Cyclization of trienes

In addition to the stepwise mechanism, Dautzenberg and Platteeuw proposed another platinum-catalyzed cyclization mechanism (23). This might correspond simply to a disguised stepwise aromatization where the further reaction of unsaturated intermediates is very rapid compared with their desorption. Thus, hydrogen pressure would govern the probability of desorption versus further reaction. Since the cyclization of triene is irreversible, a very low steady-state surface triene concentration must be sufficient to ensure a measurable reaction rate. 

Cyclization of trienes.1 In combination with 2,2-bipyridyl (bpy), an iron(O) species prepared by reduction of iron(III) 2,4-pentanedionate with A1(C2H5)3 (3 equiv.) promotes cyclization of trienes (1) in which a 1,3-diene unit is tethered to an ally lie or homoallylic ether group. vic-Disubstituted cyclopentanes or cyclohexanes are formed, and the cisltrans disposition of the substituents is controlled by the geometry of the allylic double bond. Thus (Z,E-)1 is cyclized to trans-2, whereas (E,E)-1 is cyclized to cis-2. 

The limitation to die widespread synthetic use of the thermal or photochemical cyclization of trienes are twofold the difficulty in preparing the starting, geometrically correct triene array and the periselec-dvity (i.e. the competition widi other reactions occurring from he same substrate). Much of the following discussion is limited to the latter topic although it must be recognized that an efficacious synthesis of... 

Iron complexes can also be employed for ene cyclization of triene systems (Scheme 26). Though a chiral bisoxazoline complex exhibits not only higher 1,3-stereoinduction but also diastereoselectivity, no asymmetric induction was observed by the use of chiral bisoxazoline iron complex [70]. 

Scheme 26. Ene-type cyclization of triene system catalyzed by iron complex...

The study of simple model compounds confirmed that the thermal cyclization of trienes was disrotatory (Scheme 2.8). 

Brown et al. also carried out the synthesis of membrarollin (Scheme 48) [48]. Following the oxidative cyclization of triene 179 to give 180, dihydroxylation of the remaining olefin and a subsequent orflioformate-initiated cyclization of 182 gave the second tetrahydrofuran ring of membrarollin as 183. 

The cyclization of the enediynes 110 in AcOH gives the cyclohexadiene derivative 114. The reaction starts by the insertion of the triple bond into Pd—H to give 111, followed by tandem insertion of the triple bond and two double bonds to yield the triene system 113, which is cyclized to give the cyclohexadiene system 114. Another possibility is the direct formation of 114 from 112 by endo-rype. insertion of an exo-methylene double bond[53]. The appropriately structured triyne 115 undergoes Pd-catalyzed cyclization to form an aromatic ring 116 in boiling MeCN, by repeating the intramolecular insertion three times. In this cyclization too, addition of AcOH (5 mol%) is essential to start the reaction[54]. 

Aqueous hydrofluoric acid dissolved in acetonitrile is a good catalyst for intramolecular Diels-Alder reactions [9] This reagent promotes highly stereoselective cyclizations of different triene esters (equation 8) The use of other acids, such as hydrochloric, acetic, and trifluoroacetic acid, results in complete polymerization of the starting trienes [9] (equation 8)... 

Figure 30.7 Photochemical cyclizations of conjugated dienes and trienes. The two processes occur with different stereochemistry because of their different orbital symmetries.

Recently reported289 is an analogous reaction involving the acid-catalyzed cyclization of (lZ,3 ,5Z)-l,6-diphenylhexa-l,3.5-triene-l,6-diamine (14) in refluxing toluene to 2,7-diphenyl-3//-azepine (15). The l,6-bis(4-tolyl) and 1,6-dibenzyl derivatives behave similarly, but give substantially lower yields (14-18%). 

In intramolecular Diels-Alder reactions, two rings are formed in one step. The reaction has been used to synthesize a number of interesting ring systems.29 The intramolecular cyclization of ( )-l-nitrodeca-l,6,8-triene at 80 °C affords an endo cycloadduct with the tram ring fusion preferentially, as shown in Eq. 8.18. In contrast, (Z)-nitroalkenes produce a nearly 1 1 mixture of cis- and tra/w-fused cycloadducts.30... 

It will be clear from the results so far presented that both C5 and C dehydrocyclization products can be formed, with aromatization proceeding (one would expect) by further dehydrogenation of the initially formed C6 ring-closure species. There is another pathway for the production of aromatics based upon cyclization of a linear triene (133), but this is of relatively small importance, and is only significant at all at quite high temperatures and low hydrogen partial pressures. 

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... 

The asymmetric cascade cyclization-hydrosilylation of triene 89 under similar conditions gave bicyclopentane derivative 90 in a high yield, although the enantioselectivity was diminished (Scheme 29).84b... 

In parallel investigations, Danishefsky and coworkers accomplished the preparation of the 16-membered lactone of a model epothilone system via an alternative C9,C10 disconnection [14] (Scheme 4). In this case, coupling of epoxy-alcohol 17 with acids 18a and 18b afforded trienes 19a and 19b respectively. RCM of 19a under the influence of ruthenium initiator 3 produced dienes 20a as a 1 1 mixture of Z -isomers. Under identical conditions, cyclization of 19b produced a single product 20b (tentatively assigned as the Z-isomer). The variable stereoselectivity observed in these reactions was inconsequential since the olefinic functionality could be reduced to afford the corresponding saturated macrolactones. Schrock s molybdenum initiator 1 promoted the cyclization of 19a and 19b with similar efficacy [14]. 

Fig. 1 summarizes cyclizations of the two prototype molecules, (Z) hex-3-ene-l,5-diyne and (Z) hept-3,5,6-triene-l-yne. In all of these processes, bonds are formed from in-plane 7t-orbitals in the presence of an orthogonal 7i-system. However, it is clear that the properties of the newly formed cyclic conjugated systems can be quite... 

Diels-Alder catalysis.1 This radical cation can increase the endo-selectivity of Diels-Alder reactions when the dienophile is a styrene or electron-rich alkene. This endo-selectivity obtains even in intramolecular Diels-Alder reactions. Thus the triene 2, a mixture of (Z)- and (E)-isomers, cyclizes in the presence of 1 to 0° to the hydroindanes 3 and 4 in the ratio 97 3. Similar cyclization of (E)-2 results in 3 and 4 in the ratio 98 2 therefore, the catalyst can effect isomerization of (Z)-2 to (E)-2. Even higher stereoselectivity is observed when the styrene group of 2 is replaced by a vinyl sulfide group (SC6H5 in place of QHtOCT ). 

An interesting approach to carbobicyclic polyhydroxylated compounds was proposed by Jarosz.43 It was based on a Lewis acid transformation of sugar allyltins 82 into dieno-aldehydes 83 with the fi-geometry across the internal double bond exclusively. The Wittig-type reaction of 83 afforded a triene, which underwent cyclization under high pressure, providing derivatives of bicyclo[4.3.0]nonane 84. Alternatively, dienoaldehyde 83 was converted into the phosphonate 85, which afforded the bicyclo[4.4.0]-decene derivatives (86) upon reaction with an aldehyde and simultaneous cyclization of the resulting triene.43 (Fig. 29). 

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]. 

The process is much more rapid over platinum. Dautzenberg and Plat-teeuw (23) assumed the formation and thermal cyclization of hexatriene [similarly to the earlier suggestion with respect to oxides (22)]. However, it is not likely that such an extremely unstable intermediate would leave the catalyst surface just in order to cyclize and then rapidly readsorb to complete aromatization. Still, thermal cyclization cannot be a priori excluded at high temperatures where the equilibrium concentration of triene is higher and its adsorptivity lower, but its appearance may be rather exceptional. We suggest, instead, a surface cyclization step of dj-l,3,5-hexatriene. 

Essentially the same triple peak system also appeared with Pt-black, but the entire spectrum was shifted toward lower temperatures (r ,a,j = 155°, 175°, and 195°C, respectively). 7>a s-hexatriene gave the same spectrum, but with cw-triene a fourth, low-temperature peak appeared at 140°C. This should correspond to the facile cyclization of cij-triene. The fact that a peak of similar appears when benzene is desorbed from the catalyst is another strong argument against the purely thermal (noncatalytic) character of cyclization of c/s-l,3,5-hexatriene. 

Two different pathways lead from arachidonate to prostaglandins, prostacyclins, and thromboxanes, on the one hand, or leuko-trienes on the other. The key enzyme for the first pathway is prostaglandin synthase [2]. Using up O2, it catalyzes in a two-step reaction the cyclization of arachidonate to prostaglandin H2, the parent substance for the prostaglandins, prostacyclins, and thromboxanes. Acetylsalicylic acid (aspirin) irreversibly ace-tylates a serine residue near the active center of prostaglandin synthase, so that access for substrates is blocked (see below). 

McDonald and coworkers studied a series of tandem endo-selective and stereospecific oxacyclization of polyepoxides by reaction with Lewis acid [92-95]. Polyepoxides, such as 50, can be obtained from the epoxidation of triene 49 with ketone 26 (Scheme 8). This cascade cyclization of polyepoxides provides an efficient method to synthesize substituted polycyclic ether structures, which are present in a number of biologically active marine natural products. 

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