A New Total Synthesis of Withasomnine

References

• Morimoto , A. , Noda , K. , Watanabe , T. and Takasugi , H. 1968 . Tetrahedron Lett. , : 5707
   PubMed Web of Science ®Google Scholar
• Onaka , T. 1968 . Tetrahedron Lett. , : 5711
   PubMed Web of Science ®Google Scholar
• 1971 . Itsuu Kenkyusho Nempo , 75
   Google Scholar
• 1972 . C. A. , 77 : 48328e
   Google Scholar
• Zubek , A. 1969 . Pharmazie , 24 : 382
   PubMedGoogle Scholar
• 1969 . C. A. , 71 : 113137j
   Google Scholar
• Takano , S. , Imamura , Y. and Ogasawara , K. 1982 . Heterocycles , 19 : 1223
   Google Scholar
• Ranganathan , D. and Bamezai , S. 1985 . Synth. Commun. , 15 : 259
   Web of Science ®Google Scholar
• Morimoto , A. and Takasugi , T. 1971 . C. A. , 75 : P49073p See also:
   Google Scholar
• Fusco , R. 1969 . “ Pyrazoles ” . In “The chemistry of heterocyclic compounds” , Edited by: Weissberger , A. and Wiley , R. H. vol 22 , 10 New York, London, , Sydney : Interscience Publishers . 71, See for instance:
   Google Scholar
• Elguero , J. 1984 . “ Pyrazoles and their benzo derivatives ” . In “Comprehensive heterocyclic chemistry” , Edited by: Katritzky , A. R. and Rees , Ch. W. vol. 5 , 229 Oxford, , England : Pergamon Press Ltd. . and 277
   Google Scholar
• Ghosh , B. N. 1916 . J. Chem. Soc. , 109 : 105
   Google Scholar
• A pure sample of thioketal 6a was isolated by preparative tlc (hexane 95-AcOEt 5, 3 elutions). Oil; ir (film): 2240 (CN) cm−1; pmr (CDCl3, 90 MHz) δ 0.85 (t, J = 6 Hz, 2 CH 3 CH2), 2.50 (t, J = 7 Hz, 2 SCH 2CH2), 3.90 (d, J = 6 Hz, (-S)2CH-CH(CN)C6H5), 4.20 (d, J = 6 Hz, (-S)2 CH-CH(CN)C6H5), 7.40 (s, 5 aromatic H)
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• Although irrlevant for the purposes of the synthesis, compund 3b was the only intermediate which apparently was obtained as a mixture of geometric isomers, as evidenced by the two partially superimposed triplets at δ 2.80 and 2.90 in the pmr spectrum (SCH 2CH2 for each isomer). For the same reason, the structures of the other intermediates even though geometrically pures were not assigned and thus the structures drawn in this paper does not necessarily represent the correct geometrical isomer
   Google Scholar
• Cahiez , G. , Alexakis , A. and Normant , J. F. 1978 . Tetrahedron Lett. , : 3013
   Google Scholar
• Aldehyde 4: oil; ir (film): 2740 and 1685 (unsaturated CH-0), 1615 (C[dbnd]C) cm−1; pmr (CDCl3, 90 MHz) δ 0.90 (t, J = 6 Hz, CH 3-CH2), 2.80 (t, J = 7 Hz, SCH 2CH2), 7.30 (S, 5 aromatic H), 7.40 (s, CH[dbnd]C), 9.30 (S, CH[dbnd]O)
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• Traces of acid easily cyclizes 5a into the tetrahydrofuran 10: oil; ir (film): 1610 (C[dbnd]C), 1100 (C-O) cm−1; pmr (CDCl3, 90 MHz) δ 0.85 (t, J = 6 Hz, CH 3CH2), 2.60 (t, J = 7 Hz, SCH 2CH2), 3.80 (complex signal, OCH 2CH2), 4.60 (t, J = 6 Hz, CH[dbnd]C-CH(OR)CH2), 6.25 (s, CH[dbnd]C), 7.25 (s, 5 aromatic H)
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• See reference 1a. Ir (KBr): 3200–2850 (OH and NH), 1600 (C[dbnd]C) cm−1; pmr (CDCl3, 90 MHz) δ 1.85 (quintet, J = 6 Hz, CH2 CH 2CH2), 2.90 (t, J = 6 Hz, pyrazole-CH 2CH2), 3.65 (t, J = 6 Hz, HOCH 2-CH2), 5.75 (broad s, OH and NH, exchanges with D2O), 7.20–7.40 (m, 5 aromatic H), 7.60 (s, pyrazole C-H). As expected, cyclization of the derived crude tosylate 8b with NaH gave withasomnine in 33% yield, along with recovered 8a (30 % yield)
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• From our point of view the formation of 8a under this reaction conditions is remarkable, as far as the hydrolysis of an unactivated primary chloro derivative requires somewhat harsh conditions. Perhaps, ring opening of the alicyclic ring in withasomnine by HO− (pyrazolyl anion as leaving group) explains this unusual chloride “hydrolysis”. A similar explanation can also be advanced for the conversion 2c → 8c (see text), although the direct displacement of an intermediate chloropropylpyrazole 8d by the highly nucleophilic n-butyl mercaptide anion seems equally plausible. Anyway, it is also surprising that no ether formation (by solvent participation) had been isolated from these reactions in alcoholic solvents
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