Preparation of Polyfunctionalized Aromatic Nitriles from Aryl Oxazolines.

A selective ortho,ortho'-functionalization of readily available aryl oxazolines by two successive magnesiations with sBu2 Mg in toluene followed by trapping reactions with electrophiles, such as (hetero)aryl iodides or bromides, iodine, tosyl cyanide, ethyl cyanoformate or allylic bromides (39 examples, 62-99 % yield) is reported. Treatment of these aryl oxazolines with excess oxalyl chloride and catalytic amounts of DMF (50 °C, 4 h) provided the corresponding nitriles (36 examples, 73-99 % yield). Conversions of these nitriles to valuable heterocycles are reported, and a tentative mechanism is proposed.

Copper-mediated cross-coupling of functionalized arylmagnesium reagents with functionalized alkyl and benzylic halides.

[reaction: see text]. Functionalized arylmagnesium halides, prepared via an iodine-magnesium exchange, undergo a smooth cross-coupling reaction with functionalized primary alkyl iodides and benzylic bromides in the presence of CuCN.2LiCl, either in stoichiometric (with trimethyl phosphite as an additive) or catalytic quantities.

Remote C-H activation of phenyl-substituted alkenes by BH(3).THF: mechanism and applications.

[reaction: see text] The hydroboration of tetrasubstituted alkenes and, in particular, bicyclic alkenes with BH(3).THF at 50 degrees C provides, via a highly stereoselective 1,2-rearrangement and a remote C-H activation, a diol in which the relative stereochemistry of three centers has been controlled. A mechanistic study provides general rules for remote C-H activation and leads to new synthetic applications.

Stereoselective synthesis of secondary organozinc reagents and their reaction with heteroatomic electrophiles.

[figure: see text] Various trisubstituted olefins were converted to configurationally stable diorganozinc compounds with high diastereoselectivity. Their reaction with various electrophiles centered on tin, sulfur, bromine, and phosphorus provided the desired substitution products with retention of configuration. Novel, functionalized organocopper reagents such as 4 and chiral diphosphine 5 have been prepared.

Formal enantioselective Michael addition with umpolung of reactivity.

By a sequence comprising asymmetric hydroboration, boron-zinc exchange, and transmetalation with copper, allylations, alkynylations, and allenylations of unsaturated ketals or acetals can be performed with good enantioselectivities (see scheme, (-)-IpcBH2 =(-)-isopinocampheylborane, TMS=Me3 Si). The products correspond to a formal Michael addition with inversion of polarity.

Stereoselective preparation of highly functionalized (Z)-3-magnesiated enoates by an iodine-magnesium exchange reaction.

3-Iodoenoates are converted into the corresponding alkenylmagnesium species with complete retention of configuration of the double bond; both direct reaction and copper(I)-mediated reactions with various electrophiles provide polyfunctional enoates.

Potassium tert-butoxide catalyzed addition of carbonyl derivatives to styrenes

A catalytic amount of t-BuOK in DMSO allows the addition of ketones or imines to styrenes at 40 degrees C in good to excellent yield. Nitriles add to styrenes in NMP or in DMSO at room temperature.

Stereoselective preparation and reactions of configurationally defined dialkylzinc compounds

The reaction of cyclic and open-chain diastereomerically pure secondary organoboranes with diisopropylzinc allows the preparation of secondary dialkylzinc reagents with good to excellent retention of configuration as shown by deuterolysis and CuI- and Pd0-mediated reactions with electrophiles. The importance of a high boron-zinc exchange rate to obtain high diastereoselectivity has been shown. Improvement of the configurational stability and stereomeric purity of the zinc intermediates has been obtained by using mono-isopinocampheylborane ((-)-IpcBH2) providing optically active dialkylzinc compounds (up to 96% ee) with enhanced diastereoselectivities.

New allene synthesis via carbocupration-zinc carbenoid homologation and beta-elimination sequence.

[reaction: see text] Polysubstituted propadienes are obtained in good to excellent yields by the consecutive carbocupration-homologation-beta-elimination reactions on the easily accessible alkynyl sulfoxides or sulfones. This one-pot reaction also allows the preparation of functionalized allenes.

Preparation of new polyfunctional magnesiated heterocycles using a chlorine-, bromine-, or iodine-magnesium exchange

The reaction of heteroaryl iodides with i-PrMgBr (ca. 1.0 equiv) in THF provides the corresponding magnesiated heterocycles. Functional groups such as an ester, cyano, or chloride functions are tolerated in these new Grignard reagents if the exchange can be performed below -20 degrees C. This is the case for all heterocycles bearing electron-withdrawing groups or chelating functions facilitating the iodine-magnesium exchange. In many cases, the exchange can be extended to heteroaryl bromides, and a case of a chlorine-magnesium exchange is described with tetrachlorothiophene. This new preparation of functionalized heteroarylmagnesium compounds provides after reaction with various electrophiles a new entry to a broad range of polyfunctional pyridines, imidazoles, furanes, thiophenes, pyrroles, antipyrines, and uracil derivatives. The application of the halogen-magnesium exchange in the solid phase allows the performance of solid-phase synthesis, with potential applications for combinatorial chemistry.

New polyfunctional magnesium reagents for organic synthesis

The iodine-magnesium exchange reaction allows the preparation of polyfunctional aryl, heteroaryl, or alkenyl magnesium reagents at low temperature. These reagents display the typical reactivity of Grignard compounds and undergo various copper-catalyzed reactions such as allylation or 1,4-addition. Using this halogen-metal exchange reaction, it was possible to generate polyfunctional magnesium reagents on the solid phase.

Preparation of new chiral borane-protected P,N-ferrocenyl ligands via a methoxy directed ortho-lithiation.

We have shown that the readily prepared (ferrocenyl)benzylic methyl ethers of type 1 can be ortho-metalated with tert-BuLi with high diastereoselectivity. This reaction has been used to prepare new borane-protected P,N-substituted ferrocenes of type 2 in high diastereomeric and enantiomeric purity. The chiral heterocyclic aminophosphines 2 may be of interest as chelating ligands for asymmetric metal catalysis.

Ferrocenyl Ligands with Two Phosphanyl Substituents in the alpha,varepsilon positions for the Transition Metal Catalyzed Asymmetric Hydrogenation of Functionalized Double Bonds.

The choice of the substituents at the benzylic position of diphosphane 1 allows the selection of the absolute configuration of the product that is obtained from the transition metal catalyzed enantioselective hydrogenation of various beta-dicarbonyl compounds, alpha-acetamidocinnamic acid derivatives, and dimethyl itaconate (see scheme).