Allylic Functionalization of Unactivated Olefins with Grignard Reagents

New advances in the functionalization of unactivated olefins with carbon nucleophiles have provided more efficient and practical approaches to convert inexpensive starting materials into valuable products. Recent examples have been reported with stabilized carbon nucleophiles, tethered carbon nucleophiles, diazoesters, and trifluoromethane donors. A general method for functionalizing olefins with aromatic, aliphatic, and vinyl Grignard reagents was developed. In a one‐pot process, olefins are oxidized by a commercially available reagent to allylic electrophiles, which undergo selective copper‐catalyzed allylic alkylation with Grignard reagents. Products are formed in high yield and with high regioselectivity. This was utilized to synthesize a series of skipped dienes, a class of compounds that are prevalent in natural products and are difficult to synthesize by known allylic alkylation methods.     

Novel cross-coupling reactions between organotellurides and Grignard reagents employing a MnCl2/CuI catalytic system

We present a general protocol for the cross-coupling reaction of Grignard reagents and organic tellurides. Aryl Grignard reagents react stereospecifically with vinyl tellurides in the presence of a catalytic amount of manganese (II) chloride and copper (I) iodide to produce good yields of the corresponding cross-coupling products.     

Diversity‐Oriented Enantioselective Synthesis of Highly Functionalized Cyclic and Bicyclic Alcohols

The copper‐catalyzed hetero‐allylic asymmetric alkylation (h‐AAA) of functionalized Grignard reagents that contain alkene or alkyne moieties has been achieved with excellent regio‐ and enantioselectivity. The corresponding alkylation products were further transformed into a variety of highly functionalized cyclic and bicyclic alcohols with excellent control over the chemo‐, regio‐, and stereoselectivity.     

Cu‐Catalyzed Asymmetric Allylic Alkylation of Phosphonates and Phosphine Oxides with Grignard Reagents

An efficient and highly enantioselective copper‐catalyzed allylic alkylation of phosphonates and phosphine oxides with Grignard reagents and Taniaphos or phosphoramidites as chiral ligands is reported. Transformation of these products leads to a variety of new phosphorus‐containing chiral intermediates.     

Copper catalyzed asymmetric synthesis of chiral allylic esters

The complex derived from Taniaphos ligand 4 and CuBr*Me2S catalyzes the asymmetric addition of Grignard reagents to 3-bromopropenyl esters 1 to provide allylic esters 2 in high yields and high chemio-, regio-, and enantioselectivities. The work demonstrates that allylic asymmetric alkylation (AAA) can be done on substrates bearing a heteroatom at the gamma-position. The method is a practical route to chiral, nonracemic allylic alcohols. The use of functionalized substrates 1 or Grignard reagents leads to more complex products 2, which can be further manipulated as demonstrated in conversion to (S)-5-ethyl-2(5H)-furanone 6 and (S)-benzoic acid-cyclopent-2-enyl ester 7.     

Etude comparative de l'alkylation des tetraphenylporphyrines de l'etain et de leurs formes reduites par les reactifs de grignard

A comparative study of alkylation by Grignard reagents of PSn(OH)₂ (P = tetraphenylporphyrin (TPP), tetraphenylchlorine (TPC), tetraphenylisobacteriochlorine (TPiBC)) shows that dialkylstannylisobacteriochlorines are the most easily obtained. The presence of transition metals in the magnesium crystals directs the reaction towards reduction of the macrocycle instead of alkylation on tin. This is supplementary proof for the intervention of a single electron transfer mechanism (SET) in alkylation of a macrocycle by Grignard reagents.These results fit very well with earlier electrochemical experiments and the measurements of the reduction potentials of the Group IVB metalloporphyrins and their reduced forms.     

Synthesis of carboxylic amides by ring-opening of oxazolidinones with Grignard reagents

Treatment of N-alkyl-oxazolidin-2-ones with Grignard reagents gives tertiary carboxylic amide products. Various substituted oxazolidinones can be used as illustrated with phenyl, benzyl or isopropyl groups on the 4-position, and methyl, benzyl or p-methoxybenzyl groups on the 3-position (the nitrogen atom). A selection of Grignard reagents were successful, including allyl, benzyl, alkyl and phenyl magnesium halides. The organomagnesium species attacks the carbonyl group and promotes ring-opening of the oxazolidinone. The product tertiary amides are useful substrates for stereoselective transformations and were applied to a highly selective enolate alkylation and to a ring-closing metathesis reaction to a six-membered lactam and hence a formal synthesis of the alkaloids (-)-coniine and (+)-stenusine.     

Alkylation of Pyridines at Their 4‐Positions with Styrenes plus Yttrium Reagent or Benzyl Grignard Reagents

A new regioselective alkylation of pyridines at their 4‐position was achieved with styrenes in the presence of yttrium trichloride, BuLi, and diisobutylaluminium hydride (DIBAL‐H) in THF. Alternatively, similar products were more simply prepared from pyridines and benzyl Grignard reagents. These reactions are not only a useful preparation of 4‐substituted pyridines but are also complementary to other relevant reactions usually giving 2‐substituted pyridines.     

Alkylation des carbenoides par des nucleophiles. : II. Substitution nucleophile de l'halogene de carbenoides α phosphonates catalysee par le cuivre(I)

The addition of a catalytic amount (12%) of a copper(I) salt to a mixture of an α-lithio-α-chloroalkylphosphonate and an alkyllithium RLi or a Grignard reagent RMgX leads to the formation of a new organometallic reagent in which the R group has replaced the chlorine atom of the carbenoid. This nucleophilic alkylation of carbenoids can be performed with secondary-alkyl Grignard reagents, and with aryllithium, alkenyllithium and alkynyllithium reagents in good yields (60–80%).     

Nickel-phosphine complex-catalyzed Grignard coupling—II : Grignard coupling of heterocyclic compounds

A general, versatile method for alkylation and arylation of haloheterocyclic compounds is reported. In the presence of a catalytic quantity of [NiCl₂(dppp)], where dppp stands for Ph₂P(CH₂)₃PPh₂, bromothiophenes, halopyridines, haloquinoline, and haloisoquinolines reacted with alkyl and aryl Grignard reagents at room temperature or at ether refluxing temperature to give the cross-coupling products. The coupling reaction has been applied to the synthesis of isoquinoline alkaloids. Reactivities of 2-thienyl and 2-pyridyl Grignard reagents have also been examined.     

Reaction of (bromodifluoromethyl)phenyldimethylsilane with organometallic reagents

A new fluorine-containing organosilicon compound, (bromodifluoromethyl)-phenyldimethylsilane (II), was synthesized by the N-bromosuccinimide (NBS) bromination of difluoromethyl)phenyldimethylsilane (I), which was prepared from phenyldimethylsilyllithium and chlorodifluoromethane. Compound II reacted with dimethyl sulfoxide to give dimethyl sulfide and phenyldimethylfluorosilane in quantitative yield. The reaction of II with nucleophiles, such as sodium ethoxide, Grignard or lithium reagents, afforded products arising from cleavage of the carbonsilicon bond. In contrast, the reaction of II with Grignard reagents in the presence of appropriate catalysts (Group VIII transition metal salts or complexes) afforded the homo-coupling product of II, 1,2-bis-(phenyldimethylsilyl)-1,1,2,2-tetrafluoroethane (IV), in excellent yield. The silver(I) salt-catalyzed reaction of II with ethylmagnesium bromide gave the cross-coupling product, (1,1-difluoropropyl)phenyldimethylsilane (V) as well as III and IV. When cuprous bromide was employed as catalyst, the reaction of II with ethylmagnesium bromide afforded 1-phenyldimethylsilyl-1-propene (VI) and 3-phenyldimethylsilyl-2-pentene (VII) as main products.     

Lewis base activation of grignard reagents with N-heterocyclic carbenes. Cu-free catalytic enantioselective additions to gamma-chloro-alpha,beta-unsaturated esters

Direct activation of alkylmagnesium halides with a chiral bidentate N-hetrocyclic carbene (NHC), formed in situ from the imidazolinium chloride precursor, is reported. The Cu-free catalytic asymmetric allylic alkylation (AAA) of alpha-alkyl-gamma-chloro-alpha,beta-unsaturated esters with alkyl-based Grignard reagents is promoted in the presence of 5-10 mol % of the chiral imidazolinium salt to afford synthetically versatile beta,gamma-unsaturated esters. Products bear all-carbon quaternary sterogenic centers generated in 3.5-13.3:1 regioselectivity, 63-98% ee, and in up to 80% isolated yield of the SN2' product. The in-situ-generated chiral NHC promotes enantioselectivity while altering the reactivity of the Grignard reagents: there is only approximately 30% conversion and <2% allylic alkylation in the absence of chiral carbene.     

CamTHP*OH: a camphor-derived delta-lactol auxiliary for the effective desymmetrization of attached glycinamide residues. Asymmetric synthesis of alpha-amino carbonyl compounds

Stereoselective allylation of camphor and subsequent terminal hydroformylation affords a new delta-lactol auxiliary (camTHP*OH) on multigram scale. Stereoselective condensation with glycine dimethylamide and Cbz protection affords a camTHP*-desymmetrized glycinamide building block which undergoes efficient and highly diastereoselective metal enolate alkylation reactions. Acid-mediated deprotection affords the N-Cbz-protected alpha-amino amide products which may be converted directly to alpha-amino ketones on treatment with Grignard or organolithium reagents without loss of stereochemical integrity. [reaction: see text]     

Comparison of Derivatization Methods for the Determination of Butyl- and Phenyl-tin Compounds in Mussels by Gas Chromatography

Two different derivatization methods, alkylation with Grignard reagents, and ethylation with sodium tetraethylborate, were compared for the determination of organotin compounds, viz. tributyltin, dibutyltin, monobutyltin, triphenyltin, diphenyltin and monophenyltin, in mussel samples. Temperature, reaction time and concentration of Grignard reagents were optimized in the former method; in the latter the effect of pH, concentration of sodium tetraethylborate and reaction time were studied. In the derivatization with Grignard reagents hexyl, pentyl, propyl, ethyl and methyl were used as alkyl Grignard groups. A critical evaluation of the different derivatization methods is presented. © 1997 John Wiley & Sons, Ltd.     

Trapping of photochemical intermediates as a tool in organic synthesis. Preparation of spiroaziridinopyridones, a new heterocyclic system

Whereas alkyl lithium and Grignard reagents both at rt and at −80°C thermally react with 3-methylisoxazolo[5,4-b]pyridine giving alkylation and/or isoxazole ring opening products, sodium malonate and sodium boron hydride react only under UV irradiation. Selective trappings of ketenimine or azirine intermediates give an enaminopyridone or two diasteroisomeric spiroaziridinopirydones. Regioselective opening of the aziridine ring with perchloric acid gives 3(1-amino-ethyl)-1H-pyridin-2-one.     

Cerium chloride-promoted nucleophilic addition of grignard reagents to ketones an efficient method for the synthesis of tertiary alcohols

In the presence of anhydrous cerium(III) chloride, Grignard reagents react with Ketones to afford addition products in high yields, even though the substrates are susceptible to abnormal reactions with Grignard reagents alone.     

Z-Selective copper-catalyzed asymmetric allylic alkylation with Grignard reagents

Allylic gem-dichlorides undergo regio- and enanantioselective (er up to 99:1) copper-catalyzed allylic alkylation with Grignard reagents affording chiral Z-vinyl chlorides. This highly versatile class of synthons can be subjected to Suzuki cross coupling affording optically active Z-alkenes and 1,3-cis,trans dienes.     

Copper-Catalyzed Regiodivergent Internal Allylic Alkylations

We report a copper-catalyzed, regioselective, and stereospecific alkylation of unbiased internal allylic carbonates with functionalized alkyl and aryl Grignard reagents. The reactions exhibit high stereospecificity and regioselectivity for either S_N2 or S_N2′ products under two sets of copper-catalyzed conditions, which enables the preparation of a broad range of products with E-alkene selectivity. Density functional theory calculations reveal the origins of the regioselectivity based on the different behaviors of homo- and heterocuprates.     

Synthesis of thiazole aminophosphine oxides, aminophosphonic and aminophosphinic acids and Cu(II) binding abilities of thiazole aminophosphonic acids

A series of new aminophosphine oxides, aminophosphonic and aminophosphinic acids derived from thiazole was synthesized by addition of phosphine oxides or silylated phosphorus esters to the corresponding thiazole aldimines. The thiazole aldimines were obtained from 2-thiazole aldehyde and primary amines by a standard procedure. The corresponding phosphine oxides were obtained by alkylation of diethyl phosphite or ethyl phenylphosphinate with the appropriate Grignard reagents. The silylated phosphorus esters were prepared from trimethyl phosphite and from methyl- or phenylphosphinic ethyl ester by treatment with bromotrimethylsilane. The coordination ability towards Cu(II) ions are described for two obtained aminophosphonate ligands.     

Iron-catalysed, hydride-mediated reductive cross-coupling of vinyl halides and Grignard reagents

An iron-catalysed, hydride-mediated reductive cross-coupling reaction has been developed for the preparation of alkanes. Using a bench-stable iron(II) pre-catalyst, reductive cross-coupling of vinyl iodides, bromides and chlorides with aryl- and alkyl Grignard reagents successfully gave the products of formal sp(3)-sp(3) cross-coupling reactions.