1387, 1200, 1135, 812, 740, 701 cm-1. 1H NMR (300 MHz, CDCl3): δ = 7.97 (d, 1 H, J = 8.7 Hz), 7.76 (dd, 1 H, J = 7.8 Hz), 7.72 (d, 1 H, J = 8.7 Hz), 7.20-7.42 (m, 12 H), 7.06 (d, 1 H, J = 8.7 Hz), 6.41 (s, 1 H), 5.27-5.40 (br s, 1 H). 13C NMR (75 MHz, CDCl3): δ = 152.9, 141.8, 133.5, 129.8, 129.7, 129.3, 129.2, 128.9, 127.3, 126.9, 123.3, 123.0, 120.3, 119.9, 48.6. MS (EI): m/z = 310 [M+]. Anal. Calcd (%) for C23H18O: C, 89.03; H, 5.80. Found: C, 89.4; H, 5.64.
Compound 5e: white solid; mp 86-88 °C. IR (KBr): 3444, 2964, 3024, 2964, 2855, 2372, 1876, 1599, 1509, 1444, 1331, 1254, 1090, 823, 743 cm-1. 1H NMR (200 MHz, CDCl3 + DMSO): δ = 1.62 (d, J = 7.0 Hz, 3 H), 4.20 (q, J = 7.0 Hz, 1 H), 6.62 (d, J = 8.6 Hz, 2 H), 7.02 (d, J = 8.6 Hz, 2 H), 6.83 (dt, J = 1.1, 8.9 Hz, 2 H), 6.93-7.06 (m, 2 H), 7.21-7.30 (m, 1 H), 8.57 (br s, 1 H, NH), 10.13 (s, 1 H, OH). 13C NMR (100 MHz, CDCl3): δ = 153.9, 136.4, 135.5, 126.7, 125.4, 119.7, 119.3, 117.9, 116.9, 113.8, 113.7, 110.0, 34.6, 21.4. MS (EI): m/z = 238 [M+ + H]. HRMS: m/z calcd for C16H16NO: 238.1231; found: 238.1239.

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Optically active p-methoxy α-phenyl ethanol was obtained from the corresponding ketone following the standard reduction procedure using CBS catalyst; ee was calculated using chiral HPLC.