(1R,3S)-Methyl 6,7-dimethoxy-1-(4-methoxyphenyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxylate

The title compound, C20H23NO5, is the third in a series of tetrahydoisoquinoline (TIQ) compounds that are precursors to novel chiral catalysts. The N-containing six-membered ring assumes a half-boat conformation. No hydrogen bonding is observed in the crystal structure.

The title compound, C 20 H 23 NO 5 , is the third in a series of tetrahydoisoquinoline (TIQ) compounds that are precursors to novel chiral catalysts. The N-containing six-membered ring assumes a half-boat conformation. No hydrogen bonding is observed in the crystal structure.

Comment
The title compound was derived from commercially available L-DOPA and anisaldehyde. Diastereomers formed during the first step of the synthesis were separated to yield subsequent derivatives and the title compound with the stereochemistry as illustrated in Fig. 1. The title compound is the third report in a series of molecules containing a tetrahydroisoquinoline backbone and is a precursor to one of the molecules that we previously reported ((1R,3S)-methyl 2-benzyl-6,7-dimethoxy-1-phenyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylate), (Naicker et al., 2009). The molecule has been reported previously and the absolute stereochemistry of the diastereomer was confirmed to be R,S at C4 and C2 positions respectively by proton NMR (Aubry et al., 2006).
There are a number of common features found in this structure and that of the the unprotected secondary amine system.
First, the N-containing six membered ring assumes a half boat conformation. This differs from last report for the (1R,3S)-2-benzyl-6,7-dimethoxy-1-phenyl-1,2,3,4 tetrahydroisoquinolin-3-yl diphenylmethanol structure (Naicker et al., 2010) and previous reports by Alberach et al. (2004) and Aubry et al. (2006) where the heteroatomic ring adopted a half chair conformation. Second, given the presence of the secondary amine, ether and in this example ester functional groups, no hydrogen bonding is observed in any of the structures of this series, (see Fig. 2).

Experimental
A solution of the Cbz protected trans-6,7-dimethoxy-1-(4-methoxyphenyl)-TIQ methyl ester (1.0 g, 0.21 mmol) in THF (20 ml) was added to a suspension of activated 10 wt% Pd/C (500 mg) in dry MeOH (20 ml). The mixture was connected to a hydrogen source at one atmosphere and stirred at room temperature for 1 h. Completion of the reaction was monitored through TLC in hexane/ethyl acetate (50/50, R f = 0.6). The Pd/C was filtered through a Celite pad and washed with methanol (20 ml). The filtrate was evaporated under reduced pressure affording the crude amino ester, which was purified by column chromatography using ethyl acetate/hexane (50:50) as the eluent to yield pure title compound (0.70 g, 93%) as a yellow solid. m.p. = 392-393 K. Crystals suitable for X-ray diffraction were obtained by slow evaporation of the title compound in MeOH at room temperature.