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Synlett 2005(13): 2067-2071  
DOI: 10.1055/s-2005-871963
LETTER
© Georg Thieme Verlag Stuttgart · New York

New Bisphosphine Ligands for Palladium-Catalyzed Desymmetrization of meso-Cyclopent-2-en-1,4-diol Biscarbamate

Dongbo Zhao, Zheng Wang, Kuiling Ding*
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Road, Shanghai 200032, P. R. China
Fax: +86(21)64166128; e-Mail: kding@mail.sioc.ac.cn;
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Publication History

Received 8 June 2005
Publication Date:
12 July 2005 (online)

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Abstract

A new class of bisphosphine ligands (5, 6) with a cyclo­butane backbone have been designed and synthesized on the basis of a privileged C 2 scaffold of head-to-head coumarin dimer, among which ligand 5a was found to show excellent activity and enantioselectivity in Pd-catalyzed desymmetrization of the biscarbamate of meso-cyclopent-2-en-1,4-diol, affording oxazolidin-2-one in up to 90% yield with 97% ee.

Key words

C 2-symmetric - bisphosphine - palladium - desymmetrization - meso-diols

9

Synthesis of ( S,S , S , S )-5a.
Anhyd CH2Cl2 (4 mL) was added to the diamine 11a (0.06 g, 0.2 mmol), 2-(diphenylphosphino)benzoic acid (0.15 g, 0.48 mmol), DCC (0.12 g, 0.6 mmol) and 5 mol% DMAP. The resultant yellow, chalky mixture was stirred at r.t. until TLC indicated complete reaction. The mixture was filtered through Celite to remove dicyclohexylurea, and the filter cake was washed with CH2Cl2 (2 × 10 mL). The filtrate was concentrated in vacuo and chromatographed on silica gel with EtOAc-hexane (1:2) as eluent to afford diamide 5a as an amorphous white solid (0.08 g, 50%). [α]D 20 -26.0 (c 1.02, CHCl3). IR (KBr): ν = 2930, 2852, 1654, 1628, 1584, 1493, 1460, 1435, 1328, 1245, 1027, 745, 696 cm-1. 1H NMR (300 MHz, CDCl3): δ = 3.75 (s, 6 H), 4.42 (d, J = 8.4 Hz, 2 H), 5.13 (br, 2 H), 6.15 (d, J = 8.4 Hz, 2 H), 6.87-7.51 (m, 36 H). 31P NMR (121.46 MHz, CDCl3): δ = -10.04. 13C NMR (75 MHz, CDCl3): δ = 167.78, 158.13, 141.06, 140.74, 138.52, 138.35, 137.98, 137.68, 134.97, 134.29, 134.01, 133.74, 130.54, 129.05, 128.81, 128.71, 128.57, 127.17, 126.69, 121.14, 110.66, 55.72, 52.75, 40.29. MS (EI): m/z (%) = 305 (100), 285 (45), 306 (29), 56 (28), 91 (25), 57 (24), 147 (24), 277 (20). MS (ESI): m/z = 875.1 (100) [M+ + 1]. HRMS (MALDI): m/z calcd for C56H49O4N2P2 [M+ + 1]: 875.3162; found: 875.3144.

10

Synthesis of ( S , S , S , S )-5b.
Following the same procedure for the preparation of (S,S,S,S)-5a, reaction of (S,S,S,S)-11b with 2-(diphenylphosphino)benzoic acid afforded (S,S,S,S)-5b as a white solid (yield 78%). [α]D 20 -32.2 (c 1.04, CHCl3). IR (KBr): ν = 2929, 1627, 1584, 1531, 1492, 1461, 1435, 1245, 1026, 747, 696, 545 cm-1. 1H NMR (300 MHz, CDCl3): δ = 2.69-2.73 (m, 2 H), 2.98-3.07 (m, 2 H), 3.25-3.33 (m, 2 H), 3.83 (s, 6 H), 4.30 (d, J = 6.6 Hz, 2 H), 6.29 (br, 2 H), 6.78-7.44 (m, 36 H). 31P NMR (121.46 MHz, CDCl3): δ = -8.86. 13C NMR (75 MHz, CDCl3): δ = 169.50, 157.65, 141.95, 141.61, 137.10, 137.00, 136.30, 136.04, 134.29, 134.23, 134.18, 134.01, 133.90, 130.34, 129.21, 129.05, 128.95, 128.84, 128.79, 128.34, 127.96, 127.92, 127.68, 120.90, 109.82, 55.49, 41.82, 39.52, 36.73. MS (ESI): m/z (%) = 903.45 (100) [M+ + 1]. HRMS (FT): m/z calcd for C58H52O4N2NaP2 [M+ + Na]: 925.3295; found: 925.3277.

13

Synthesis of ( S , S , S , S )-6a.
Anhyd CHCl3 (5 mL) was added to the freshly prepared dichloride 8b (0.2 mmol) and 2-(diphenylphosphino)aniline (0.17 g, 0.6 mmol). The resultant yellow mixture was stirred at r.t. until TLC indicated complete reaction. The mixture was concentrated in vacuo and chromatographed on silica gel with EtOAc-hexane (1:3) as eluent to afford diamide 6a as an amorphous white solid (0.16 g, 95%). [a]D 20 -36.9 (c 1.09, CHCl3). IR (KBr): ν = 3302, 1671, 1574, 1506, 1494, 1434, 1289, 1248, 1028, 746, 696 cm-1. 1H NMR (300 MHz, CDCl3): δ = 3.66-3.81 (m, 8 H), 4.79-4.89 (m, 2 H), 6.61-7.54 (m, 36 H), 7.90-8.10 (m, 2 H). 31P NMR (121.46 MHz, CDCl3): δ = -21.27. 13C NMR (75 MHz, CDCl3): δ = 170.59, 157.44, 141.73, 141.47, 135.97, 135.87, 135.19, 135.10, 134.15, 134.10, 133.90, 133.84, 133.65, 130.23, 129.44, 129.18, 129.06, 128.98, 128.15, 127.62, 127.53, 126.97, 126.83, 124.88, 122.68, 120.83, 110.06, 55.76, 55.72, 45.73, 39.53. MS (ESI): m/z (%) = 875.5 (100) [M+ + 1]. HRMS (FT): m/z calcd for C56H49O4N2P2 [M+ + 1]: 875.3162; found: 875.3163.

14

Following the same procedure for the preparation of 6a, reaction of 8c with 2-diphenylphosphino)aniline afforded (S,S,S,S)-6b as a white solid (yield 80%). [α]D 20 -28.7 (c 1.00, CHCl3). IR (KBr): ν = 1682, 1575, 1508, 1450, 1434, 1288, 1244, 745, 695 cm-1. 1H NMR (300 MHz, CDCl3): δ = 3.70-3.74 (m, 2 H), 4.96-5.01 (m, 4 H), 5.17 (d, J = 12.3 Hz, 2 H), 6.68-7.54 (m, 46 H), 7.90-8.10 (m, 2 H). 31P NMR (121.46 MHz, CDCl3): δ = -21.32. 13C NMR (75 MHz, CDCl3): δ = 170.46, 156.41, 154.96, 141.77, 141.51, 137.54, 136.13, 136.03, 135.10, 135.00, 134.13, 133.87, 133.80, 133.55, 130.44, 130.27, 129.37, 129.04, 128.97, 128.94, 128.90, 128.84, 128.09, 127.92, 127.84, 127.71, 127.21, 127.14, 124.88, 122.81, 121.27, 111.76, 70.24, 70.19, 45.95, 39.70. MS (ESI): m/z (%) = 1027.35 (30) [M+ + 1]. HRMS (FT): m/z calcd for C68H56O4N2P2Na [M+ + Na]: 1049.3608; found: 1049.3616.

17

A General Procedure for Pd-Catalyzed Intramolecular Cyclization of meso -Biscarbamate 15. To a Schlenk tube containing [Pd(C3H5)Cl]2 (1.3 mg, 0.0036 mmol, 2.5 mol%) and chiral ligand 5a (0.009 mmol, 6.0 mol%) was added dried THF (2 mL), and the mixture was stirred at r.t. for 30 min. Then, addition of biscarbamate 15 (74.8 mg, 0.15 mmol) was followed by Et3N (0.024 mL, 0.15 mmol). The resulting clear solution stirred at the indicated temperature for the stated times, and then was quenched with a sat. aq NH4Cl solution (5 mL). The aqueous phase was extracted with Et2O, the combined organic phase was separated and dried over Na2SO4. After removal of the solvent under reduced pressure, the residue was submitted to flash chromatography on silica gel with hexane-EtOAc (3:1) as eluent to product (3R,4S)-16 as a colorless oil in 90% yield. [α]D 20 -136.6 (c 0.90, CHCl3); 97% ee. IR (KBr): ν = 1771, 1355, 1191, 1172, 1146, 1090, 707, 663, 609, 562, 542 cm-1. 1H NMR (300 MHz, CDCl3): δ = 2.45 (s, 3 H), 2.67-2.69 (m, 1 H), 2.82-2.84 (m, 1 H), 5.11 (ddd, J = 8.3, 5.8, 1.8 Hz, 1 H), 5.29 (dd, J = 7.4, 1.3 Hz, 1 H), 6.02-6.04 (m, 2 H), 7.36 (d, J = 8.1 Hz, 2 H), 7.95 (d, J = 8.4 Hz, 2 H). MS (ESI): m/z (%) = 279.95 (5) [M+ + 1]. HRMS (FT): m/z calcd for C13H14NO4S [M+ + 1]: 280.0638; found: 280.0636. The ee was determined with HPLC on a Chiralcel AD column, flow rate: 1.0 mL/min, n-hexane-i-PrOH = 85:15, 30.6 min (3S,4R), 36.6 min (3R,4S); λ = 254 nm.