Enantio- and Diastereoselective Synthesis of Tetrahydrofurochromenes by Sequential Asymmetric Homoaldol Reaction and a Mukaiyama-Type Tetrahydrofuran­ Cyclization

Abstract

Herein, we report on a flexible strategy for the stereoselective construction of highly substituted tetrahydrofurochromene derivatives by Mukaiyama-type cyclizations of enantioenriched enol carbamates with O-protected salicylaldehydes. The chromenes are generated as pure diastereomers and under complete chirality transfer.

Key words

heterocycles - homoaldol reaction - lithiation - salicylaldehydes - stereoselective synthesis

References

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1

Responsible for X-ray crystal structure data.

12

The chromenols 12 were isolated as mixtures of anomers in ratios between 61:29 and 91:9 (measured by ¹H NMR in CDCl₃). The configuration at the anomeric carbon atom was not determined.

17

Racemic material of compounds 12-15 were obtained starting with racemic homoaldol adducts 6 prepared by analogous TMEDA mediated deprotonation-substitution.

19

NMR data are given for the major anomer of chromenol 12; see ref. 12.