Addition of Lithiated Tertiary Aromatic Amides to Epoxides and Aziridines: Asymmetric Synthesis of (S)-(+)-Mellein

Abstract

Addition of ortholithiated or laterally lithiated amides to epoxides or aziridines provides, in some cases stereoselectively, products which may cyclise to yield benzopyranones in good enantiomeric excess.

lithiation - directed metallation - synthesis - epoxide - benzopyranone - isochromanone

References and Notes

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Asymmetry was introduced into a comparable reaction of 2-alkylbenzoate esters by the use of a chiral lithium amide base, see:

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<A NAME="RD01006ST-12">12</A> A previous report had indicated lack of reactivity between lithiated tertiary amides and epoxides in the absence of BF₃, see: Choukchou-Braham N. Asakawa Y. Lepoittevin J.-P. Tetrahedron Lett.  1994,  35:  3949 

<A NAME="RD01006ST-13">13</A> The synthesis of alcohols 3 by addition of lithiated amides to aldehydes is in contrast stereoselective with respect to the axis and the benzylic stereogenic centre, but non stereoselective with regard to the relationship between the two centers, see: Clayden J. Pink JH. Westlund N. Frampton CS. J. Chem. Soc., Perkin. Trans. 1  2002,  901 

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X-ray crystallographic data have been deposited with the Cambridge Crystallographic Database, reference 288095.

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<A NAME="RD01006ST-21">21</A>

Additions of ortholithiated amides to aziridines failed even in the presence of Lewis acids.

<A NAME="RD01006ST-22">22</A>

Crystallographic data have been deposited with the Cambridge Crystallographic database, reference 288094.