Cycloadditions of dienynes

The [Rh(NHC)Cl(COD)]/AgSbF6-catalysed intramolecular 4 + 2-cycloaddition of dienynes and the intramolecular 5 + 2-cycloaddition of alkyne vinylcyclopropanes formed the corresponding bicyclic cycloadducts in 91-99% yields within 10 min.8... 

RXN73 Tandem Cycloisomerization-Cycloaddition of Dienynes with 1,3-Dienes via Metallodienes... 

Scheme 2-68. [4+2] cycloaddition of dienynes catalyzed by cationic Rh complexes. 

Lewis-acid catalysis is effective in intermolecular as well as intramolecular /zomo-Diels-Alder reactions. Thus, complex polycyclic compounds 93 have been obtained in good yield by the cycloaddition of norbornadiene-derived dienynes 92 by using cobalt catalyst, whereas no reaction occurred under thermal conditions [91] (Scheme 3.18). 

Beside [2+2+2] cycloaddition, [4+2] and [5+1] cycloadditions represent other approaches for the construction of six-membered ring systems. In parhcular, the intermolecular and intramolecular [4+2] cycloadditions of diene and alkyne have been extensively studied, and a variety of transition-metal complexes-including those of Fe, Ni and Rh-have been reported as efficient catalysts. The first enanh-oselective reaction was achieved with a chiral Rh complex, although the substrates were limited to dienynes with a substituent on the diene terminus [36]. Later, Shibata and coworkers developed an intramolecular and enanhoselective [4+2] cycloaddition using an Ir-BDPP (l,3-bis(diphenylphosphino)pentane) complex (Scheme 11.24) [37], where dienynes with an unsubstituted diene terminus were transformed into bicyclic cyclohexa-1,4-diene with up to 98% ee. 

Further research on this subject was recently reported, in relation to the use of dienynes as substrates for intramolecular cycloaddition. While thermal intramolecular [4+2] cycloadditions of enynes with alkenes only took place at high temperatures, the gold(I) catalyzed transformations provided bi- or tri-cyclic ring systems under mild conditions [152]. 

J. Marco-Contelles, Synthesis of polycyclic molecules via cascade radical carbocycliza-tions of dienynes the first SnPh3 radical-mediated (2 + 2 + 2] formal cycloaddition of dodeca-l,6-dien-ll-ynes, Chem. Commun. (Cambridge), (1996)2629-2630. 

Alkynes are poor dienophiles in the Diels- Alder reaction decomposition occurs by an attempted thermal intramolecular Diels-Alder reaction of dienynes at 160 °C. In contrast, the Ni-catalysed [4+2] cycloaddition of the dienyne 50 proceeded smoothly at room temperature using tri(hexafluoro)isopropyl phosphite to give 51, which was converted to the yohimbine skeleton 52 [15]. The same reaction is catalysed by RhCl(Ph3P)3 in trifluoroethanol [16]. Intramolecular Diels-Alder reactions of the 6,8-dieneyne 53 and the 1,3,8-triene 55, efficiently catalysed by [Rh(dppe)(CH2CH2)2]SbF6 at room temperature, gave 54 and 56 [17],... 

Cyclization of dienynes.1 This Ni(0) catalyst in combination with a triarylphos-phite, particularly tri-o-biphenyl phosphite, permits intramolecular cycloaddition at 25° of [4+2] dienynes, in which the diene and the alkyne are separated by 3- and 4-atom units. This reaction is a useful route to products containing a cyclohexadiene group, which are oxidized to an arene by DDQ. 

Few examples from the literature show the viability of performing a 2 + 2, 4 + 2 or 5 + 1 cycloaddition combined with the PKR. An early contribution by Smit showed a photochemical 2 + 2 cyclization performed on PK product 178 which was obtained by selective reaction of dienyne 177. It is not clear from the work if product 179 is obtained in a one pot fashion or stepwise (Scheme 52) [169]. 

Fenestranes are compounds of theoretical interest in which the central carbon atom undergoes severe planarization distortion. Reactions sequences involving double intramolecular Pauson-Khand reactions of ene-diynes, or intramolecular Pauson-Khand of dienynes followed by photochemical [2 + 2] cycloaddition, successfully lead to [5.5.5.5]- or [4.5.5.5]fenestrane, respectively [42], For instance, compound 37 was obtained from ene-diyne 36 in moderate yield as a single all-czs stereoisomer [43] (Scheme 18). 

Lewis acid catalyzed versions of [4 4- 2] cycloadditions are restricted to functionalized dieno-philes. Nonfunetionalized alkenes and alkynes cannot be activated with Lewis acids and in thermal [4 + 2] cycloadditions these suhstrates usually show low reactivity. It has been reported that intcrmolecular cycloaddition of unactivated alkynes to dienes can be accelerated with low-va-lent titanium, iron or rhodium catalysts via metal-mediated - -complex formation and subsequent reductive elimination39 44. Usually, however, low product selectivities are observed due to side reactions, such as aromatization, isomerization or oligomerization. More effective are nickel-catalyzed intramolecular [4 4- 2]-dienyne cycloadditions which were developed for the synthesis of polycycles containing 1.4-cyclohexadienes45. Thus, treatment of dienyne 1, derived from sorbic acid, with 10mol% of Ni(cod)2 and 30 mol % of tris(o-biphenyl) phosphite in tetrahydrofuran at room temperature affords bicyclic 1,4-dienes 2, via intramolecular [4 + 2] cycloaddition, with excellent yield and moderate to complete diastereocontrol by substituents attached to the substrate. The reaction is sensitive towards variation in the catalyst and the ligand. 

Similarly, intramolecular [4 4- 2] cycloaddition of unactivated dienynes is also catalyzed and dramatically accelerated by low-valent rhodium complexes, e.g., Wilkinson s catalyst [chloro-tris(triphenylphosphane)rhodium] and phosphite analogs, under mild conditions46. Thus, ( , )-l-(2-propynyloxy)-2,4-hexadiene (3, Z = O) and similar dienynes, with 5 mol% of chlorotris(tri-phenylphosphane)rhodium in 2,2,2-trifluoroethanol for 30 minutes at 55 C. give up to quantitative yield of the cycloadducts with excellent to complete diastereoselection. According to control... 

The enantioselective intramolecular [2+2+2] cycloaddition of 1,4-dienynes 429 gave the bicyclo[2.2,l]heptene skeleton 430, accompanied by a small amormt of 431 (Scheme 2-43). For Ais reaction, dienynes cormecting the alkyne and the other alkene components with 1,1-disubstituted alkene moieties were employed. For this reaction, dienynes connecting the alkyne and the other alkene components with 1,1-disubstituted alkene moieties were employed. Each product of this reaction represents a unique class of cycloadducts that possess two quaternary carbon stereocenters. 

Shibata further expanded the scope of the [2+2+2] cycloaddition by varying the substitution pattern of dienyne 433 to form 5-6-5 tricyclic and 5-6-S-6 tetracyclic systems 434 with excellent enantioselectivity (up to 99% ee) (Scheme 2-45). ... 

In 2008, a gold-catalyzed cycloaddition of captodative dienynes with nitriles to provide pyridines was developed [114], The reaction proceeded via intermolecular hetero-dehydro-diels-alder cycloaddition and gave the desired pyridines in good yields regioselectively (Scheme 3.56). 

Sagae, H., Noguchi, K., Hirano, M., Tanaka, K. (2008). Rhodium-catalyzed enantio-and diastereoselective intramolecular [2+2+2] cycloaddition of unsymmetrical dienynes. Chemical Communication, 3804-3806. 

An elegant approach to a partial synthesis of chlorothricolide utilizes the cycloaddition of the dienyne (153), whilst the triene (154) was used in a... 

With a common nickel(O) catalyst, prepared by the reduction of Ni(acac)2 with Et2A10Et in the presence of tris(l,1,1,3,3,3-hexafluoro-2-propyl)phosphite, the dienyne undergoes stereo-controlled cycloaddition (eq 10). Nickel(O) also catalyzes intramolecular [4+2] cycloadditions of nitrogen-containing dienynes, providing a novel method for the synthesis of hydroisoquinolines (eq 11). A typical Ni(0) catalyst derived from Ni(cod>2 and tris(l,l,l,3,3,3-hexafluoro-2-propyl)phosphite at room temperature. 

Silyl-substituted diazomethanes are regarded as a silylcarbene precursor or as a diazomethane equivalent, as they coordinate, after loss of nitrogen, to transition metals to generate metal-carbene complexes and participate in a variety of metal-catalyzed reactions and the silyl substituent is readily lost in many cases after the total transformation. For example, nickel-catalyzed cycloaddition reactions of dienynes proceed with incorporation of a silylmethyl group to give seven-membered carbocycles having an allylsilane functionality (Scheme 3-69). ... 

Scheme 3-69. Nickel-catalyzed cycloaddition of trimetyl(diazomethyl)silane with dienynes.

The nickel(0)-catalyzed stereoselective intramolecular [4+ 2] cycloaddition between dienes and unactivated allenes or alkynes has been shown to be an efficient complement to the uncatalyzed concerted Diels-Alder reaction that often requires stereoelectronic restrictions. In a typical reaction, treatment of dienyne with 10 mol% Ni(COD)2 and 30mol% of tri-o-biphenyl phosphite at room temperature... 

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