Preparation of tertiary amines by the reaction of iminium ions derived from unsymmetrical aminals with zinc and magnesium organometallics.

We report a convenient one-pot preparation of polyfunctional tertiary amines, including various biorelevant phenethylamines or ephedrine derivatives, via the reaction of new functionalized iminium ions with a variety of zinc and magnesium organometallic reagents. These iminium ions were generated from unsymmetrical aminals, obtained by the in situ addition of various amides to Tietze's iminium salt [Me2NCH2(+)CF3COO(-)]. A functionalized aniline, prepared by this method, was converted to a quinolidine via an intramolecular Heck reaction.

Isoxazole-embedded allylic zinc reagent for the diastereoselective preparation of highly functionalized aldol-type derivatives bearing a stereocontrolled quaternary center.

Highly functionalized aldol-type products bearing a β-quaternary center and a stereoselectively controlled γ-hydroxy function are readily prepared by the diastereoselective addition of an allylic zinc reagent embedded in an isoxazole ring to various aromatic and heteroaromatic aldehydes, in the presence of Lewis acids, such as MgCl2 or LaCl3⋅2 LiCl. After reductive cleavage of the N-O bond by using Fe, NH4Cl, aldol-type products bearing a stereocontrolled β-quaternary center and a γ-hydroxy group were observed. The benzylic reactivity of the isoxazolylmethylzinc reagent towards other electrophiles, such as acid chlorides, aryl and allylic halides, as well as aldehydes in the presence of BF3⋅OEt2 are also described.

Preparation and reactions of heteroarylmethylzinc reagents.

We report a general preparation of heteroarylmethylzinc chlorides by direct zinc insertion into heteroarylmethyl chlorides, along with a facile and straightforward synthesis of these heterocyclic chloromethyl precursors. We demonstrate that heteroarylmethylzinc reagents undergo various reactions including cross-couplings, allylations, acylations, and addition reactions to aldehydes, leading to polyfunctional heterocyclic products. Furthermore, these heteroaromatic zinc compounds prove to be versatile reagents for the preparation of various N- and O-heterocycles and give access to an analogue of a CB1 modifier.

Preparation of heterocyclic amines by an oxidative amination of zinc organometallics mediated by Cu(I): a new oxidative cycloamination for the preparation of annulated indole derivatives.

Functionalized heterocyclic zinc reagents are easily aminated by an oxidative amination reaction of zinc amidocuprates prepared from various lithium amides. For the oxidation step, PhI(OAc)(2) proved to be the best reagent. The required heterocyclic zinc organometallics can be prepared either by direct metalation, by magnesium insertion in the presence of ZnCl(2), or by transmetalation of a suitable magnesium reagent.

Functionalized magnesium organometallics as versatile intermediates for the synthesis of polyfunctional heterocycles.

In the last few years, we have demonstrated that the halogen/magnesium-exchange reaction is a unique method for preparing a variety of new functionalized aryl, alkenyl, heteroaryl magnesium compounds which has considerably extended the range of functionalized Grignard reagents available for synthetic purposes. A variety of functional groups such as an ester, nitrile, iodide, imine and even sensitive groups like nitro, hydroxyl and boronic ester can be tolerated in these organomagnesium compounds. We wish to describe the application of this halogen/magnesium-exchange reaction for the preparation of a broad range of five- and six-membered functionalized heteroaryl magnesium compounds and their reactions with various electrophiles providing a new entry to a range of polyfunctional heterocycles such as thiophene, furan, pyrrole, imidazole, thiazole, antipyrine, pyridine, quinoline and uracil derivatives.