Cascade reactions alkyne termination

It is worth mentioning that some precursors easily catalyze the reductive carbonylation of alkynes from the C0/H20 couple. Here, the main role of water is to furnish hydrogen through the water-gas-shift reaction, as evidenced by the co-production of CO2. In the presence of Pd /KI terminal alkynes have been selectively converted into furan-2-(5H)-ones or anhydrides when a high concentration in CO2 is maintained. Two CO building blocks are incorporated and the cascade reactions that occur on palladium result in a cyclization together with the formation of an oxygen-carbon bond [37,38]. Two examples are shown in Scheme 4. 

A new cascade reaction of aromatic aldehydes with terminal conjugated alkynes produces a range of polycyclic aromatic hydrocarbons.195 The effect of temperature on regioselectivity is discussed. 

Cascade Reactions Initiated by Addition of O-Centered Radicals to Alkynes (Self-Terminating Radical Oxygenations)... 

However, their intermolecular addition reactions with alkynes are mostly aimed at synthesizing substituted aLkenes, ° and only very few cascade reactions that are initiated by P radical addition to C = C triple bonds have been reported. Renaud and coworkers developed a simple one-pot procedure for the cyclization of terminal alkynes mediated by dialkyl phosphites (Scheme 2.35). In this radical chain procedure, dialkyl phosphite radicals, (R0)2P =0, undergo addition to the C = C triple bond in 190, which triggers a radical translocation (l,5-HAT)/5-eAO cyclization cascade. The sequence is terminated by hydrogen transfer from dialkyl phosphite to the intermediate 194 and regeneration of P-centered radicals. 

Application of carbon-carbon cross-coupling/67C-electrocyclization cascade reactions in pyridine synthesis is well known. Larock and coworkers developed a palladium-catalyzed coupling of vinylic imines 279 with terminal alkynes 280 followed by subsequent copper-catalyzed cyclization of 281 to give aryl, vinyl, and alkyl-substituted pyridines 282 in moderate yields. ... 

A cascade Heck reaction with termination by nucleophiles is considered to start with an oxidative addition of a heteroatom-carbon bond (starter) onto a palladium(O) species (startup reaction), followed by carbopalladation of a nonaromatic carbon-carbon double or triple bond without subsequent dehydropalladation (relay), a second and possibly further carbopalladation of a carbon-carbon double or triple bond (second etc. relay). The terminating step is a displacement of the palladium residue by an appropriate nucleophile. It is crucial for a successful cascade carbopalladation that no premature dehydropalladation takes place, and that can be prevented by using alkynes and 1,1-disubstituted alkenes (or certain cycloalkenes) as relay stations since they give kinetically stable alkenyl- or neopentylpalladium intermediates, respectively. In addition, reaction of haloalkenes with alkenes in certain cases may form rr-allyl complexes, which are then trapped by various nucleophiles. 

The Au(III)-catalyzed double hydroamination cascade reaction of ortho-alkynyla-nilines 167 with terminal alkynes 168 affording N-vinylindoles 169 was reported by li (Scheme 9.63) [221]. In the case of alkyl-substituted acetylenes, this protocol provided mixtures of isomeric N-vinylindoles with both terminal and internal double bonds. This transformation is believed to occur via the Au(III)-catalyzed cydoisomerization of transient key alkynyl imines, similar to 162 utilized by Yamamoto, which were generated via the initial Au(111)-catalyzed hydroamination of the corresponding anilines 167 with alkynes 168. 

A formal [3 + 2] cydoaddition route leading to the preparation of di- and tri-substituted indoles 264 from ortho-haloanilines 261 and copper(I) acetylides 262 was introduced by Castro (Scheme 9.92) [75, 76, 111], simultaneously with the mentioned earlier coupling-cyclization reaction en route to benzofurans 57 (Scheme 9.21). It is believed that this stoichiometric in copper cascade reaction proceeded with the generation of an intermediary ortho-alkynylaniline 263 [77]. Attempts to turn this reaction into a more practical catalytic process, using basic conditions to generate Cu(I)-acetylide from a terminal alkyne in the presence of Cul, provided poor yields of the respective indoles 264. 

Domino or cascade reactions provide valuable approaches, especially to various carbo- and heterocyclic systems with three, four, or even more annelated rings. The Heck reaction has successfully been employed in various inter-inter-, intra-inter-, inter-intra-, as well as all-intramolecular reaction cascades, hi this section, the termination of these processes by alkenes, arenes, and related ir-bond systems such as alkynes and allenes will be described. A cascade Heck reaction is considered to consist of an oxidative addition of a heteroatom-carbon bond to palladium (starter), carbopalladation of a nonaromatic carbon-carbon double or triple bond without immediate dehydropalladation (relay), one, two, or more fimher car-bopalladation(s) of a carbon-carbon double or triple bond, and eventually ensuing dehydropalladation. Crucial for a cascade reaction of this kind to occur is the blockage or retardation of a dehydropalladation at one of the intermediate stages by using 1,1-disubsti-tuted alkenes and appropriately substimted cycloalkenes, bicycloalkenes, or alkynes as relays since they give kinetically stable alkyl- or alkenylpalladium intermediates, respectively. 

Scheme 7.19 Preparation of a pyrazolo[5,l-a]isoquinoline through the cascade reaction of l-(2-bromophenyl)buta-2,3-dien-l-one with hydrazine hydrate and a terminal alkyne...

A three-component reaction for the synthesis of functionalized benzimidazoles from terminal alkynes, o-aminoanilines, and / -tolylsulfonyl azide is developed by Wang and coworkers (Scheme 8.52). The C(sp)-H bond of alkyne was activated in this reaction via Cul-catalyzed azide-alkyne cycloaddtion (CuAAC) reaction which could lead to the formation of a ketenimine intermediate by the release of N2- The benzimidazoles could be obtained by intramolecular nucleophilic addition and subsequent elimination of amide intermediate with 2% H2SO4 under reflux conditions [91]. They also developed another protocol for the synthesis of substituted benzimidazole derivatives via a sequential three-component cascade reaction from sulfonyl azides, alkynes, and 2-bromoanilines using Cul as catalyst. Similarly, the C-H bond of alkyne was activated at the process of copper-catalyzed azide-alkyne cycloaddtion (CuAAC) reaction [92]. 

In 2010, Gouverneur and coworkers reported a novel cascade cyclization-intermolecular alkynylation reactions toward the synthesis of five-membered 0-heterocycles. /i-Alkynyl-y-butenolides 2 could be efficiently prepared from allenoates 1 and terminal alkynes in the presence of a gold catalyst with the use of Selectfluor as an external oxidant (Scheme 12.1) [5]. This process involves a direct C(sp)-H functionalization of terminal alkynes. This novel gold-catalyzed cascade cyclization oxidative cross-coupling process provides a basis for the development of novel cascade reactions combining traditional gold catalysis and intermolecular oxidative alkynylation. 

Recently, Briones et al. reported an Rh-catalyzed cascade reaction, which could transform styryldiazoacetates 63 and terminal alkynes into cyclopentadienes 64 in one pot (Scheme 5.43) [41]- The first step of this cascade process is the Ru-catalyzed cyclopropenation of alkynes by metal carbenoids, affording isolatable... 

SCHEME 5.43 Rh-catalyzed cascade reaction of vinyldiazomethanes and terminal alkynes. 

SCHEME 5.57 Cu(I)-catalyzed three-component cascade reaction of sulfonyl azides, terminal alkynes, and nucleophiles. 

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