An easy and efficient method to produce gamma-amino alcohols by reduction of beta-enamino ketones

Abstracts

Reduction of beta-enamino ketones 2 with NaBH4 in glacial acetic acid gave gamma-amino alcohols 1 in 70% to 98% yield with diastereomeric excesses, preferentially the syn product, from 44% to 90%. The stereochemistry of these compounds was confirmed by analysis of their tetrahydro-1,3-oxazine derivatives 3.

amino alcohols; enamino ketones; oxazines; stereoselective reduction

A redução de beta-enamino cetonas 2 com NaBH4 em ácido acético glacial produziu gama-amino álcoois 1 em 70% a 98% de rendimento, com excessos diastereoméricos, preferencialmente o produto syn, de 44% a 90%. A estereoquímica desses compostos foi confirmada pela análise de seus derivados tetraidro-1,3-oxazinas 3.

SHORT REPORT

An easy and efficient method to produce g-amino alcohols by reduction of b-enamino ketones

Maria Inês N. C. Harris; Antonio C. H. Braga^*

Instituto de Química, Universidade Estadual de Campinas, CP 6154, 13083-970 Campinas -SP, Brazil

ABSTRACT

Reduction of b-enamino ketones 2 with NaBH₄ in glacial acetic acid gave g-amino alcohols 1 in 70% to 98% yield with diastereomeric excesses, preferentially the syn product, from 44% to 90%. The stereochemistry of these compounds was confirmed by analysis of their tetrahydro-1,3-oxazine derivatives 3.

Keywords: amino alcohols, enamino ketones, oxazines, stereoselective reduction

RESUMO

A redução de b-enamino cetonas 2 com NaBH₄ em ácido acético glacial produziu g-amino álcoois 1 em 70% a 98% de rendimento, com excessos diastereoméricos, preferencialmente o produto syn, de 44% a 90%. A estereoquímica desses compostos foi confirmada pela análise de seus derivados tetraidro-1,3-oxazinas 3.

Introduction

The synthesis of g-amino alcohols 1 is of great interest due to the pharmacology of these compounds and their derivatives. This functionality is found in several antibiotics and other biologically active natural products.¹ Several synthetic methods have been described for the synthesis of g-amino alcohols 1 from diols,² hydroxazols,³ lactams⁴ and lactones,⁵ but the more important methods are those where one can obtain g-amino alcohols 1 by reduction of 1,3-difunctionalized unsaturated compounds containing nitrogen and oxygen, such as b-hydroxy oximes,⁶b-enamino ketones 2,^7-11 and, more frequently, by the reduction of b-amino ketones.^1,12-15

g-Amino alcohols 1, mainly syn, can be synthesized by reduction of b-enamino ketones 2 with Na in PrⁱOH/tetrahydrofuran or with CeCl₃/ LiBH₄/tetrahydrofuran.⁹ On the other hand, the combination of NaBH₄ in a carboxylic acid media has yielded an efficient reducing reagent.¹⁶

We wish to report herein a simple and efficient method to produce g-amino alcohols 1 through the reduction of b-enamino ketones 2 with NaBH₄ in glacial acetic acid, which has been sucessfully used in our laboratory.¹⁷

Results and Discussion

Difficulties in reduction of b-enamino ketones 2 have been reported.¹⁰ The use of NaBH₄ in a carboxylic acid medium is well known,¹⁶ but its use in the reduction of b-enamino ketones 2 has not been explored. Our results show that the reaction of b-enamino ketones 2 with NaBH₄ in glacial acetic acid (3 hours at room temperature, Scheme 1), produces a mixture of syn/anti g-amino alcohols 1, the syn isomer being the major product (Table 1).¹⁸

When the reaction is carried out without temperature control, the reaction produces the a,b-unsaturated ketone 6 while at 0 °C (hexane/HOAc, CH₂Cl₂/HOAc or HOAc as solvent) the product is a mixture of reactant 2, g-amino alcohol 1 and the corresponding Mannich base 5. Another important observation is that, by this methodology, it is impossible to reduce 3-(N-benzylamino)-2-cyclohexen-1-one.

A mechanism is suggested where chelated intermediate 4 is reduced to produce b-amino ketone 5 and g-amino alcohol 1 (Scheme 2).

Quantitative conversion of g-amino alcohols 1 to the corresponding tetrahydro-1,3-oxazine derivatives 3 (formol in diethyl ether, Scheme 3),¹⁹ allow us to assign the syn stereochemistry to the major g-amino alcohol 1 after inspection of their ¹H and ¹³C NMR spectra. Using the syn-3a compound as an example (Scheme 4), we can see the hydrogen atoms H₄ and H₆ as a double quartet of doublets at 3.27 ppm (J 3.3, 6.3, 11.1 Hz) and 3.68 ppm (J 2.7, 6.3, 12.3 Hz) respectively. These hydrogen atoms and H_5e are in a axial-equatorial situation (q @ 60°), with coupling constants 2.7 Hz (J_H4-H5e) and 3.3 Hz (J_H6-H5e). The ¹H NMR spectrum shows the axial-axial (q @ 180°) relation between H_5a and hydrogen atoms H₆ and H₄ (J_H4-H5a 11.1 Hz; J_H6-H5a 12.5 Hz). Furthermore we can see H_5e and H_5a as a double triplet at 1.57 ppm (J 2.7, 13.5 Hz) and 1.42 ppm (J 11.1, 13.0 Hz), respectively. The analysis of the ¹³C NMR spectrum (Scheme 5) allows the assignement of the secondary carbons at 40.03 ppm and 85.76 ppm (C₅ and C₂ respectively), and the tertiary carbons at 53.90 ppm and 73.43 ppm (C₄ and C₆ respectively). The chemical shifts of the methyl groups were assigned mainly based on the protective anisotropic effect of the phenyl group at C₄. The chemical shift of the carbon C₆ in the syn-3a isomer and in the anti-3a isomer are 73.43 and 68.14 ppm respectively. This upfield shift (ca. 5 ppm) is compatible with a g-gauche exocyclic interaction, showing the axial methyl group at C₄.

In conclusion, the reduction of b-enamino ketones 2 with NaBH₄ in acetic acid is a very simple and fast method to obtain g-amino alcohols 1 (with preferential syn configuration) in good chemical yields.

Experimental

General

¹H NMR and ¹³C NMR spectra were recorded on a GEMINI-300 MHz instrument, using CDCl₃ as a solvent and TMS as internal reference. The IR spectra were recorded on a Perkin Elmer 1600-FTIR (film in NaCl cell) instrument. Elemental analyses were performed on a Perkin Elmer 2400 instrument. The mass spectra were recorded on a HP 5988ª instrument. The gas chromatographic analysis were performed on a Shimadzu GC/MS Class 5000 chromatograph equipped with a Simplicity-1 (SUPELCO) column. The products were purified by flash chromatography or PLC using SiO₂ as a stationary phase.

General procedure to obtain g-amino alcohol, (1). To a solution of b-enamino ketone (2, 1 mmol) in glacial acetic acid (6 mL), was slowly added NaBH₄ (4 mmol). The reaction was kept at 18-20 °C. The reaction was stirred for 3 hours, and then neutralized with an aqueous solution of 30% NaOH (approximatelly 12 mL) in an ice bath. The reaction mixture was extracted with CH₂Cl₂, the organic phases were combined, dried over MgSO₄, and concentrated.

4-(N-Phenylamino)-pentan-2-ol, (1a). IR (neat) n_max/cm^-1: 3350, 3050, 3025, 2970, 2925, 1600, 1500, 1320, 1250, 1130, 750, 690. MS m/z (%): 179(37), 164(15), 120(100), 104(7.6), 93(24), 77(22), 45(24). ¹H NMR syn-1a d: 1.14(d, J 6.2 Hz, 3H), 1.18(d, J 6.2 Hz, 3H), 1.57(AA'XY, 2H), 3.41(s, large, 2H), 3.66(sext, J 6.5 Hz, 1H), 4.01(sext, J 6.0 Hz, 1H), 6.57-6.79(m, 3H), 7.12-7.24(m, 2H). ¹³C NMR syn-1a d: 147.13, 129.46, 118.98, 115.29, 67.97, 49.89, 45.76, 23.98, 21.46. ¹H NMR anti-1a d: 1.17(2 d, 6H), 1.43-1.70(m, 2H), 3.20(s, large, 2H), 3.76(m, 1H), 3.91(m, 1H), 6.49-6.67(m, 3H), 7.00-7.10(m, 2H). ¹³C NMR anti-1a d: 147.73, 129.37, 117.61, 113.73, 67.25, 46.05, 45.70, 24.04, 21.32. Anal. Calc. for C₁₁H₁₇NO: C, 73.70; H, 9.56; N, 7.82%. Found: C, 73.91; H, 9.56; N, 7.62%.

4-(N-Benzylamino)-pentan-2-ol, (1b). IR (neat) n_max/cm^-1: 3346, 3286, 3076, 2964, 2925, 1452, 1374, 1165, 1129, 1088, 742, 698. MS m/z (%): 193(5), 178(15), 134(83), 106(28), 91(100). ¹H NMR syn-1b d: 1.12(d, J 6.3 Hz, 3H), 1.17(d, J 8.1 Hz, 3H), 1.20-1.55(m, 2H), 2.92(dqd, J 2.7, 6.3, 10.6 Hz, 1H), 3.71(d, J 13.0 Hz, 1H), 3.90(s, large, 1H), 3.93(d, J 13.0 Hz, 1H), 3.94(dqd, J 2.3, 5.8, 17.0 Hz, 1H), 7.20-7.36(m, 5H). ¹³C NMR syn-1b d: 139.24, 128.72, 128.49, 127.48, 68.94, 54.08, 50.64, 44.91, 23.87, 20.82. ¹H NMR anti-1b d: 1.15(d, J 8.1 Hz, 3H), 1.21(d, J 6.6 Hz, 3H), 1.43(ddd, J 2.7, 5.1, 14.4 Hz, 1H), 1.70(ddd, J 3.3, 9.0, 14.4 Hz, 1H), 3.12(dqd, J 3.2, 3.9, 6.6 Hz, 1H), 3.50(s, large, 2H), 3.74(d, J 12.6 Hz, 1H), 3.86(d, J 12.6 Hz, 1H), 4.15(dqd, J 3.0, 6.2, 9.0 Hz, 1H), 7.20-7.37(m, 5H). ¹³C NMR anti-1b d: 139.51, 128.73, 128.43, 127.45, 65.03, 51.48, 51.97, 45.06, 23.56, 19.76. Anal. Calc. for C₁₂H₁₉NO: C, 74.55; H, 9.91; N, 7.25%. Found: C, 74.48; H, 10.17; N, 7.31%.

4-(N-isopropylamino)-pentan-2-ol, (1c). IR (neat) n_max/cm^-1: 3340, 3274, 2965, 2927, 1560, 1461, 1382, 1163, 1133, 1084. MS m/z (%): 145(0.2), 130(15), 86(65), 45(25). ¹H NMR syn-1c d: 1.08(d, J 6.0 Hz, 3H), 1.10(d, J 5.6 Hz, 3H), 1.11(d, J 6.2 Hz, 3H), 1.14(d, J 6.2 Hz, 3H), 1.20-1.40(m, 1H), 1.53(ddd, J 2.2, 2.8, 14.0 Hz, 1H), 3.00(hept, J 6.4 Hz, 1H), 3.05(m, 1H), 3.97(dqd, J 1.8, 6.2, 10.7 Hz, 1H), 4.30(s, large, 2H). ¹³C NMR syn-1c d: 69.07, 51.68, 45.35, 45.03, 24.23, 24.01, 21.72, 21.13. ¹H NMR anti-1c d: 1.10(d, J 6.2 Hz, 3H), 1.13(d, J 6.3 Hz, 3H), 1.18(d, J 6.3 Hz, 3H), 1.20(d, J 6.6 Hz, 3H), 1.20-1.40(m, 1H), 1.65(ddd, J 3.3, 8.1, 13.0 Hz, 1H), 3.00(hept, J 6.4 Hz, 1H), 3.26(dqd, J 3.8, 6.3, 6.7 Hz, 1H), 4.16(dqd, J 3.2, 5.9, 8.4 Hz, 1H), 4.30(s, large, 2H). ¹³C NMR anti-1c d: 65.03, 48.25, 45.77, 41.23, 23.51, 22.70, 22.05, 19.51.

1-Phenyl-3-(N-isopropylamino)-butan-1-ol, (1d). IR (neat) n_max/cm^-1: 3270, 3200, 3040, 3020, 2980, 2880, 1470, 1380, 1330, 1100, 1070, 750, 700. MS m/z (%): 207(4.6), 192(2), 107(4.6), 105(6.9), 86(100), 77(20), 70(37). ¹H NMR syn-1d d: 1.30-1.35(3d, 9H), 1.67(td, J 10.7, 14.5 Hz, 1H), 1.92(td, J 2.5, 14.5 Hz, 1H), 3.21(hept, J 6.2 Hz, 1H), 3.18-3.35(dqd, J 2.6, 5.8, 7.0 Hz, 1H), 4.47(s, large, 2H), 5.07(dd, J 1.5, 10.6 Hz, 1H), 7.37-7.60(m, 5H). ¹³C NMR syn-1d d: 145.55, 128.11, 126.79, 125.53, 75.08, 51.63, 46.38, 45.30, 24.39, 21.93, 21.83. ¹H NMR anti-1d d: 1.00(d, J 6.3 Hz, 3H), 1.03(d, J 6.3 Hz, 3H), 1.07(d, J 6.3 Hz, 3H), 1.65(ABMX, J 3.9, 7.0, 14.0 Hz, 1H), 1.74(ABMX, J 3.6, 6.0, 15.0 Hz, 1H), 2.82(hept, J 6.3 Hz, 1H), 2.90(m, 1H), 3.82(s, large, 2H), 4.88(dd, J 3.7, 6.7 Hz, 1H), 7.06-7.30(m, 5H). ¹³C NMR anti-1d d: 150.09, 131.91, 130.34, 129.71, 75.19, 51.93, 49.63, 47.58, 27.83, 26.82, 24.70. Anal. Calc. for C₁₃H₂₁NO: C, 75.32; H, 10.21; N, 6.75%. Found: C, 75.10; H, 10.22; N, 6.26%.

4-(N-Pyrrolidinyl)-pentan-2-ol, (1e). IR (neat) n_max/cm^-1: 3400, 2980, 2940, 2880, 2830, 1455, 1160, 1150. MS m/z (%): 157(4.2), 142(9), 96(100), 70(24), 56(20), 45(24). ¹H NMR syn-1e d: 0.97(d, J 6.6 Hz, 3H), 1.13(d, J 6.2 Hz, 3H), 1.34(ddd, J 1.8, 3.6, 14.5 Hz, 1H), 1.52(td, J 10.9, 14.0 Hz, 1H), 1.70-1.80(AA'B₂, 4H), 2.57-2.80(AA'B₂, 4H), 3.17(dqd, J 3.3, 6.9, 10.5 Hz, 1H), 3.96(dqd, J 2.0, 6.2, 10.3 Hz, 1H), 6.24(s, large, 1H). ¹³C NMR syn-1e d: 69.08, 55.56, 46.70, 41.94, 23.67, 23.23, 12.43. ¹H NMR anti-1e d: 1.21(d, J 6.2 Hz, 3H), 1.25(d, J 6.6 Hz, 3H), 1.55(ddd, J 2.6, 7.0, 14.0 Hz, 1H), 1.83(ddd, J 6.1, 10.6, 14.0 Hz, 1H), 1.94-2.20(m, 4H), 3.09(t, J 6.5 Hz, 4H), 3.50(sext, J 6.6 Hz, 1H), 3.90(dqd, J 1.8, 5.6, 11.0 Hz, 1H), 5.20(s, large, 1H). ¹³C NMR anti-1e d: 64.43, 57.62, 51.48, 41.05, 23.52, 23.28, 17.28.

General procedure to obtain tetrahydro-1,3-oxazines, (3). To a solution of g-amino alcohol (1, 1mmol) in diethyl ether (1 mL), was added a solution of 40% formaldehyde (0.1 mL). The reaction was stirred for 16-20 hours at room temperature. After this time, diethyl ether (approximatelly 5 mL) was added, and the solution was dried over MgSO₄, filtered and concentrated in vacuo. The yield was quantitative.

3-Phenyl-4,6-dimethyl-tetrahydro-1,3-oxazine, (3a). IR (neat) n_max/cm^-1: 2960, 2920, 1600, 1485, 1370, 1250, 1240, 1175, 1100, 1000, 700. MS m/z (%): 192(7), 191(50), 190(11), 176(58), 132(83), 120(50), 119(83), 118(22), 106(33), 105(83), 104(91), 91(14), 77(100). ¹H NMR syn-3a d: 1.02(d, J 6.3 Hz, 3H), 1.26(d, J 6.3 Hz, 3H), 1.42(dt, J 11.1, 13.0 Hz, 1H), 1.57(dt, J 2.7, 13.5 Hz, 1H), 3.73(ddq, J 3.3, 6.3, 11.1 Hz, 1H), 3.68(ddq, J 2.7, 6.3, 12.3 Hz, 1H), 4.39(d, J 9.3 Hz, 1H), 4.73(d, J 9.3 Hz, 1H), 7.06-7.33(m, 5H). ¹³C NMR syn-3a d: 147.57, 129.02, 126.32, 124.83, 85.76, 73.43, 53.90, 40.03, 21.70, 20.04. ¹H NMR anti-3a d: 1.16(d, J 6.3 Hz, 3H), 1.25(dt, J 2.0, 13.0 Hz, 1H), 1.41(d, J 6.9 Hz, 3H), 1.75(ddd, J 5.4, 12.0, 13.8 Hz, 1H), 3.95(m, 2H), 4.83(d, J 11.1 Hz, 1H), 4.98(d, J 11.4 Hz, 1H), 6.85(t, J 8.4 Hz, 1H), 7.03(d, J 7.8 Hz, 2H), 7.22(dd, J 7.2, 8.7 Hz, 2H). ¹³C NMR anti-3a d: 150.88, 129.35, 120.65, 119.08, 74.85, 68.14, 52.79, 35.76, 22.07, 17.07. Anal. Calc. for C₁₂H₁₇NO: C, 75.35; H, 8.96; N, 7.32%. Found: C, 74.80; H, 8.80; N, 7.37%.

3-Benzyl-4,6-dimethyl-tetrahydro-1,3-oxazine, (3b). IR (neat) n_max/cm^-1: 2980, 2940, 1450, 1370, 1200, 1050, 740, 700. MS m/z (%): 206(3), 205(17), 204(8), 190(38), 146(14), 92(42), 91(100). ¹H NMR syn-3b d: 1.13(d, J 6.0 Hz, 6H), 1.20-1.40(m, 2H), 2.95(m, 1H), 3.47(d, J 13.5 Hz, 1H), 3.47(m, 1H), 3.79(d, J 13.5 Hz, 1H), 3.92(d, J 10.2 Hz, 1H), 4.21(d, J 10.2 Hz, 1H), 7.20-7.40(AA'BBC, 5H). ¹³C NMR syn-3b d: 139.43, 128.39, 127.74, 126.32, 83.00, 72.79, 55.29, 48.92, 37.29, 21.74, 20.16. ¹H NMR anti-3b d: 1.17(d, J 6.0 Hz, 3H), 1.25(d, J 6.0 Hz, 3H), 1.10-1.20(AXYZ, 1H), 1.88(AXYZ, 1H), 2.98(q, J 6.0 Hz, 1H), 3.81(dqd, 1H), 3.96(AA', 2H), 4.25(d, J 11.0 Hz, 1H), 4.65(d, J 11.0 Hz, 1H), 7.40-7.20(m, 5H). ¹³C NMR anti-3b d: 139.67, 128.50, 128.23, 126.89, 78.47, 67.80, 56.92, 49.28, 32.58, 22.20, 18.10. Anal. Calc. for C₁₃H₁₉NO: C, 76.06; H, 9.33; N, 6.82%. Found: C, 76.58; H, 9.23; N, 6.60%.

3-Isopropyl-4,6-dimethyl-tetrahydro-1,3-oxazine, (3c). MS m/z (%): 157(20), 142(100), 114(9), 100(14), 98(45), 56(81). ¹H NMR syn-3c d: 0.92(d, J 6.6 Hz, 3H), 1.09(d, J 6.6 Hz, 6H), 1.15(d, J 6.9 Hz, 3H), 1.03-1.24(m, 2H), 2.75(dqd, J 3.0, 12.0 Hz, 1H), 3.22(hept, J 6.0 Hz, 1H), 3.39(dqd, J 3.0, 6.0, 12.0 Hz, 1H), 3.82(d, J 8.7 Hz, 1H), 4.49(d, J 9.0 Hz, 1H). ¹³C NMR syn-3c d: 78.47, 72.65, 52.55, 45.03, 41.38, 21.98, 21.68, 19.63, 17.18. ¹H NMR anti-3c d: 1.02-1.24(m, 1H), 1.09(d, J 6.6 Hz, 6H), 1.27(d, J 6.3 Hz, 3H), 1.99(d, J 7.2 Hz, 3H), 1.62(m, 1H), 3.03(hept, J 6.0 Hz, 1H), 3.15(quint, J 6.0 Hz, 1H), 3.65(dqd, J 3.0, 6.0, 10.5 Hz, 1H), 4.36(AA', 2H). ¹³C NMR anti-3c d: 75.72, 67.20, 51.07, 46.92, 34.72, 22.81, 22.33, 21.82, 18.87.

6-Phenyl-3-isopropyl-4-methyl-tetrahydro-1,3-oxazine, (3d). IR (neat) n_max/cm^-1: 2967, 2922, 2871, 1604, 1495, 1452, 1383, 1210, 1079. MS m/z (%): 220(4.3), 219(26.5), 205(10.6), 204(67.4), 174(5.6), 140(5.2). ¹H NMR syn-3d d: 1.02(d, J 6.4 Hz, 3H), 1.20(d, J 6.5 Hz, 3H), 1.26(d, J 6.7 Hz, 3H), 1.69(AA'Y, 2H), 2.99(dqd, J 3.2, 6.4, 10.7 Hz, 1H), 3.36(hept, J 6.6 Hz, 1H), 4.45(dd, J 3.7, 10.6 Hz, 1H), 4.65(d, J 8.9 Hz, 1H), 4.84(d, J 8.9 Hz, 1H), 7.21-7.45(m, 5H). ¹³C NMR syn-3d d: 142.63, 128.42, 127.51, 125.96, 79.76, 79.68, 53.13, 45.67, 41.89, 21.96, 19.72, 16.93. ¹H NMR anti-3d d: 1.14(d, J 6.4 Hz, 3H), 1.18(d, J 6.5 Hz, 3H), 1.34(d, J 7.2 Hz, 3H), 1.60(m, 1H), 1.93(ddd, J 6.0, 11.8, 13.4 Hz, 1H), 3.15(quint, J 6.6 Hz, 1H), 3.25(m, J 6.3 Hz, 1H), 4.59(AA', 2H), 4.60(dd, J 3.2, 9.7 Hz, 1H), 7.20(m, 5H). ¹³C NMR anti-3d d: 143.57, 127.91, 126.78, 125.38, 76.33, 73.57, 51.68, 47.31, 35.55, 22.86, 21.95, 18.80. Anal. Calc. for C₁₄H₂₁NO: C, 76.06; H, 9.33; N, 6.82%. Found: C, 76.58; H, 9.23; N, 6.60%.

3-Benzyl-4-methyl-6-terc-butyl-tetrahydro-1,3-oxazine, (3f). IR (neat) n_max/cm^-1: 2956, 2869, 1188, 1105, 1027, 734, 698. MS m/z (%): 232(9), 190(12), 146(15), 118(4), 91(100). ¹H NMR syn-3f d: 0.71(s, 9H), 1.02(d, J 6.6 Hz, 3H), 1.12(dt, J 2.8, 11.3 Hz, 1H), 1.29(AXYZ, 1H), 2.79(dqd, J 3.0, 6.6, 11.3 Hz, 1H), 2.87(dd, J 11.3, 2.6 Hz, 1H), 3.35(d, J 13.5 Hz, 1H), 3.65(d, J 13.5 Hz, 1H), 3.83(dd, J 0.9, 9.8 Hz, 1H), 4.20(d, J 9.8 Hz, 1H), 6.93-7.21(m, 5H). ¹³C NMR syn-3f d: 139.34, 128.74, 127.95, 126.56, 84.55, 83.34, 55.07, 48.26, 34.01, 29.41, 25.64, 20.44.

Acknowledgment

The authors thank the FINEP-Financiadora de Estudos e Projetos for financial support.

References

1. For a general review see: Gevorgyan, G. A.; Agababian, G.; Russ. Chem. Rev. 1984, 53, 581; Jäger, V.; Bub, V.; Liebigs Ann. Chem. 1980, 101; Wang, Y. F.; Izawa, T.; Kobayashi, S.; Ohno, M.; J. Am. Chem. Soc. 1982, 104, 6465; Heitsch, H.; König, W. A.; Decker, H.; Bormann, C.; Fiedler, H. P.; Zähner, H.; J. Antibiotics 1989, 42, 711; Wovkulich, P. M.; Uskokovic, M. R.; J. Am. Chem. Soc. 1981, 103, 3956; Jäger, V.; Schwab, W.; Bub, V.; Angew. Chem. Int. Ed. Engl. 1981, 20, 601.

2. White, D. W.; Gibbs, D. E.; Verkade, J. G.; J. Am. Chem. Soc. 1979, 101, 1937.

3. Liguori, A.; Romeo, G.; Sindona, G.; Ucella, N.; Chem. Ber. 1988, 121, 105.

4. Bongini, A.; Cardillo, G.; Orena, M.; Porzi, G.; Sandri, S.; Chem. Lett. 1988, 87.

5. Arisa, J.; Font, J.; Ortuño, R. M.; Tetrahedron 1990, 46, 1931.

6. Narasaka, K.; Ukaji, Y.; Yamazaki, S.; Bull. Chem. Soc. Jpn. 1986, 59, 525.

7. Maroni, P.; Cazaux, L.; Tisnes, P.; Zambeti, M.; Bull. Soc. Chim. Fr. P II 1980, 179.

8. Matsumura, Y.; Fujiwara, J.; Maruoka, K.; Yamamoto, H.; J. Am. Chem. Soc. 1983, 105, 6312.

9. Bartoli, G.; Cimarelli, C.; Palmieri, G.; J. Chem. Soc., Perkin Trans. 1 1994, 537.; Bartoli, G.; Cupone, G.; Dalpozzo, R.; De Nino, A.; Maiuolo, L.; Procopio, A.; Tagarelli, A.; Tetrahedron Lett. 2002, 43, 7441.

10. Greenhill, J. V.; Chem. Soc. Rev. 1977, 6, 277.

11. Schuda, P. F.; Ebner, C. B.; Morgan, T. M.; Tetrahedron Lett. 1986, 27, 2567.

12. Barluenga, J.; Aguilar, E.; Fustero, S.; Olano, B.; Viado, A. L.; J. Org. Chem. 1992, 57, 1219.

13. Katritzky, A.; Harris, P. A.; Tetrahedron 1990, 46, 987.

14. Pilli, R. A.; Russowsky, D.; Dias, L. C.; J. Chem. Soc., Perkin Trans. 1 1990, 1213.

15. Tramontini, M.; Synthesis 1982, 605.

16. For a comprehensive review of uses of borohydrides in carboxylic acid media see: Gribble, G. W.; Nutaitis, C. F.; Org. Prep. Proc. Int. 1985, 17, 317; Gribble, G. W.; Chem. Soc. Rev. 1998, 27, 395.

17. Harris, M. I. N. C.; PhD. Thesis, Universidade Estadual de Campinas, Brazil, 1993; Braga, A. C. H.; Harris, M. I. N. C.; Br PI 9.502.467-0, 1995. (CA 128:243740).

18. It is well known that the reaction of NaBH₄ with neat carboxilic acids or solutions of carboxilic acids in nonprotic solvents leads to the formation of acyloxyborohydrides.¹⁶ In order to understand the real nature of the reducing agent, studies with sodium triacetoxyborohydride are in progress.

19. Barluenga, J.; Olano, B.; Fustero, S.; J. Org. Chem. 1985, 50, 4052.

Received: March 9, 2004

Published on the web: September 28, 2004

Publication Dates

• Publication in this collection
  24 Jan 2005
• Date of issue
  Dec 2004

History

• Accepted
  28 Sept 2004
• Received
  09 Mar 2004