Dienynes intramolecular cycloaddition

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]. 

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. 

The all-carbon dienynes 28a-d and 30a-c were prepared and their intramolecular cycloadditions studied (Schemes 18 and 19). No reaction was observed upon treatment of 28a at 150 °C in the absence of the catalyst. However, under cobalt-catalyzed conditions, cycloadditions occur smoothly. 

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. 

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... 

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],... 

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... 

Similarly, enynes substituted at the alkyne with an aryl group led to products resulting from a formal intramolecular [4 + 2] cycloaddition occurring at an unusual low temperature (equation 64). On the other hand, substrates with = H or = Me, R = H gave cyclobutenes with Au(i)25,34 qj. catalysts. Dienynes react with cationic Au(I) catalysts leading to products of formal [4 + 2] cycloaddition as well (equation 65). Somewhat related cyclizations of allenes with alkynes and diynes have been described. 

A Rh-catalyzed intramolecular [3 + 2 + 2] cycloaddition afforded synthetically relevant 5,7,5-fused tricyclic sy -cycloadducts from readily available dienyne precursors with high diastereo- and chemoselectivity (14CEJ10255). 

The scope of Pauson-Khand type reactions has been expanded by exploring the use of various carbon components. Dienyne 350 is a versatile substrate, which can be subjected to two cycloaddition pathways (Scheme 2-21). In 2003, Wender et al. reported the Rh-catalyzed PK-type reaction of350. Under unoptimized conditions, 350 underwent three competing cycloadditions, i.e., 1) an intramolecular [4+2] cycloaddition to afford product 351, 2) a new version of a [2+2+1] cycloaddition to afford product 352, and 3) an unprecedented [4+2+1] cycloaddition to afford product 353. After further refinement, the [2+2+1] product 352 was obtained in excellent yield.t >... 

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. 

A control reaction using 1,3-dienyne 432, which was obtained by double bond isomerization of 1,4-dienyne 429, did not proceed at all even under reflux conditions (Scheme 2-44). This result suggested that bicyclic compound 431 was, indeed, formed through metallcycle C and not through the intramolecular [4+2] cycloaddition pathway. 

The first intramolecular Rh-catalyzed [4+2] cycloaddition was reported by Livinghouse and co-workers in 1990 (Scheme Ether-tethered dienyne... 

Dienyne cycloadditions afford cyclohexene rings bearing 1-4 potential stereogenic centers. In this field, ene-yne-ene [2-1-2-I-2] cycloaddition was achieved enantioselectively thanks to the use of cationic rhodium in the presence of chiral ligands [10]. The related enantioselective ene-ene-yne cycloaddition challenge was first overcome intramolecularly by Shibata in 2006 with concomitant formation of two quaternary stereogenic centers (Scheme 7.6) [11]. 

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. 

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. 

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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