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Synlett 2012(6): 925-929  
DOI: 10.1055/s-0031-1290607
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of 2-Aryl-Substituted Chromans by Intramolecular C-O Bond Formation

Yu Wang, Robert Franzén*
Department of Chemistry and Bioengineering, Tampere University of Technology, Korkeakoulunkatu 8, 33101 Tampere, Finland
Fax: +358(3)31152108; e-Mail: robert.franzen@tut.fi;
Further Information

Publication History

Received 30 December 2011
Publication Date:
15 March 2012 (online)

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Abstract

A synthetic route for the preparation of 2-aryl-substituted chromans from commercially available starting materials and utilizing either a palladium- or copper-catalyzed intramolecular cyclization of aryl bromides is described. Chromans with stereocontrol at C-2 can thus be obtained via a palladium-catalyzed asymmetric allylic etherification procedure utilizing a chiral indole-phosphine oxazoline (IndPHOX) ligand.

Key words

intramolecular cyclization - chromans - chalcones - palladium - copper

11

General Procedure for Palladium-Catalyzed Intramolecular Cyclization: To a mixture of Pd(OAc)2 (2.4 mg, 0.0105 mmol), ligand 11 (3.1 mg, 0.0105 mmol) and Cs2CO3 (0.17 g, 0.525 mmol), compound 9 (0.35 mmol) in toluene (1.2 mL) was added. After stirring under 90 ˚C for reported time, the reaction mixture was cooled to r.t., diluted with Et2O, and filtered through a pad of celite. The resulting solution was purified by silica gel chromatography (n-hexane-EtOAc, 30:1).

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The by-product was 1-(furan-2-yl)-3-phenylpropan-1-one, isolated in 22% yield. For the reaction mechanism, see reference 7b.

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General Procedure for Copper-Catalyzed Intramolecular Cyclization: To a mixture of CuI (2.8 mg, 0.015 mmol), 2-aminopyridine (2.8 mg, 0.03 mmol) and NaOMe (12 mg, 0.225 mmol), compound 9 (0.15 mmol) in diglyme (0.7 mL) was added. After stirring under 100 ˚C for reported time, the reaction mixture was cooled to r.t., quenched with H2O, and extracted with Et2O. The extracts were washed with brine and dried over MgSO4. The solvent was removed in vacuo and the residue was purified by column chromatography (n-hexane-EtOAc, 30:1).

17

The reported ee is the average value of three entries.

18

2-(2-Bromophenyl)chroman (20): [α]D ²0 +71.2 (c = 0.95, CHCl3, 89% ee). ¹H NMR (300 MHz, CDCl3): δ = 7.54-7.61 (m, 2 H), 7.36 (td, J = 7.7, 1.2 Hz, 1 H), 7.10-7.19 (m, 3 H), 6.86-6.93 (m, 2 H), 5.38 (td, J = 10.2, 2.2 Hz, 1 H), 3.00-3.10 (m, 1 H), 2.75-2.83 (m, 1 H), 2.31-2.39 (m, 1 H), 1.85-1.94 (m, 1 H). ¹³C NMR (75 MHz, CDCl3): δ = 155.4, 141.3, 133.0, 130.0, 129.4, 128.1, 127.8, 127.7, 122.3, 121.8, 120.8, 117.2, 77.3, 29.1, 25.5. HRMS (ESI+): m/z [M + Na]+ calcd for C15H13ONaBr: 311.0047; found: 311.0015.

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[α]D ²0 +27.7 (c = 0.5, CH2Cl2, 87% ee).

22

2-([1,1′-Biphenyl]-2-yl)chroman (22): [α]D ²0 -36.5 (c = 0.40, CHCl3, 89% ee). ¹H NMR (300 MHz, CDCl3): δ = 7.64-7.67 (m, 1 H), 7.25-7.46 (m, 8 H), 7.00-7.11 (m, 2 H), 6.80-6.88 (m, 2 H), 5.05-5.10 (m, 1 H), 2.71-2.78 (m, 2 H), 2.01-2.09 (m, 2 H). ¹³C NMR (75 MHz, CDCl3): δ = 155.8, 141.2, 141.0, 139.3, 130.4, 129.8, 129.6, 128.5, 128.2, 128.0, 127.5, 127.4, 126.7, 122.2, 120.5, 117.3, 75.2, 30.1, 25.9. HRMS (ESI+): m/z [M + Na]+ calcd for C21H18ONa: 309.1255; found: 309.1263.