Palladium-catalyzed alkynation

Closely related to the Heck reaction is the Sonogashira reaction i.e. the palladium-catalyzed cross-coupling of a vinyl or aryl halide 20 and a terminal alkyne 21 ... 

A synthetically useful virtue of enol triflates is that they are amenable to palladium-catalyzed carbon-carbon bond-forming reactions under mild conditions. When a solution of enol triflate 21 and tetrakis(triphenylphosphine)palladium(o) in benzene is treated with a mixture of terminal alkyne 17, n-propylamine, and cuprous iodide,17 intermediate 22 is formed in 76-84% yield. Although a partial hydrogenation of the alkyne in 22 could conceivably secure the formation of the cis C1-C2 olefin, a chemoselective hydrobora-tion/protonation sequence was found to be a much more reliable and suitable alternative. Thus, sequential hydroboration of the alkyne 22 with dicyclohexylborane, protonolysis, oxidative workup, and hydrolysis of the oxabicyclo[2.2.2]octyl ester protecting group gives dienic carboxylic acid 15 in a yield of 86% from 22. 

Palladium-catalyzed reaction of alkyne 47 with a variety of aryl and vinyl halides afforded alkenes 48 in good yield. Cyclization to quinolines 49 was performed by treating 4 8 with TsOH in EtOH <96T(52)10225>. 

Larock R (2005) Palladium-Catalyzed Annulation of Alkynes. 14 147-182 Larrow JF, Jacobsen EN (2004) Asymmetric Processes Catalyzed by Chiral (Salen)Metal Complexes 6 123-152... 

Over the last decade, the chemistry of the carbon-carbon triple bond has experienced a vigorous resurgence [1]. Whereas construction of alkyne-con-taining systems had previously been a laborious process, the advent of new synthetic methodology based on organotransition metal complexes has revolutionized the field [2]. Specifically, palladium-catalyzed cross-coupling reactions between alkyne sp-carbon atoms and sp -carbon atoms of arenes and alkenes have allowed for rapid assembly of relatively complex structures [3]. In particular, the preparation of alkyne-rich macrocycles, the subject of this report, has benefited enormously from these recent advances. For the purpose of this review, we Emit the discussion to cychc systems which contain benzene and acetylene moieties only, henceforth referred to as phenylacetylene and phenyldiacetylene macrocycles (PAMs and PDMs, respectively). Not only have a wide... 

R = n-CeHia, Ph, p-Tol, NC(CH2)a, HC=C(CH2)5, 3-HC=C-C6H4, 1-cyclohexenyl, SiMea Scheme 5-17 Palladium-catalyzed hydrophosphorylation of alkynes... 

Scheme 5-18 Stoichiometric reactions relevant to the proposed mechanism for palladium-catalyzed hydrophosphonylation of alkynes...

Scheme 5-19 Palladium-catalyzed bis-hydrophos-phorylation of alkynes...

Scheme 5-23 The effect of added phosphinic acid on palladium-catalyzed hydrophosphinylation of alkynes...

Scheme5-24 Eq. (1) Proposed mechanism for Eq. (2) Stoichiometric reactions relevant to the phosphinic acid-modified palladium-catalyzed proposed mechanism hydrophosphinylation of alkynes.

This reaction typifies the two possibilities of reaction routes for M-catalyzed addition of an S-X (or Se-X) bond to alkyne (a) oxidative addition of the S-X bond to M(0) to form 94, (b) insertion of alkyne into either the M-S or M-X bond to provide 95 or 96 (c) C-X or C-S bond-forming reductive elimination to give 97 (Scheme 7-21). Comparable reaction sequences are also discussed when the Chalk-Harrod mechanism is compared with the modified Chalk-Harrod mechanism in hydrosily-lations [1,3]. The palladium-catalyzed thioboratiori, that is, addition of an S-B bond to an alkyne was reported by Miyaura and Suzuki et al. to furnish the cis-adducts 98 with the sulfur bound to the internal carbon and the boron center to the terminal carbon (Eq. 7.61) [62]. 

Palladium-catalyzed procedures have also been developed for addition of stannanes to alkynes,143 and these reactions usually occur by syn addition. 

On the other hand, Li et al. reported the first palladium-catalyzed 1,4-addition of terminal alkynes to vinyl ketones in water with high yields (Eq. 4.36).60 At nearly the same time, Chisholm et al. reported such a reaction catalyzed by Rh(acac)(CO)2 (acac = acetylacetonoate) in the presence of /m(o-mcthoxyphcnyl)phosphine in aqueous dioxane... 

Later, a nickel-catalyzed cascade conversion of propargyl halides and propargyl alcohol into a pyrone in water was reported. The reaction involved a carbonylation by CO and a cyanation by KCN (Eq. 4.55).96 Recently, Gabriele et al. explored a facile synthesis of maleic acids by palladium catalyzed-oxidative carbonylation of terminal alkynes in aqueous DME (1,2-dimethoxyethane) (Eq. 4.56).97... 

The palladium-catalyzed annulation of alkynes by functionally-substituted aryl and vinylic halides or triflates provides a veiy convenient and efficient approach to a wide variety of heterocycles and carbocycles. This chemistry has lead to the discovery of a number of novel palladium-catalyzed processes in which the palladium migrates from one carbon to another within the molecule providing a unique way to form carbon-carbon bonds in remote locations within the same molecule. 

A wide variety of heterocycles can be readily prepared by the heteroannulation of alkynes. For example, the palladium-catalyzed annulation of internal alkynes by 2-iodoanilines provides easy access to 2,3-disubstituted indoles by a process that involves initial reduction of Pd(OAc)2 to Pd(0), oxidative addition of the aryl halide to Pd(0), c/s-addition of the arylpalladium... 

Another recent development in the field of palladium-catalyzed reactions with alkynes is a novel multicomponent approach devised by the Lee group. Starting from a-bromovinyl arenes and propargyl bromides, the assembly ofeight-membered car-bocycles can be realized via a cross-coupling/[4+4] cycloaddition reaction. The authors also presented the combination of a cross-coupling and homo [4+2], hetero [4+2], hetero [4+4] or [4+4+1] annulation leading to various cyclic products [147]. 

Palladium-catalyzed coupling of the borane derived from A with 1-bromo-1-pentyne to give B as well as the coupling of iodoalkene C with alkyne D were the two key-steps. 

Benzo-fused pyrrolizines can be prepared from the palladium-catalyzed reaction of alkynes with imines of 2-halogenoanilines. Pyrimidine-substituted alkynes react in the same way, to produce the pyrimidine-fused pyrrolizines 161 <2001JOC412> (Scheme 48). 

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