François Couty

Copper‐Mediated Coupling of 1,1‐Dibromo‐1‐alkenes with Nitrogen Nucleophiles: A General Method for the Synthesis of Ynamides

Mild reaction conditions are the advantage of the title reaction, which allows straightforward entry to a variety of ynamides starting from readily available 1,1-dibromo-1-alkenes, which act as attractive alkynylating agents (see scheme; EWG = electron-withdrawing group, DMF = N,N-dimethylformamide).

Increasing the Reactivity of Nitrogen Catalysts

This review article presents how nitrogen-centred Lewis bases were modified in order to increase their reactivity in catalytic processes. As examples, we focus on alcohol acylation and Morita-Baylis-Hilman reactions in order to showcase the fundamental parameters at play in transformations initiated by catalysts bearing respectively an active sp(2) or sp(3) nitrogen atoms. These two aspects are epitomised by two leading compounds, the Steglich base 4-dimethylaminopyridine (DMAP), and 1,4-diazabicyclo[2.2.2]octane (DABCO). Throughout this review, we stress the role played and the information brought by physical organic chemistry. Comprehension of these complex transformations relies on the fundamental knowledge of parameters, such as, nucleophilicity, nucleofugality, Lewis basicity, and crucially also the knowledge of their divergent impacts on each elementary step of the catalytic cycle.

De Novo Synthesis of 1,4-Dihydropyridines and Pyridines

An efficient and general method for the synthesis of 1,4-dihydropyridines and pyridines based on a lithiation/isomerization/intramolecular carbolithiation sequence is reported. This procedure provides an efficient, divergent, and straightforward entry to a wide range of polysubstituted dihydropyridines and pyridines starting from readily available N-allyl-ynamides.

Copper-Catalyzed Oxidative Alkynylation of Diaryl Imines with Terminal Alkynes: A Facile Synthesis of Ynimines

An efficient copper-mediated method for the oxidative alkynylation of diaryl imines with terminal alkynes is reported. This reaction provides the first catalytic and general synthesis of ynimines and allows for an easy preparation of these useful building blocks. An improved copper-catalyzed oxidative dimerization of imines to azines and the synthesis of dienes and azadienes from ynimines are also described.

A straightforward synthesis of enantiopure 2-cyano azetidines from β-amino alcohols

Enantiopure 2-cyano azetidines were prepared in high yields from β-amino alcohols. This synthesis was shown to be general and is based on two important steps: (i) chlorination of a N-cyanomethylated β-amino alcohol and (ii) a 4-exo-trig ring closure through the alkylation of a lithiated α-amino nitrile. The former step is stereoselective when ephedrine-derived β-amino alcohols are used. In the case of a phenylglycinol-derived β-amino alcohol, this step also involves a rearrangement.

Highly stereoselective ring expansion of enantiopure α-hydroxyalkyl azetidines

Abstract Stereodefined α-hydroxyalkyl azetidines, prepared in a few steps from enantiopure β-amino alcohols, are chlorinated or transformed into methanesulfonyloxymethyl derivatives in good yields. Heating of these compounds in chloroform or dimethylformamide induces a stereospecific ring enlargement to give 3-chloro or 3-methanesulfonyloxy pyrrolidines. The ease of this rearrangement depends on the nature of the migrating group (Cl − or MsO − ), of the class of the starting alcohol (primary or secondary) and of the relative stereochemistry of the starting material.

Intramolecular carbocupration of N-aryl-ynamides: a modular indole synthesis.

A modular indole synthesis based on an intramolecular 5-endo-dig carbocupration starting from readily available N-aryl-ynamides is reported. A variety of ynamides are converted to indoles in moderate to good yields and with varying substitution pattern on the indole ring. This further extends the synthetic utility of ynamides in organic synthesis and provides additional insights on the use of intramolecular carbometalation reactions.

Asymmetric synthesis of pipecolic acid derivatives

Abstract Condensation of chiral N-homoallyl β-amino alcohols with glyoxal produces iminium ions which are cyclized with complete stereoselectivity. These substrates, whose reactivity is closely dependent on the substitution pattern of the ethylenic moiety, undergo ene-iminium cyclizations that ultimately lead to homochiral pipecolic acid derivatives.

Cyclization of a chiral oxazolidine as a key-step for the synthesis of functionalized piperidines

Abstract Bicyclic oxazolidine 6 , a potential precursor for the synthesis of enantiopure piperidines and indolizidines, was synthesized from (R) -phenylglycinol. A stereoselective addition of cyanide anion on this compound afforded ultimately (2 S ,3 S )-3-hydroxypipecolic acid 9 .

Chiral oxazolidinones from N-Boc derivatives of β-amino alcohols. Effect of a N-methyl substituent on reactivity and stereoselectivity

Abstract Treatment of N-tert-butoxycarbonyl derivatives of homochiral β-amino alcohols with p-toluenesulfonyl chloride affords 2-axazolidinones. These heterocycles were produced by intramolecular nucleophilic attack of the carbamate moiety in an intermediate tosylate. The presence of a N-methyl substituent enhanced the cyclization rate and this effect was studied by AM1 calculations.