José M. Aurrecoechea

Palladium-catalyzed sequential oxidative cyclization/coupling of 2-alkynylphenols and alkenes: a direct entry into 3-alkenylbenzofurans.

A new Pd-catalyzed tandem intramolecular oxypalladation/Heck-type coupling between 2-alkynylphenols and alkenes is reported, leading to 3-(1-alkenyl)benzofurans. Participating alkenes include those substituted with an electron-withdrawing group (ester, ketone, amide, nitrile, sulfone), as well as styrene. Remarkably, beta-substituted-alpha,beta-unsaturated carbonyl-type derivatives also participate effectively. The ready availability of substituted alkynylphenols, together with flexibility in the alkene choice, makes this simple strategy a versatile one for the synthesis of structurally diverse benzofuran derivatives.

A General Synthesis of Alkenyl-Substituted Benzofurans, Indoles, and Isoquinolones by Cascade Palladium-Catalyzed Heterocyclization/Oxidative Heck Coupling

Structurally diverse C3-alkenylbenzofurans, C3-alkenylindoles, and C4-alkenylisoquinolones are efficiently prepared by using consecutive Sonogashira and cascade Pd-catalyzed heterocyclization/oxidative Heck couplings from readily available ortho-iodosubstituted phenol, aniline, and benzamide substrates, alkynes, and functionalized olefins. The cyclization of O- and N-heteronucleophiles follows regioselective 5-endo-dig- or 6-endo-dig-cyclization modes, whereas the subsequent Heck-type coupling with both mono- and disubstituted olefins takes place stereoselectively with exclusive formation of the E isomers in most cases.

Synthesis of vicinal diamines by SmI2-promoted reduction of N-(N′,N′-Dialkylaminoalkyl)benzotriazoles

Abstract N-(N′,N′-Dialkylaminoalkyl)benzotriazoles, derived from aldehydes and secondary amines, react with one equivalent of samarium iodide (SmI 2 ), under mild conditions to afford tertiary vicinal diamines, as a result of C-C coupling between two dialkylaminoalkyl moieties.

Palladium-catalyzed cyclization/Heck- and cyclization/conjugate-addition-type sequences in the preparation of polysubstituted furans.

Palladium-catalyzed heterocyclization-coupling sequences have been developed starting from buta-1,2,3-trienyl carbinols and electron-deficient alkenes. Polysubstituted furans are formed where the heterocyclic ring originates from the elements of the butatrienyl carbinol while the electron-deficient olefin is incorporated as a C-3 substituent. In most cases, the reaction proceeds via a Heck-type pathway leading to the efficient formation of 3-vinylfurans. However, couplings with methyl vinyl ketone display a divergent behavior to afford selectively either Heck- or hydroarylation-type products depending on reaction conditions.

Synthesis of 2,3-disubstituted pyrrolidines by intramolecular addition of α-aminoalkyl radicals to electron deficient CC bonds

2,3-Disubstituted pyrrolidines are prepared by SmI2-promoted cyclization of α-amino radicals generated from N-(α-benzotriazolylalkyl)alkenylamines containing a Cue5fbC bond activated by an electron withdrawing substituent. The diastereoselectivity of cyclization is moderate and depends on the nature of the substituent at the pyrrolidine 2-position.

Synthesis of tetrasubstituted furans by sequential SmI2-promoted reduction and Pd-catalyzed cyclization

Abstract Tetrasubstituted furans are obtained in a one-pot, two-step sequence comprising SmI 2 -promoted reduction of a readily available 4,5-epoxyalk-2-ynyl ester followed by Pd(0)-promoted cyclization of the resulting 2,3,4-trien-1-ol in the presence of an aryl halide or triflate.

Palladium-catalyzed cyclization/allylation of in situ-generated α-hydroxy-[3]-cumulene samarium alkoxides: synthesis of allylated furans

Abstract Samarium alkoxides of α-hydroxy-[3]-cumulenes, generated in situ by SmI 2 -promoted reduction of appropriate epoxypropargyl esters, are found to participate in novel Pd-catalyzed cyclization/allylation sequences in the presence of allylic bromides. This results in the efficient regioselective formation of polysubstituted furans incorporating the allyl unit.

Synthesis of 2,4-, 3,4- and 2,3,4-substituted pyrrolidines by cyclization of neutral C-centered α-aminoalkyl radicals

Abstract The effect of substitution at C-3 or C-4 of the 2-azahex-5-enyl chain has been studied in the SmI 2 -promoted cyclizations of neutral α-aminoalkyl radicals generated from N -(α-benzotriazolyl)alkenylamines. 2,4-, 3,4- and 2,3,4-substituted pyrrolidines are obtained in this manner in uniformly high yields but with stereoselectivities which depend markedly on the substitution pattern. Thus, a methyl substituent at C-4 (hex-5-enyl numbering) effectively controls the stereochemistry over three contiguous stereogenic centers whereas substituents at C-3 are found to exert a very poor control. Stereochemical results are rationalized according to the existing models for radical ring-closures.

Ortho-lithiation of 2-(benzothiazol-2-ylthio)pyridine: preparation of 2,3-disubstituted pyridines

Lithiation en position 3 de la pyridine; les produits de l reaction avec des electrpiles (p-tolualdehyde, chloro trimethyl silane, methanol deuterie) ([R-3 pyridyl-2thio]-2 benzothiazoles) subissent une scission pour donner des alkylthio-2 R-3 pyridines et/ou des R-3 1H-pyridinethiones-2

Regio- and stereoselective samarium diiodide-promoted intermolecular coupling between vinyloxiranes and ketones. Synthesis of 2-alken-1,5-diols

Reduction of vinyloxiranes with SmI2-HMPA at low temperatures in the presence of ketones results in the efficient formation of 2-alken-1,5-diols with predominant or exclusive (E) configuration. In the absence of HMPA higher temperatures are needed for the coupling and the regioisomeric 1,3-diols are also obtained.