Propargylic coupling

Allylic and Propargylic Coupling With a Halide Substrate... 

Allylic and Propargylic Coupling with a Halide Substrate De-halogen-coupling... 

Scheme 3.51 Pd-catalyzed alkynyl-propargyl coupling producing l-trimethylsilyl-6-methyl-l-heptyn-4,5-diene [174a].

Scheme 5-96. Alkenyl-propargyl coupling reactions of zinc reagents. ...

In alkenes, the magnitude of allylic coupling CJ) depends on the extent of overlap of the carbon-hydrogen crbond with the rbond. A similar type of interaction occurs in alkynes, but with an important difference. In the case of propargylic coupling (Fig. 5.12), a C—H (7 orbital on the carbon a to the triple bond always has partial overlap with the alkyne 7t system because the triple bond consists of two perpendicular r bonds, effectively creating a cylinder of electron density surrounding the C—C intemuclear axis. 

Pyrrole derivatives are prepared by the coupling and annulation of o-iodoa-nilines with internal alkynes[291]. The 4-amino-5-iodopyrimidine 428 reacts with the TMS-substituted propargyl alcohol 429 to form the heterocondensed pyrrole 430, and the TMS is removed[292]. Similarly, the tryptophane 434 is obtained by the reaction of o-iodoaniline (431) with the internal alkyne 432 and deprotection of the coupled product 433(293]. As an alternative method, the 2,3-disubstituted indole 436 is obtained directly by the coupling of the o-alky-nyltrifluoroacetanilide 435 with aryl and alkenyl halides or triflates(294]. 

The unsaturated c.vo-enol lactone 17 is obtained by the coupling of propargylic acetate with 4-pentynoic acid in the presence of KBr using tri(2-furyl)-phosphine (TFP) as a ligand. The reaction is explained by the oxypalladation of the triple bond of 4-pentynoic acid with the ailenyipailadium and the carbox-ylate as shown by 16, followed by reductive elimination to afford the lactone 17. The ( -alkene bond is formed because the oxypalladation is tnins addition[8]. 

Copper(I) halide-catalyzed coupling reactions of perfluoro Gngnard reagents with allyl and propargyl halides have been reported [256], The acetylenic copper compound may be an intermediate in these reactions. 

Scheme 5.1-27 The zinc triflate-catalyzed coupling of alkynes with aldehydes to give propargyl alcohols in an ionic liquid.

Whereas triethyl (l-methyl-2-yl)indolyl borate (119) undergoes Pd-catalyzed coupling with propargyl carbonates in an 8 2 manner yielding 2-allenylindoles <96H(43)1591>, conducting this reaction in the presence of CO (10 atm) affords cyclopenta[fe]indoles 120 <96CC2409>. 

Palladium And/Or Copper-Mediated Cross-Coupling Reactions Between 1-Alkynes And Vinyl, Aryl, 1-Alkynyl, 1,2-Propadienyl, Propargyl And Allylic Halides Or Related Compounds. A Review, Rossi. R. Carpita, A. Beilina, F. Org. Prep. Proceed. Int., 1995, 27, 129... 

The subsequent chain extension can be accomplished by the pedestrian step-by-step homologation sequence via the acyclic diyne 12 or by a more efficient block-to-block strategy. The step-by-step approach includes protiodesilylation of diyne 12 followed by coupling with the propargyl chloride 9 following the same protocol as for the preparation of 12 from 11 and subsequent repetitions of protiodesilylation and alkylation with chloride 9 to reach stages 16 and 18, respectively (Scheme 3). 

A second, more convenient approach was tried starting with dicyclopropyla-cetylene 56 [15-17] which, after deprotonation with tert-butyllithium at both propargylic positions, yielded the bisaldehyde 57 upon treatment with dimethyl-formamide. The latter was converted to the bis(dibromoethenyl) derivative 58, and this in turn to the dibromotriyne 59 by standard methods (Scheme 11) [18]. The dibromide 59 was coupled with the ethynylcyclopropylheterocuprate 50 to give the terminally bis-protected pentayne 60. 

Eventually, indole acetic acid 2 was prepared from iodoaniline 28 and propargyl alcohol derivative 61 via the newly developed coupling reaction followed by a cyanide displacement-hydrolysis sequence, as shown in Scheme 4.16. 

The C,0-bis-TES side chain 61 was prepared quantitatively from propargyl alcohol and TESC1 using n-BuLi as a base. Pd-catalyzed coupling of iodoaniline 28 with bis-TES side chain 61 in the presence of 1.5equiv of MgS04 and 5equiv of... 

Another example of the addition of terminal alkynes to C=N in water is the coupling of alkynes with in-situ-generated A-acylimines (Eq. 4.32) and A-acyliminium ions (Eq. 4.33). In 2002, Li et al. developed a coupling reaction of alkynes with A-acylimines and A-acyliminium ions mediated by Cu(I) in water to generate propargyl amide derivatives.57 Either an activated imine derivative or imininum derivative was proposed as the intermediate, respectively. 

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