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Intramolecular alkyne germylzincation giving access to a wide range of germoles is achieved from triarylhydrogermanes in the presence of diethylzinc and AIBN as radical initiator. The reaction proceeds through activation of the Ge-H bond, leading to a heteroarylzinc intermediate after cyclisation, which can then be involved in a post-functionalisation reaction. Our results show that only 5

The sustainable production of industry-relevant chemicals, ranging from biofuels to pharmaceuticals, requires the development of efficient functionalization of biomass-derived building blocks, such as furan derivatives. Herein we report directed iridium-catalyzed C3–H silylation of furfural compounds, which grants access to versatile synthetic platforms. This transformation was developed on furfuryl derivatives, using imines as directing groups, and trialkylsilanes or bis(trimethylsilyl)methylsilane as silylating agents, in the presence of a hydride scavenger. Subsequently, fluoride-mediated activation strategies were applied to the C3–SiMe(OSiMe3)2 furfural derivatives. This strategy enables a wide range of transformations, namely arylation, alkenylation, alkynylation, allylation and alkylation, as well as halogenation and trifluoromethylation. A variety of high value-added products were thus easily obtained from the same common C3-silylated furfural platform.

This review is an update to the earlier Science of Synthesis coverage of the synthesis of propargylsilanes (Section 4.4.38). It covers the literature published between 2000 and 2021.Propargylsilanes can be prepared by a rather large array of methods that rely either on reactions involving C–Si bond formation, or on the manipulation of organosilicon-containing precursors to install a C≡C triple bond. For the first strategy, electrophilic silylation of propargyl or allenyl metals by reaction with halosilanes is the most frequently encountered; however, approaches such as propargylic carbene insertions into hydrosilanes, nucleophilic substitution or addition reactions with silylboranes and other silylmetals, or the rearrangement of propargylic silyl ethers have been developed more recently to diversify the silicon source. For the second type of approach, in addition to established transformations such as alkynylation of silylmethyl halides, α-silyloxiranes, or acylsilanes, the allylic substitution of allylic phosphates or elimination reactions of heteroatom-substituted allylsilanes have also recently gained interest. Moreover, a large body of work has been devoted to accessing elaborated propargylsilanes from simple pre-existing propargylsilane units through functionalization at the acetylenic carbon. Given the relevance of propargylsilanes in the context of stereoselective synthesis, there is persistent interest in the preparation of chiral, nonracemic propargysilanes, and significant progress in this area has been achieved over the last two decades, notably through the implementation of asymmetric catalysis.

International audience; The stereoselective germylzincation of internal alkynes delivering trisubstituted vinylgermanes is achieved via a radical chain process involving Ph3GeH and Et2Zn with AIBN as initiator. Excellent levels of regiocontrol are observed for non-symmetric (aryl, alkyl)-substituted alkynes, as well as for propargylic alcohols with aryl-, alkyl-, or silyl-substituted alkynes. The germylzincation reaction can be combined in one pot with the Cu(I)-mediated electrophilic substitution of the C(sp 2)-Zn bond to obtain synthetically challenging tetrasubstituted vinylgermanes.

International audience; This minireview covers recent progress in the functionalization of C(sp2)−Si bonds by intramolecular activation by alkoxides. Such processes involve the formation of a cyclic hypervalent silicon intermediate that allows carbon‐to‐oxygen migration of the organosilyl group and thus the formation of a carbanionic species poised to undergo electrophilic substitution. The C(sp2)−Si bond cleavage can be “endocyclic” (Brook rearrangement) or “exocyclic”. Organosilicon reagents are invaluable tools in the hands of the modern chemist that allow accomplishing a number of synthetically useful transformations. While some are standard reactions, others are more complex transformations, such as the Brook rearrangement and its variants. This carbon‐to‐oxygen silyl migration represents a privileged method to generate transient carbanionic species well suited to undergo functionalization upon electrophilic substitution in the presence of an electrophile. This minireview focuses on recent advances in C(sp2)−Si bond functionalization through intramolecular activation by alkoxides. The key elements of reactivity will be highlighted in the introduction to allow the proper understanding of the migration process. Then, an overview of the reactivity of substrates incorporating the C(sp2)−Si motif and their synthetic applications will be provided.

International audience; The silyl-and germylzincation of terminal or internal propargylic alcohols by reaction with (Me3Si)3SiH/Et2Zn, [(Me3Si)3Si]2Zn/Et2Zn or Ph3GeH/Et2Zn is examined. These reactions proceed through the addition of silicon-or germanium-centered radicals across the carbon-carbon triple bond followed by the trapping by diethylzinc of the produced vinyl radical through homolytic substitution at the zinc atom. The influence of the hydroxy unit on the regio-and stereoselectivity of these reactions is discussed and compared to its role played in radical hydrosilylation and hydrogermylation reactions. Protocols developed to achieve the β-regioselective silylzincation of propargyl alcohol and the α-regioselective germylzincation of internal propargylic alcohols are particularly important, as they occur with trans stereoselectivity. For both procedures the C(sp 2)-Zn bond remains available for subsequent in-situ electrophilic substitution leading overall to net alkyne trans difunctionalization.

International audience; Aryl- and hetaryl-substituted acetylenes undergo regio- and stereoselective silylzincation by reaction with [(Me3Si)3Si]2Zn in the presence of Et2Zn (10–110 mol%) as additive. The distinctive feature of this addition across the C−C triple bond is its trans stereoselectivity. The radical nature of the silylzincation process is supported by diagnostic experiments and DFT calculations, which also corroborate the role played by steric effects to obtain that stereoselectivity. The procedure can be combined in one-pot with the copper(I)-mediated electrophilic substitution of the C(sp2)−Zn bond, with retention of the double bond geometry. This makes it valuable for the synthesis of stereodefined di- and trisubstituted vinylsilanes.

We report that triflic acid, a strong Bronsted acid, is a very powerful alternative to FeCl3 to mediate the hydroarylation of N-Ac indoles, which delivers regioselectively 3-arylindolines, 3,3-spiroindolines or 2-arylindolines. Mechanistic explorations point towards the existence of a highly electrophilic intermediate by simultaneous activation of the acetyl and of the C2=C3 bond by protons.

The methylenation/hydrogenation cascade reaction of aldehydes or ketones through a domino process involving two ensuing steps in a single pot is realized. The compatibility of Matsubara's reagent and Wilkinson's complex give a combination that allows, under dihydrogen, the transformation of a carbonyl function into a methyl group. This new method is suitable to introduce an ethyl motif from aromatic and aliphatic aldehydes with total chemoselectivity and total retention of α-stereochemical purity. The developed procedure is also extended to the introduction of methyl groups from ketones.

An efficient E-selective semihydrogenation of internal alkynes was developed under low dihydrogen pressure and low reaction temperature from commercially available reagents: Cl

International audience; An efficient E-selective semihydrogenation of internal alkynes was developed under low dihydrogen pressure and low reaction temperature from commercially available reagents: Cl2Pd(PPh3)2, Zn 0 and ZnI2. Kinetic studies and control experiments underline the significant role of ZnI2 in this process under H2 atmosphere, establishing that the transformation involves syn-hydrogenation followed by isomerization. This simple and easy-to-handle system provides a route to E-alkenes under mild conditions.

4-Aminopropargylic acetates afford 4-amino-1-allenylsilanes upon reaction with the lithium (triorganosilyl)zincate (PhMe2Si)3ZnLi. The reaction is both stereoselective and stereospecific and proceeds through syn-silylzincation of the carbon–carbon triple bond followed by subsequent anti-β-elimination of the acetate group.

International audience

Lithium alkynyl(disilyl)zincates obtained from metalated ethynyloxiranes, as well as from N - tert -butanesulfinyl(ethynyl)aziridines or N - tert -butanesulfonyl(ethynyl)aziridines, undergo 1,2-migration of the organosilyl group with ring opening of the oxirane or aziridine ring by S N i displacement. A developed protocol that involves n BuLi for the metalation step offers a straightforward approach to the corresponding δ-oxy- and δ-amino α-silyl allenylzinc intermediates. The reagents derived from the epoxides are amenable to subsequent in situ condensation with aldehydes or ketones to provide 1,3-diols but not those derived from aziridines that only react sluggishly in similar condensations.

Herein, we report a mechanistic exploration of the unusual FeCl

The tandem 1,4-addition–aldol condensation reaction of diethylzinc, α,β-unsaturated chiral enantiopure oxazolidines derived from 2-phenylglycinol, and carbonyl compounds is disclosed. The reaction proceeds through a radical-polar crossover mechanism involving the aldol condensation of a trisubstituted zinc enolate through a Zimmerman–Traxler transition state. Installation of a 2-pyridine moiety at the hemiaminal position of the chiral auxiliary allows obtaining both excellent asymmetric induction and diastereoselectivity (up to >90 % de). The developed protocol is suitable for aromatic and aliphatic aldehydes, as well as ketones.

International audience; Herein, we report a mechanistic exploration of the unusual FeCl3-mediated hydroarylation of N-Ac indoles. Electron density topology analysis of a crystal, in situ IR monitoring, Hammett and Taft studies as well as DFT computations allowed us to determine that activation of acetyl with FeCl3 and of the C2C3 bond with a proton is involved.

The performance of tert-butanesulfinamides as nitrogen nucleophiles in Pd(0)-catalyzed allylic substitution reactions has been investigated. Metalated N-alkyl and N-acetyl sulfinamides have been identified as suitable partners for the reaction with π-allyl–palladium complexes. The cross-coupling of N-acetyl tert-butanesulfinamide with 2- or 3-substituted linear allylic carbonates is achieved in the presence of Pd(OAc)2 (5 mol%) and dppe (7.5 mol%) and does not require an additional base. The reaction proceeds in high yields (59–98%) to produce the corresponding E-configured linear allylic sulfinamides in a totally regioselective and highly diastereoselective manner. The sulfur atom remains configurationally stable throughout the allylation process, and thus the coupling products are obtained in enantiomerically pure form.

International audience; Sulfur-, oxygen-, and phosphorus-substituted terminal alkynes undergo regio- and stereoselective silylzincation by reaction with (Me2PhSi)2Zn, (Me3Si)3SiH/Et2Zn or [(Me3Si)3Si]2Zn/Et2Zn. The addition across the C–C triple bond always occurs with β-regioselectivity but the stereoselectivity is tunable: (Me2PhSi)2Zn for cis and (Me3Si)3SiH/­Et2Zn or [(Me3Si)3Si]2Zn/Et2Zn for trans. The procedures making use of the zinc reagents (Me2PhSi)2Zn and [(Me3Si)3Si]2Zn can be combined in one-pot with a subsequent stereoretentive copper(I)-mediated electrophilic substitution of the intermediate C(sp2)–Zn bond. These stereodivergent protocols offer a regio- and stereoselective access to trisubstituted vinylsilanes decorated with sulfur-, oxygen-, and phosphorus substituents with either double-bond geometry.

The rearrangement of acetylenic epoxides mediated by low-valence organotitanium and organozirconium reagents is ­reported to give conjugated enynes. Moderate to good yields and high selectivities are obtained when using the organozirconium(II) Negishi reagent in toluene at 20 °C; whereas only poor yields and low selectivities are achieved with the organotitanium(II) Sato reagent. The process is stereospecific and involves formation of titana- and zirconacyclopropenes by oxidative insertion of the low-valence titanium and zirconium reagents into the carbon–carbon triple bond of the acetylenic epoxides. These metallacyclopropenes then rearrange to afford stereodefined propargylmetals through the epoxide ring-opening. Conjugated enynes are finally produced by β-elimination of metal oxide.

Zinc reagents (Me2PhSi)2Zn and [(Me3Si)3Si]2Zn undergo highly regio- and stereoselective addition across the carbon–carbon triple bond of nitrogen-, sulfur-, oxygen-, and phosphorus-substituted terminal alkynes in the absence of copper or any other catalyst. Both reagents yield exclusively β-isomers, and the stereoselectivity is determined by the silyl group: Me2PhSi for cis or (Me3Si)3Si for trans. These stereodivergent silylzincation protocols offer an efficient access to heteroatom-substituted vinylsilanes with either double bond geometry, including trisubstituted vinylsilanes by one-pot electrophilic substitution of the intermediate C(sp2)–Zn bond by copper(I)-mediated carbon–carbon bond formation.

The use of tert-butanesulfinamides as nitrogen nucleophiles in carbon-nitrogen bond forming reactions is reviewed. This field has grown in the shadow of the general interest in N-tert-butanesulfinyl imines for asymmetric synthesis and occupies now an important place in its own right in the chemistry of the chiral amine reagent tert-butanesulfinamide. This article provides an overview of the area and emphasizes recent contributions wherein the tert-butanesulfinamides act as chiral auxiliaries or perform as nitrogen donors in metal-catalyzed amination reactions.

Herein an extremely versatile, well-defined, low-valent cobalt catalyst [Co(PMe3)4] capable of intermolecular and intramolecular imine-directed C2-alkylation and alkenylation of indoles is reported. The reaction proceeds in the absence of reducing agents or additives, affording a range of substituted indoles and dihydropyrroloindoles in high yields and regioselectivities. With the aid of deuterium labeling studies and DFT (Density Functional Theory) calculations, a mechanism is proposed that is based on a Ligand-to-Ligand Hydrogen Transfer pathway.

A method to extend the scope of the aza-Piancatelli reaction between 2-furylcarbinols and anilines is depicted. We found that 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) is the solvent of choice for this transformation, as it outcompetes the usual solvents in terms of rate and yield. Side reactions and other issues raised by the title reaction are prevented, thereby providing an avenue to complex molecules that were previously inaccessible. Lewis acidity studies and computations were carried out to unveil the role of HFIP. Based on these results, we propose that HFIP is, in fact, acting as a Lewis acid and that its acidity can be enhanced when combined with a calcium(II) salt.

Zinc reagents (Me2PhSi)2Zn and [(Me3Si)3Si]2Zn undergo highly regio- and stereoselective addition across the carbon-carbon triple bond of nitrogen-, sulfur-, oxygen-, and phosphorus-substituted terminal alkynes in the absence of copper or any other catalyst. Both reagents yield exclusively β-isomers, and the stereoselectivity is determined by the silyl group: Me2PhSi for cis or (Me3Si)3Si for trans. These stereodivergent silylzincation protocols offer an efficient access to heteroatom-substituted vinylsilanes with either double bond geometry, including trisubstituted vinylsilanes by one-pot electrophilic substitution of the intermediate C(sp(2))-Zn bond by copper(I)-mediated carbon-carbon bond formation.

International audience; Herein an extremely versatile, well-defined, low-valent cobalt catalyst [Co(PMe3)(4)] capable of intermolecular and intramolecular imine-directed C2-alkylation and alkenylation of indoles is reported. The reaction proceeds in the absence of reducing agents or additives, affording a range of substituted indoles and dihydropyrroloindoles in high yields and regioselectivities. With the aid of deuterium labeling studies and DFT (Density Functional Theory) calculations, a mechanism is proposed that is based on a Ligand-to-Ligand Hydrogen Transfer pathway.

A modular entry to enantiopure (E)-2-substituted 3-alkylideneprolines is disclosed in 5 or 6 steps from tert-butanesulfinamide.

International audience; Herein, we report the first catalytic version of a cobalt-catalysed reductive homocoupling of benzyl halides which proceeds with low catalyst loadings (0.5 to 5 mol%). By synthetizing each cobalt intermediate we demonstrate that reaction proceeds through two single electron transfers (SET) and that dimethylzinc is only involved in the regeneration of the catalytic species.

The use of tert-butanesulfinamides as nitrogen nucleophiles in carbon–nitrogen bond forming reactions is reviewed. This field has grown in the shadow of the general interest in N-tert-butanesulfinyl imines for asymmetric synthesis and occupies now an important place in its own right in the chemistry of the chiral amine reagent tert-butanesulfinamide. This article provides an overview of the area and emphasizes recent contributions wherein the tert-butanesulfinamides act as chiral auxiliaries or perform as nitrogen donors in metal-catalyzed amination reactions.

A comparative study of the metallotropic equilibrium between 1-chloro-3-(trimethylsilyl)propargyl and -allenyl metals was undertaken by means of lithio-, titano-, and zinco-carbenoids. The lithium and zinc species were shown to react mainly in their allenic metallotropic forms, whereas the titanium species proved to react in both its propargylic and allenic forms. The configurational stability of these organometallics was next examined using a modification of the Hoffmann test. In each case, the organometallic was reacted with a chiral enantiopure electrophile. A comparison of the diastereomeric ratios obtained at low and high conversion rates of the reagent allows assessment of its configurational stability. The lithium species thus exhibited a configurational lability at −125 °C in Trapp mixture on the time scale of its reaction with (+)-camphor, while the titanium analogue proved to be configurationally stable at −40 °C in THF/Et2O on the time scale defined by its reaction with (S)-N-tritylprolinal. In...

The preparation of 5-substituted 2,3-methanopyrro- lidines by the stereoselective cyclization of zincated α-amino ni- triles derived from enantiopure α-branched homoallylamines has been investigated. The formation of trans adducts in excellent dia- stereoselectivities (up to >98:2) and good yields (up to 71%) is ob- served. The absolute configuration and enantiomeric excess are dependent on the nitrogen protecting group. 2,3-Methanopyrrolidines {2-azabicyclo(3.1.0)hexane de- rivatives} are interesting molecules that have attracted in- terest both for their use as scaffolds in biologically active peptide mimics 1,2 and as synthetic intermediates for nitro- gen-containing compounds. 3 In contrast with the prepara- tion of 2,3-methanopyrrolidines in racemic form, 1a,3,4 general synthetic methods for the preparation of enantio- pure 2,3-methanopyrrolidines are not common. 1b-e,5-7

N-(tert-Butylsulfinyl)-α-(aminomethyl)acrylates with tethered silylated alkynes undergo a tandem 1,4-addition/carbozincation reaction upon exposure to dialkylzinc compounds in the presence of air. The process follows a zinc-radical-transfer mechanism and provides vinylzinc adducts that can react subsequently with electrophiles. High levels of chiral induction (dr > 90:10) from the tert-butylsulfinyl directing group are achieved during the radical 5-exo-dig cyclization by adding samarium(III) triflate. The sequence overall provides straightforward modular access to enantiopure (E)-4-alkylidene-β-prolines from tert-butanesulfinamide.

A domino 1,4-addition/alkyne carbozincation sequence basedon a radical zinc-atom transfer process is disclosed. Two efficientmulticomponent approaches to 3-alkylidenetetrahydrofurans from β-(propargyloxy)enoatesbearing pendant alkynes (including ynamides) have been established:one involving the direct addition of dialkylzincs, and the secondinvolving the dimethylzinc-mediated addition of alkyl iodides. Bothsequences utilize the stereoselective formation of intermediatealkylidenezincs well suited for in situ functionalizationwith electrophiles. 1 Introduction 2 1,4-Addition/Cyclization of Dialkylzincs on β-(Propargyl-oxy)enoates 2.1 β-(Propargyloxy)enoates with a Pendant TerminalAlkyne 2.2 β-(Propargyloxy)enoates with a Pendant Substituted Alkyne 2.3 β-(Propargyloxy)enoates with a Pendant Ynamide 3 1,4-Addition/Cyclization of Alkylzinc Halides on β-(Propargyloxy)enoates 4 Dialkylzinc-Mediated 1,4-Addition/Cyclization ofAlkyl Iodides on β-(Propargyloxy)enoates 5 Conclusion; Current and Future Work

The stereoselective synthesis of alkynyl 1,2-amino alcohols by the addition of 3-chloro- and 3-methoxymethoxy- allenylzincs to chiral tert-butylsulfinylimines is described. The methodology is applicable to the preparation of alkynyl 2-amino-1,3-diols (O,N,O stereotriads) using a-alkoxy tert-butylsulfinylimines as chiral starting materials. The scope and limitations of the methodology along with recent applications to the efficient asymmetric syntheses of natural and/or bioactive alkaloids and polyhydroxylated alkaloids are presented.

The asymmetric total synthesis of (+)-6-epi-castanospermine (1) is described herein. In this synthesis the diastereoselective addition of a racemic allenylzinc reagent to an enantiopure α-alkoxy-tert-butylsulfinylimine is the key step and is followed by the formation of a piperidine ring by ring-closing metathesis and subsequent syn-dihydroxylation of an alkene.

The rapid, high-yielding synthesis of (2S,3R)-3-hy- droxy-2-phenylpiperidine, a known advanced key intermediate of some non-peptide human NK-1 receptor antagonists such as (+)- CP-99,994, (+)-CP-122,721 and (+)-LP-733,060, is reported. This synthesis involves the stereoselective addition of racemic 3-(meth- oxymethoxy)allenylzinc bromide to enantiopure (RS,E)-N-2-ben- zylidene-2-methylpropane-2-sulfinamide and a ring-closing metathesis reaction as the key steps. Following this procedure, (2S,3R)-3-hydroxy-2-phenylpiperidine is obtained in seven steps in 56.2% overall yield.

International audience; The high-yielding and highly efficient stereoselective synthesis of enantiopure anti,anti and syn,anti acetylenic 2-amino-1,3-diol stereotriads from r-alkoxy-tert-butanesulfinylimines bearing a stereocenter r to the imino group is reported. The stereoselectivity of the reaction of these tert-butanesulfinyl (tBS)-imines with allenylzinc (()-1 was found to be controlled only by the configuration of the tBS group. An excellent kinetic resolution of the racemic allenylzinc species was observed, allowing a high stereocontrol no matter what the configuration or the protecting group of the r-alkoxy group.

A novel bicyclo[8.3.1]enediyne was readily synthesized by chromium-mediated dearomatization of 2,6-bis(trimethyl­silyl)anisole. The enediyne undergoes Bergman cyclization with a half-life of 14.4 hours at 142 °C.