Lithium acetylides as alkynylating reagents for the enantioselective alkynylation of ketones catalyzed by lithium binaphtholate

Chiral lithium binaphtholate effectively catalyzed the enantioselective alkynylation of ketones using lithium acetylide as an alkynylating agent. This is the first example of the catalytic enantioselective addition of lithium acetylide to carbonyl compounds without the aid of other metal sources.     

Electronic effect on the regioselectivity in the ring opening of para-substituted phenyloxiranes by acetylides

The electronic effect on the regioselectivity in the alkynylation of phenyloxiranes was investigated using three kinds of metal acetylides. BF₃ mediated lithium acetylide provided either the α- or β-alkynylated products by controlling the effect of the para-substituents of the phenyloxiranes. LiClO₄ mediated lithium acetylide and titanium acetylide, on the other hand, afforded predominantly the β- and α-products, respectively.     

Mechanism of acylation of lithium phenylacetylide with a Weinreb amide

Additions of lithium phenylacetylide to a Weinreb amide are described. Dimeric lithium acetylide reacts via a monosolvated monomer-based transition structure. The robust tetrahedral intermediate forms sequentially a C(1) 2:2 mixed tetramer with the excess lithium acetylide and a 1:3 (alkoxide-rich) mixed tetramer. The stabilities of the mixed tetramers are consistent with a pronounced autoinhibition.     

One-pot formation and derivatization of di- and triynes based on the Fritsch-Buttenberg-Wiechell rearrangement

A divergent, one-pot synthesis of functionalized polyynes has been developed. Beginning with the appropriately substituted dibromoolefinic precursor, a carbenoid Fritsch-Buttenberg-Wiechell (FBW) rearrangement is used to generate the lithium acetylide of a conjugated polyyne framework, and subsequent trapping with carbon-based electrophiles provides for in situ formation of a wide range of di- and triynes. The lithium acetylide formed from the FBW reaction can also undergo transmetalation to provide the corresponding zinc, copper, tin, or platinum acetylides, leading to the divergent formation of symmetrical and unsymmetrical conjugated acetylenes, as well as ynones.     

Synthesis of mono- and diarylacetylenes

Arylacetylenes have been synthesized by CC coupling of lithium acetylide with aryl bromide in the presence of a palladium(0) catalyst.     

Diastereoselective alkynylation of N-p-tolylsulfinylimines with aluminum acetylides

The addition of alkynyl dimethyl aluminum compounds onto N-p-tolylsulfinylimines was investigated. The reaction was proved to be totally regioselective, leading to propargylamines with high diastereoselectivity (up to 99% de). Addition of aluminum derivatives gave a reversal of diastereoselectivity compared to the addition reaction of lithium acetylide.     

Synthesis of substituted acetylenic epoxides followed by indium-catalyzed rearrangement to 2,3,5-trisubstituted furans

Syntheses of various aromatic and aliphatic 2,3,5-trisubstituted furans from acetylenic epoxides are described. These epoxides are directly prepared by nucleophilic ring closure of propargylic alkoxides generated by lithium acetylide addition to α-haloketones.     

Synthesis and Ritter Reaction of 2-Ethynyladamantan-2-ol

The reaction of adamantan-2-one with lithium acetylide gave 2-ethynyladamantan-2-ol. The latter reacted with acetonitrile in the presence of sulfuric acid through formation of an intermediate classical carbocation, leading to 2-acetylamino-2-ethynyladamantane and 1-acetylamino-2-acetyladamantane at a ratio of 20:1.     

Synthesis of N-methoxy-N-methyl-beta-enaminoketoesters: new synthetic precursors for the regioselective synthesis of heterocyclic compounds

[Structure: see text] Weinreb amides react with the lithium or sodium acetylide of ethyl propynoate in a hitherto unexplored acyl substitution-conjugate addition sequence to furnish (E)-N-methoxy-N-methyl-beta-enaminoketoesters. This approach provides a diverse entry to densely functionalized heterocyclic compounds, including pyrazoles through regioselective cyclocondensations with hydrazines in a microwave-assisted reaction.     

Enhanced solid-state metathesis routes to carbon nanotubes

Ignition of three solids creates multiwalled carbon nanotubes in seconds. A solid-state metathesis (exchange) reaction between hexachloroethane (C2Cl6) and lithium acetylide (Li2C2) with 5% cobalt dichloride (CoCl2) added as an initiator produces up to 7% carbon nanotubes, as observed via transmission electron microscopy. Using the concept that sulfur can promote nanotube growth, the reaction yield can be increased to 15% by switching to CoS as the initiator. The more readily available, inexpensive calcium carbide (CaC2) can be substituted for lithium acetylide while maintaining comparable yields. Switching initiators to FeS can be used to further enhance the yield. A systematic study of the C2Cl6/CaC2 reaction system indicates that a yield up to 25% can be realized by using 6% FeS as the initiator. Reaction temperatures for the C(2)Cl6/CaC2 system of up to 3550 degrees C are calculated using thermodynamic data assuming quantitative yield and adiabatic conditions.     

First asymmetric synthesis of a differentially silyl-protected tris(alkynyl)methyl methyl ether

For an improved synthesis of the recently described expanded octamethoxycubane with a central C56 core, formally obtained by inserting buta-1,3-diynediyl moieties into all C(sp3)-C(sp3) bonds of octamethoxycubane, the preparation of the optically pure methyl ether of a differentially silyl-protected trispropargylic alcohol was required. The key step of the preparation involved a diastereoselective addition of a lithium acetylide to an optically active alkynyl ketone under Cram chelation control.     

Addition of alkynyl anions to aldimines containing α-hydrogens: a novel synthesis of β-aminoacetylenes

Alkynylboranes (or alkynylborates), prepared $\text{in situ}$ from lithium acetylide and BF₃ · Et₂O, added to aldimines containing α-hydrogens to afford β-aminoacetylenes in good yields.     

Total synthesis of microcarpalide

[reaction: see text] An efficient, convergent approach for the total synthesis of microcarpalide (1) is described. The synthetic strategy features the Sharpless asymmetric dihydroxylation, regioselective epoxide opening with various nucleophiles such as a lithium acetylide and cuprates derived from the vinyl stannane and the vinyl iodide for the construction of a C7-C8 trans-double bond and Yamaguchi macrolactonization as the key steps.     

5,7,12,14-Tetrafunctionalized 6,13-Diazapentacenes

The synthesis, property evaluation, and single crystal X-ray structures of four 5,7,12,14-tetrafunctionalized diazapentacenes are presented. The synthesis of these compounds either starts from tetrabromo-N,N-dihydrodiazapentacene or from a diazapentacene tetraketone. Pd-catalyzed coupling or addition of a lithium acetylide gave the precursors that furnish, after further redox reactions, the diazapentacenes as stable crystalline materials. The performance of the tetraphenyl-substituted compound as n-channel semiconductor was evaluated in organic field effect transistors.     

Total synthesis of (-)-pironetin

[structure: see text] The asymmetric total synthesis of pironetin, a compound that shows plant growth regulatory activity, immunosuppressive as well as a remarkable antitumoral activity, is described. The approach involves the use of three very efficient Evans oxazolidinone-mediated syn-aldol condensations, a high-yielding coupling between lithium acetylide ethylenediamine complex and a tosylate followed by methylation, and selective reduction to establish the C12-C13 (E) double bond.     

An Improved Alternative Norgestrel Preparation

Ethynyl cerium chloride, prepared in situ from ethynyl magnesium bromide or lithium acetylide and anhydrous cerium chloride efficiently added to 13-ethyl-3-methoxy-gona-3,5-diene-17-one 2. Aqueous HCl hydrolysis of intermediate enol ether 3 gave high yields of norgestrel 4.     

Some Transformations of (-)-(1S,4R)-1-Vinyl-7,7-dimethyl-bicyclo[2.2.1]heptan-2-one

Reactions were studied of (-)-(1S,4R)-1-vinyl-7,7-dimethylbicyclo[2.2.1]heptan-2-one with ethyl acetate lithium derivative, potassium acetylide, ozone, with a system OsO₄-N-methylmorpholine N-oxide, and some subsequent transformations of the products obtained.     

Sequential addition reaction of lithium acetylides and Grignard reagents to thioiminium salts from thiolactams leading to 2,2-disubstituted cyclic amines

The reaction of thioiminium salts derived from γ- and δ-thiolactams with lithium acetylides and Grignard reagents proceeded sequentially to give 2,2-disubstituted pyrrolidines and piperidines in moderate to high yields. In the initial step of the reaction, 2-(methylthio)pyrrolidines and -piperidines may be formed. The use of lithium (trimethylsilyl)acetylide gave the products most effectively. Aryl-, alkyl-, and allylmagnesium halides were used as Grignard reagents. Silylcarbocyclization of N-allyl 2-ethynyl cyclic amines with HSiMe₂Ph in the presence of a catalytic amount of Rh₄(CO)₁₂ was carried out to give trisubstituted hexahydro-1H-pyrrolizines and octahydroindolizines.     

Construction of unusual and congested polycyclic structures via benzannulated enediynyl alcohols derived from truxenone

Condensation between truxenone (8) and the lithium acetylide derived from 0.9, 2.5, and 5.0 equiv of 1-ethynyl-2-(phenylethynyl)benzene produced the corresponding benzannulated enediynyl alcohol 9, diol 14, and triol 16, respectively. On exposure of these alcohols to thionyl chloride, cascade cyclization reactions occurred to furnish polycyclic compounds 13, 15, and 18 in a single operation. The unusual architectures of these polycyclic compounds were established by NMR spectroscopy and X-ray structure analyses.     

Synthesis of the ABC fragment of the pectenotoxins

[reaction: see text] A highly stereocontrolled synthesis of the C1-C16 ABC spiroacetal-containing fragment 5 of PTX7 (4) has been achieved. Appendage of the C ring to the AB fragment involved Wittig reaction of spiroacetal aldehyde 8 with a stabilized ylide 9 followed by displacement of allylic iodide 27 with a lithium acetylide to afford enyne 7. Fructose-derived chiral dioxirane and dihydroxylation were then used to introduce the correct functionality in the tetrahydrofuran C ring.