Copper-catalyzed anti-stereocontrolled ring opening of oxabicyclic alkenes with grignard reagents

[reaction: see text] A general copper-catalyzed procedure for the stereoselective ring opening of [2.2.1]-oxabicyclic alkenes with Grignard reagents is described. In the presence of catalytic amounts of CuCl/PPh(3) the reaction occurs with very high or complete anti selectivity in all cases.     

Copper-catalyzed asymmetric ring opening of oxabicyclic alkenes with Grignard reagents

[reaction: see text] Simple Grignard reagents were applied in copper-catalyzed asymmetric ring-opening reactions of oxabenzonorbornadiene derivatives using spiro phosphoramidite ligands. Excellent anti-stereoselectivities and good enantioselectivities were achieved.     

Copper-catalyzed asymmetric allylic substitution with aryl and ethyl Grignard reagents

Phenyl- and ethyl-magnesium bromides undergo regioselective asymmetric allylic substitution with high enantioselectivity under the catalysis of chiral amidophosphane-copper(I) complexes.     

Copper-catalyzed asymmetric conjugate addition with Grignard reagents and SimplePhos ligands

Herein we report the copper-catalyzed asymmetric conjugate addition of Grignard reagents to cyclic and acyclic enones, with SimplePhos as chiral ligands. A variety of Grignard reagents can be added to a range of cyclic and acyclic enones, with moderate to good enantioselectivities (ee’s up to 86%).     

Copper-catalyzed asymmetric ring opening of oxabicyclic alkenes with organolithium reagents

A highly efficient method is reported for the asymmetric ring opening of oxabicyclic alkenes with organolithium reagents. Using a copper/chiral phosphoramidite complex together with a Lewis acid (BF(3)·OEt(2)), full selectivity for the anti isomer and excellent enantioselectivities were obtained for the ring opened products.     

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.     

Fe-catalyzed three-component dicarbofunctionalization of unactivated alkenes with alkyl halides and Grignard reagents

A highly chemoselective iron-catalyzed three-component dicarbofunctionalization of unactivated olefins with alkyl halides (iodides and bromides) and sp²-hybridized Grignard reagents is reported. The reaction operates under fast turnover frequency and tolerates a diverse range of sp²-hybridized nucleophiles (electron-rich and electron-deficient (hetero)aryl and alkenyl Grignard reagents), alkyl halides (tertiary alkyl iodides/bromides and perfluorinated bromides), and unactivated olefins bearing diverse functional groups including tethered alkenes, ethers, protected alcohols, aldehydes, and amines to yield the desired 1,2-alkylarylated products with high regiocontrol. Further, we demonstrate that this protocol is amenable for the synthesis of new (hetero)carbocycles including tetrahydrofurans and pyrrolidines via a three-component radical cascade cyclization/arylation that forges three new C–C bonds.

A highly selective iron-catalyzed three-component dicarbofunctionalization of unactivated alkenes with alkyl halides and sp²-hybridized Grignard reagents is reported.     

Copper-catalyzed cross-coupling of nonactivated secondary alkyl halides and tosylates with secondary alkyl Grignard reagents

Practical catalytic cross-coupling of secondary alkyl electrophiles with secondary alkyl nucleophiles under Cu catalysis has been realized. The use of TMEDA and LiOMe is critical for the success of the reaction. This cross-coupling reaction occurs via an S(N)2 mechanism with inversion of configuration and therefore provides a general approach for the stereocontrolled formation of C-C bonds between two tertiary carbons from chiral secondary alcohols.     

Iron-mediated and -catalyzed metalative cyclization of electron-withdrawing-group-substituted alkynes and alkenes with Grignard reagents

Treatment of ethyl (E)‐5,5‐bis[(benzyloxy)methyl]‐8‐(N,N‐diethylcarbamoyl)‐2‐octen‐7‐ynoate with an iron reagent generated from FeCl₂ and tBuMgCl in a ratio of 1:4 (abbreviated as FeCl₂/4 tBuMgCl) afforded ethyl [4,4‐bis[(benzyloxy)methyl]‐2‐[(E)‐(N,N‐diethylcarbamoyl)methylene]cyclopent‐1‐yl]acetate in good yield. Deuteriolysis of an identical reaction mixture afforded the bis‐deuterated product ethyl [4,4‐bis[(benzyloxy)methyl]‐2‐[(E)‐(N,N‐diethylcarbamoyl)deuteriomethylene]cyclopent‐1‐yl]deuterioacetate, thus confirming the existence of the corresponding dimetalated intermediate. The latter intermediate can react with halogens or aldehydes to facilitate further synthetic transformations. The amount of FeCl₂ was reduced to catalytic levels (10 mol % relative to enyne), and catalytic cyclizations of this sort proceeded with yields comparable to those of the aforementioned stoichiometric reactions. The cyclization of diethyl (E,E)‐2,7‐nonadienedioate with a stoichiometric amount of FeCl₂/4 tBuMgCl, followed by the addition of sBuOH as a proton source, afforded a mixture of 2‐(ethoxycarbonyl)‐3‐bicyclo[3.3.0]octanone and its enol form in good yield. The use of aldehyde or ketone in place of sBuOH afforded 2‐(ethoxycarbonyl)‐3‐bicyclo[3.3.0]octanone, which has an additional hydroxyalkyl side chain. Additionally, the metalation of a carbon–carbon unsaturated bond in N,N‐diethyl‐5,5‐bis[(benzyloxy)methyl]‐7,8‐epoxy‐2‐octynamide or (E)‐3,3‐dimethyl‐6‐(N,N‐diethylcarbamoyl)‐5‐hexenyl p‐toluenesulfonate with FeCl₂/4 tBuMgCl or FeCl₂/4 PhMgBr was followed by an intramolecular alkylation with an epoxide or alkyl p‐toluenesulfonate to afford 5,5‐bis[(benzyloxy)methyl]‐3‐[(E)‐(N,N‐diethylcarbamoyl)methylene]‐1‐cyclohexanol or N,N‐diethyl(3,3‐dimethylcyclopentyl)acetamide after hydrolysis. In both cases, the remaining metalated portion α to the amide group was confirmed by deuteriolysis and could be utilized for an alkylation with methyl iodide.     

Copper-catalyzed enantioselective conjugate addition of Grignard reagents to acyclic enones using monodentate phosphoramidite ligands

Herein, we report efficient catalysts based on phosphoramidites for the asymmetric copper-catalyzed conjugate addition of Grignard reagents to acyclic α,β-unsaturated ketones. A variety of Grignard reagents can be added to aliphatic and aromatic acyclic enones with good yields and moderate to good enantioselectivities.     

Copper-catalyzed intermolecular hydroamination of alkenes

[reaction: see text] Regioselective additions of arylsulfonamides to vinylarenes, norbornene, and cyclohexadiene were achieved using a copper-diphosphine catayst under mild reaction conditions. These processes appear to be ligand-accelerated.     

Copper-catalyzed intermolecular aminochlorination of alkenes

A copper-catalyzed radical and regioselective aminochlorination of alkenes using N-fluoro-benzenesulfonimide (NFSI) and TMSCl as nitrogen and chlorine sources respectively is reported.     

Copper-catalyzed oxytrifluoromethylation of unactivated alkenes

A mild, versatile, and convenient method for the efficient oxytrifluoromethylation of unactivated alkenes based on a copper-catalyzed oxidative difunctionalization strategy has been developed. This methodology provides access to a variety of classes of synthetically useful CF(3)-containing building blocks from simple starting materials.     

Reactions of methylchlorodisilanes with Grignard reagents

Reactions of Cl₂MeSiSiMeCl₂ with RMgCl make it possible to obtain and isolate pure disilanes containing a smaller number of functional groups, namely, RMeClSiSiMeCl₂ (R = Ph), RMeClSiSiMeRCl (R = Prⁱ, Ph), and R₂MeSiSiMeRCl (R = Buⁱ). The reaction of Cl₂MeSiSiMeCl₂ with BuⁿMgCl is the least selective. The chlorides obtained were reduced with LiAlH₄ into the corresponding hydrides.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 954–957, May, 1995.     

Copper-catalyzed desymmetrization of oxabenzonorbornadienes with aluminum reagents

The desymmetrization of oxabenzonorbornadienes with aluminum reagents and SimplePhos as chiral ligand is described. The corresponding homoallylic alcohols are obtained in high yield, diastereoselectivity, and enantiomeric excess. Furthermore the first anti enantioselective desymmetrization with aromatic nucleophiles is reported.     

Copper-catalyzed asymmetric conjugate addition of Grignard reagents to trisubstituted enones. Construction of all-carbon quaternary chiral centers

The copper-catalyzed asymmetric conjugate addition of Grignard reagents to trisubstituted cyclic enones affords enantioenriched all-carbon quaternary centers with up to 96% ee. The chiral ligand is a diaminocarbene, directly generated in situ. The combination of Grignard reagent and diaminocarbene is unprecedented in conjugate addition, and the additon of the phenyl group, on such enones, cannot be done by other conjugate addition methods.     

Reaction of furfurylidene acetone with Grignard reagents

The interaction of furfurylidene acetone with methylmagnesium iodide and ethylmagnesium halides has been studied. In the first case 2-methyl-4-(2-furyl)-3-buten-2-ol is formed as the product of 1,2-addition (yield 73 %). In the second case 4-(2-furyl)-2-hexanone (42 %) is the result of 1,4-addition, whereas 3-methyl-5-(2-furyl)-3-heptanol (45 %) is formed by consecutive 1,2- and 1,4-addition. In all cases the products of 1,3-addition were found.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 921–923, May, 1993.     

Reactions of Grignard reagents with 1,3-dicyanoadamantane

Reactions of Grignard reagents RMgX (R = Me, Et, Pr, Bu; X = Br, I) with 1,3-dicyanoadamantane (1) were studied. Optimum conditions for the synthesis of monoaddition products of Grignard reagents to compound 1 were established. The first stage of the reaction of cyanoadamantane 1 with MeMgBr was studied by the MNDO-PM3 method. According to calculations, the more preferable reaction mechanism involves formation of a six-membered cyclic intermediate containing two Mg atoms, two C atoms, and one Br and one N atom.