1,3-Enynes from alkynes

The dimerization of alkynes is a useful method for forming compounds such as enynes from simple alkynes [13]. The iridium-catalyzed dimerizahon of 1-alkyries was first reported by Crabtree, and afforded (Zj-head-to-head enynes using [Ir(biph)(PMe3)Cl] (biph = biphenyl-2,2 -diyl) as a catalyst [14]. Thereafter, an iridium complex generated in situ from [Ir(cod)Cl]2 and a phosphine ligand catalyzed the dimerizahon of 1-alkynes 1 to give (Tj-head-to-head enyne 2, fZj-head-to-head enyne 3, or 1,2,3-butatriene derivatives 4 in the presence of hiethylamine... 

Hydroboration-protonolysis is thus a general, stereospecific and versatile route from alkynes to alkenes, enynes and dienes. 

The reaction of dienes, diynes, or en-ynes with transition metals " (usually cobalt) " forms organometalhc coordination complexes. In the presence of carbon monoxide, the metal complexes derived primarily from enynes (alkene-alkynes) form cyclopentenone derivatives in what is known as the Pauson-Khand... 

Sonogashira coupling. Stereodefmed enynes including those bearing an alkoxy substituent (i.e., enol and ynol ethers) are readily prepared from alkynes on coupling with alkenyl iodides. Alkynylsilanes can be used instead of 1-alkynes in the coupling with alkenyl and aryl triflates. ... 

Scheme 27 Catalytic synthesis of enynes from terminal alkynes can result in the formation of mixtures of products...

Dienes and l,S-enynn. pentenes (derived from alkynes. are treated with alkynylmetals. Pi w ith iodine gives 1,5-enynes. 

A route to alkynylarenes and enynes from 1-alkynes involves formation of alkynylboronic esters [lithioalkynes -I- (/-PrOl B] and Suzuki coupling in situ. Suzuki cross-coupling using thallium(I) ethoxide as promoter is superior to TlOH because of its stability, commercial availability, and ease of use. A convenient method for assembling conjugated polyenes is assured. 

Z)-Alkenes. The method for generating (Z)-alkenes from alkynes can be extended to conjugated and methylene-skipped enynes. On quenching the titanacyclopropene intermediates with D O, dideuterio products are obtained. 

Oxidative addition of aryl (or vinyl) halide to Pd(0) precursor forms the monoarylpalladium complex that is the common intermediate in the catalytic cross-coupling reactions of haloarene with organometallic compounds of main group elements such as Mg, Si, and Sn. Alkynylcopper, formed from alkyne, Cu(I) salt and base in the reaction mixture, transfers the ligand to the above Pd complex, giving an intermediate complex with aryl (or vinyl) and alkynyl ligands bonded to Pd. Reductive elimination of arylacetylene (or enyne) occurs... 

Brown and Molander have shown that alkenylcopper reagents, generated stereospecifically from alkynes via alkenylboranes, undergo cross-coupling with 1-bromo- (or 1-iodo-) 1-alkynes with retention of configuration to give conjugated enynes (Scheme 79). 

Scheme 26 Regio- and stereoselective synthesis of (Z)-enynes from aliphatic and aromatic alkynes...

Starting from alkynes, hydrozirconation reactions lead to alkenyl zirconyl compounds that in turn can be cross-coupled with halides to give enynes. The total synthesis of the polyenyne xerulin is a showcase of this reaction sequence (Scheme 5-111). 

Kinoshita A, Sakakibara N, Mori M. Novel 1,3-diene synthesis from alkyne and ethylene by ruthenium-catalyzed enyne metathesis. 7. Aw. Chem. Soc. 1997 119 12388-12389. 

Tonogaki K, Mori, M. An improved 1,3-diene synthesis from alkyne and ethylene using cross-enyne metathesis. Tetrahedron Lett. 2002 43 2235-2238. 

Z)-l-Bromo-l-alkenes were efficiently prepared in high yields stereoselective-ly by microwave irradiation of the corresponding anti-2,3-dibromoalkanoic acids in DMF using EtjN as a base. Microwave-assisted one-pot syntheses of terminal alkynes and enynes from 2,3-dibromoalkanoic acids were also developed (Kuang et al., 2005a). 

The insertion of alkynes into a chromium-carbon double bond is not restricted to Fischer alkenylcarbene complexes. Numerous transformations of this kind have been performed with simple alkylcarbene complexes, from which unstable a,/J-unsaturated carbene complexes were formed in situ, and in turn underwent further reactions in several different ways. For example, reaction of the 1-me-thoxyethylidene complex 6a with the conjugated enyne-ketimines and -ketones 131 afforded pyrrole [92] and furan 134 derivatives [93], respectively. The alkyne-inserted intermediate 132 apparently undergoes 671-electrocyclization and reductive elimination to afford enol ether 133, which yields the cycloaddition product 134 via a subsequent hydrolysis (Scheme 28). This transformation also demonstrates that Fischer carbene complexes are highly selective in their reactivity toward alkynes in the presence of other multiple bonds (Table 6). 

The fact that pentacarbonyl carbene complexes react with enynes in a chemo-selective and regiospecific way at the alkyne functionality was successfully applied in the total synthesis of vitamins of the Kj and K2 series [58]. Oxidation of the intermediate tricarbonyl(dihydrovitamin K) chromium complexes with silver oxide afforded the desired naphthoquinone-based vitamin K compounds 65. Compared to customary strategies, the benzannulation reaction proved to be superior as it avoids conditions favouring (E)/(Z)-isomerisation within the allylic side chain. The basic representative vitamin K3 (menadione) 66 was synthesised in a straightforward manner from pentacarbonyl carbene complex 1 and propyne (Scheme 38). 

While diene metathesis or diyne metathesis are driven by the loss of a (volatile) alkene or alkyne by-product, enyne metathesis (Fig. 2) cannot benefit from this contributing feature to the AS term of the reaction, since the event is entirely atom economic. Instead, the reaction is driven by the formation of conjugated dienes, which ensures that once these dienes have been formed, the process is no longer a reversible one. Enyne metathesis can also be considered as an alkylidene migration reaction, because the alkylidene unit migrates from the alkene part to one of the alkyne carbons. The mechanism of enyne metathesis is not well described, as two possible complexation sites (alkene or alkyne) exist for the ruthenium carbene, leading to different reaction pathways, and the situation is further complicated when the reaction is conducted under an atmosphere of ethylene. Despite its enormous potential to form mul-... 

Enynes 71 react with aldehydes 61 in the presence of the [Ni(COD)J/SIPr catalytic system to afford two distinct products 72 and 73 (Scheme 5.20) [20b], The enone 72 is derived from aldehyde addition with the alkyne moiety while the adduct 73 arises from the aldehyde addition with the alkene moiety. The product distribution is dependent on the substituent on either the alkyne or alkene moieties. The reaction between 71 and ketones 74 led to the unprecedented formation of pyrans 75 (Scheme 5.20). The reaction showed to be highly regioselective in aU the cases, the carbonyl carbon was bound to the olefin. 

AUylzirconium complexes are conveniently obtained by the regio- and stereoselective hydrozirconation of allene [127-133] and can be, for example, used subsequently for the MAO-catalyzed allylzirconation of alkynes to prepare enyne derivatives [132]. Alternatively, the preparation of (E)-l,3-dienes from aldehydes and the appropriate allylstannane zirconocene derivative (R = SnBu,) is accomplished (Scheme 8-17) [131], Note that addition of [Cp2Zr(H)Cl[n (1) on the aUenyl reagent with the... 

As predicted from the comparative rates for C=C over C=C hydrozirconation cited earlier, a (poly)enyne is selectively hydrozirconated at the alkyne moiety, whatever the position of the alkene function [138, 210] in the molecule. It can be exempUfied by the chemoselective hydrozirconation of 1,3-butenyne. One exception to this chemoselectivity has been reported, which showed the terminal alkene to react with 1 but leaving the TMS-substituted alkyne function intact (Scheme 8-25). 

In a reaction similar to the (>-alkoxide elimination reactions seen with zir-conocenes, catalytic Rh(OH)(cod)2 and 2 eq. of arylboronic acids gave cyclic products 165 from enynes 166 (Scheme 35) [100]. In this reaction, transmet-allation of Rh - OR with B - Ph gave Rh - Ph species 167, which inserted into the alkyne, cyclized to 168, and finally underwent [>-alkoxidc elimination to provide Rh-OCH3. This reaction is limited to the formation of five-membered rings, but it can also undergo cascade type reactions of enediynes to give multicyclic products [100]. 

Based on his previous work on the catalytic double addition of diazo compounds to alkynes173 using Cp RuCl(COD),174 Dixneuf has developed an efficient one-step synthesis of alkenyl bicyclo[3.1.0]-hexane derivatives of type 163 from enyne precursors 162 (Scheme 43). The catalytic cycle starts with the formation of an Ru=CHR species. It then adds to an alkyne to form ruthenacyclobutene 166, which evolves into vinylcarbene 167. [2 + 2]-Cycloaddition of 167 gives ruthenacyclobutane 168. The novelty in this transformation is the subsequent reductive elimination to give 170 without leading to the formation of diene 169. This can be attributed to the steric hindrance of the CsMes-Ru group. 

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