Alkyne derivatives intermolecular reactions

Intermolecular cyclotrimerization of alkynes using Wilkinson s catalyst has also afforded substituted carbazole derivatives. This reaction was extended to an intramolecular version by offering the possibility for a six-membered ring annotation that cannot be achieved easily in the corresponding intermolecular version. Intramolecular cyclotrimerization is completely regioselective due to an additional tether. 

With the exception of propynoic acid derivatives, all alkynes undergo the reaction. On the other hand, generally, only strained olefins react efficiently in the intermolecular PKR whereas electron deficient alkenes give the reaction only in limited examples. With respect to regioselectivity, the bulkier substituent of the alkyne is placed adjacent to the carbonyl in the cyclopen-tenone product. Unsymmetrical olefins usually give mixtures of regioisomers... 

Some of the most useful synthetic transformations of terminal alkynes involve intermolecular and intramolecular homo- and cross-coupling reactions between their. sp-carbon centers, leading to butadiyne or polyyne derivatives. The two most widely used and practical systems are (i) oxidative homocoupling reactions, i.e. Glaser and Eglington reactions and (ii) heterocoupling reactions, i.e. Chodkiewicz-Cadiot coupling of a terminal alkyne with a haloalkyne. 

Under enyne cross-metathesis conditions, the intermolecular reaction of the a,(D-dienes 153, derived from the MBH reaction, with different terminal alkynes 154 afforded triene intermediates that cyclized spontaneously under the reaction conditions to give substituted cis-hexahydro-l/f-indenes 155 (Scheme 4.45), which can be further transformed into steroid analogues via TBS deprotection and oxidation. However, metathesis reactions starting with 156 only furnished trienes 157 [as EfZ) mixtures] and no spontaneous intramolecular cycloaddition occurred. Even at elevated reaction temperatures, trienes 157 cyclized only slowly to give octahydronaphthalene diastereomers. With deprotection of the TBS and subsequent Dess-Martin oxidation, trienes 157 could be converted exclusively into cw-fused 7-substituted 6,7-dehy-drodealone-l-one-lO-carboxylic esters 158 in 50-60% yields. Moreover, c ross-metathesis of TBS-unprotected MBH adduct 159 with alkynes 154 along with treatment with Dess-Martin periodinane (DMP) in one pot could conveniently produce the corresponding bicyclic ketones 160 in moderate yields. ... 

As part of our investigation of the hydroarylation of alkynes (or alkenylation of arenes) catalyzed by electrophilic transition metal complexes, our group reported the intra- and intermolecular reaction of indoles with alkynes catalyzed by gold (see Ref. [118, 133] in Chap. 1). Thus, alkynyUndole III-l cycUzes readily in the presence of a cationic gold(I) complex to give azepino[4,5-h]indole derivative III-2, whereas the use of AuCls leads to indoloazocine III-3 by a S-endo-dig process, this cyclization mode has not been observed in other hydroarylation of alkynes (Scheme 4.7). Under certain forcing conditions, aUenes and tetracyclic compounds were also obtained (see Refs. [118, 133] in Chap. 1). 

Indole and isoquinolone nuclei are prominent structural units frequently found in numerous natural products and pharmaceutically active compounds. Thus, the search for new methodologies to obtain these scaffolds with different substitution patterns is a current major objective in organic synthesis. Similar to benzofuran synthesis, Aluraez et al. observed that the palladium-catalyzed cascade intramolecular alkyne aminopaUadation/intermolecular Heck-type coupling reaction under oxidative conditions is an efficient methodology for the synthesis of indole 217 and isoquinolone 219 derivatives, starting from readily available aniline 216 or benzamide 218 substrates and functional alkenes [77] (Scheme 6.60). 

This solid-phase technique has made possible efficient syntheses of bi- and polycyclic systems from precursors frequently generated via Nicholas cations, (e.g. eq 60) and has been used for intermolecular reactions with methy lenecyclopropane (eq 61) and methylenecyclobutane to give spirocyclic cyclopentenone derivatives. (1) is the majorproduct when the alkyne is terminal (R = H), but only (2) was isolated when EtC2Et or Me3 SiC2Me were used. ... 

The benzene derivative 409 is synthesized by the Pd-catalyzed reaction of the haloenyne 407 with alkynes. The intramolecular insertion of the internal alkyne, followed by the intermolecular coupling of the terminal alkyne using Pd(OAc)2, Ph3P, and Cul, affords the dienyne system 408, which cyclizes to the aromatic ring 409[281]. A similar cyclization of 410 with the terminal alkyne 411 to form benzene derivatives 412 and 413 without using Cul is explained by the successive intermolecular and intramolecuar insertions of the two triple bonds and the double bond[282]. The angularly bisannulated benzene derivative 415 is formed in one step by a totally intramolecular version of polycycli-zation of bromoenediyne 414[283,284],... 

Non-heteroatom-stabilised Fischer carbene complexes also react with alkenes to give mixtures of olefin metathesis products and cyclopropane derivatives which are frequently the minor reaction products [19]. Furthermore, non-heteroatom-stabilised vinylcarbene complexes, generated in situ by reaction of an alkoxy- or aminocarbene complex with an alkyne, are able to react with different types of alkenes in an intramolecular or intermolecular process to produce bicyclic compounds containing a cyclopropane ring [20]. 

Aryl- and alkenylcarbene complexes are known to react with alkynes through a [3C+2S+1C0] cycloaddition reaction to produce benzannulated compounds. This reaction, known as the Dotz reaction , is widely reviewed in Chap. Chromium-Templated Benzannulation Reactions , p. 123 of this book. However, simple alkyl-substituted carbene complexes react with excess of an alkyne (or with diynes) to produce a different benzannulated product which incorporates in its structure two molecules of the alkyne, a carbon monoxide ligand and the carbene carbon [128]. As referred to before, this [2S+2SH-1C+1C0] cycloaddition reaction can be carried out with diyne derivatives, showing these reactions give better yields than the corresponding intermolecular version (Scheme 80). 

Malacria and coworkers [274] used an intermolecular trimerization of alkynes to gain efficient access to the skeleton of the phyllocladane family. Thus, the Co-cata-lyzed reaction of the polyunsaturated precursor 6/4-4 gave 6/4-5 in 42% yield. Here, six new carbon-carbon bonds and four stereogenic centers are formed. The first step is formation of the cyclopentane derivative 6/4-6 by a Co-catalyzed Conia-ene-type reaction [275] which, on addition o f his( Iri me ill y I si ly 1) e thy ne (btmse), led to the benzocyclobutenes 6/4-7 (Scheme 6/4.2). The reaction is terminated by the addition of dppe and heating to reflux in decane to give the desired products 6/4-5 by an electrocyclic ring opening, followed by [4+2] cycloaddition. 

Click chemistry has been particularly active in various fields this year. For example, ample applications of click chemistry have been seen in carbohydrate chemistry. Various /weiido-oligosacchardies and amino acid glycoconjugates were synthesized via an intermolecular 1,3-dipolar cycloaddition reaction using easily accessible carbohydrate and amino acid derived azides and alkynes as building blocks <06JOC364>. The iterative copper(I)-catalyzed... 

Sonogashira reactions of both a-halothiophenes [117] and P-halothiophenes [118] proceed smoothly even for fairly complicated molecules as illustrated by the transformation of brotizolam (134) to alkyne 135 [119]. Interestingly, 3,4-bis(trimethylsilyl)thiophene (137), derived from the intermolecular cyclization of 4-phenylthiazole (136) and bis(trimethylsilyl)acetylene, underwent consecutive iodination and Sonogashira reaction to make 3,4-bisalkynylthiophenes [120], Therefore, a regiospecific mono-i/wo-iodination of 137 gave iodothiophene 138, which was coupled with phenylacetylene to afford alkynylthiophene 139. A second iodination and a Sonogashira reaction then provided the unsymmetrically substituted 3,4-bisalkynylthiophene 140. 

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