Intramolecular hydrogen bond activation: Thiourea-organocatalyzed enantioselective 1,3-dipolar cycloaddition of salicylaldehyde-derived azomethine ylides with nitroalkenes

An organocatalytic strategy for the synthesis of tetrasubstituted pyrrolidines with monoactivated azomethine ylides in high enantiomeric excess and excellent exo/endo selectivity is presented. The key to success is the intramolecular activation via hydrogen bonding through an o-hydroxy group, which allows the dipolar cycloaddition to take place in the presence of azomethine ylides bearing only one activating group. The intramolecular hydrogen bond in the azomethine ylide and the intermolecular hydrogen bond with the catalyst have been demonstrated by DFT calculations and mechanistic proofs to be crucial for the reaction to proceedThe Spanish Government (CTQ2015-64561-R, CTQ2016- 76061-P) and the European Research Council (ERC-CG, contract number 647550) are acknowledged. We acknowledge the generous allocation of computing time at the CCC (UAM). S.D.-T. gratefully acknowledges the “Ramón y Cajal” program (RYC-2010-07019). Financial support from the Spanish Ministry of Economy and Competitiveness, through the “Maria de Maeztu” Program of Excellence in R&D (MDM- 2014-0377

Copper(I)-Catalyzed Formal Carboboration of Alkynes: Synthesis of Tri- and Tetrasubstituted Vinylboronates

The first copper-catalyzed formal carboboration of alkynes, in which a C–B bond and a C–C bond are created in a single catalytic cycle, is presented. The reaction proceeds with high regioselectivity and <i>syn</i>-stereoselectivity to form tri- and tetrasubstituted vinylboronic esters from commercially available bis­(pinacolato)­diboron. A subsequent cross-coupling reaction gives access to highly substituted alkenes

Asymmetric Synthesis of 1,2-Diamines bearing Tetrasubstituted Centers from Nonstabilized Azomethine Ylides and <i>N</i>‑Sulfinylketimines under Brønsted Acid Catalysis

The first asymmetric cycloaddition of nonstabilized azomethine ylide and <i>N</i>-sulfinylimines is presented. In reactions with aryl–alkyl and heteroaryl–alkyl ketimines, excellent diastereoselectivities and good yields are obtained in all cases, regardless of the electronic character of the substituents at the aromatic rings. Moreover, the cycloadducts obtained can easily be deprotected in acid media, giving access to free 1,2-diamines which are prevalent in many natural and pharmaceutical products

Asymmetric Intramolecular Pauson–Khand Reaction Mediated by a Remote Sulfenyl or Sulfinyl Group

In this work, we report the use of the asymmetric intramolecular Pauson–Khand reactions of 4-aryl-4-cyano-1,6-enynes for obtaining enantiomerically enriched bicyclo[3.3.0]­octenones, and the influence of both the quaternary stereocenter and the sulfur functions located at <i>ortho</i>-position of the aryl group, on their stereoselectivity and reactivity. The sulfenyl derivatives bearing substituted or unsubstituted triple bonds and mono- and disubstituted alkene moieties afford bicyclo[3.3.0]­octenones in high yields with complete diastereocontrol. These results are explained by assuming the association of the lone electron pair at sulfur to the Co–alkyne complexes

Asymmetric Synthesis of Rauhut–Currier type Products by a Regioselective Mukaiyama Reaction under Bifunctional Catalysis

The reactivity and the regioselective functionalization of silyl–diene enol ethers under a bifunctional organocatalyst provokes a dramatic change in the regioselectivity, from the 1,5- to the 1,3-functionalization. This variation makes possible the 1,3-addition of silyl–dienol ethers to nitroalkenes, giving access to the synthesis of tri- and tetrasubstituted double bonds in Rauhut–Currier type products. The process takes place under smooth conditions, nonanionic conditions, and with a high enantiomeric excess. A rational mechanistic pathway is presented based on DFT and mechanistic experiments

Asymmetric Synthesis of Secondary and Tertiary Propargylic Alcohols by Umpolung of Acetylenic Sulfones and <i>ortho</i>-Sulfinyl Carbanions

The generation of diastereomerically enriched secondary benzyl propargyl alcohols by the asymmetric addition of <i>ortho</i>-sulfinylbenzyl carbanions to sulfonylacetylene derivatives via formation of a Csp–Csp³ bond is described. This reaction proceeds through an unusual α-attack (<i>anti</i>-Michael addition) of the <i>ortho</i>-sulfinylbenzyl carbanions, followed by elimination of the arylsulfonyl moiety. The scope of this alkynylation reaction is also discussed. Moreover, the development of a new approach for the synthesis of optically active tertiary benzylpropargyl alcohols is described, discussing the possible stereocourse of the reaction so as the influence of the ether 18-crown-6 and steric importance of acetylenic substituent

Asymmetric Synthesis of Secondary and Tertiary Propargylic Alcohols by Umpolung of Acetylenic Sulfones and <i>ortho</i>-Sulfinyl Carbanions

The generation of diastereomerically enriched secondary benzyl propargyl alcohols by the asymmetric addition of <i>ortho</i>-sulfinylbenzyl carbanions to sulfonylacetylene derivatives via formation of a Csp–Csp³ bond is described. This reaction proceeds through an unusual α-attack (<i>anti</i>-Michael addition) of the <i>ortho</i>-sulfinylbenzyl carbanions, followed by elimination of the arylsulfonyl moiety. The scope of this alkynylation reaction is also discussed. Moreover, the development of a new approach for the synthesis of optically active tertiary benzylpropargyl alcohols is described, discussing the possible stereocourse of the reaction so as the influence of the ether 18-crown-6 and steric importance of acetylenic substituent

Control of the Dual Reactivity (Iminium-Dienamine) of β‑Arylmethyl α,β-Unsaturated Aldehydes in Organocatalytic 1,3-Dipolar Cycloadditions with <i>N</i>‑Benzoyl <i>C,N</i>-Cyclic Azomethine Imines

1,3-Dipolar cycloadditions of <i>C,N</i>-cyclic azomethine imines with α,β-unsaturated aldehydes can be performed with complete control of the regio-, <i>exo</i>-, and enantioselectivity under aminocatalytic conditions. The so far never studied competence of the iminium-dienamine reactivity inherent to β-alkyl α,β-unsaturated aldehydes was studied, which was possible by allowing achievement of complete control of the chemoselectivity in reactions of the β-arylmethyl derivatives with azomethine imines by using different additives and organocatalysts, whose role has been rationalized by DFT calculations and chemical proofs. Thus, it has been possible to selectively obtain the pyrazolidines resulting from both the attack to the C2–C3 (via iminium) and the C3–C4 (via dienamine) bonds at the starting enals, which can be used as precursors of interesting tetrahydroisoquinolinic compounds

A Bifunctional Photoaminocatalyst for the Alkylation of Aldehydes: Design, Analysis, and Mechanistic Studies

A bifunctional photoaminocatalyst based on imidazolidinone and thioxanthone is presented. The preparation of these catalysts proceeds in a two-step synthesis that allows an easy tuning of the steric properties. The photophysical and electrochemical data of the imidazolidinone photocatalysts have been determined, indicating that the catalysts can work under visible light conditions. To corroborate the experimental observations, ground state geometry optimization and energy transition studies of thioxanthone and bifunctional catalyst <b>4c</b> were optimized by time-dependent density functional theory (TD DFT) calculations. The alkylation of aldehydes with this photoaminocatalyst works with high enantioselectivities and yields due to the stereoelectronic properties of the catalyst. A rational mechanistic cycle based on different mechanistic experiments, TD DFT calculations, and laser flash photolysis is presented

A Bifunctional Photoaminocatalyst for the Alkylation of Aldehydes: Design, Analysis, and Mechanistic Studies

A bifunctional photoaminocatalyst based on imidazolidinone and thioxanthone is presented. The preparation of these catalysts proceeds in a two-step synthesis that allows an easy tuning of the steric properties. The photophysical and electrochemical data of the imidazolidinone photocatalysts have been determined, indicating that the catalysts can work under visible light conditions. To corroborate the experimental observations, ground state geometry optimization and energy transition studies of thioxanthone and bifunctional catalyst <b>4c</b> were optimized by time-dependent density functional theory (TD DFT) calculations. The alkylation of aldehydes with this photoaminocatalyst works with high enantioselectivities and yields due to the stereoelectronic properties of the catalyst. A rational mechanistic cycle based on different mechanistic experiments, TD DFT calculations, and laser flash photolysis is presented