Synlett 2006(1): 0133-0136  
DOI: 10.1055/s-2005-922783
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© Georg Thieme Verlag Stuttgart · New York

Phosphorodiamidic Acid as a Novel Structural Motif of Brønsted Acid Catalysts for Direct Mannich Reaction of N-Acyl Imines with 1,3-Dicarbonyl Compounds

Masahiro Terada*, Keiichi Sorimachi, Daisuke Uraguchi
Department of Chemistry, Graduate School of Science, Tohoku University, Aoba-ku, Sendai 980-8578, Japan
Fax: +81(22)7956602; e-Mail: mterada@mail.tains.tohoku.ac.jp;
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Publikationsverlauf

Received 7 October 2005
Publikationsdatum:
16. Dezember 2005 (online)

Abstract

Phosphorodiamidic acid 1 was developed as an efficient Brønsted acid catalyst for the direct Mannich reaction of N-acyl imines with 1,3-dicarbonyl compounds. Phosphorodiamidic acids were proposed as a novel structural motif of enantioselective ­Brønsted acid catalysts because they possess unique features, including the capability of introducing various substituents to the nitrogen atoms and the preparation from readily available chiral diamines in a short step. We demonstrated that chiral phosphorodiamidic acid 1b derived from binaphthalene bis(sulfonamide) functioned as an enantioselective catalyst to give the Mannich product in an optically active form.

1

Present address: Sagami Chemical Research Center, Ayase 252-1193, Japan.

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Preparation of Phosphorodiamidic Acid ( 1a).
N,N′-Ditosylbenzene-1,2-diamine (208.3 mg, 0.5 mmol), prepared according to the literature procedure, [23] was dissolved into pyridine (1 mL) under nitrogen atmosphere. To the resulting solution was added phosphorus oxychloride (115.0 mg, 0.75 mmol) at r.t. After being stirred for 12 h at ambient temperature, H2O (1 mL) was poured into the reaction mixture. The resulting suspension was stirred for additional 30 min. Then, EtOAc was added and all pyridine was removed by reverse extraction with 1 N HCl. The organic phase was dried over Na2SO4. After being concentrated, the residue was purified by column chromatography. Compound 1a was isolated as a white solid in 90% yield. 1H NMR (270 MHz, DMSO-d 6,): δ = 2.30 (6 H, s), 6.79-6.86 (2 H, m), 7.17-7.24 (2 H, m), 7.31 (4 H, d, J = 8.4 Hz), 8.02 (4 H, d, J = 8.4 Hz). 13C NMR (67.8 MHz, DMSO-d 6): δ = 21.0, 113.1 (d, J P-C = 5.4 Hz), 122.9, 126.8 (t, J P-C = 10.3 Hz), 127.9, 129.5, 135.7, 144.2. IR (KBr): 3425, 3072, 1375, 1175, 1119 cm-1. HRMS (ESI): m/z calcd for C20H19N2O6PS2 [M - H]-: 477.0349. Found: 477.0351.

16

The distribution of keto-enol tautomers of 3 in CDCl3 was measured by 1H NMR. The percentages of the enol form are listed as follows: 3a: 72%; 3b: 61%; 3c: >98%; 3d: 6%; 3e: 6%; 3f: 21%; 3g: <2%.

17

Although in the case of unsymmetrical 1,3-dicarbonyl compounds, keto esters 3d,e and keto amide 3f, the diastereomeric mixtures were obtained, their ratios were changed during the course of experiment.

20

Compound (R)-1b: [α]D 150 (c 0.99, CHCl3). 1H NMR (270 MHz, DMSO-d 6): δ = 3.33 (6 H, s), 6.23 (4 H, d, J = 8.1 Hz), 6.74 (2 H, d, J = 7.6 Hz), 7.01 (4 H, d, J = 8.1 Hz), 7.10 (2 H, t, J = 7.6 Hz), 7.37 (2 H, t, J = 7.6 Hz), 7.43 (2 H, d, J = 7.6 Hz), 7.73 (2 H, d, J = 7.6 Hz), 7.75 (2 H, d, J = 7.6 Hz). 13C NMR (67.8 MHz, DMSO-d 6): δ = 20.9, 125.3, 125.4, 125.8, 127.1, 127.4 (d, J P-C = 1.0 Hz), 127.8, 128.1 (t, J P-C = 1.5 Hz), 130.8 (t, J P-C = 1.5 Hz), 131.1 (d, J P-C = 1.0 Hz), 131.5 (d, J P-C = 1.0 Hz), 132.1, 134.5-134.6 (m), 137.6-137.8 (m), 140.6 (d, J P-C = 4.9 Hz). IR (KBr): 3458, 3055, 2910, 1344, 1171, 1113 cm-1. HRMS (ESI): m/z calcd for C34H27N2O6PS2 [M - H]-: 653.0975. Found 653.0975.

21

Compound 4e: white solid; R f = 0.20 (hexane-EtOAc, 2:1). HPLC analysis Chiralpak AD-H (hexane-EtOH, 80:20, 1.0 mL/min, 254 nm, 10 °C) 19.1 (S), 27.3 (R) min. 1H NMR (270 MHz, CDCl3): δ = 2.12 (3 H, s), 2.32 (3 H, s), 4.41 (1 H, d, J = 4.9 Hz), 6.06 (1 H, dd, J = 9.2, 4.9 Hz), 7.22-7.54 (8 H, m), 7.77-7.86 (2 H, m), 7.97 (1 H, br d, J = 9.2 Hz). 13C NMR (67.8 MHz, CDCl3): δ = 29.8, 31.6, 52.3, 70.0, 126.3, 127.1, 127.8, 128.6, 128.8, 131.8, 133.7, 139.2, 166.8, 202.6, 205.9. IR (KBr): 3369, 3032, 2918, 1724, 1639, 1522 cm-1. HRMS (ESI): m/z calcd for C19H19NaNO3 [M + Na]+: 332.1257. Found: 332.1260.

22

The absolute configuration of Bz-product 4e was determined after transformation into the stereochemically known N-benzoylphenylglycine methyl ester. The stereochemical determination of 4a and the experimental procedure for derivatization of 4 to N-protected glycine methyl ester were described in ref. 8a.