Dienynes, 4 + 3 + 2-cycloaddition

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. 

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]. 

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]. 

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... 

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. 

P Volume 1,1991,283 pp. 109.50/ 69.50 ISBN 1-55938-180-9 CONTENTS Introduction to the Series An Editor s Foreword, Albert Padwa. Preface, Brian Halton. Strain in Organic Chemistry A Perspective, Brian Halton. Gem-Dihalocyclopropanes in Chemical Synthesis, Martin G. Banwell and Monica E. Re-um. 1-Halo- and 1, 2-Dihalocyclopropenes Useful Synthetic Intermediates, Mark S. Baird. Cyciization and Cycloaddition Reactions of Cyclopropenes, Albert Padwa and Glen E. Fryx-ell. New Synthetic Pathways From Cyclobutanones, Edward Lee-Ruff. Cyclic Alkynes, Enynes and Dienynes A Synthetic Challenge, Herbert Meier. Index. 

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). 

Au(I) " or Pt(II) 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 more complex mechanism via enyne cyclization and metathesis followed by metalladiene cycloaddition is discussed in the formation of bicyclo[3.1.0]hexanes from dienynes and dienes in the presence of a palladacyclopentadiene catalyst. ... 

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... 

Cycloaddition. Cyclopropanation of the double bond(s) in dienynes is observed, with the ip-hybridized carbon atom(s) behaving like carbene(s). The transformation is highly efficient while giving intriguing polycyclic isomers. ... 

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

The intermediacy of the cyclic allene was also demonstrated by a different trapping experiment. Pyrolysis of the dienyne in the presence of styrene gave, among many other products, the two 2 -h 2 cycloaddition product of the cyclic allene." ... 

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. 

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). ... 

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

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

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