Cyclic substrates, 1,3-dienes

Conjugated dienes can be epoxidized to provide vinylepoxides. Cyclic substrates react with Katsuki s catalyst to give vinylepoxides with high ees and moderate yields [17], whereas Jacobsen s catalyst gives good yields but moderate enantiose-lectivities [18]. Acyclic substrates were found to isomerize upon epoxidation (Z, )-conjugated dienes reacted selectively at the (Z)-alkene to give trans-vinylepoxides (Scheme 9.4a) [19]. This feature was utilized in the formal synthesis of leuko-triene A4 methyl ester (Scheme 9.4b) [19]. 

The reaction also tolerated the thiol group on the cyclic substrate butylthio-cyclooctene 37 was ring-opened in the presence of an excess of ethene to give a good yield of the diene 38 (Eq. 30). 

Use of a symmetrical acyclic alkene limits the possible metathesis products to the desired diene (for example 45) and products formed from polymerisation of the cyclic substrate. Competing ROMP was suppressed in these reactions by using dilute conditions and a tenfold excess of hex-3-ene. By adding the cyclic substrate slowly to a solution of the catalyst and ris-hex-3-ene (which was significantly more reactive than the trans isomer), less than two equivalents of the acyclic alkene were used without causing a significant drop in the cross-metathesis yield. 

This control, however, can be tested only in acyclic dienes, which lack of the conformational rigidity of cyclic substrates. Loss of the stereochemical information could be due to isomerization of the starting diene [18b,19c], to two-step processes [18], or to the reversible formation of an exciplex which, depending on the substrate structure, may have a zwitterionic and/or diradical character [19]. 

Allenic hydrocarbons, including cyclic ones, underwent chlorine addition under radical conditions only one double bond reacted [12], A number of conjugated dienes added chlorine in their reaction with (dichloroiodo)benzene under radical conditions. Both 1,2- and 1,4-addition occurred their ratios varied, depending on the substitution of the non-cyclic substrate and the size of the cyclic ones trans products were normally favoured [13]. 1,6-Dienes were cyclized to 1,2-bis chloromethyl cyclopentanes [14] ... 

Hetero-Diels-Alder Reactions of Aldehydes. Cyclic conjugated dienes, such as 1,3-cyclohexadiene, are excellent substrates for the hetero-Diels-Alder reaction with ethyl glyoxylate catalyzed by Cu[(5, 5 )-t-Bu-box] (OTf)2 (eq 7). The rate of this reaction is dependent on the counterion and the solvent. To obtain... 

Disubstituted peroxides are cleaved reductively by the same reagents as are used for hydroperoxides. The usual products are alcohols derived from the two substituents, but considerable selectivity is possible with some substrates. This is illustrated by the reduction of cyclic endoperoxides of the general formula (50) these compounds are available from the cycloaddition of singlet oxygen to cyclic conjugated dienes. The reduction of such compounds provides a good method of synthesis of cis-1,4-diols, which can be formed with retention of the double bond or with reduction of it (Scheme 29). It is also possible to prepare unsaturated epoxides by reduction with triphenylphosphine or other phosphorus(III) reagents. 

Lest the reader think, given the examples presented thus far, that the reaction is confined to cyclic substrates, acyclic systems also participate rather effectively in the DPM process and thus highlighting its generality. Particularly notable open-chain substrates used in the early stages of the study of the DPM rearrangement were the hexa-substituted 1,4-dienes 11 (the... 

Given the need for photoactivation, an often encountered additional requirement for substrates participating in DPM reactions is the presence of a strong chromophore as provided, for example, by the presence of a phenyl group on at least one of the double bonds. In acyclic 1,4-dienes, the central sp -hybridized carbon normally needs to be tetrasubstituted otherwise, competing 1,2-hydrogen shifts can occur. This requirement does not apply, however, to those cyclic substrates where isomerization would lead to an anti-Bredt olefin (as would be the case for the conversion of barrelene to semibullvalene, 6 7, shown in Scheme 9.2). 

Anderson and Aranyos documented the alkoxycarbonylation of hydroxy 1,3-dienes 8 however, they used stoichiometric amounts of Pd(OAc)2 (Scheme 12). At first, the substrates react with Pd(II) to form an intermediate 7r-allylpaUadium complex 9, which is subsequently carbonylated to give either the 1,2- or the 1,4-addition product (10 and 11). With acyclic substrates the selectivity is 95 5 in favor of the 1,4-addition product (Scheme 13). In the case of cyclic substrates, however, the selectivity depends on the solvent and the CO pressure. The best results with 8 were obtained in a THF/DMF mixture (1 1) and a CO pressure of 1 atm to give a 4 1 mixture in favor of the 1,4-addition product 11. 

Another interesting transformation is the intramolecular metathesis reaction of 1,6-enynes. Depending on the substrates and catalytic species, very different products are formed by the intramolecular enyne metathesis reaction of l,6-enynes[41]. The cyclic 1,3-diene 71 is formed from a linear 1,6-enyne. The bridged tricyclic compound 73 with a bridgehead alkene can be prepared by the enyne metathesis of the cyclic enyne 72. The first step of... 

The MT0/H202/pyridine system enjoys a broad substrate scope and has become the method of choice for the epoxidation of di-, tri-, and tetrasubstituted olefins. As an added benefit, it gives high diastereoselectivities for a number of cyclic dienes (Table 12.1). 

C12-C13 would facilitate the ring closure, monocyclic diene 170 was chosen as the metathesis substrate. Indeed, exposure of 170 to catalyst A provided cycliza-tion product 171 in 94% yield within 6 h, without the aid of a cyclic conformational constraint. 

Helmchen and coworkers employed a,co-amino-1,3-dienes as substrates [51]. By using palladium complexes with chiral phosphino-oxazolines L as catalysts, an enantiomeric excess of up to 80 % was achieved. In a typical experiment, a suspension of Pd(OAc)2, the chiral ligand L, the aminodiene 6/1-90 and an aryltriflate in dimethylformamide (DMF) was heated at 100 °C for 10 days. Via the chiral palladium complex 6/1-91, the resulting cyclic amine derivative 6/1-92 was obtained in 47% yield and 80% ee (Scheme 6/1.23). Using aryliodides the reaction time is shorter, and the yield higher (61 %), but the enantiomeric excess is lower (67% ee). With BINAP as a chiral ligand for the Pd°-catalyzed transformation of 6/1-90 and aryliodide, an ee-value of only 12% was obtained. 

The substrate 139 reacts with phenylsulphenyl chloride, affording cyclic phos-phonium salt 143 which decomposes on heating to the corresponding 1,3-diene (Scheme 58) [107],... 

Ketone p-toluenesulphonyl hydrazones can be converted to alkenes on treatment with strong bases such as alkyl lithium or lithium dialkylamides. This reaction is known as the Shapiro reaction68. When w./i-LinsaUi rated ketones are the substrates, the products are dienes. This reaction is generally applied to the generation of dienes in cyclic systems where stereochemistry of the double bond is fixed. A few examples where dienes have been generated by the Shapiro reaction have been gathered in Table 669. 

The first approach involves RCM of a polymer bound diene 77 and results in the formation of a cyclic product 78 which remains attached to the polymer support. This product can undergo further manipulation, with cleavage from the resin occurring at a later stage. In a second, complementary approach, RCM proceeds with concomitant cleavage of the substrate from the resin (80 81). The latter protocol is highly attractive since only compounds possessing the correct... 

Catalytic ring-closing metathesis makes available a wide range of cyclic alkenes, thus rendering a number of stereoselective olefin functionalizations practical. The availability of effective metathesis catalysts has also spawned the development of a variety of methods that prepare specially-outfitted diene substrates that can undergo catalytic ring closure. The new metathesis catalysts have already played a pivotal role in a number of enantioselective total syntheses. 

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