Copper-Catalyzed Enantioselective Borylative Allyl–Allyl Coupling of Allenes and Allylic gem-Dichlorides

A catalytic asymmetric reaction between allenes, bis(pinacolato)diboron, and allylic gem-dichlorides is reported. The method involves the coupling of a catalytically generated allyl copper species with the allylic gem-dichloride and provides chiral internal 1,5-dienes featuring (Z)-configured alkenyl boronate and alkenyl chloride units with high levels of chemo-, regio-, enantio-, and diastereoselectivity. The synthetic utility of the products is demonstrated with the synthesis of a range of optically active compounds. DFT calculations reveal key noncovalent substrate–ligand interactions that account for the enantioselectivity outcome and the diastereoselective formation of the (Z)-alkenyl chlorideFinancial support from the AEI (PID2020-118237RB-I00), European Research Council (863914), Xunta de Galicia (ED431C 2022/27; Centro singular de investigación de Galicia accreditation 2019-2022, ED431G 2019/03), and the European Regional Development Fund (ERDF) is gratefully acknowledged. M.P.-S. and A.M.A.-C. thank AEI and Xunta de Galicia, respectively, for predoctoral fellowships. We also thank the use of RIAIDT-USC analytical facilities and CESGA (Xunta de Galicia) for computational timeS

Copper-catalyzed protoboration of borylated dendralenes: a regio- and stereoselective access to functionalized 1,3-dienes

A copper-catalyzed protoboration of borylated dendralenes is reported. The method employs an NHC–Cu catalyst and provides access to 1,4-addition products with excellent levels of chemo-, regio- and stereoselectivity. The resulting diene bis(boronates) are oxidized to the corresponding diene diols which are synthetically versatile building blocksFinancial support from the AEI (CTQ2017-88451-R), Xunta de Galicia (ED431C 2018/04; Centro singular de investigación de Galicia accreditation 2019–2022, ED431G 2019/03) and the European Union (European Regional Development Fund – ERDF) is gratefully acknowledged. E. R.-C. thanks Xunta de Galicia for predoctoral fellowshipS

Bifunctional Skipped Dienes through Cu/Pd-Catalyzed Allylboration of Alkynes with B2pin2 and Vinyl Epoxides

A method for the use of vinyl epoxides in catalytic allylboration of alkynes is described. This transformation allows for the synthesis of bifunctional skipped dienes bearing both an allylic alcohol and an alkenylboronate from simple starting materials with high regio- and stereoselectivity. These two functionalities provide these products with highly versatile reactivity, as shown by their stereocontrolled conversion into cyclic boron compounds and polyenesFinancial support from AEI (PID2020-118237RB-I00), the European Research Council (863914), the Xunta de Galicia (Centro singular de investigación de Galicia accreditation 2019-2022, ED431G 2019/03), and the European Regional Development Fund (ERDF) is gratefully acknowledged. N.V.-G. thanks AEI for an FPI Predoctoral FellowshipS

Enantio- and Diastereoselective Copper-Catalyzed Allylboration of Alkynes with Allylic gem-Dichlorides

A highly chemo-, regio-, enantio- and diastereoselective coupling of terminal alkynes, bis(pinacolato)diboron and allylic gem-dichlorides is reported. The method uses a chiral NHC−Cu catalyst which generates, in a single step, synthetically versatile chiral skipped dienes bearing a Z-alkenyl chloride, a trisubstituted E-alkenyl boronate and a bis-allylic stereocenter. Allylic gem-dichlorides are shown to be efficient substrates for catalytic asymmetric allylboration of alkynes. The method employs a chiral NHC−Cu catalyst capable of generating in a single step chiral skipped dienes bearing a Z-alkenyl chloride, a trisubstituted E-alkenyl boronate and a bis-allylic stereocenter with excellent levels of chemo-, regio- enantio- and diastereoselectivity. This high degree of functionalization makes these products versatile building blocks as illustrated with the synthesis of several optically active compounds. DFT calculations support the key presence of a metal cation bridge ligand–substrate interaction and account for the stereoselectivity outcomeFinancial support from the AEI (PID2020-118237RB-I00), Xunta de Galicia (ED431C 2018/04; Centro singular de investigación de Galicia accreditation 2019–2022, ED431G 2019/03) and the European Union (European Regional Development Fund - ERDF) is gratefully acknowledged. A. M. A.-C. thanks Xunta de Galicia for a predoctoral fellowship.S

Direct C–H Allylation of Unactivated Alkanes by Cooperative W/Cu Photocatalysis

Here we report a photocatalytic methodology that enables the direct allylation of strong aliphatic C–H bonds with simple allylic chlorides. The method relies on a cooperative interaction of two metal catalysts in which the decatungstate anion acts as a hydrogen-atom abstractor generating a nucleophilic carbon-centered radical that engages in an SH2′ reaction with an activated allylic π-olefin–copper complex. Because of this dual catalysis, the protocol allows for the functionalization of a range of chemical feedstocks and natural products under mild conditions in short reaction timesFinancial support from the European Research Council (ERC-CoG 863914-BECAME), Agencia Estatal de Investigación (PID2020-118237RB-I00), Xunta de Galicia (ED431C 2018/04; Centro singular de investigación de Galicia accreditation 2019-2022, ED431G 2019/03), and the European Regional Development Fund (ERDF) is gratefully acknowledgedS

Copper-catalyzed O-alkenylation of phosphonates

Copper catalysis allows the direct oxygen alkenylation of dialkyl phosphonates with alkenyl(aryl)iodonium salts with selective transfer of the alkenyl group. This novel methodology proceeds with a wide range of phosphonates under mild conditions and gives straightforward access to valuable enol phosphonates in very good yields.Financial support from the AEI (CTQ2017-88451-R), Xunta de Galicia (ED431F 2016/006; ED431C 2018/04; Centro singular de investigación de Galicia accreditation 2016-2019, ED431G/09) and the European Union (ERDF) is gratefully acknowledged. N. V.-G. thanks AEI for a predoctoral FPI fellowshipS

Palladium-catalysed direct cross-coupling of secondary alkyllithium reagents

Palladium-catalysed cross-coupling of secondary C(sp3) organometallic reagents has been a long-standing challenge in organic synthesis, due to the problems associated with undesired isomerisation or the formation of reduction products. Based on our recently developed catalytic C-C bond formation with organolithium reagents, herein we present a Pd-catalysed cross-coupling of secondary alkyllithium reagents with aryl and alkenyl bromides. The reaction proceeds at room temperature and on short timescales with high selectivity and yields. This methodology is also applicable to hindered aryl bromides, which are a major challenge in the field of metal catalysed cross-coupling reactions

Catalytic Asymmetric Synthesis of Butenolides and Butyrolactones

γ-Butenolides, γ-butyrolactones, and derivatives, especially in enantiomerically pure form, constitute the structural core of numerous natural products which display an impressive range of biological activities which are important for the development of novel physiological and therapeutic agents. Furthermore, optically active γ-butenolides and γ-butyrolactones serve also as a prominent class of chiral building blocks for the synthesis of diverse biological active compounds and complex molecules. Taking into account the varying biological activity profiles and wide-ranging structural diversity of the optically active γ-butenolide or γ-butyrolactone structure, the development of asymmetric synthetic strategies for assembling such challenging scaffolds has attracted major attention from synthetic chemists in the past decade. This review offers an overview of the different enantioselective synthesis of γ-butenolides and γ-butyrolactones which employ catalytic amounts of metal complexes or organocatalysts, with emphasis focused on the mechanistic issues that account for the observed stereocontrol of the representative reactions, as well as practical applications and synthetic potentialsWe gratefully acknowledge generous support from The Netherlands Organization for Scientific Research (NWO-CW, Top grant to B.L.F.), the Royal Netherlands Academy of Arts and Sciences (KNAW), the Ministry of Education, Culture and Science (Gravitation Programme 024.001.035), the European Research Council (Advanced Investigator Grant 694345 to B.L.F.), and the Spanish Ministry of Economy and Competitiveness (Ramón y Cajal contract to M.F.-M.). B.M. gratefully thanks the Chinese National Natural Science Foundation (21606200) and the start-up fund from Zhejiang University of Technology for financial supportS

Tandem Long Distance Chain-Walking/Cyclization via RuH2(CO)(PPh3)3/Brønsted Acid Catalysis: Entry to Aromatic Oxazaheterocycles

NOTICE: This is the peer reviewed version of the following article: Bernárdez, R., Suárez, J., Fañanás-Mastral, M., Varela, J. A., Saá, C. (2016). Tandem Long Distance Chain-Walking/Cyclization via RuH2(CO)(PPh3)3/Brønsted Acid Catalysis: Entry to Aromatic Oxazaheterocycles. Org. Lett., 18, 4, 642-645. [doi: 10.1021/acs.orglett.5b03499]. This article may be used for non-commercial purposes in accordance with American Chemical Society Terms and Conditions for self-archiving.A novel route to 1,3-oxazaheterocycles based on cooperative Ru–H/Brønsted acid catalysis is reported. The use of the commercially available RuH2(CO)(PPh3)3 complex allows for an efficient long distance chain-walking process while the Brønsted acid is responsible for generation of an electrophilic iminium ion which is trapped intramolecularly by an alcohol moiety. The alcohol, besides its nucleophilic function, also plays an important role in the stabilization of the Ru catalyst.This work was supported by MINECO (Spain) (projects CTQ2011-28258 and CTQ2014-59015R), Xunta de Galicia (project GRC2014/032) and the European Regional Development Fund (projects CTQ2014-59015R and GRC2014/032). R. B. thanks MEC for a predoctoral FPU fellowship and J. S. thanks XUGA for a postdoctoral contract. M. F.-M. thanks MINECO for a "Ramón y Cajal" contractS

[2+1] Cycloaddition of Catalytic Ruthenium Vinyl Carbenes: A Stereoselective Controlled Access to (Z)- and (E)-Vinyl Epoxypyrrolidines

NOTICE: This is the peer reviewed version of the following article: Padín, D., Cambeiro, F., Fañanás-Mastral, M., Varela, J. A., Saá, C. (2017). [2+1] Cycloaddition of Catalytic Ruthenium Vinyl Carbenes: A Stereoselective Controlled Access to (Z)- and (E)-Vinyl Epoxypyrrolidines. ACS Catalysis, 7, 2, 992-996. [doi: 10.1021/acscatal.6b02929]. This article may be used for non-commercial purposes in accordance with American Chemical Society Terms and Conditions for self-archivingAza-alkynals undergo a cyclization reaction with diazo compounds in the presence of catalytic amounts of Cp*RuCl(cod) to afford vinyl epoxypyrrolidines, valuable building blocks for the synthesis of biologically active molecules. Ruthenium vinyl carbene intermediates have been invoked to explain the overall [2 + 1] cycloaddition (epoxy-annulation reaction). The reaction proceeds under mild conditions and in short reaction times (5–80 min) with complete (Z)- or (E)-stereoselectivity on the vinyl substituent, depending on the nature of the diazo compound used. Theoretical calculations support a mechanistic rationale to explain this controlled process.This work was supported by the Spanish MINECO (project CTQ2014-59015R), the ERDF and the Xunta de Galicia (project GRC2014/032). We also thank the ORFEO-CINQA network (CTQ2014-51912REDC). D. P. thanks MEC for a predoctoral FPU fellowship (FPU15/02132). M. F.-M. thanks MINECO for a “Ramón y Cajal” contractS