Barbier Conditions Research Articles

DTBB-catalysed lithiation of 1,2-bis(phenylsulfanyl)ethene: does 1-lithio-2-phenylsulfanylethene really exist?

The reaction of ( Z)- or ( E)-1,2-bis(phenylsulfanyl)ethene ( 1 ) with an excess of lithium and a catalytic amount of 4,4′-di- tert-butylbiphenyl (DTBB, 2.5 mol%) in the presence of a carbonyl compound as electrophile (Barbier conditions) in THF at −78 °C leads, after hydrolysis with water at temperatures ranging between −78 °C and rt, to a mixture of the corresponding ( Z/ E)-unsaturated 1,4-diols 2 , the diastereomers ratio being independent of the stereochemistry of the starting materials. Allylic alcohols 3 are the main by-products, resulting from a lithium–hydrogen exchange on some of the lithiated intermediates along the whole process. A mechanistic explanation for the observed behaviour is given.

An Environmentally Friendly α‐Hydroxyallylation Reaction of the Garner Aldehyde: A Comparative Assessment of Alternative Barbier Conditions.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Reductive ring opening of cis- and trans-2,3-diphenyloxirane: a common intermediate

The reaction of both cis- and trans-2,3-diphenyloxirane ( 7 and 4 , respectively) with an excess of lithium and a catalytic amount of 4,4′-di- tert-butylbiphenyl (DTBB, 2.5 mol%) in the presence of different carbonyl compounds as electrophiles (Barbier conditions) in THF at temperatures ranging between −80 and −50 °C gives the same organolithium intermediate 5 and consequently, the same 1,3-diols 6 . In the case of cis-epoxide an inversion of the configuration at the benzylic carbanionic center can explain the obtained results. Only for the dicyclopropyl ketone derivative ( 6h ) some amount (14%) of the corresponding epimer ( 6′ h ) resulting from a process with retention of the configuration of the intermediate is obtained. In representative cases, the structure of the final products ( 6 ) was unequivocally determined by X-ray diffraction analysis.

An environmentally friendly α-hydroxyallylation reaction of the Garner aldehyde: a comparative assessment of alternative Barbier conditions

The reaction of 3-bromo-propenyl acetate with the Garner aldehyde promoted by zinc or indium metal is studied in different solvents; besides the stereoselectivity, attention is focused on a comparative environmental assessment of different experiments carried out in NH 4Cl, THF or DMF, using green chemistry metrics and a qualitative analysis of environmental risks.

Preparation of lithium stannide mixtures in organic solvents. A alternate source of lithium in organolithium chemistry

Lithium stannides were prepared from lithium naphthalenide and tin (II) chloride or tin (0) powder in THF solvent at room temperature under dry argon atmosphere. They were characterized with elemental analysis, XRD, and solid 6,7Li NMR. Stabilities and reactivities of lithium stannides prepared from different conditions were tested and showed they were stable for a limited time at low temperatures. Best reactivity was obtained when they were prepared from tin (II) chloride and an excess of lithium naphthalenide. The lithium stannide mixture can reductively cleave carbon–halogen bonds and yield pinacol coupling with aldehydes. Organolithium compounds prepared from lithium stannides and organic halides add to ketones or aldehydes under Barbier conditions.

Stereoselective Barbier‐Type Allylation Reaction of Trifluoromethyl Aldimines.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Stereoselective Barbier-type allylation reaction of trifluoromethyl aldimines.

Trifluoromethyl aldimines could react, under Barbier conditions in the presence of activated zinc, in DMF at room temperature or in THF at reflux, with various allyl bromides to provide the corresponding homoallylamines. Secondary homoallyl trifluoromethylamines were stereoselectively obtained from the optically active aldimine 12 with an excellent diastereoisomeric excess (98%).

3‐Bromo‐propenyl Acetate in Organic Synthesis. The Zinc‐Promoted α‐Hydroxyallylation of Ketones.

AbstractFor Abstract see ChemInform Abstract in Full Text.

3‐Bromopropenyl Esters in Organic Synthesis: Indium‐ and Zinc‐Mediated Entries to Alk‐1‐ene‐3,4‐diols.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Diastereoselective Zinc‐Mediated Barbier‐Type Allylation and Propargylation of 3‐Formylcephalosporins

AbstractWe describe the allylation and propargylation of 3‐formylcephalosporins under zinc‐mediated, aqueous Barbier conditions, from which the corresponding homoallylic alcohols are produced in good yields and with good‐to‐excellent diastereoselectivity. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

3-Bromo-propenyl acetate in organic synthesis. The zinc-promoted α-hydroxyallylation of ketones

3-Bromo-propenyl acetate easily undergoes oxidative addition by zinc, both under Barbier or Grignard conditions. The resulting acetoxyallylzinc species are reported to react efficiently with ketones, thus widening the scope of the 3-bromo-propenyl acetate route to homoallylic alcohols. Barbier conditions in water or a Grignard two-step protocol in the THF/DMSO binary solvent system are used, depending on the ketone reactivity.

3-Bromopropenyl esters in organic synthesis: indium- and zinc-mediated entries to alk-1-ene-3,4-diols.

Metallic indium and zinc readily add to 3-bromopropenyl acetate (5) and benzoate (6) either in THF or in water, affording the corresponding 3-acyloxyallyl organometallic compounds. Nucleophilic addition to aldehydes opens a route to alk-1-ene-3,4-diols 2 in good to excellent yields. Two synthetic protocols were developed, the former involving indium in THF under Grignard conditions and the latter involving zinc in aqueous ammonium chloride under Barbier conditions. The diastereoselectivity, under all the conditions examined, mainly depends on the nature of the carbonyl compound; conjugated aldehydes afford syn adducts 2, while unconjugated aldehydes display the opposite anti stereopreference.

A Convergent Method for the Synthesis of Highly Enantiomerically Enriched Cyclic Silanes with Silicon-Centered Chirality

A preparatively straightforward methodology has been developed which allows the assembly of silicon-containing carbocycles as mixtures of diastereomers with silicon as the sole center of stereogenic information. One-step construction of the chiral cyclic silanes is realized by reaction of equimolar amounts of a dibromide and a chirally modified dichlorosilane under Barbier conditions giving access to several monofunctionalized 1-sila-1,2,3,4-tetrahydronaphthalenes and a corresponding phenanthrene derivative. Facile large scale syntheses of 3-(2-bromoaryl)propyl bromides as well as dichlorosilanes have been elaborated. This highly convergent methodology relies on the novel (-)-menthyl-oxy-substituted dichlorosilanes, which have the chiral auxiliary for the subsequent optical resolution installed. These enantiopure dichlorosilanes are useful building blocks for a general and modular one-step approach to silanes with silicon-centered chirality since this strategy avoids the linear sequences reported in literature. The optical resolution has been exemplarily optimized for the 1-phenyl-1-sila-1,2,3,4-tetrahydronaphthalene derivative and the absolute configuration has been established by X-ray crystallography. The chiral auxiliary is stereospecifically displaced by simple reduction providing the highly enantioenriched silane (er = 98:2) which is enantiospecifically chlorinated as verified by a Walden inversion at silicon.

Can We Aminate Grignard Reagents under Barbier Conditions?

AbstractFor Abstract see ChemInform Abstract in Full Text.

Can we aminate Grignard reagents under Barbier conditions?

The reaction of aryl bromides with acetone O-(2,4,6-trimethylphenylsulfonyl)oxime and magnesium in THF at reflux temperature for 3 h provides a one-pot procedure for amination of aryl Grignard reagents under Barbier conditions.

α-Lithioenamines by chlorine-lithium exchange: versatile acyl anion equivalents

The reaction of α-chloroenamines 1 with an excess of lithium and a catalytic amount of 4,4’-ditert-butylbiphenyl (DTBB) in THF at –90 oC followed by reaction with an electrophile (D2O, Me3SiCl, PhCOCH=CHPh/BF3, CO2, CyNCO) and final hydrolysis gave the expected functionalized enamines 2. In the case of aldehydes (t-BuCHO, n-C5H11CHO, PhCHO) it was necessary to perform the lithiation in the presence of the electrophile (Barbier conditions) at – 40 oC. Hydrolysis of the obtained enamines either with silica gel or with hydrochloric acid yielded the expected functionalized ketones 3.

Barbier-type diastereoselective allylation of alpha-amino aldehydes with an enantiopure 2-sulfinylallyl building block.

An optimized procedure for the diastereoselective allylation under aqueous Barbier conditions of a series of alpha-amino aldehydes with our new chiral building block (S(s))-3-chloro-2-(p-tolylsulfinyl)-1-propene [(S(s))-1a] to afford enantiomerically pure sulfinylamino alcohols in good yields and diastereoselectivites is reported. High levels of diastereoinduction can be achieved from alpha-amino aldehydes configurationally related to natural alpha-amino acids.

An efficient stereoselective synthesis of (2 S,4 S,5 R)-(−)-bulgecinine

N-Benzyl- N-carbobenzyloxy- O- tert-butyldimethylsilyl- d-serinal ( 6 ) was reacted under Barbier conditions with allyl bromide affording diastereoselectively (82:18) the anti-adduct 5 , which was subsequently transformed into (2 S,4 S,5 R)-(−)-bulgecinine ( 1 ).

Carbohydrate Carbocyclization by a Novel Zinc-Mediated Domino Reaction and Ring-Closing Olefin Metathesis

A general method for carbocyclization of carbohydrates is described using two consecutive organometallic transformations: a novel zinc-mediated domino reaction to give functionalized dienes followed by ring-closing olefin metathesis. In the first reaction, methyl ω-deoxy-ω-iodo glycosides undergo reductive elimination with zinc to produce a terminal double bond. This also liberates the aldehyde which is immediately alkylated in situ by various organozinc reagents. The alkylation occurs under Barbier conditions with methylene iodide and several allyl bromides. Zinc plays a dual role by both promoting the reductive elimination and activating the alkyl halide. Vinylation is carried out by adding divinylzinc. When a new stereogenic center is generated, moderate to excellent stereocontrol is generally observed. An amino group can be introduced by trapping the intermediate aldehyde as an imine prior to the alkylation. The reductive elimination−allylation sequence can also be promoted by indium metal. All the a...

Diastereoselective allylation of aldehydes with an enantiopure 2-sulfinylallyl halide under environmentally friendly Barbier-type conditions

[reaction: see text] A simple, efficient, and diastereoselective zinc-promoted allylation of aldehydes with enantiopure (Ss)-3-chloro-2-(p-tolylsulfinyl)-1-propene [(Ss)-1] under aqueous Barbier conditions is described. The observed diastereoselectivity can be explained via an acyclic antiperiplanar transition state model.