Functionalization of heterocyclic compounds using polyfunctional magnesium and zinc reagents.

In this review we summarize the most important procedures for the preparation of functionalized organzinc and organomagnesium reagents. In addition, new methods for the preparation of polyfunctional aryl- and heteroaryl zinc- and magnesium compounds, as well as new Pd-catalyzed cross-coupling reactions, are reported herein. Experimental details are given for the most important reactions in the Supporting Information File 1 of this article.

Preparation of functionalized cyclic enol phosphates by halogen-magnesium exchange and directed deprotonation reactions.

Cyclic enol phosphates were magnesiated by a halogen/magnesium exchange reaction or deprotonation using TMP-derived magnesium amide bases. The resulting magnesium reagents react readily with a wide range of electrophiles like allyl bromides and acid chlorides or can be used in Pd-catalyzed cross-coupling reactions. Several optically pure enol phosphates were prepared starting from readily available d-(+)-camphor derivatives.

Preparation of highly functionalized alkylzinc halides from alkyl bromides using Mg, ZnCl2 and LiCl.

Alkyl bromides bearing various functional groups are smoothly converted to functionalized alkylzinc reagents by the direct insertion of magnesium in the presence of LiCl and ZnCl(2).

Preparation of polyfunctional arylmagnesium, arylzinc, and benzylic zinc reagents by using magnesium in the presence of LiCl.

The presence of LiCl considerably facilitates the insertion of magnesium into various aromatic and heterocyclic bromides. Several functional groups, such as -OBoc, -OTs, -Cl, -F, -CF(3), -OMe, -NMe(2), and -N(2)NR(2), are well tolerated. The presence of a cyano group leads in some cases to competitive reduction of the organic halide to the corresponding ArH compound.

Regio- and chemoselective synthesis of fully substituted thiophenes.

A full functionalization of all four positions of the thiophene ring was achieved. Starting from readily available 2,5-dichlorothiophene, successive magnesiations of the 3- and 4-positions using TMPMgCl x LiCl furnish, after trapping with various electrophiles, 3,4-difunctionalized dichlorothiophenes. Subsequent dechlorination and metalation or magnesium insertion into the C-Cl bond provides fully functionalized thiophenes in high yields.

Polyfunctional benzylic zinc chlorides by the direct insertion of magnesium into benzylic chlorides in the presence of LiCl and ZnCl2.

Benzylic zinc chlorides bearing various functional groups are smoothly prepared by the direct insertion of magnesium into benzylic chlorides in the presence of LiCl and ZnCl(2).