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Search for "carbolithiation" in Full Text gives 6 result(s) in Beilstein Journal of Organic Chemistry.
Synthesis and applications of alkenyl chlorides (vinyl chlorides): a review
- Daniel S. Müller
Beilstein J. Org. Chem. 2026, 22, 1–63, doi:10.3762/bjoc.22.1
Graphical Abstract
Figure 1: Representative alkenyl chloride motifs in natural products. References: Pinnaic acid [8], haterumalide ...
Figure 2: Representative alkenyl chloride motifs in pharmaceuticals and pesticides. References: clomifene [25], e...
Figure 3: Graphical overview of previously published reviews addressing the synthesis of alkenyl chlorides.
Figure 4: Classification of synthetic approaches to alkenyl chlorides.
Scheme 1: Early works by Friedel, Henry, and Favorsky.
Scheme 2: Product distribution obtained by H NMR integration of crude compound as observed by Kagan and co-wo...
Scheme 3: Side reactions observed for the reaction of 14 with PCl5.
Scheme 4: Only compounds 15 and 18 were observed in the presence of Hünig’s base.
Scheme 5: Efficient synthesis of dichloride 15 at low temperatures.
Scheme 6: Various syntheses of alkenyl chlorides on larger scale.
Scheme 7: Scope of the reaction of ketones with PCl5 in boiling cyclohexane.
Scheme 8: Side reactions occur when using excess amounts of PCl5.
Scheme 9: Formation of versatile β-chlorovinyl ketones.
Scheme 10: Mixture of PCl5 and PCl3 used for the synthesis of 49.
Scheme 11: Catechol–PCl3 reagents for the synthesis of alkenyl chlorides.
Scheme 12: (PhO)3P–halogen-based reagents for the synthesis of alkenyl halides.
Scheme 13: Preparation of alkenyl chlorides from alkenyl phosphates.
Scheme 14: Preparation of alkenyl chlorides by treatment of ketones with the Vilsmeier reagent.
Scheme 15: Preparation of electron-rich alkenyl chlorides by treatment of ketones with the Vilsmeier reagent.
Scheme 16: Cu-promoted synthesis of alkenyl chlorides from ketones and POCl3.
Figure 5: GC yield of 9 depending on time and reaction temperature.
Figure 6: Broken reaction flask after attempts to clean the polymerized residue.
Figure 7: GC yield of 9 depending on the amount of CuCl and time.
Scheme 17: Treatment of 4-chromanones with PCl3.
Scheme 18: Synthesis of alkenyl chlorides from the reaction of ketones with acyl chlorides.
Scheme 19: ZnCl2-promoted alkenyl chloride synthesis.
Scheme 20: Regeneration of acid chlorides by triphosgene.
Scheme 21: Alkenyl chlorides from ketones and triphosgene.
Scheme 22: Various substitution reactions.
Scheme 23: Vinylic Finkelstein reactions reported by Evano and co-workers.
Scheme 24: Challenge of selective monohydrochlorination of alkynes.
Scheme 25: Sterically encumbered internal alkynes furnish the hydrochlorination products in high yield.
Scheme 26: Recent work by Kropp with HCl absorbed on alumina.
Scheme 27: High selectivities for monhydrochlorination with nitromethane/acetic acid as solvent.
Figure 8: Functionalized alkynes which typically afford the monhydrochlorinated products.
Scheme 28: Related chorosulfonylation and chloroamination reactions.
Scheme 29: Reaction of organometallic reagents with chlorine electrophiles.
Scheme 30: Elimination reactions of dichlorides to furnish alkenyl chlorides.
Scheme 31: Elimination reactions of allyl chloride 182 to furnish alkenyl chloride 183.
Scheme 32: Detailed studies by Schlosser on the elimination of dichloro compounds.
Scheme 33: Stereoselective variation caused by change of solvent.
Scheme 34: Elimination of gem-dichloride 189 to afford alkene 190.
Scheme 35: Oxidation of enones to dichlorides and in situ elimination thereof.
Scheme 36: Oxidation of allylic alcohols to dichlorides and in situ elimination thereof.
Scheme 37: Chlorination of styrenes with SOCl2 and elimination thereof.
Scheme 38: Chlorination of styrenes with SOCl2 and elimination thereof.
Scheme 39: Fluorine–chlorine exchange followed by elimination.
Scheme 40: Intercepting cations with alkynes and trapping of the alkenyl cation intermediate with chloride.
Scheme 41: Investigations by Mayr and co-workers.
Scheme 42: In situ activation of benzyl alcohol 230 with BCl3.
Scheme 43: In situ activation of benzylic alcohols with TiCl4.
Scheme 44: In situ activation of benzylic alcohols with FeCl3.
Scheme 45: In situ activation of benzylic alcohols with FeCl3.
Scheme 46: In situ activation of aliphatic chlorides and alcohols with ZnCl2, InCl3, and FeCl3.
Scheme 47: In situ generation of benzylic cations and trapping thereof with alkynes.
Scheme 48: Intramolecular trapping reactions affording alkenyl halides.
Scheme 49: Intramolecular trapping reactions affording alkenyl chlorides.
Scheme 50: Intramolecular trapping reactions of oxonium and iminium ions affording alkenyl chlorides.
Scheme 51: Palladium and nickel-catalyzed coupling reactions to afford alkenyl chlorides.
Scheme 52: Rhodium-catalyzed couplings of 1,2-trans-dichloroethene with arylboronic esters.
Scheme 53: First report on monoselective coupling reactions for 1,1-dichloroalkenes.
Scheme 54: Negishi’s and Barluenga’s contributions.
Scheme 55: First mechanistic investigation by Johnson and co-workers.
Scheme 56: First successful cross-metathesis with choroalkene 260.
Scheme 57: Subsequent studies by Johnson.
Scheme 58: Hoveyda and Schrock’s work on stereoretentive cross-metathesis with molybdenum-based catalysts.
Scheme 59: Related work with (Z)-dichloroethene.
Scheme 60: Further ligand refinement and traceless protection of functional groups with HBpin.
Scheme 61: Alkenyl chloride synthesis by Wittig reaction.
Scheme 62: Alkenyl chloride synthesis by Julia olefination.
Scheme 63: Alkenyl chloride synthesis by reaction of ketones with Mg/TiCl4 mixture.
Scheme 64: Frequently used allylic substitution reactions which lead to alkenyl chlorides.
Scheme 65: Enantioselective allylic substitutions.
Scheme 66: Synthesis of alkenyl chlorides bearing an electron-withdrawing group.
Scheme 67: Synthesis of α-nitroalkenyl chlorides from aldehydes.
Scheme 68: Synthesis of alkenyl chlorides via elimination of an in situ generated geminal dihalide.
Scheme 69: Carbenoid approach reported by Pace.
Scheme 70: Carbenoid approach reported by Pace.
Scheme 71: Ring opening of cyclopropenes in the presence of MgCl2.
Scheme 72: Electrophilic chlorination of alkenyl MIDA boronates to Z- or E-alkenyl chlorides.
Scheme 73: Hydroalumination and hydroboration of alkynyl chlorides.
Scheme 74: Carbolithiation of chloroalkynes.
Scheme 75: Chlorination of enamine 420.
Scheme 76: Alkyne synthesis by elimination of alkenyl chlorides.
Scheme 77: Reductive lithiation of akenyl chlorides.
Scheme 78: Reactions of alkenyl chlorides with organolithium reagents.
Scheme 79: Reactions of alkenyl chlorides with organolithium reagents.
Scheme 80: Addition–elimination reaction of alkenyl chloride 9 with organolithium reagents.
Scheme 81: C–H insertions of lithiumcarbenoids.
Scheme 82: Pd-catalyzed coupling reactions with alkenyl chlorides as coupling partner.
Scheme 83: Ni-catalyzed coupling of alkenylcopper reagent with alkenyl chloride 183.
Scheme 84: Ni-catalyzed coupling of heterocycle 472 with alkenyl chloride 473.
Scheme 85: Synthesis of α-chloroketones by oxidation of alkenyl chlorides.
Scheme 86: Tetrahalogenoferrate(III)-promoted oxidation of alkenyl chlorides.
Scheme 87: Chlorine–deuterium exchange promoted by a palladium catalyst.
Scheme 88: Reaction of alkenyl chlorides with thiols in the presence of AIBN (azobisisobutyronitrile).
Scheme 89: Chloroalkene annulation.
Carbolithiation of N-alkenyl ureas and N-alkenyl carbamates
- Julien Lefranc,
- Alberto Minassi and
- Jonathan Clayden
Beilstein J. Org. Chem. 2013, 9, 628–632, doi:10.3762/bjoc.9.70
- incorporating an α-aryl substituent, we show that they will also undergo attack at the β-carbon by organolithium nucleophiles, leading to the products of carbolithiation. The carbolithiation of E and Z N-alkenyl ureas is diastereospecific, and N-tert-butoxycarbonyl N-alkenyl carbamates give carbolithiation
- products that may be deprotected in situ to provide a new connective route to hindered amines. Keywords: carbamate; carbolithiation; carbometallation; organolithium; stereospecificity; styrene; urea; Introduction Enamines and N-acyl enamines are in general nucleophiles, reacting with electrophiles at the
- in an enamine carbolithiation reaction [9]. Similar reactivity is observed with related O-carbamoyl enols [10][11][12]. The organolithium resulting from the enamine carbolithiation is nucleophilic at the atom α to nitrogen, and such carbolithiations have been used to generate hindered organolithiums
Graphical Abstract
Scheme 1: Carbolithiation of ureas 1.
Scheme 2: Diastereospecific carbolithiation of ureas 3.
Scheme 3: Diastereospecific carbolithiation of ureas 5.
Figure 1: X-ray crystal structure of urea 6c.
Scheme 4: Synthesis of N-alkenyl carbamates 9–11.
Figure 2: X-ray crystal structure of carbamate E-10.
Scheme 5: Umpolung carbolithiation of carbamates 9 and 10.
Intramolecular carbolithiation cascades as a route to a highly strained carbocyclic framework: competition between 5-exo-trig ring closure and proton transfer
- William F. Bailey and
- Justin D. Fair
Beilstein J. Org. Chem. 2013, 9, 537–543, doi:10.3762/bjoc.9.59
- [3.3.0.03,7]octane) framework by an intramolecular carbolithiation cascade involving three coupled 5-exo-trig cyclizations of the vinyllithium derived from 2-bromo-4-vinyl-1,6-heptadiene by lithium–bromine exchange was investigated. The cascade does not afford the stellane; rather, the cascade is terminated
- temperature. Keywords: carbolithiation cascade; carbometallation; intramolecular carbolithiation; intermolecular proton transfer; lithium–halogen exchange; strained hydrocarbons; Introduction The first publication describing an intramolecular carbolithiation appeared in 1968: Drozd and co-workers reported
- constructing a highly strained system by an intramolecular carbolithiation cascade involving three coupled 5-exo-trig cyclizations. Although many strained molecules could have been selected for this exploration, the stellane framework (tricyclo[3.3.0.03,7]octane [18][19]), 1, with its mesmerizing symmetry, was
Graphical Abstract
Scheme 1: Retrosynthetic plan.
Scheme 2: Preparation of 2.
Scheme 3: Generation of 3 by lithium–bromine exchange.
Scheme 4: Cascade products.
Figure 1: Reaction progress of the attempted triple-cyclization cascade.
Scheme 5: Proton transfer that foils final cyclization.
Scheme 6: Preparation of iodide 7 and an authentic sample of 5.
Scheme 7: Evidence for the intermolecular nature of the formal [1,4]-proton transfer.
Inter- and intramolecular enantioselective carbolithiation reactions
- Asier Gómez-SanJuan,
- Nuria Sotomayor and
- Esther Lete
Beilstein J. Org. Chem. 2013, 9, 313–322, doi:10.3762/bjoc.9.36
- inter- and intramolecular enantioselective carbolithiation reactions carried out in the presence of a chiral ligand for lithium, such as (−)-sparteine, to promote facial selection on a C=C bond. This is an attractive approach for the construction of new carbon–carbon bonds in an asymmetric fashion, with
- the possibility of introducing further functionalization on the molecule by trapping the reactive organolithium intermediates with electrophiles. Keywords: alkenes; asymmetric synthesis; carbolithiation; carbometallation; enantioselectivity; lithium; Introduction The carbolithiation reaction has
- chiral ligands for lithium, thus opening new opportunities for their application in asymmetric synthesis. The naturally occurring alkaloid (−)-sparteine, which has been until recently inexpensive and commercially available, is the most widely used chiral ligand in enantioselective carbolithiation
Graphical Abstract
Scheme 1: Intermolecular carbolithiation.
Scheme 2: Carbolithiation of cinnamyl and dienyl derivatives.
Scheme 3: Carbolithiation of cinnamyl alcohol.
Scheme 4: Carbolithiation of styrene derivatives.
Scheme 5: Carbolithiation of α-aryl O-alkenyl carbamates.
Scheme 6: Carbolithiation-rearrangement of N-alkenyl-N-arylureas.
Scheme 7: Carbolithiation of N,N-dimethylaminofulvene.
Scheme 8: Carbolithiation of enynes.
Scheme 9: Intramolecular carbolithiation.
Scheme 10: Carbolithiation of 5-alkenylcarbamates.
Scheme 11: Carbolithiation of cinnamylpiperidines.
Scheme 12: Carbolithiation of alkenylpyrrolidines.
Scheme 13: Enantioselective carbolithiation of N-allyl-2-bromoanilines.
Scheme 14: Effect of the ligand in the carbolithiation reaction.
Scheme 15: Effect of the alkene substitution in the carbolithiation reaction.
Scheme 16: Effect of the ring substitution in the carbolithiation reaction.
Scheme 17: Enantioselective carbolithiation of allyl aryl ethers.
Scheme 18: Formation of six-membered rings: pyrroloisoquinolines.
Scheme 19: Formation of six-membered rings: tetrahydroquinolines.
Intramolecular carbolithiation of N-allyl-ynamides: an efficient entry to 1,4-dihydropyridines and pyridines – application to a formal synthesis of sarizotan
- Wafa Gati,
- Mohamed M. Rammah,
- Mohamed B. Rammah and
- Gwilherm Evano
Beilstein J. Org. Chem. 2012, 8, 2214–2222, doi:10.3762/bjoc.8.250
- 10.3762/bjoc.8.250 Abstract We have developed a general synthesis of polysubstituted 1,4-dihydropyridines and pyridines based on a highly regioselective lithiation/6-endo-dig intramolecular carbolithiation from readily available N-allyl-ynamides. This reaction, which has been successfully applied to the
- formal synthesis of the anti-dyskinesia agent sarizotan, further extends the use of ynamides in organic synthesis and further demonstrates the synthetic efficiency of carbometallation reactions. Keywords: carbolithiation; carbometallation; dihydropyridines; organolithium reagents; pyridines; sarizotan
- carbolithiation of ynamides, which may provide an interesting entry to highly functionalized 1,4-dihydropyridines [27][28][29] and pyridines [30][31][32][33], most useful building blocks in organic synthesis and medicinal chemistry as well. Our strategy is summarized in Scheme 1 and is based on the following
Graphical Abstract
Scheme 1: Strategy for the synthesis of (1,4-dihydro)pyridines by deprotonation/intramolecular carbolithiatio...
Scheme 2: Feasibility of the deprotonation/intramolecular carbolithiation.
Scheme 3: Synthesis of the starting N-allyl-ynamides.
Scheme 4: Intramolecular carbolithiation of N-allyl-ynamides to 1,4-dihydropyridines and pyridines.
Scheme 5: 2,3-Disubstituted pyridines by trapping of the intermediate metallated 1,4-dihydropyridine.
Scheme 6: Formal synthesis of the anti-dyskinesia agent, 5-HT1A receptor agonist, dopamine D2 receptor ligand...
Asymmetric synthesis of tertiary thiols and thioethers
- Jonathan Clayden and
- Paul MacLellan
Beilstein J. Org. Chem. 2011, 7, 582–595, doi:10.3762/bjoc.7.68
- arylation (by rearrangement) of thiocarbamates offering the best prospects. Further developments in this area – particularly with regard to carbolithiation reactions [79] – are to be expected. Seven out of the ten top selling drugs in the USA in 2009 contain sulfur. Figures in italics are total retail sales
Graphical Abstract
Figure 1: Seven out of the ten top selling drugs in the USA in 2009 contain sulfur. Figures in italics are to...
Figure 2: Naturally occurring organosulfur compounds glutathione and (R)-thioterpineol.
Figure 3: Methods for the synthesis of chiral tertiary thiol 1.
Scheme 1: Preparation of thioethers 4 from α-hydroxy esters.
Scheme 2: Nucleophilic substitution in α-aryl-α-hydroxy esters.
Scheme 3: Preparation of α,α-dialkylthioethers.
Scheme 4: Preparation of α-cyanothioacetate 12.
Scheme 5: Synthesis of (R)-(+)-spirobrassinin.
Scheme 6: Opening of cyclic sulfamidates with thiol nucleophiles.
Scheme 7: Synthesis of androgen 20.
Scheme 8: Synthesis of (+)-BE-52440A.
Scheme 9: The Mitsunobu reaction.
Scheme 10: Mitsunobu substitution at a quaternary centre.
Figure 4: Initially assigned structure of hexacyclinol.
Scheme 11: Preparation of thioether 29.
Scheme 12: Thioethers 33 prepared from phosphinites 31.
Scheme 13: Preparation of enantiomerically pure thiol 39.
Scheme 14: Thioethers prepared by a modified Mitsunobu reaction.
Scheme 15: Nucleophilic conjugate addition.
Scheme 16: Asymmetric addition to cyclic enones.
Scheme 17: Preparation of thioether 45.
Scheme 18: Catalytic kinetic resolution of the enantiomers of enone 46.
Scheme 19: Organocatalytic conjugate addition to nitroalkenes 49.
Scheme 20: Preparation of β-amino acid 54.
Scheme 21: Sulfur migration within oxazolidine-2-thiones 56.
Scheme 22: Preparation of thiols 62 by self-regeneration of stereocentres.
Scheme 23: Synthesis of (5R)-thiolactomycin.
Scheme 24: Preparation of tertiary thiols and thioethers via α-thioorganolithiums.
Scheme 25: Diastereoselective methylation of organolithium 71.
Scheme 26: Addition to lithiated thiocarbamate 75.
Scheme 27: Configurational lability in unhindered α-lithiothiocarbamates.
Scheme 28: Configurational stability in bulky α-lithiothiocarbamates.
Scheme 29: Asymmetric functionalisation of secondary benzylic thiocarbamates.
Scheme 30: Methylation of lithioallyl thiocarbamates.
Scheme 31: Asymmetric preparation of tertiary allylic thiols.
Scheme 32: Asymmetric preparation of thiols 96 by aryl migration in lithiated thiocarbamates.
