The addition of lithium carbenoids to isocyanates provides a versatile access N-substituted 2-haloacetamides: the reaction tolerates presence variously functionalized substituents on nitrogen atom, including sterically demanding ones and reactive halogens. No erosion enantiopurity was observed in case optically active isocyanates. One substrates prepared has been employed Charette's type chemoselective Grignard reagent an α-chloroketone.

Abstract β,γ‐Unsaturated aldehydes with all‐carbon quaternary or tertiary α‐centers were rapidly assembled from ketones through a unique synthetic operation consisting of 1) C 1 homologation, 2) Lewis acid mediated epoxide–aldehyde isomerization, and 3) electrophilic trapping. The equivalence vinyl oxirane β,γ‐unsaturated aldehyde is the key concept this previously undisclosed tactic. Mechanistic studies labeling experiments suggest that an enolate crucial intermediate. homologating...

The addition of carbon (Grignard and organolithium reagents) hydride nucleophiles (Schwartz reagent) to isocyanates isothiocyanates constitutes a versatile, direct high yielding approach the synthesis functionalized (thio)amide derivatives including haloamides formamides.

The transfer of a reactive nucleophilic CH₂X unit into preformed bond enables the introduction fragment featuring exact and desired degree functionalization through single synthetic operation.

Abstract A straightforward TMSCF 3 ‐catalyzed conversion of Weinreb amides into esters through the treatment with sodium alkoxides is reported. The procedure documents a genuine selectivity for esterification primary alcohols featuring diverse substitution pattern. constitutive N‐ methoxy fragment these acylating agents responsible unique reactivity they display, thus enabling to explore as competent nucleophilic elements. protocol compatible fully transfer stereochemical information...

A straightforward synthesis of variously functionalized α,β-unsaturated α′-haloketones has been achieved through the chemoselective addition halomethyllithium carbenoids to Weinreb amides at −78 °C. comparative study employing corresponding esters under same reaction conditions pointed out that instability tetrahedral intermediate formed from latter is responsible for observed formation carbinols instead desired haloketones.

The tetrahedral intermediates generated upon the addition of halolithium carbenoids (LiCH2X and LiCHXY) to Weinreb amides have been intercepted fully characterized as O-TMS heminals. commercially available N-trimethylsilyl imidazole is ideal trapping agent whose employment, combined with a straightforward neutral Alox chromatographic purification, enables isolation such labile species. procedure could be advantageously extended also for obtaining heminals from N-acylpyrroles. These manifest...

Abstract An efficient, chemoselective approach to spiro‐epoxyoxindoles via the addition of chloromethyllithium followed by ring‐closure intermediate alkoxide is reported. Chemoselectivity fully preserved in presence different electrophilic sites. The synthetic potential selected spiro‐epoxyindoles has been exploited copper(I)‐catalyzed intramolecular oxyarylation an alkyne and formation N,N ‐dimethylisoindigo dihalocarbenoids. magnified image

The acylation of α-substituted carbanion-type reagents (MCR1R2X; X = halogen, OR, SR, NR3R4, SeR, etc.) with Weinreb amides constitutes a highly versatile and flexible approach for accessing α-functionalized ketones. In this short review we will present series transformations—from our own the work others—documenting general applicability methodology. Chemoselectivity is uniformly manifested including critical substrates featuring additional electrophilic functionalities or sterically...

Treatment of widely available isocyanates with monohalolithium and dihalolithium carbenoids provides a valuable protocol for the one-pot preparation α-halo- α,α-dihaloacetamide derivatives. While can be prepared by smooth lithium–halogen exchange, corresponding dihalo compounds proved to highly dependent on base used realize deprotonation, lithium 2,2,6,6-tetramethylpiperidine emerging as optimal. The clear advantages procedure are: (a) broad scope that employed; (b) preservation optical...

α-Functionalized organolithium reagents (e.g., LiCH₂X) are versatile for accomplishing homologations of carbon- and heteroatom-type electrophiles. The proper selection the reaction conditions allows one to direct their intrinsic ambiphilicity towards nucleophilic character. Herein, homologation various electrophiles ranging from Weinreb amides isocyanates, carbonyl derivatives, chalcogenides – with a particular focus on chemoselectivity processes is summarized. 1 Introduction 2...

A synthesis of β-oxonitriles is reported via the generation R(1)R(2)CLiCN species followed by trapping with variously decorated Weinreb amides. The optimization study revealed that lithiation acetonitriles best accomplished deprotonation MeLi-LiBr at low temperature. protocol can be conveniently adapted to α-mono or α,α-disubstituted cyanoketones. (15)N- and (17)O-NMR data are for selected compounds.

The nucleophilic addition of widely available and variously functionalized organolithium reagents to isothiocyanates represents a straightforward, high-yielding, one-pot method access secondary thioamides. simple reaction conditions required the broad scope (>50 cases examples) makes it robust reliable both complex thioamides, including enantiopure ones. Noxious unpleasant-smelling sulfurating agents, usually employed in literature established methods, are avoided during whole synthetic...

Diselenoacetals, previously considered byproducts in homologation tactics en route to α-selenoketones, are herein found be excellent starting materials for this purpose. The easy selenium/lithium exchange they undergo affords seleno carbanions which smoothly added Weinreb amides chemoselectively prepare α-aryl- and α-alkyl methylketones through a single chemical operation. No racemization events observed the presence of optically pure materials.

The iodine(III) reagents vinylbenziodoxolones (VBX) were employed to vinylate a series of aliphatic and aromatic thiols, providing E-alkenyl sulfides with complete chemo- regioselectivity, as well excellent stereoselectivity. methodology displays high functional group tolerance proceeds under mild transition metal-free conditions without the need for excess substrate or reagents. Mercaptothiazoles could be vinylated modified conditions, resulting in opposite stereoselectivity compared...

The hitherto few explored α‐halomethyl amidine motif has been assembled through the addition of a lithiated (di)‐halomethane (i.e. carbenoid) to easily accessible N,N’‐diaryl substituted carbodiimides. Despite inherent low electrophilicity these heterocumulenes – as quantitatively determined in Mayr’s previous studies their sp‐hybridized carbon atom acts competent site attack for tamed nucleophiles. overall high‐yielding transformation featuring genuine chemoselective profile documented by...

Abstract Chloromethyllithium carbenoid has been chemoselectively added to cyclic enones (5‐, 6‐ and 7‐membered systems, including two natural products) provide chloromethyl allylic alcohols. Under the optimized reaction conditions neither concomitant ( n+1 ) homologation nor conjugate addition or Simmons–Smith‐like cyclopropanation takes place. The presence of LiBr is estimated play a dual role, namely as stabilizer mild Lewis acid activator CO group. Notably, mesomeric effect caused by...

A series of phosphine oxides and H-phosphinates were vinylated in the presence iodine(iii) reagents vinylbenziodoxolones (VBX), providing corresponding alk-1-enyl phosphinates good yields with complete chemo- regioselectivity. The vinylation proceeds open flask under mild transition metal-free conditions.

An efficient and widely applicable preparation of γ-hydroxy-α,β-acetylenic esters is described by means a one-pot dehydrobromination 2-bromoacrylate ester with LTMP followed the electrophilic addition transient propiolate to different aldehydes in eco-friendly solvent 2-MeTHF.

A straightforward chromatography-free preparation of Weinreb amides starting from acid halides has been achieved in the biphasic medium 2-MeTHF/water. Analytically pure compounds were isolated excellent yields simply after removal 2-MeTHF, which absolutely avoids use any contaminant organic solvent within whole process due to its (practically) immiscibility with water.