3190
Instead 6-methoxy-2-aminotetralin 8 was obtained, presumably via ipso attack and rearrangement
(Scheme 3).
Scheme 3. Cyclisation of para methoxy compound
The unexpected product was confirmed by preparation of the authentic 6- and 7-methoxy-2-
aminotetralins from the corresponding 2-tetralones.3 This rearrangement appears to be limited to the
cyclisation of the alcohols, as the corresponding acid17 and amino acid18 gave the expected 7-methoxy
product. Cyclisation of the m-methoxy compound 5d afforded a 3:1 mixture of the 6- and 8-methoxy-2-
aminotetralins resulting from cyclisation at both the ortho and para positions. No cyclised product was
observed with electron deficient aromatics 5b and 5c. The parent compound 7e (R1–R4=H) was readily
obtained from iodobenzene.
The aminotetralins were obtained in high enantiomeric excess (>97%)19 despite the PVG being
only 88–93% ee. Presumably recystallisation of the Heck product 4 and the phthalimide protected
aminotetralin 6, enhanced the enantiomeric excess of these intermediates, and there was no degradation
of optical purity in the cyclodehydration step.
To conclude we have demonstrated a short, novel and economic asymmetric synthesis of 2-
aminotetralins from PVG, which can be synthesised using the optimised conditions outlined in this
communication. In addition both enantiomers of vinylglycinol are readily available, >98% ee,20 from
PVG by hydrazinolysis, formation of the benzoic acid salt and crystallisation. Studies in the use of these
versatile building blocks are currently ongoing.
Acknowledgements
This work was carried out as part of a collaboration with Eastman Fine Chemicals. We would like to
thank Professor B. M. Trost for useful discussions. We are grateful to Catherine Rippé and Will Spearing
for the development of analytical methods.
References
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