摘要:
WOOSimple one-pot transformations of toluene-p-sulfonates of 2,3=epoxy alcohols into allylic alcohols mzn33s -5 Nobutaka Fujii," Hiromu Habashita," Masako Akaji," Kazuo Nakai," Toshiro Ibuka,*@ Masahiro Fujiwara," Hirokazu Tamamura" and Yoshinori Yamamoto a Faculty of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-01,Japan Department of Chemistry, Tohoku University, Sendai 980, Japan A simple synthetic method for the preparation of scalemic allylic alcohols from toluene-p-sulfonates of scalemic 2,3- epoxy alcohols is reported. Satisfactory yields are obtained by treatment of toluene-p-sulfonates of 2,3-epoxy alcohols with potassium iodide followed by triphenylphosphine and iodine in a one-pot synthesis. Allylic alcohol functionality-bearing compounds are often vital structural units of biologically active compounds.In addition, the importance of scalemic allylic alcohols t as key intermediates for the synthesis of various types of compounds has focused widespread synthetic attention on these moieties. During synthetic studies directed towards the botryococcene family terpenoids, we needed a simple synthetic route which would allow the convenient preparation of scalemic allylic alcohols from readily available scalemic 2,3-epoxy alcohols or related compounds. Existing syntheses of allylic alcohols from 2,3-epoxy alcohols or similar substrates include: (i) titanocene(II1)-induced deoxygenation of 2,3-epoxy alcohols 1; (ii) reduction of tosylates 2 with zincxopper in the presence of sodium iodide; (iii) telluride(I1)-mediated ' or sodium-mediated' reduction of mesylates 3; and (iv) reduction of iodides 4 with zinc-copper,* zinc or alkyllithiums.'' We now R' OH I I R' / R' H H 2 X=OTs 4 3 X=OMS Scheme 1 R' = R2 = alkyl describe the simple transformation of tosylates of type 2 into allylic alcohols of type 5 by treatment with potassium iodide followed by triphenylphosphine or 4-(dimethy1amino)phenyl-diphenylphosphine (CDMAPDP) in the presence of iodine in a one-po t mariner. The requisite scalemic tosylates 6-14 (ee or de > 90%) shown in Scheme 2 for the present study were readily prepared in high yields from the corresponding scalemic 2,3-epoxy alcohols which in turn were obtained by Sharpless asymmetric epoxidation of the respective allylic alcohols.Although all controlling factors involved in the overall one- 7 The term scalemic refers to unequal mixtures of enantiomers (C. H. Heathcock, B. L. Finkelstein, E. T. Jarvi, P. A. Radel and C. R. Hadley, J. Org. Chem., 1988,53, 1922), pot transformation are not clear, the following conclusions may be drawn: (i) a mixed solvent of acetone and DMF (6:1 -3: 1) is the solvent of choice, since although conversion of the tosylates into the corresponding iodides by treatment with potassium iodide in refluxing acetone is rather sluggish, acceleration of the reaction is accomplished by the addition of DMF; (ii) without isolation of the intermediate iodides, effective conversion of the iodides into the corresponding allylic alcohols can be achieved by successive addition of triphenylphosphine (1-1.5 equiv.) and iodine (0.01-0.5 equiv.) to a stirred solution of the iodides; (iii) in cases where the protecting groups in starting tosylates are rather acid sensitive (substrates 13 and 14), 4-DMAPDP (1.5 equiv.) and iodine (1 equiv.) serve as substitutes for tri- phenylphosphine and a catalytic amount of iodine; and (iv) triphenylphosphine or 4-DMAPDP could not be replaced by trialkylphosphines such as tributylphosphine. Although a mechanistic rationale for the transformations of intermediates into allylic alcohols by treatment with triarylphos- phine and iodine as reported here is somewhat difficult, it is clear from the preliminary experiments shown in Scheme 2 that the desired allylic alcohols could be obtained by using a simple procedure.The compatibility of diverse protecting groups under the reaction conditions used for the present transform- ation is also an advantage of this technology. In summary, a new one-pot method for the synthesis of allylic alcohols from the corresponding tosylates of 2,3-epoxy alcohols has been developed. Experimental The following are sample procedures by the use of triphenyl-phosphine or 4-(dimethy1amino)phenyldiphenylphosphine(4-DMAPDP). (2S)-1-Benzyloxybut-3en-2-oll9 A mixture of the toxylate 10 (348 mg, 1 mmol), KI (498 mg, 3 rnmol), acetone (6 cm3) and DMF (1 cm3) was heated under reflux for 1 h. It was then cooled to O"C, and tpi- phenylpkosphine (262 mg, 1 mmol) and iodine (25 mg, 0.1 mmol) were added sequentially with stirring, and the whole was stirred at 0 "C for 1 h.The mixture was extracted with Et20, and the extract was washed successively with 5% Na,S,O, and brine, and dried over MgSO,. The usual work-up followed by flash chromatography over silica gel with hexane-EtOAc (4 : 1) gave 169 mg (95%yield) of the title compound 19 as a colourless oil; Kugelrohr distillation, 140 "C/2 mmHg (Found: C, 74.1; H, 7.9. Cl1HI4O2 requires C, 74.3; H, 8.2%); [a];' -4.0 (c 1.37 in CHCI,); 6,(270 MHz; CDC1,) 2.49 (I H, d, J 3.6$), 3.38 (1 H, dd, J9.6 and 7.9), 3.55 (1 H, dd, J9.6 and 3.5), 4.35 (1 H, m), 8 J Values in Hz. J. Chem. Soc., Perkin Trans, 1,1996 865 (2S,3S,4R)-1-tevt-Butyldimethylsiloxy-2,3-O-isopropylidene-&OTs i, ii, v hex-5-en-2,3,4-triol23_____c 75%U U 6 15 0~~ i, ii,vi ~0"h;-7 90% s -Me -ePoT -iii.MM i, iii,vi Me. -eMe p hehe 9:91% MeMe' 8 Me 17 i, ii, vii-I I 93% 6H UI, 9 18 i, ii, vii IBnO 95% H 10 19 H oH MOMOW MOM0 H MOMO 11 76% 20 ?H i,ii, ix BnO*OTS -U 93% H 11 12 21 Me-' Me 13 22 Me Y OTs i iv x -TBDMSOTBDMSO 71% 14 23 Scheme 2 Abbreviations: Ts = toluene-p-sulfonyl; Bn = benzyl; MOM = methoxymethyl; TBDMS = tert-butyldimethylsilyl. Rea-gents and conditions: i, KI (3 equiv.), acetone-DMF (6 : l -3: l), reflux, 1 -2 h; ii, PPh, (I equiv.); iii, PPh, (1.5 equiv.); iv, 4-(dimethyl-amino)phenyldiphenylphosphine (1.5 equiv.); v, I, (1 molx), 0 OC, 20 min; vi, I, (5 molx), 0 "C -room temp., 1h; vii, I, (10 molx), 0 "C, I h; viii, I, (20 molx), 0 "C, 45 min; ix, I, (50 molx), 0 "C, 1h; x, I, (100 molx), 0 "C, 1 h.4.58(2H,s),5.20(1 H,ddd,J10.5, 1.5and1.5),5.36(1H,ddd, J 17.5, 1.5 and 1.5), 5.84 (1 H, ddd, J 17.5, 10.5 and 5.6) and 7.25-7.40 (5 H, m). A mixture of the tosylate 14 (160 mg, 0.34 mmol), KI (169 mg, 1.02 mmol), acetone (2 cm3) and DMF (0.5 cm3) was heated under reflux for 1 h. It was then cooled to OOC, and 4-DMAPDP (155 mg, 0.5 1 mmol) and iodine (86 mg, 0.34 mmol) were added sequentially with stirring, and the whole was stirred for 1 h at 0 "C.To this solution were added 5% NaHCO, (5 cm3) and 5% Na2S203(2 cm3), and the mixture was stirred for 10 min. The mixture was extracted with Et,O-EtOAc (4: l), and the extract was washed with brine and dried over MgSO,. The usual work-up followed by flash chromatography over silica gel with hexane-EtOAc (5: 1) gave 73 mg (71% yield) of the title compound 23 as a colourless oil; Kugelrohr distillation, 125"C/1 mmHg [Found (FAB): (M + H)', 303.1997. C15H3104Sirequires M + H, 303.19911; +25.3 (c 0.734 in CHCI,); 6,(270 MHz; CDCl,) 0.08 (6 H, s, SiMe,), 0.90 (9 H, s, Me x 3), 1.40(3 H, s), 1.42 (3 H, s), 2.68 (1 H, d, JS.O), 3.65-3.71 (1 H, m), 3.79-3.83 (1 H, m), 3.97 (2 H, m), 4.22 (1 H, m), 5.23-5.43 (2 H, m), 5.94 (1 H, ddd, J 17.5, 10.6 and 5.6); m/z FAB-LRMS 303 (MH'), 287,245,228,187,175,159,131,117, 89 and 73 (base peak).Acknowledgements We thank Dr T. R. Burke, Jr., NCI, NIH, Bethesda, U.S.A., for reading the manuscript and providing useful comments. References 1 Chem. Eng. News, Sept. 11,1995,27. 2 T. Ibuka, H. Habashita, A. Otaka, N. Fujii, Y. Oguchi, T. Uyehara and Y. Yamamoto, J. Org. Chem., 1991,56, 4370; A. Kumar and D. C. Dittrner, J. Org. Chem., 1994, 59, 4760; W. Adam, K. Peters and M. Renz, Angew. Chem., Int. Ed. Engl., 1994, 33, 1107; A. B. Charette and J.-F. Marcoux, Synlett, 1995, 11917;P. A. Evans, A. B. Holmes and K. Russell, J. Chem. SOC.,Perkin Trans. I, 1994, 3397; S. C. Bergmeier and D. M. Stanchina, Tetrahedron Lett., 1995,36,4533. 3 J.D. White, G. N. Reddy and G. Spessard, J. Chem. SOC.,Perkin Trans. I, 1993, 759 and references cited therein. 4 J. S. Yadav, D. Shinivas and T. Shekharam, Tetrahedron Lett., 1994, 35, 3625. 5 Y. Nishiguchi, H. Kuramoto and A. Takuwa, Tetrahedron Lett., 1995,36,3353. 6 R. P. Discordia and D. C. Dittmer, J. Org. Chem., 1990, 55, 1414; D. C. Dittmer, Y. Zhang and R. P. Discordia, J. Org Chem., 1994, 59, 1004. 7 A. Yasuda, H. Yarnamoto and H. Nozaki, Bull. Chem. SOC.Jpn., 1979,52, 1757. 8 L. A. Sarandeses, A. Mourino and J.-L. Luche, J. Chem. Soc., Chem. Cummun., 1991, 818; E. Balmer, A. Germain, W. P. Jackson and B. Lygo, J. Chem. Soc., Perkin Trans. 1,1995,2193. 9 A. V. Rao, E. R. Reddy, B. V. Joshi and J. S. Yadav, Tetrahedron Lett., 1987,28, 6497. 10 J. A. Marshall and R. Sedrani, J. Org. Chem., 1991, 56, 5496; J. A. Marshall and A. W. Garofalo, J. Org. Chem., 1993, 58, 3675; D. R. Williams, P. A. Jass, H.-L. A. Tse and R. D. Gaston, J. Am. Chem. Soc., 1990,112,4552. Paper 6/01566B Received 5th March 1996 Accepted 6th March 1996 866 J. Chem. Soc., Perkin Trans. 1,1996
ISSN:1472-7781
DOI:10.1039/P19960000865
出版商:RSC
年代:1996
数据来源: RSC