1,5-allenynes

Caution-. Use rubber gloves during the work-up, the allenyne alcohol probably is a skin irritant. 

Allenynes 160 were also cyclized chemo- and regioselectively to methylen-eyclopentane derivatives 161 and 162 using Rh(acac)(CO)2 as the catalyst and silanes or alkoxysilanes as the reductant (Eq. 32) [96]. The major product resulted from initial insertion of the internal Jt-bond of the allene into the Rh-Si bond. Only 1,1-disubstituted allenes were used for this reaction others may show less selectivity for the internal Jt-bond of the allene. 

Extensions of the electrophilic activation of the alkyne moiety as well as an alkene moiety have been developed and applied. The applications include various reactions, for instance, Friedel-Crafts type alkylations,323 anchimeric assistance of heteroatomic moiety generally followed by rearrangements (see below), implementation of more sophisticated functional groups such as ynamides and allenynes, which are discussed below. 

Currently, these reactions are typically conducted with Rh(l) or Ir catalysts. The Pauson-Khand-type reaction of allenynes has also witnessed important developments, especially in its applications to natural products synthesis.388 Brummond s group has been very productive in both areas. Duality in the reaction of allenynes is shown below. In the context of diversity-oriented synthesis, simply changing the reaction conditions gives versatile heterocycles in high yields (Scheme 116).389... 

Catalysis of platinum dichloride has provided an intriguing panel of reactions of allenynes just by subtle modifications in the substitution pattern (Scheme 119). Thus, while the reaction of the allenyne 473 gives the previously unknown hydrindene product 474, the reaction of allenyne 475 that does not have a methyl group at the internal... 

Rhodium complexes catalyze hydrosilylation-cyclization of 1,6-allenynes in the presence of (MeO SiH.77 To avoid complex product distributions, the use of substrates possessing fully substituted alkyne and allene termini is imperative. As shown in the cyclization of 1,6-allenyne 62a, the regiochemistry of silane incorporation differs from that observed in the rhodium-catalyzed hydrosilylation-cyclization of 1,6-enynes (see Section 10.10.2.3.2). For allenyne substrates, allene silylation occurs in preference to alkyne silylation (Scheme 40). 

Malacria and co-workers76 were the first to report the transition metal-catalyzed intramolecular cycloisomerization of allenynes in 1996. The cobalt-mediated process was presumed to proceed via a 7r-allyl intermediate (111, Scheme 22) following C-H activation. Alkyne insertion and reductive elimination give cross-conjugated triene 112 cobalt-catalyzed olefin isomerization of the Alder-ene product is presumed to be the mechanism by which 113 is formed. While exploring the cobalt(i)-catalyzed synthesis of steroidal skeletons, Malacria and co-workers77 observed the formation of Alder-ene product 115 from cis-114 (Equation (74)) in contrast, trans-114 underwent [2 + 2 + 2]-cyclization under identical conditions to form 116 (Equation (75)). 

PtCl2 was shown to catalyze a similar Alder-ene transformation, as in the cycloisomerization of allenyne 117 to triene 118 (Equation (76)).78 In the same study, it was noticed that tetrasubstituted allenes cyclized to bicyclic compounds, such as 120 (Scheme 23), under identical PtCl2 conditions, presumably due to A(1,3) strain in intermediate 119. 

Brummond and Shibata independently reported the Rh(i)-catalyzed cycloisomerization of allenynes to cross-conjugated trienes. The rhodium conditions were shown to have broad functional group tolerance. Brummond et al 9 observed rate and selectivity enhancements when they switched to an iridium catalyst (Equation (77)). The rate acceleration observed in the Alder-ene cyclization of aminoester containing allenyne 121 (Equation (78)) was attributed to the Thorpe-Ingold effect.80... 

Thus far, the [5 + 2 + 1]-reaction works efficiently with alkynyl esters, amides, aldehydes, and ketones or an alkynyl-substituted allene44 as the two-carbon component (Scheme 58). Just as in the case of the [5 + 21-cycloaddition of VCPs and allenynes, the [5 + 2 + l]-reaction is selective for the allene over the alkyne subunit (Equation (35)). 

Distannation of allenynes initially takes place at the allene moiety (Scheme 34).159,161 Upon heating, the produced allylstannane moiety further undergoes palladium-catalyzed intramolecular allylstannation of the alkyne moiety, affording the corresponding cyclized product. 

Reaction of the stannylborane 9 with an allenyne gives a cyclization product, in which the boryl and stannyl groups are introduced to the acetylenic terminus and the allenic central carbon, respectively (Equation (104)).159 Based on the assumption that an unsaturated functionality initially inserts into the Pd-B bond of (boryl)(stannyl)palladium(n) species, it seems likely that the alkyne moiety is more reactive than the allene moiety in this reaction. 

Allenylcopper reagents can be generated from allenyllithium precursors by treatment with stoichiometric amounts of CuBr (Table 9.6) [12]. These intermediates were not characterized, per se, but subsequent reaction with alkenyl iodides led to allenynes in high yield. Thus it is assumed that the reagents are allenic rather than propargylic. The same intermediates afford 2-alkynylsulfmamides on treatment with N-sulfmylaniline (Table 9.7) [13], Cyclization to the N-phenyldihydroisothiazole S -oxides proceeds in nearly quantitative yield on treatment with base. 

The thermal [2 + 2]-cycloaddition of allenyne 68 was used for the preparation of a naphtho[a]cyclobutene skeleton 69 [66]. 

When a terminal alkyne is offered intramolecularly as in allenyne 108, the highly substituted phenols 110 were formed (Scheme 15.29) [65]. The reaction proceeds through an initial isomerization to the corresponding furan 109, which could be proved by the direct use of that furans [66-68],... 

In 1996, Malacria et al. [139] reported on cobalt-mediated reactions of the related allenynes. Heating the allenyne 222 in the presence of cpCo(CO)2 accompanied by a photochemical activation of this organometallic compound delivered the cross-conjugated trienes 223 (Scheme 15.71). The second triple bond present in the substrate did not participate in the reaction, underlining the higer reactivity of the allene unit. 

Furthermore, PtCl2 prove to be active for the conversion of allenynes. New types of products are then observed. Depending on the substrate, here either the cross-conjugated 236 or the bicylic 1,3-dienes 238 are the products (Scheme 15.74) [144]. 

Wilkinson s catalyst also allows the intramolecular cycloisomerization of allenynes 243 to interesting cross-conjugated trienes 244 (Scheme 15.76) [146], Similar compounds are observed as side-products in Pauson-Khand reactions of allenynes [147]. 

Narasaka and co-workers found that the PKR of an allenyne proceeds at room temperature under atmospheric pressure of CO, affording a bicyclo[4.3.0]nonane skeleton (Scheme 16.46) [47]. 

The promoter is also effective for the intramolecular PKR of following hexacarbo-nyldicobalt complexes of a,a>-allenynes (Scheme 16.49) [54],... 

Livinghouse and co-workers reported that a (methythio)alkyne is a superior substrate for Co2(CO)8-catalyzed PKR of allenynes (Scheme 16.50) [55]. 

Scheme 16.72 Ti-mediated allenyne cyclization followed by condensation with an aldehyde.

Ti-mediated cyclization of an allenynes having a leaving group provides a five-membered ring with cross-conjugated trienes which might be produced by the elimination of an alkoxy group from a titanacycle (Scheme 16.73) [79]. 

A cobalt-mediated formal Alder ene reaction of an allenyne takes place to give a mixture of adducts and ( 4-cycloliexadiene)cobalt complexes (Scheme 16.77) [88], The reaction may proceed via coordination and ensuing jt-allyl complex formation. 

Allenyne represents an interesting substrate for the intramolecular Pauson-Khand(-type) reaction, where an allene moiety acts as an ene component. Here, there are two possible reaction pathways (Scheme 11.21) (i) the reaction of an external tr-bond of allene moiety gives a bicyclic dienone (type A) or (ii) the reaction of an internal 7i-bond gives a bicyclic cyclopentenone with an alkylidene substituent (type B). 

Although all of the reported Rh-catalyzed reactions of allenynes were of type A, an Ir catalyst resulted in a different regioselectivity. That is, when allenynes with two substituents on the allene terminus were used under a low partial pressure of CO, the type B reaction proceeded exclusively such that bicyclic cyclopentenones with an aLkylidene substituent were obtained (Scheme 11.22) [34]. However, when [RhCl(CO)(PPh3)2] was used as a catalyst under the same reaction conditions in place of [IrCl(CO)(PPh3)2], the type A reaction was predominant These results imply that the metal centers of the catalysts control the regioselectivity of two ole-finic moieties of allene to some extent... 

The key step employed a rhodium(l)-catalysed allenic Pauson-Khand reaction to generate the tricyclic ring system 276 from the allenyne 275. However, all attempts to introduced the missing methyl group by a 1,4-addition protocol failed to provide the completed neodolastane framework. Allenyne 275 was synthesized from the enone 274 by a multistep procedure. The quaternary atom was constructed by sequential enolate alkylations. 

The mechanism proposed for this allenic Alder-ene reaction is shown in Scheme 8.3. The rhodium] I) catalyst coordinates with the allenyne V forming intermediate VI, which undergoes an oxidative addition to form the metaUocycle VII. The metaUocycle then undergoes a /9-hydride elimination producing triene intermediate VIII, which... 

Evidence for this mechanism includes (1) an experiment showing a 4.5% nOe between and of the triene in Eq. (14), validating the -stereochemistry of the exo-cyclic olefin and (2) preparation of a hexadeuterated allenyne that was subjected to the reaction conditions which gave complete transfer of a deuterium atom to the exocyclic double bond of the triene (Eq. 15). 

---