Cu-Catalyzed Chemodivergent, Stereoselective Propargylic Dearomatization and Etherification of 2-Naphthols.

The first stereoselective propargylic dearomatization of 2-naphthol derivatives is reported using a chiral CuII-L10 complex. The reaction shows chemodivergent reactivity and produced propargyl dearomatization and etherification product for differently substituted 2-naphthols. Both the reactions generate the desired products in high yields with excellent chemo- and stereoselectivities (up to 99% ee, dr = 9:1) by using only 2 mol % catalyst loading. Dearomatization products contain a contiguous all-carbon quaternary-tertiary stereocenter and a terminal alkyne functionality.

Copper Catalyzed One-Pot Three-Component Imination-Alkynylation-aza-Michael Sequence: Enantio- and Diastereoselective Syntheses of 1,3-Disubstituted Isoindolines and Tetrahydroisoquinolines.

An enantio- and diastereoselective syntheses of 1, 3-disubstituted isoindolines and tetrahydroisoquinolines via CuI-Pybox-diPh catalyzed one-pot imination-alkynylation-aza-Michael sequence has been reported. The three-component reaction produces one C-C and two C-N bonds sequentially with high yield (up to 92%), enantioselectivity (up to 99%), and diastereoselectivity (up to 9:1) in a single operation. Furthermore, the synthetic utility of the product has been demonstrated by LiAlH4 reduction of ester and hydrogenation of alkyne functionality without losing the stereoselectivity.

Synthesis of Functionalized Benzo[b]furans via Oxidative Cyclization of o-Cinnamyl Phenols.

Disclosed herein is an efficient synthetic route for the synthesis of functionalized 2-benzyl benzo[b]furans via a regioselective 5-exo-trig intramolecular oxidative cyclization of ortho-cinnamyl phenols using [PdCl2(CH3CN)2] as catalyst and benzoquinone as an oxidant. Further, a sequential ortho-cinnamylation of phenols using cinnamyl alcohols catalyzed by Re2O7, followed by an oxidative cyclization using the above Pd catalyst, is performed. The reaction showed broad substrate scope with good to excellent yields.

Co(III)-Carbene Radical Approach to Substituted 1H-Indenes.

A new strategy for the catalytic synthesis of substituted 1H-indenes via metalloradical activation of o-cinnamyl N-tosyl hydrazones is presented, taking advantage of the intrinsic reactivity of a Co(III) carbene radical intermediate. The reaction uses readily available starting materials and is operationally simple, thus representing a practical method for the construction of functionalized 1H-indene derivatives. The cheap and easy to prepare low spin cobalt(II) complex [Co(II)(MeTAA)] (MeTAA = tetramethyltetraaza[14]annulene) proved to be the most active catalyst among those investigated, which demonstrates catalytic carbene radical reactivity for a nonporphyrin cobalt(II) complex, and for the first time catalytic activity of [Co(II)(MeTAA)] in general. The methodology has been successfully applied to a broad range of substrates, producing 1H-indenes in good to excellent yields. The metallo-radical catalyzed indene synthesis in this paper represents a unique example of a net (formal) intramolecular carbene insertion reaction into a vinylic C(sp(2))-H bond, made possible by a controlled radical ring-closure process of the carbene radical intermediate involved. The mechanism was investigated computationally, and the results were confirmed by a series of supporting experimental reactions. Density functional theory calculations reveal a stepwise process involving activation of the diazo compound leading to formation of a Co(III)-carbene radical, followed by radical ring-closure to produce an indanyl/benzyl radical intermediate. Subsequent indene product elimination involving a 1,2-hydrogen transfer step regenerates the catalyst. Trapping experiments using 2,2,6,6-tetra-methylpiperidine-1-oxyl (TEMPO) radical or dibenzoylperoxide (DBPO) confirm the involvement of cobalt(III) carbene radical intermediates. Electron paramagnetic resonance spectroscopic spin-trapping experiments using phenyl N-tert-butylnitrone (PBN) reveal the radical nature of the reaction.

Synthesis of air- and moisture-stable, storable chiral oxorhenium complexes and their application as catalysts for the enantioselective imine reduction.

Air-/moisture-stable, crystalline, and storable chiral salicyloxazoline based oxorhenium(V) complexes have been synthesized and their catalytic application for the asymmetric reduction of ketimines using hydrosilane as hydride source is disclosed. A broad substrate scope, high yields, and excellent enantioselectivities (up to 99 %) are attained. Furthermore, the syntheses of enantiopure α-amino esters, γ- and δ-lactams, and isoindolinones have also been carried out using this methodology. Finally, the method has been applied to synthetic targets of pharmaceutical relevance, such as R-(+)-salsolidine and R-(+)-crispine A.

Organocatalytic, Enantioselective Synthesis of 1- and 3-Substituted Isochromans via Intramolecular Oxa-Michael Reaction of Alkoxyboronate: Synthesis of (+)-Sonepiprazole.

The enantioselective oxa-Michael reaction of alkoxyboronate strategy was demonstrated to provide a new and practical route to enantioriched 1- and 3-substituted isochromans using a chiral bifunctional organocatalyst. Furthermore, this methodology was extended to the enantioselective synthesis of (+)-sonepiprazole, a dopamine receptor antagonist.

Organocatalytic, enantioselective, intramolecular oxa-Michael reaction of alkoxyboronate: a new strategy for enantioenriched 1-substituted 1,3-dihydroisobenzofurans.

An unprecedented strategy for the synthesis of enantioenriched 1-substituted 1,3-dihydroisobenzofurans via an enantioselective oxa-Michael reaction of o-alkoxyboronate containing chalcone (II) has been accomplished employing cinchona alkaloid based squaramide bifunctional organocatalyst in the presence of proton source. The corresponding alkoxyboronate intermediates have been readily prepared in situ from o-formyl chalcones using neutral borane as hydride source and a tertiary amine moiety which is a counterpart of the catalyst.

Stereoselective direct reductive amination of ketones with electron-deficient amines using Re2O7/NaPF6 catalyst.

The first example of direct reductive amination (DRA) of ketones with electron-deficient amines (EDA) such as Cbz-, Boc-, EtOCO-, Fmoc-, Bz-, ArSO2-, etc. protected amines have been achieved using catalytic Re2O7/NaPF6. Excellent chemoselectivities as well as diastereoselectivity (for 2-alkyl cyclohexanones) were obtained.

The direct reductive amination of electron-deficient amines with aldehydes: the unique reactivity of the Re2O7 catalyst.

An unprecedented direct reductive amination of electron-deficient amines such as Cbz-, Boc-, EtOCO-, Fmoc-, Bz-, ArSO(2)-, Ar(2)PO-, etc. protected amines with aldehydes is achieved using the Re(2)O(7) catalyst and silanes as the hydride source. Excellent regioselective mono-alkylation and chemoselective reductive-amination were observed.

Direct substitution of hydroxy group of π-activated alcohols with electron-deficient amines using Re2O7 catalyst.

The first example of simple Re(2)O(7)-catalyzed direct dehydrative coupling between allylic alcohols with electron-deficient amines has been achieved under mild and open flask conditions. The protocol has also been successfully applied to benzylic and propargylic alcohols. The mechanistic proof for the S(N)1-type process has also been provided.