Trienes, cross-conjugated

The orbital phase is continuons in the linear conjugate triene and discontinuous in the cross-conjugate trine. The electron delocalization between the terminal bonds is favored in the linear triene and disfavored in the cross-conjugate triene. The linear triene is more stable. The continuity-discontinuity of orbital phase underlies the thermodynamic stabilities of non-cyclic conjugated molecules. 

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)). 

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... 

If the alkenes and acetylenes that are subjected to the reaction mediated by 1 have a leaving group at an appropriate position, as already described in Eq. 9.16, the resulting titanacycles undergo an elimination (path A) as shown in Eq. 9.58 [36], As the resulting vinyltitaniums can be trapped by electrophiles such as aldehydes, this reaction can be viewed as an alternative to stoichiometric metallo-ene reactions via allylic lithium, magnesium, or zinc complexes (path B). Preparations of optically active N-heterocycles [103], which enabled the synthesis of (—)-a-kainic acid (Eq. 9.59) [104,105], of cross-conjugated trienes useful for the diene-transmissive Diels—Alder reaction [106], and of exocyclic bis(allene)s and cyclobutene derivatives [107] have all been reported based on this method. 

Cross-conjugated trienes have attracted interest in polymer chemistry and theoretical chemistry as well as in synthetic chemistry.11 Although a palladium complex catalyzed 1,2-propadiene dimerization in the presence of water or an amine produced hydroxylated or aminated 2,3-dimethyl-2,3-butadiene,12 the method was not applied to the synthesis of cross-conjugated trienes. Another interesting feature... 

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. 

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]. 

A rhodium-catalyzed allenic Alder ene reaction effectively provides cross-conjugated trienes in very good yields (Scheme 16.70) [77]. The reaction most likely involves ft -hydride elimination of an intermediate rhodium metallacycle to afford an appending olefin and ensuing reductive elimination of a metallohydride species to give the exocyclic olefin. 

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]. 

Scheme 16.73 Stereoselective preparation of cyclic cross-conjugated trienes.

Vinyl iodide coupled to 1 gave the rather sensitive and reactive cross-conjugated diene 243 in 37-43% yield. When a dienophile 244-R was added to the reaction mixture prior to work-up, the corresponding monoadducts of type 247 were isolated in 15-65% yield. Heating a mixture of 1, vinyl iodide, and a dienophile 244-R in the presence of palladium catalyst yielded the corresponding bisadducts 250 resulting from a domino Diels-Alder addition onto the cross-conjugated triene 243 (Scheme 57) [147,148]. 

Brummond [28] was the first to illustrate that cross-conjugated trienes could be obtained via an allenic Alder-ene reaction catalyzed by [Rh(CO)2Cl]2 (Eq. 14). Selective formation of the cross-conjugated triene was enabled by a selective cycloisomerization reaction occurring with the distal double bond of the aUene. Typically directing groups on the allene, differential substitution of the aUene termini, or intramolecularization are required for constitutional group selectivity. However, rhodium(f), unlike other transition metals examined, facihtated selective cyclization with the distal double bond of the allene in nearly aU the cases examined. 

The cross-conjugated trienes have potential in many different types of diversification strategies. For example, the triene clearly lends itself to inter- and intramolecular Diels-Alder reactions. Incorporation of the hydroxymethyl group on the tether allows attachment of functionality suitable for reactions subsequent to the Alder-ene reactions. As depicted in Scheme 8.5, propargyl tosylamides A, alkynyl silanes B, acrylate esters C, and propargyl ethers D can all be readily prepared from 39... 

The ether-tethered allenyne 4 is converted into a cross-conjugated triene, the 5,6-dihydro-2tf-pyran 5, in a Rh-catalysed allenic Alder ene reaction <02JA15186> and allylic halides undergo a Pd-catalysed coupling reaction with 3,4-allen-l-ols to give 5,6-dihydro-2//-pyrans (Scheme 2) <02JOC6104>. 

Furthermore, azo dienophiles have been employed in diene-transmissive hetero Diels-Alder reactions of cross-conjugated trienes which allow the straightforward construction of polycyclic compounds [297]. Theoretical interest has been directed to the hetero Diels-Alder reaction of diethyl azo di-carboxylate with 1,3-cyclohexadiene whose concerted course was demonstrated by means of a high pressure study [298]. 

Surprisingly few examples of the use of allenes as the ene components in ene reactions have been reported. In a series of papers, Taylor and coworkers reported that alkylallenes undergo thermal ene reactions with DMAD, hexafluoro-2-butyne and 3,3,3-trifluoropropyne to give cross-conjugated trienes. Similar reactions occur between allenes and hexafluoroacetone and electron-deficient azo compounds. " ... 

Scheme 3-16 A Heck reaction cascade forming cross-conjugated trienes [54, 69a]. A — Pd(OAc)2, PPha, DMF, 80 °C. B = [Pd2(dba)3 CHCI3], TOTP, HO Ac, QHe, 20 C = PdCOAc), PPhj, Phi,...

Another type of reductive cyclization is the conversion of allenyl derivatives containing a remote alkyne unit, leading to cyclic cross-conjugated trienes. ... 

The cross-conjugated triene 10 afforded two products the unstable adduct 11 from addition to the more highly substituted double bond predominated. ... 

Woo, S., Squires, N., Fallis, A. G. Indium-mediated "i-pentadienyla-tion of aldehydes and ketones cross-conjugated trienes for diene-transmissive cycloadditions. Org. Lett. 1999,1, 573—575. 

The ynallenes 15 undergo a Rh-catalysed Alder-ene reaction which produces the cross-conjugated triene. Addition of a different Rh catalyst promotes an intramolecular DA reaction and an oxatricycle results which can take part in a further cycloaddition with added dienophiles. The consequence of this one-pot three step sequence is the construction of a partially reduced 2-oxapyrene <05T6180>. 

Selective hydrogenation of vinylacetylenes to dienes is more difficult than selective hydrogenation of an isolated triple bond, except if the triple bond is in a terminal position. Cross-conjugated trienes can be obtained from 7 after partial hydrogenation over deactivated Pd-on-CaC03 ... 

CycUzation. Another pattern of cyclization for 1,5-diynes is revealed for the Rh-catalyzed process. The products have a hve-membeied ring adorned with the cross-conjugated triene system. ... 

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