Synthesis of terminal acetylenes

This protocol is applied to the synthesis of the starting monomers for acetylenic nanoarchitectures. For example, geminally bis-deprotected tetraethynylethene 97 is prepared by Pd-catalyzed alkynylation followed by deprotection with K2C03 in MeOH [Eq. (36)] [54c]. Perethynylated ethene 97 is a synthetic precursor of expanded radialenes, which are novel carbon-rich materials. 

Similar couplings of hexabromobenzene 98 with TMSA proceeds easily under normal conditions to afford the completely sixfold-coupled product followed by desilylation with KOH to give hexaethynylbenzene 99 in 28% yields [Eq. (37)] [55]. 1,2,4,5-Tetraiodobenzene 100 also undergoes tetrasubstitution to give 1,2,4,5-tetraethynylbenzene 101 after desilylation. This product is converted into linear oligo(biphenylene) 103 [Eq. (38)] [56]. 

Finally, SiMe3 and GeMe3 protected dialkynes 113 and 118 can be regioselectivity deprotected by protodesilation or protodegermylation. Thus, catalytic amounts of CuBr in THF/MeOH or in aqueous acetone lead exclusively to protodegermylation. On the other 

A relatively inexpensive 2-methyl-3-butyn-2-ol is also a useful protecting reagent for stable and volatile arylalkynes. Base-catalyzed retro-Favorsky elimination of acetone from alcohols RC CC(CH3)2OH can be successfully applied to prepare terminal acetylenes [Eq. (39)] 1601. Treatment with KOH at elevated temperatures is required for elimination of acetone. Many procedures are reported. 

A remarkable success in this field is the one-pot synthesis of the dehydroannulene 124 using the Pd-catalyzed cross-coupling and deprotection sequence. It makes 124, an interesting [4 +2] annulenc and organometallic ligand, readily available [Eq. (40)J [611. 

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Recently, direct synthesis of terminal acetylenes via Pd-catalyzed cross-coupling of aryl or alkenyl halides with ethynylmetals was developed by Negishi and co-workers (Section ni.2.8.2). ... 

A general synthesis of terminal acetylenes (278) has been developed by Ikegami et al, whereby the vinylstannane derivatives (277), prepared from the aldehydes (276), are treated with lead tetra-acetate. The method will tolerate a wide range of sensitive functionality, such as double bonds, epoxides, and silyl and THP ethers. 

Methyl ketones are important intermediates for the synthesis of methyl alkyl carbinols, annulation reagents, and cyclic compounds. A common synthetic method for the preparation of methyl ketones is the alkylation of acetone derivatives, but the method suffers limitations such as low yields and lack of regioselectivity. Preparation of methyl ketones from olefins and acetylenes using mercury compounds is a better method. For example, hydration of terminal acetylenes using HgSO gives methyl ketones cleanly. Oxymercuration of 1-olefins and subsequent oxidation with chromic oxide is... 

The two reactions described above can be applied for the synthesis of symmetrical -acetylenes only. Unsymmetrical bis-acetylenes can be prepared by using the Cadiot-Chodkiew icz reaction For that method a terminal alkyne 1 is reacted with a bromoalkyne 8 in the presence of a copper catalyst, to yield an unsymmetrical coupling product 9 ... 

In 1980 Sonogashira reported a convenient synthesis of ethynylarenes - the Pd-catalyzed cross-coupfing of bromo- or iodoarenes with trimethylsilylacetylene followed by protiodesilylation in basic solution [15]. Prior to this discovery, formation of terminal acetylenes required manipulation of a preformed, two-carbon side chain via methods that include halogenation/dehydrohalogenation of vinyl- and acetylarenes, dehalogenation of /1,/1-dihaloalkenes, and the Vils-meier procedure [ 14]. With the ready availability of trialkylsilylacetylenes, the two-step Sonogashira sequence has become the cornerstone reaction for the construction of virtually all ethynylated arenes used in PAM and PDM synthesis (vide infra). 

Cross-coupling of terminal acetylenes used as nucleophiles with aryl or alkenyl halides (referred to as the Sonogashira-Hagihara, or SH, reaction) is a versatile method of synthesis for acetylenic compounds, which are rapidly gaining importance as advanced new materials and building blocks for implementing unusual molecular architectures. 

The idea of synthesizing imide oligomers which carry acetylenic terminations appeared attractive because homopolymerization through acetylenic endgroups occurs without any volatile evolution and provides materials with good properties. Landis et. al (8,9) published the synthesis of such acetylene terminated imide oligomers from benzophenone tetracarboxylic anhydride, aromatic diamine and 3-ethynylaniline via the classical route. As usual, the amide acid is formed as an intermediate which, after chemical cyclodehydration, provides the polymide. Since ethynyl-terminated polyimide is used as a matrix resin for fiber composites, processing is possible via the amide acid, which is soluble in acetone, or via the fully imidized prepolymer, which is soluble in NMP. The chemical structure of the fully imidized ethynyl-terminated polyimide is provided in Fig. 44. 

Oxidative coupling of terminal acetylenes in the presence of copper(I) catalysts is the best method of preparing symmetrically substituted butadiyne derivatives,5 and has been applied to the coupling of trimethylsilyl-acetylene. Better yields are obtained using the Hay procedure in which the catalyst is the TMEDA complex of copper(I) chloride.7 The procedure submitted here is an improved version of Walton and Waugh s synthesis of BTMSBD by the Hay coupling of trimethylsilylacetylene.2 BTMSBD has also been prepared by... 

Hydroboration of terminal acetylenes with boron halides permits the stereospecific synthesis of ( )-l-chloro(or bromo)alk-l-enes919. BBr3 adds to terminal acetylenes in a regio- and stereoselective manner to yield /Lhalovinylboranes, which are very useful syn-thons92a 923. B-bromo- and B-iodo-9 borabicyclo[3.3.1]nonane react similarly924"926. 

While investigating catalytic aminomercuration of terminal acetylenes, Barluenga and coworkers92 93 have developed a facile synthesis of / -allyloxyenamines 117. These substrates readily undergo the Claisen rearrangement at a relatively low temperature to... 

ETHYNE via generation and trapping of an unstable phosphorylaied carbanion is illustrated. The methodology is well suited for the synthesis of a wide variety of terminal acetylenic compounds. 

Terminal Acetylene with sp -carbon Halides 5.3.5.1 Synthesis of internal acetylenes... 

A mild and efficient synthesis of terminal alkynes starts with readily accessible methyl ketones and converts them to the corresponding enolates with LDA. The eno-lates produced are trapped with diethyl chlorophosphate to give enol phosphates, which possess a good leaving group for elimination. Subsequent treatment of the enol phosphates with LDA furnishes the corresponding lithium alkynylides and on protonation of these, the corresponding terminal acetylenes. 

Sonogashira, K. Palladium-catalyzed alkynylation. Handbook of Organopalladium Chemistry for Organic Synthesis 2002,1,493-529. Sonogashira, K. Development of Pd-Cu catalyzed cross-coupling of terminal acetylenes with sp -carbon halides. J. Organomet. Chem. 

Oxidative coupling of terminal acetylenes (1, 168169).3 Yamamoto and Sond-heimer have reported the synthesis of a tetraalkylated tetradehydro[18]annulenedione (5), of interest as a possible quinone, from (1). The acetylene (1) is oxidatively coupled... 

Cuprous ammonium chloride. The combination of cuprous chloride and ammonium chloride in a slightly acidic aqueous solution catalyzes oxidative (air) coupling of terminal acetylenes to diacetyienes. - The groups NHa, OH, COjH, and COjR do not interfere, in the synthesis formulated, cross coupling was accomplished in a mixture of ethanol and 0.08 A hydrochloric acid containing the catalyst. 

Synthesis of heterocycles. Quilico and co-workers used the reagent for the synthesis of 3-chloroisoxazoles from the Grignard derivatives of terminal acetylenes. 

Treatment of terminal acetylenes with hydrogen iodide, generated in situ from TMSCl, sodium iodide, and water, provides a highly regioselective synthesis of 2-iodo-l-alkenes. Followed by addition of cuprous cyanide, the protocol offers a convenient one-pot preparation of 2-substituted acrylonitriles in fair to good yield (eq 90). In contrast, when the reaction with arylacetylene proceeds in DMSO and with catalytic amount of sodium iodide, the 3-arylpropynenitrile is obtained as the preferred product. 

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