American Chemical Society
jo070786k_si_002.cif (29.09 kB)

Diastereomeric Reissert Compounds of Isoquinoline and 6,7-Dimethoxy-3,4-dihydroisoquinoline in Stereoselective Synthesis

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posted on 2007-07-20, 00:00 authored by Harry W. Gibson, Michael A. G. Berg, Jennifer Clifton Dickson, Pierre R. Lecavalier, Hong Wang, Joseph S. Merola
Chiral acid chlorides were reacted with isoquinoline and 6,7-dimethoxy-3,4-dihydroisoquinoline to form diastereomeric Reissert compounds 811 and 1821, respectively. The best diastereoselectivity (80:20) was achieved in formation of the 9-phenylmenthyl derivative 20. The diastereomers of 2-l-menthoxycarbonyl-1,2-dihydroisoquinaldonitriles (S)-8/(R)-8), formed in equal amounts, were inseparable. However, the individual diastereomers of 2-cholesteryloxycarbonyl-1,2-dihydroisoquinaldonitriles ((R)-11 and (S)-11) and the 2-l-menthoxycarbonyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinaldonitriles ((S)-19/(R)-19)) were each readily purified. (S)-8/(R)-8 (1:1) via the corresponding anions (NaH, −40 °C, DMF) with pivaldehyde yielded in 82:18 predominance the S-diastereomer of 1-isoquinolyl tert-butyl carbinyl l-menthyl carbonate ((S)-12), which was obtained in pure form by a single recrystallization; hydrolysis produced 99% pure S-(−)-1-isoquinolyl tert-butyl carbinol [(S)-16]. Reactions of the anions of diastereomeric Reissert compounds, either as mixtures or pure single species, with aromatic aldehydes and alkyl halides proceeded with at best modest selectivity (diastereomeric ratios up to 66:34 and 72:28, respectively). Therefore, it is concluded that the Reissert anions are either planar or rapidly inverting tetrahedral structures.