Alkynes intermolecular addition

The hexabutyldistannane used in this reaction is not involved in the propagation sequence but may be involved in initiation or scavenging of potential chain-termination radicals. Intermolecular additions of alkyl radicals to alkynes have also been observed. 

The ruthenium-catalyzed direct addition of saturated aliphatic alcohols to non-activated alkynes remains a challenge. Only ally alcohol has been successfully involved in the intermolecular addition to phenylacetylene to produce an ether and the enal resulting from Claisen rearrangement (Equation 10.7) [24]. Thus, in refluxing toluene, in the presence of a catalytic amount of RuCl(tris(pyrazolyl) borate) (pyridine)2, a 1 1 mixture of ally P-styryl ether and 2-phenylpent-4-enal was obtained in 72% overall yield. 

Although no intermolecular additions of allenylzinc reagents to unactivated alkenes or alkynes have been apparently reported, the related intramolecular processes led to the development of synthetically useful routes towards five-membered rings. 

By analogy with allylic organometallic compounds (see Section . ), the possibility of achieving intramolecular related zinc-ene reactions involving allenylzinc species acting as ene-components has been investigated. Such reactions benefit from favorable thermodynamics and were thus expected to proceed more readily than the related intermolecular additions of allenylzincs to alkynes or alkenes. 

As noted in the introduction, in contrast to attack by nucleophiles, attack of electrophiles on saturated alkene-, polyene- or polyenyl-metal complexes creates special problems in that normally unstable 16-electron, unsaturated species are formed. To be isolated, these species must be stabilized by intramolecular coordination or via intermolecular addition of a ligand. Nevertheless, as illustrated in this chapter, reactions of significant synthetic utility can be developed with attention to these points. It is likely that this area will see considerable development in the future. In addition to refinement of electrophilic reactions of metal-diene complexes, synthetic applications may evolve from the coupling of carbon electrophiles with electron-rich transition metal complexes of alkenes, alkynes and polyenes, as well as allyl- and dienyl-metal complexes. Sequential addition of electrophiles followed by nucleophiles is also viable to rapidly assemble complex structures. 

As a combined reaction of (3-cleavage of a cyclopropylcarbinyl radical and intermolecular addition, treatment of vinylcyclopropane (266) and activated alkyne in the presence of PhSSPh and AIBN forms a cyclopentene skeleton (267), through the initial addition of a thiyl radical to the vinyl group, P-cleavage of the cyclopropylcarbinyl radical, addition of the carbon-centered radical to the alkyne, ring closure of a vinyl radical via 5-exo-trig manner, and finally subsequent P-elimination of the thiyl radical, as shown in eq. 3.107 [272-276]. Here, PhSSPh acts as a catalyst, since the thiyl radical is regenerated. Aliphatic disulfides such as... 

Vinyl carbene intermediates can also be generated from the intermolecular addition of TMS diazomethane onto an alkyne component in the presence of Ni(cod)2 as a catalyst. If a diene moiety is also present, as in 1,6-enyne system 78, reaction of the intermediate nickel carbenoid with this partner gives birth to the fused 5,7-bicyclic system 79 in fair yields (Scheme 34). Several mechanistic scenarios are possible from generic precursor 78, including a metathesis-type sequence to generate a nickelacyclobutane 80, followed by... 

In 1967, Heiba and Dessau reported perhaps one of the earliest examples of a radical cychzation cascade that is initiated by intermolecular addition of C-centered radicals to alkynes. Reaction of carbon tetrachloride with 1-heptynes 1 in the presence of benzoyl peroxide (BPO) as radical initiator resulted, among other products, in the formation of 1,1-dichlorovinylcyclopentane derivatives 2 in moderate yields (Scheme 2.1). °... 

In contrast to intramolecular cyclizations, the intermolecular addition of O-centered radicals to ti systems as initiating step in complex radical cyclization cascades has only recently attracted considerable attention. The reason for the low number of papers published on O radical addition to alkenes and alkynes could originate from the perception that O-centered radicals, such as alkoxyl radicals, RO, or acyloxyl radicals, RC(0)0", may not react with 7t systems through addition at rates that are competitive to other pathways, for example, allylic hydrogen abstraction and p-fragmentation in the case of RO" or decarboxylation in the case of RC(0)0" (Scheme 2.9). 

The vast majority of radical cascades initiated by addition of higher main group (VI)-centered radicals to alkynes focus predominantly on S-centered radicals, mainly thiyl radicals, whereas considerably fewer intermolecular addition reactions involving radicals with the unpaired electron located on selenium or even tellurium are known. 

A diastereoselective formal addition of a 7ra i-2-(phenylthio)vmyl moiety to a-hydroxyhydrazones through a radical pathway is shown in Scheme 2.29. To overcome the lack of a viable intermolecular vinyl radical addition to C=N double bonds, not to mention a reaction proceeding with stereocontrol, this procedure employs a temporary silicon tether, which is used to hold the alkyne unit in place so that the vinyl radical addition could proceed intramolecularly. Thus, intermolecular addition of PhS" to the alkyne moiety in the chiral alkyne 161 leads to vinyl radical 163, which cyclizes in a 5-exo fashion, according to the Beckwith-Houk predictions, to give aminyl radical 164 with an a 7z-arrangement between the ether and the amino group. Radical reduction and removal of the silicon tether without prior isolation of the end product of the radical cyclization cascade, 165, yields the a-amino alcohol 162. This strategy, which could also be applied to the diastereoselective synthesis of polyhydroxylated amines (not shown), can be considered as synthetic equivalent of an acetaldehyde Mannich reaction with acyclic stereocontrol. 

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. 

Intermolecular additions of alcohols to alkynes can be coupled with other tandem reactions of the alkenyl-gold intermediate. Thus, reaction between salicylaldehyde and phenylacetylenes can give access to the isoflavanone skeleton (equation 7), whereas a three-component addition of methylenecylopropylcarbinols, arylalkynes, and alcohols leads to bicyclic compounds (equation 8). ... 

GansSuer et al. studied the tandem titanocene-mediated cyclization/inter-molecular addition to Michael acceptors [132]. After treatment with t-butyl acrylate in the presence of Zn, collidine hydrochloride and catalytic amounts of titanocene [133], epoxide 143 yielded the desired bicycUc product 144 in reasonable yield and high diastereoselectivity (Scheme 46). Remarkably, alkyne 145 led to the first example of an intermolecular addition involving a vinylic radical. The success of this reaction was attributed by the authors... 

Interestingly, the carbene precursors to 42a-c undergo competitive intermolecular addition to alkynes to provide vinylcyclopropenes (e.g. equation 17). The sulphur-... 

The intermolecular addition of a carbene to a cyclopropene to give a bicyclo-[l.l.OJbutane is not a viable synthetic method since products of ring cleavage are usually observed However, diazoalkane addition to a cyclopropene (or bis-addition to an alkyne) is known to occur and subsequent deazetation generally leads to bicyclobutane and diene by separate pathways. 

Intramolecular [ la + 2a) + 2n cycloadditions have been thoroughly investigated. The intramolecular version of the addition of alkynes to 3-heteraquadricyclanes (e.g, 1 and 4) is more selective than the intermolecular addition and gives higher yields of the cycloadduct, even with less electron-deficient alkynes. 

Intermolecular additions of silyl enolates to alkynes were introduced by Yamaguchi et al. (Scheme 10.102) [271]. In the presence of SnCl4 and I ujN reaction of SEE with terminal alkynes gives a,/ -unsaturated ketones wifh high E selectivity. 

Another conjugate addition, to the dehydroalanine derivative 38 on solid-phase, was reported by Yim et al. [19], Radical generation using t-butyl iodide and tribu-tyltin hydride afforded only 8% of the desired product, while better results were obtained with organomercurials (Scheme 8). The intermolecular addition of tosyl radicals to unactivated alkene and alkyne 39 has also been reported [20], and the reaction was found to be quite sensitive to solvent. Optimum results were obtained in toluene, although the scope is difficult to gauge with only two examples disclosed. 

A characteristic feature of the reactions of cyclic alkynes is the tendency to release ring strain by changing the hybridization at the alkyne carbons from sp to sp. This is achieved either by rearrangement reactions or by intra- or intermolecular addition reactions. 

The state of the art in catalytic intermolecular additions of carboxylic acids to terminal alkynes (Scheme 27) prior to 2000 has been reviewed by Dixneuf and Bruneau, who conclude that complexes [(p-cymene)RuCl2(PR3)] are catalysts for Markovnikov additions (toluene, 80-100°C), whereas [(dppb)Ru(methallyl)2] is the preferred catalyst for anti-Markovnikov hydrocarboxylations of alkynes with predominant selectivity for (Z)-enol esters (toluene, 50-60°C) [165, 166]. 

---