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Regio- and Stereo-chemical Effects in the Hydroboration ofΔ2-Steroidal Allylic and HomoallylicAlcohols†

 

作者: James R. Hanson,  

 

期刊: Journal of Chemical Research, Synopses  (RSC Available online 1997)
卷期: Volume 0, issue 8  

页码: 282-283

 

ISSN:0308-2342

 

年代: 1997

 

DOI:10.1039/a702014g

 

出版商: RSC

 

数据来源: RSC

 

摘要:

R2 R1 H 1 R1 = H, R2 = O 2 R1 = OH, R2 = a-H, 17b-OAc OH R1 H R1 R1 = H R1 = OH HO R1 = H R1 = OH not detected (13) OH HO (29) OH HO (8) OH OH OH R1 H R1 R1 = H R1 = OH (35) not detected R1 = H R1 = OH (17) not detected OH (20) OH (30) HO HO HO HO + + + + a-addition b-addition a-addition b-addition (28) (18 as 17b-acetate) (40 as 17b-alcohol) + 3 HO 282 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 282–283† Regio- and Stereo-chemical Effects in the Hydroboration of D2-Steroidal Allylic and Homoallylic Alcohols† James R.Hanson,* Mansur D. Liman and Sivajini Nagaratnam School of Molecular Sciences, University of Sussex, Brighton, Sussex BN1 9QJ, UK A comparison between the hydroboration of D2-steroidal 1a-allylic and 5a-homoallylic alcohols reveals that whereas both have a stereochemical directing effect, only the allylic alcohol modifies the regiospecificity of the reaction. An allylic hydroxy group has a significant effect on the products that are formed from an alkene by hydroboration and oxidation with alkaline hydrogen peroxide.1–3 In cyclic systems a significant proportion of the addition takes place adjacent and trans to the hydroxy group of the allylic alchol.4 These effects on regioselectivity may compete with the normal stereochemical directing effects of the steroid carbon skeleton.5,6 In order to evaluate the relative significance of electronic and steric contributions, we compared the results of hydroboration of the a-oriented axial allylic alcohol, 17b-acetoxy-1a-hydroxy-5a-androst-2-ene (2) and the a-oriented axial homoallylic alcohol, 5a,17b-dihydroxy- 5a-androst-2-ene (3).In both cases the axial hydroxy group is trans to the sterically directing 10b-methyl group. The substrates were prepared by literature methods.7,8,9 The hydroboration and oxidation reactions were carried out using 1 M borane in tetrahydrofuran followed by oxidation with alkaline hydrogen peroxide.The products were separated by chromatography on silica and the results are shown in Fig. 1. The structures of the products were established from the multiplicity of the CH(OH) resonances in the 1H NMR spectrum10 and by comparison with literature data.11 The axial 2b-H of 2a,17b-dihydroxy- and 2a,5a,17b-trihydroxy- 5a-androstane appeared as a triplet (J 10.9 Hz) of triplets (J 4.6 Hz) indicative of two diaxial and two axial:equatorial couplings. In 17b-acetoxy-1a,2a-dihydroxy-5a-androstane and the corresponding triol, the 2b-H (dH 3.82 and 3.85 respectively) appeared as a doublet (J 10.9 Hz) of doubledoublets (J 2.9 and 5.2 Hz).The 1b-H of the 17b-acetate was a doublet (dH 3.66, J 2.9 Hz). The smaller 1b:2a-coupling constant is probably indicative of a slightly different conformation of ring A brought about by hydrogen bonding in the 1:2 glycol. The equatorial 2a-H signals were broad singlets. The 3a,17b- and 3b,17b-dihydroxy- and 3a,5a,17b- and 3b,5a,17b-trihydroxy-5a-androstanes were known compounds. 11–13 *To receive any correspondence. †This is a Short Paper as defined in the Instructions for Authors, Section 5.0 [see J. Chem. Research (S), 1997, Issue 1]; there is therefore no corresponding material in J. Chem. Research (M). Fig. 1 Yields (%) of hydroboration products of androst-2-enesJ. CHEM. RESEARCH (S), 1997 283 The influence of the allylic hydroxy group on the regiochemistry of the reaction can be seen in the increased proportion of hydroboration of 17b-acetoxy-1a-hydroxy-5a-androst- 2-ene at C-2 compared to the unsubstituted case.However the potential 1:3-diaxial interaction with the 10b-methyl group reduces the trans directing effect of the hydroxy group. On the other hand the homoallylic 5a-hydroxy group had relatively little effect on the position of the hydroboration but increased the proportion of b-face addition possibly through the formation of bulky borate esters on the a-face of the molecule.Experimental General experimental details have been described previously.5 The steroids were crystallized from ethyl acetate or acetone:light petroleum mixtures. 5a-Androst-2-en-17-one (1) had mp 107–108 °C (lit.,7 108–109 °C). 17b-Acetoxy-1a-hydroxyandrost- 2-ene, prepared by the treatment of 17b-acetoxy-1a,2a-epoxyandrostan- 3-one with hydrazine hydrate,8 had mp 131– 133 °C (Found: C, 75.4; H, 9.8. C21H32O3 requires C, 75.9; H, 9.7%), vmax/cmµ1 3510, 1734; dH (CDCl3) 0.72 (3 H, s, 18-H), 0.81 (3 H, s, 19-H), 2.04 (3 H, s, OAc), 3.71 (1 H, brs, 1b-H), 4.59 (1 H, t, J 8 Hz, 17a-H), 5.87 (2 H, s, 2- and 3-H). 5a,17b-Dihydroxyandrost-2-ene had mp 171–173 °C (lit.,9 171–172 °C). Hydroboration Experiments.·(a) 5a-Androst-2-en-17-one (1) (1 g) in dry THF (30 cm3) was treated with 1 M borane in THF (20 cm3) under nitrogen at 0 °C for 4 h. Water (10 cm3) was added and the solution was cooled. Aqueous 10% sodium hydroxide (20 cm3) was added followed by the dropwise addition of 30% hydrogen peroxide (30 cm3).The mixture was stirred overnight. Sodium sul- fite (2 g) was added followed by acetic acid (1 cm3), water (50 cm3), dil. hydrochloric acid (100 cm3) and ethyl acetate (100 cm3). The mixture was stirred for a further 15 min. The organic phase was separated, washed with water, brine and dried. The solvent was evaporated to give a residue which was chromatographed on silica. Elution with 25% ethyl acetate:light petroleum gave 3a,17b-dihydroxy- 5a-androstane (370 mg), prisms, mp 221–223 °C (lit.,11 222–224 °C).Elution with 28% ethyl acetate:light petroleum gave 3b,17b-dihydroxy-5a-androstane (180 mg), needles, mp 167– 169 °C) (lit.,11 168 °C). Further elution with 30% ethyl acetate:light petroleum gave 2a,17b-dihydroxy-5a-androstane (302 mg), needles, mp 172–174 °C (Found: C, 77.7; H, 11.0. C19H32O2 requires C, 78.0; H, 11.0%), vmax/cmµ1 3490, 3382; dH (CDCl3) 0.73 (3 H, s, 18-H), 0.80 (3 H, s, 19-H), 3.63 (1 H, t, J 8.6 Hz, 17a-H), 3.77 (1 H, tt, J 4.6 and 10.9 Hz, 2b-H).(b) 17b-Acetoxy-1a-hydroxy-5a-androst-2-ene (2) (600 mg) in dry THF (20 cm3) was treated with 1 M borane in THF (14 cm3) and oxidized with aqueous sodium hydroxide and hydrogen peroxide as above. The product was chromatographed on silica. Elution with 20% ethyl acetate:light petroleum gave 17b-acetoxy-1a,2a-dihydroxy- 5a-androstane (110 mg), needles, mp 113–114 °C (Found: C, 68.7; H, 9.5.C21H34O4 requires C, 68.7; H, 9.8%), vmax/cmµ1 3512, 1732; dH (CDCl3) 0.77 and 0.78 (each 3 H, s, 18- and 19-H), 2.03 (3 H, s, OAc), 3.66 (1 H, d, J 2.9 Hz, 1b-H), 3.82 (1 H, ddd, J 2.9, 5.2 and 10.9 Hz, 2b-H), 4.56 (1 H, t, J 8.2 Hz, 17a-H). Irradiation of the signals at dH 0.77 and 0.78 caused an nOe enhancement of the resonances at dH 3.66 (3.1%) and 3.82 (6.5%). Further elution gave 1a,2b,17b-trihydroxy-5a-androstane (80 mg), needles, mp 152–155 °C (Found: C, 71.5; H, 10.6.C19H32O3.0.5H2O requires C, 71.8; H, 10.5%), vmax/cmµ1 3340; dH (CDCl3) 0.74 (3 H, s, 18-H), 0.77 (3 H, s, 19-H), 3.65 (1 H, t, J 8.2 Hz, 17a-H), 3.74 (3 H, s, 1b-H), 4.11 (1 H, brs, 2a-H). Irradiation of the signal at dH 0.77 produced an nOe enhancement of the signal at dH 3.74 (1.9%). Further elution gave 1a,2a,17b-trihydroxy-5a-androstane (240 mg), needles, mp 140–142 °C (Found: C, 71.4; H, 10.3. C19H32O3.0.5H2O requires C, 71.8; H, 10.5%), vmax/cmµ1 3210; dH (CDCl3) 0.74 (3 H, s, 18-H), 0.79 (3 H, s, 19-H), 3.64 (2 H, m, 1b- and 17a-H), 3.85 (1 H, ddd, J 2.9, 5.2 and 10.9 Hz, 2b-H).(c) 5a,17b-Dihydroxyandrost-2-ene (1.2 g) was treated with 1 M borane in THF (20 cm3) and oxidized with aqueous sodium hydroxide and hydrogen peroxide as above. The products were separated by chromatography on silica. Elution with 30% ethyl acetate:light petroleum gave 3a,5a,17b-trihydroxyandrostane (251 mg), plates, mp 193–195 °C (lit.,12 194–196 °C).Further elution gave 2b,5a,17b-trihydroxyandrostane (105 mg), needles, mp 207–209 °C (Found: C, 70.0; H, 11.0. C19H32O3.H2O requires C, 69.9; H, 10.5%), vmax/cmµ1 3499, 3391, 3320; dH (CDCl3) 0.74 (3 H, s, 18-H), 1.21 (3 H, s, 19-H), 3.65 (1 H, t, J 8.5 Hz, 17a-H), 4.18 (1 H, brs, 2a-H). Elution with 32% ethyl acetate:light petroleum gave 2a,5a,17b-trihydroxyandrostane (368 mg), prisms mp 201–202 °C (Found: C, 72.3; H, 10.8. C19H32O3.0.5H2) requires C, 71.9; 10.5%), vmax/cmµ1 3501, 3405, 3310; dH (CDCl3) 0.74 (3 H, s, 18-H), 1.00 (3 H, s, 19-H), 3.64 (1 H, t, J 8.4 Hz, 17a-H), 4.10 (1 H, tt, J 4.5 and 11 Hz, 2b-H).Finally elution with 35% ethyl acetate:light petroleum gave 3b,5a,17b-trihydroxy-androstane (386 mg), plates, mp 193–195 °C (lit.,13 194–105 °C). S. N. thanks the Eastern University, Sri Lanka, for study leave and the British Council for financial assistance. Received, 24th March 1997; Accepted, 22nd April 1997 Paper E/7/02014G References 1 H. C. Brown and K. A. Keblys, J. Am. Chem. Soc., 1964, 86, 1791. 2 H. C. Brown and O. J. Cope, J. Am. Chem. Soc., 1964, 86, 1801. 3 H. C. Brown and R. M. Gallivan, J. Am. Chem. Soc., 1968, 90, 2906. 4 E. Dunkelblum, R. Levene and J. Klein, Tetrahedron, 1972, 28, 1009. 5 J. R. Hanson, P. B. Hitchcock, M. Liman and S. Nagaratnam, J. Chem. Soc., Perkin Trans. 1, 1995, 2183. 6 M. Alam, J. R. Hanson, M. Liman and S. Nagaratnam, J. Chem. Res. (S), 1997, 56. 7 G. C. Wolf and R. T. Blikenstaff, J. Org. Chem., 1976, 41, 1254. 8 P. S. Wharton and D. H. Bohlen, J. Org. Chem., 1961, 26, 3616. 9 H. L. Holland, J. A. Roas and P. C. Chenchaiah, J. Chem. Soc., Perkin Trans. 1, 1988, 2027. 10 J. E. Bridgeman, P. C. Cherry, A. S. Clegg, J. M. Evans, Sir Ewart Jones, A. Kasal, V. Kumar, G. D. Meakins, Y. Morisawa, E. E. Richards and P. D. Woodgate, J. Chem. Soc. (C), 1970, 250. 11 Dictionary of Steroids, ed. R. A. Hill, D. N. Kirk, H. L. Makin and G. M. Murphy, Chapman and Hall, London, 1992. 12 K. I. H. Williams, Steroids, 1963, 1, 377. 13 S. Julia, P. A. Plattner and H. Heusser, Helv. Chim. Acta, 1952, 35, 665.

 



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