Asymmetric Tandem Additions to Chiral 2,3-Dihydronaphthyloxazolines: Synthesis of the Triptoquinone/Triptinin A Ring System

Abstract

A study to reach the diterpenoid (+)-triptoquinone A (3) or its analog (+)-triptinin A (4) via an asymmetric tandem addition to naphthyloxazolines is described. The tandem addition to the chiral dihydronophthalene 6 resulted in a 70% yield of a single diastereomer 10. Further manipulation gave the natural products’ tricyclic ring system, compounds 20 and 29 via ring-closing metathesis in 90% yield, using the Schrock catalyst. Final assault to the target compounds 3 or 4 fell short due to the failure to either reduce a neopentyl hydroxymethyl group to a methyl or to install the conjugated carboxylic acid present in 3 or 4.

Key words

ring closing metathesis - alkyllithiums - chiral oxazolines - conjugate additions - deoxygenation - triflates - tetralones

References

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12

Compound 12 was prepared as described in the experimental.

14

Attempts were made to use a vinyl bromide into the tandem product below. However, the electrophilic step in the tandem addition failed. Presumably, the azaenolate, formed upon the addition of the 2-lithiopropene, is too basic and causes elimination of HBr from 1,3-dibromobut-3-ene (Scheme [] 11).

Scheme 11

16

The yield of this reaction was dependent upon the quality of the catalyst (purchased from Strem Chemical Company) as evidenced by its often dark color.

19

300 MHz ¹H NMR spectra of 32-34 and 38 are included in the supplementary material.