Alkynes reagents

Scientific, Cellomics). For these applications, the use of azide/alkyne reagents in a click chemistry strategy is entirely appropriate and may be the best choice of all conjugation reactions, because of its exquisite chemoselectivity, bioorthogonality, and excellent reaction kinetics. 

Scheme 1 Schematic representation of cycloaromatization reactions. Double lines correspond to the out-of-plane re-systems of a bis-alkyne reagent. Only orbitals of the in-plane re-system in the reactant and of new

Figure 4 Routes to the Grubbs catalyst 22b and related alkylidene species. Routes based on ring opening (yellow dot), alkylidene transfer (green), alkyne reagents (red), chloroalkanes (blue) are shown in the figure.

Analogs of norbornadiene with heteroatom bridges may be synthesized in theory by reaction of a heterocyclopentadiene derivative with an acetylene (Schemes 3 and 4). These analogs of norbornadiene may be sources of silene or germene intermediates. The reaction of heterocyclopentadienes with acetylenes yields isolable adducts if the heteroatom is Si but not if the heteroatom is Ge. The intermediate dimethylgermene may be trapped by excess alkyne reagent (168) ... 

Figure 19 A glycorandomization technique makes use of click chemistry to create a variety of glycosidic products. Sugar is shown in blue, alkyne reagent is shown in red. Reprinted with permission from X. Fu C. Albermann C. S. Zhang J. S. Thorson, Org. Lett. 2005, 7, 1513-1515. Copyright (2005) American Chemical Society.

Scheme 71 A Structures of methionine 338, azidoalanine 339, azidohomoalanine 340, azi-donorvaline 341 and azidonorleucine 342. B Tagging of azide-modified E. coli cells 343 with a biotinylated alkyne reagent 344 [65,245]...

Cravatt s group was one of the first to see the utility of this approach for proteomics when they successfully demonstrated the ability to label enzymes in vitro and in vivo with an azido ABPP (activity-based protein profiling) probe and to detect the resulting labeled proteins in whole proteomes by the CuAAC reaction with a rhodamine-alkyne reagent (Scheme 9.29) [73]. 

Indium catalysis has been used. Sarmah et al. [103] developed a microwave-promoted imino-Diels-Alder reaction for the synthesis of benzo[/i]quinolines using In(OTf)3 (Figure 9.13). In this case, the diversity came from the aldehyde and alkyne reagents. The yields were good. 

Continuous flow capillary microreactors with embedded monometallic (Pd) or bimetallic (Pd25Zn75) catalysts have been tested in the selective hydrogenation of alkyne reagents, among which was 2-methyl-3-butyne-2-ol [155]. Under conventional reaction conditions a number of side products can be formed. 

Kuhnast B, Hinnen F, Tavitian B, DoUe F (2008) [ F]FPyKYNE, a fluoropyridine-based alkyne reagent designed for the fluorine-18 labeling of macromolecules using click chemistry. J Label Compd Radiopharm 51(9) 336-342... 

Terminal alkyne anions are popular reagents for the acyl anion synthons (RCHjCO"). If this nucleophile is added to aldehydes or ketones, the triple bond remains. This can be con verted to an alkynemercury(II) complex with mercuric salts and is hydrated with water or acids to form ketones (M.M.T. Khan, 1974). The more substituted carbon atom of the al-kynes is converted preferentially into a carbonyl group. Highly substituted a-hydroxyketones are available by this method (J.A. Katzenellenbogen, 1973). Acetylene itself can react with two molecules of an aldehyde or a ketone (V. jager, 1977). Hydration then leads to 1,4-dihydroxy-2-butanones. The 1,4-diols tend to condense to tetrahydrofuran derivatives in the presence of acids. 

The regioselectivity of the addition of terminal alkynes to epoxides is improved, when the reagents prepared from the lithiated alkynes and either trifluoroborane or chlorodiethyl-aluminum arc employed (M. Yamaguchi, 1983 S. Danishefsky, 1976). (Ethoxyethynyl)lithium-trifluoroborane (1 1) is a convenient reagent for converting epoxides to y-lactones (M. Naka-tsuka, 1990 see p. 327f. cf. S. Danishefsky, 1976). 

Another feature of the Pd—C bonds is the excellent functional group tolerance. They are inert to many functional groups, except alkenes and alkynes and iodides and bromides attached to sp carbons, and not sensitive to H2O, ROH, and even RCO H. In this sense, they are very different from Grignard reagents, which react with carbonyl groups and are easily protonated. 

The alkenylzirconium 685, prepared by hydrozirconation of a terminal alkyne with hydrozirconocene chloride, reacts with alkenyl halide to afford the conjugated diene 686(545]. The Zr reagent can be used even in the presence of the carbonyl group in 687, which is sensitive to Al and Mg reagents. 

The a-bromo-7-lactone 901 undergoes smooth coupling with the acetonyltin reagent 902 to afford the o-acetonyl-7-butyrolactone 903[763j. The o-chloro ether 904, which has no possibility of //-elimination after oxidative addition, reacts with vinylstannane to give the allyl ether 905, The o -bromo ether 906 is also used for the intramolecular alkyne insertion and transmetallation with allylstannane to give 907[764],... 

Hydrocarbons that contain a carbon-carbon triple bond are called alkynes Non cyclic alkynes have the molecular formula C H2 -2 Acetylene (HC=CH) is the simplest alkyne We call compounds that have their triple bond at the end of a carbon chain (RC=CH) monosubstituted or terminal alkynes Disubstituted alkynes (RC=CR ) have internal triple bonds You will see m this chapter that a carbon-carbon triple bond is a functional group reacting with many of the same reagents that react with the double bonds of alkenes... 

Alkynes react with many of the same electrophilic reagents that add to the carbon-carbon double bond of alkenes Hydrogen halides for example add to alkynes to form alkenyl halides... 

These compounds are sources of the nucleophilic anion RC=C and their reaction with primary alkyl halides provides an effective synthesis of alkynes (Section 9 6) The nucleophilicity of acetylide anions is also evident m their reactions with aldehydes and ketones which are entirely analogous to those of Grignard and organolithium reagents... 

Its reactions with olefins, governed by steric rather than electronic factors, are very sluggish. Even simple 1-alkenes require 8 h at 25°C for complete reaction. In contrast, alkynes are hydroborated with great ease to alkenylboranes, high steric requirements of the reagent preventing dihydroboration (117). 

---