首页   按字顺浏览 期刊浏览 卷期浏览 Intermolecular Diastereoselective Nitrile Oxide Addition with Propargylic Ethers
Intermolecular Diastereoselective Nitrile Oxide Addition with Propargylic Ethers

 

作者: Subramanian Baskaran,  

 

期刊: Journal of Chemical Research, Synopses  (RSC Available online 1997)
卷期: Volume 0, issue 11  

页码: 394-395

 

ISSN:0308-2342

 

年代: 1997

 

DOI:10.1039/a703166a

 

出版商: RSC

 

数据来源: RSC

 

摘要:

CHO NO2 MeNO2 NaOH, 0°C OMe NOH Cl H R N O Ar Ar¢ 2 Et3N 1a R = H b R = OMe AlCl3 + – O R* I OH Br I + R—Cl + R*—OH II II O O O O HO OH D-Mannitol acetone O O H O NalO4, H2O O O OH NaBH4 O O O H NaOH, PTC, 0 °C H 7 6 H anh.ZnCl2 propargyl bromide N H CO2H H N CO2CH2Ph CO2H H N CO2CH2Ph H OCO2Et O 8 9 N CO2CH2Ph H 10 OH N CO2CH2Ph H 11 O i ii iii iv 394 J. CHEM. RESEARCH (S), 1997 J. Chem. Research (S), 1997, 394–395 J. Chem. Research (M), 1997, 2459–2471 Intermolecular Diastereoselective Nitrile Oxide Addition with Propargylic Ethers Subramanian Baskaran,*a Chitra Baskarana and Girish K.Trivedib aFachbereich Chemie der Philipps-Universit�at, Marburg, D-35032, Germany bDepartment of Chemistry, Indian Institute of Technology, Powai, Mumbai 400 076, India Cycloaddition reactions of the nitrile oxide 2 are performed with simple and stereogenic propargylic ethers 3–5, 7 and 11 in moderately high yield and with considerable regioselectivity. Nitrones and nitrile oxides are amongst the most useful 1,3-dipoles in organic synthesis.Recently the topic has received renewed attention in view of the now widespread use of nitrile oxide–isoxazoline chemistry1 for the synthesis of natural products and analogues. The asymmetric 1,3-dipolar cycloaddition of a nitrone, diazomethane and a nitrile oxide using an optically active allyloxy unsaturated ester was recently reported by us.2 In continuation of our effort to utilise heterocyclic compounds as dipolarophiles in 1,3-dipolar cycloaddition reactions, we have investigated the cycloaddition of stereogenic propargylic ethers with the rac nitrile oxide 2.It has been established that3–5 allylic substrates have a strong influence in determining the p-facial selectivity and that notably high levels of diastereoselectivity are observed for cycloaddition to chiral allylic ethers and esters. Moreover it is interesting to note that intermolecular 1,3-dipolar cycloadditions between nitrile oxides and chiral propargylic ethers have been studied6 sporadically.Martin and Dupre9 have demonstrated the importance of congested nitrile oxides in the high degree of regioselectivity observed during their cycloaddition with substituted olefins, as the 5-substituted regiomer was selectively formed over the 4-substituted one. Hurd et al.10 in their studies on reactions of nitroolefins devised a method in which benzene reacts with b-nitrostyrene in the presence of anhydrous aluminium chloride to yield diphenylacetohydroximoyl chloride 1a in good yield.We have examined methods for the generation of nitrile oxides in which the stereogenic centre is in the nitrile oxide component,12 and investigated their cycloaddition with achiral and chiral alkynes. Hence, rac-1-(4-methoxyphenyl)- 1-phenylacetohydroximoyl chloride 1b, a hitherto unknown dipole precursor, was synthesised (Scheme 1). For the preparation of propargylic ethers, a retrosynthetic analysis (Scheme 2) shows that it can be constructed via two pathways.For achiral dipolarophiles we utilised strategy I and for chiral dipolarophiles we utilised strategy II. Thus compounds 4 and 5 were synthesised by coupling propargyl alcohol with rac-epichlorohydrin and benzyl chloride respectively. 13 The other two alkynes 7 and 11 were synthesised from D-mannitol and L-proline as illustrated in Schemes 4 and 5. In order to minimise the formation of furazan nitrile oxide (furoxan) dimers, the nitrile oxides were generated in situ from the corresponding oximes.The nitrile oxide generated at 0–5 °C by slow addition of Et3N to the nitrile oxide precursor 1b in dichloromethane was treated with 3–5, 7 and 11 in dichloromethane to yield mixtures of products. The resulting isoxazolines were readily separated in moderate yields by flash chromatography. Like other reports,6,14 1,3-dipolar cycloadditions of nitrile oxides 2 (Scheme 6) with the alkynes (3–5,7,11) were shown to be highly regioselective.The only regiomers detected by 1H-NMR being those with a terminal H at C-4, i.e., the sterically less hindered 5-substituted products. If it had been a 4-substituted ring, the olefinic proton signal should have appeared at around d 8, as it is flanked by both a heterocyclic *To receive any correspondence (e-mail: baskaran@ps1515. chemie.uni-marburg.de). Scheme 1 Scheme 2 Scheme 4 Scheme 5 Reagents and conditions: i, ClCOOCH2Ph, NaOH, PTC, 0 °C; ii, Et3N, ClCOOEt, THF, 0 °C; iii, NaBH4, H2O, room temp.; iv, propargyl bromide, NaOH, 0 °C, PTCOH 3 O N HO X 5 4 3 2 1 12 Ph 4-MeO-C6H4 Cl NOH 1b Et3N, CH2Cl2, 0 °C X = OMe H 1¢¢ O 4 O O O O N X H + RS SR 1b 13 O 5 O O N X 14 1b O O H O 7 O O H O 15 N O X 10 S 8 SS + SR 1b SS RR N O H CO2CH2Ph 11 N O N O X H P 11 9 6 4 1 + SR 1b SS 16 P = CO2CH2Ph 8 S N Ar H Ar¢ O S X H Ar Ar¢ N O + – + O O H H O H H O N Ar¢ H Ar O O O H 10 S 2 1 5 6 8 9 S 4 O N Ar H Ar¢ O O O H R 15a [ SS] 15b [ SR] O O H H H S N Ar¢ H Ar O R X H O O H H H S Ar¢ = p-OMeC6H4 X = OCH (No facial difference) 7 J.CHEM. RESEARCH (S), 1997 395 oxygen and a double bond. However, the appearance of ole- finic protons in the range d 6.02–6.09 indicates the formation of a 5-substituted isoxazoline ring. In the case of 4, 7 and 11 the cycloaddition provided inseparable mixtures of two diastereomers (from the OMe 1H NMR signals) in the ratio of 1:1.The formation of two diastereomers was expected because of the pre-existing chirality of dipolarophiles. The preferred formation15,16 of the adducts can be explained by the fact that the dipolarophile reacts by its preferred conformation with the rac-dipole (Fig. 1). The p-facial selectivity observed for the reaction of nitrile oxides with the dipolarophiles can be rationalised for the adduct 15 by adapting the ‘inside alkoxy group hypothesis’ proposed by Houk et al.3 for the cycloaddition of chiral allyl ethers.The preferred formation of the adduct from an alkyne is consistent15,16 with product formation via the transition state which locates the oxygen substituent in the ‘inside’ position, the hydrogen ‘outside’ and the CH2O moiety anti (Fig. 1). The two products (diastereomers) were formed by kinetic resolution of the nitrile oxide while reacting with the dipolarophile. For the compounds 15 and 16, the proton signals for the two allylic methylene protons are seen at d 4.61 and 4.50 and the vinylic protons are seen at d 6.10 and 6.03 respectively.This unequivocally confirms the formation of the 5-substituted regiomer. The 1H NMR spectra of each compound (except for 12 and 14) showed that only two diastereomers were obtained, which could be in SS and SR configuration (Fig. 1). Since the asymmetric centres in the above cases (15 and 16) are remote from the reaction centres, the absolute stereochemistry of the adducts could not be determined.All the assignments were corroborated by 13C NMR and 2D (1H-1H) COSY experiments. In conclusion, 1,3-dipolar cycloadditions on enantiomericlaly pure propargylic ethers with rac nitrile oxides occurred with moderate conversion as well as with complete regioselectivity. 5 In each case the effect12 can be attributed to the greater distance between the pre-existing and newly formed stereocentres (because of the diasteromeric nature of the products).Techniques used: IR, 1H and 13C NMR, 2D (1H-1H) COSY References: 16 Schemes: 6 Figures: 2 Received, 8th May 1997; Accepted, 12th August 1997 Paper E/7/03166A References cited in this synopsis 1 C. J. Easton, C. M. M. Hughes, G. P. Savage and G. W. Simpson, Adv. Heterocycl. Chem., 1994, 60, 261 and references cited therein. 2 S. Hariharan and G. K. Trivedi, Indian J. Chem., 1988, 27, 994; J. Vasu, P. J. Nadkarni, G. K. Trivedi and A. Steigel, Magn. Reson. Chem., 1991, 29, 645; S.Baskaran and G. K. Trivedi, J. Chem. Res., 1995, (S) 308; (M) 1853; 1996, (S) 542; S. Baskaran, J. Vasu, K. K. Ram Prasad, G. K. Trivedi and J. Chandrasekhar, Tetrahedron, 1996, 52, 4515; S. Baskaran, C. Baskaran, P. J. Nadkarni, G. K. Trivedi and J. Chandrasekhar, Tetrahedron, 1997, 53, 7057. 3 K. N. Houk, S. R. Moses, Y. D. W N. G. Rondan, J. Vager, R. Schohe and F. R. Fronczek, J. Am. Chem. Soc., 1984, 106, 3880. 4 A. P. Kozilkowski and A. K. Ghosh, J. Org. Chem., 1984, 49, 2762. 5 J. Blad, J. C. Carretero and E. Dominguez, Tetrahedron: Asymmetry, 1995, 1035 and references cited therein. 6 A. Padwa, U. Chiacchio, D. C. Dean, A. M. Schoffstall, A. Hassner and K. S. K. Murthy, Tetrahedron Lett., 1988, 29, 4169. 9 S. F. Matin and B. Dupre, Tetrahedron Lett., 1983, 24, 337. 10 C. D. Hurd, M. E. Nilson and D. M. Wiccholm, J. Am. Chem. Soc., 1950, 72, 4697. 12 A. J. Blake, E. C. Boyd, R. O. Gould and R. M. Paton, J. Chem. Soc., Perkin Trans. 1, 1994, 2841. 13 G. Mouzin, H. Cousse, J. P. Rieu and A. Duflos, Synthesis, 1983, 117. 14 For intra-cycloaddition see K. M. Short and K. B. Ziegler, Tetrahedron Let., 1993, 34, 75. 15 E. C. Boyd and R. M. Paton, Tetrahedron Lett., 1993, 34, 3169. 16 M. Mancera, I. Roffe and J. A. Galbis, Tetrahedron, 1995, 51, 6349. Scheme 6 The numbering of atoms deviates from the IUPAC rules, which are, however, obeyed in naming the compounds (see Experimental section) Fig. 1

 



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