Unsymmetrical dienes

Unsymmetrical dienes in this synthesis are often capable of high regioselectivity (eqs. 4 and 5) (82). Reaction of (81) with 2-methoxycarbonyl-l,4-ben2oquinone [3958-79-0] yields 97% of (82) [80328-15-0]. Reaction of (81) with 2,3-dicyano-l,4-ben2oquinone [4622-04-2] yields 58% of (83) [80328-16-1]. 

HCl addition to unsymmetrical dienes can be even more complicated. For example, HCl addition to isoprene (2-methyl-1,3-butadiene) might give four different 1,2-addition products and three different 1,4-addition products. 

When used in conjunction with unsymmetrical dienes with substituents in the 2-position, the term tail addition has been used to refer to addition to the methylene remote from the substituent. Head addition then refers to addition to... 

When an unsymmetrical diene reacts with an unsymmetrical dienophile, two regioisomer adducts can be formed depending on the orientation of the substituents in the adduct [37] (Equations 1.16 and 1.17). 

The orbital interaction depicted in Scheme 1.15 shows that the two cr-bonds form at the same time but do not develop to the same extent. The Diels-Alder cycloaddition of unsymmetrical starting materials is therefore concerted but asynchronous. A highly unsymmetrical diene and/or dienophile give rise to a highly unsymmetrical transition state and a stepwise pathway can be followed. 

Conjugated dienes can be acylated by treatment with acyl- or alkylcobalt tetracarbonyls, followed by base-catalyzed cleavage of the resulting jt-allyl carbonyl derivatives. The reaction is very general. With unsymmetrical dienes, the acyl... 

When an unsymmetrical diene adds to an unsymmetrical dienophile, there are two regioisomeric products (not counting stereoisomers) ... 

In the case of an unsymmetrical diene such as isoprene, different orientations of the structural units are possible depending on which end of the diene unites with the chain radical. Of the two competing reactions (6) and (7) shown on page 241, the former would appear to be the more probable one on account of the influence of the methyl substituent in stabilizing to some extent one of the resonance hybrid structures which are shown. 

It was also well established that silenes could take part as the dienophile in Diels-Alder reactions. In many cases, particularly with unsymmetric dienes such as isoprene, the reactions were not clean because, in addition to formation of the [2+4] cycloadduct 61, the possibility exists for the formation of it regioisomer 62, products of an ene reaction 63, and conceivably the [2+2] cycloaddition product 64, as shown in Eq. (23). Wiberg... 

With unsymmetrical dienes (74a and 74b) and unsymmetrical adducts, the problem of orientation of addition (cf. p. 184) arises. Initial attack will still be on a terminal carbon atom of the conjugated system so that a delocalised allylic intermediate is obtained, but preferential attack will be on the terminal carbon that will yield the more stable of the two possible cations i.e. (75) rather than (76), and (77) rather than (78) ... 

Such a conclusion is, nevertheless, connected with the synchronous character of the mechanism. If a stepwise process is involved (nonsimultaneous formation of the two new bonds), as for unsymmetric dienes and/or dienophiles or in hetero Diels-Alder reactions, a specific microwave effect could intervene, because charges are developed in the transition state. This could certainly be so for several cycloadditions [47, 48] and particularly for 1,3-dipolar cycloadditions [49]. Such an assumption has... 

Reactions of unsymmetrical dienes and/or dienophiles have also been studied101 103 104. For these reactions ab initio calculations predict concerted non-synchronous mechanisms. The values of the potential energy barriers are very sensitive to the level of calculation and reasonable values are only obtained when electron correlation is included up to the MP3 level103. 

Diels-Alder reactions with unsymmetrical dienes and/or dienophiles can lead to the formation of different isomers. One of the most interesting aspects in these systems is stereoselectivity, observed in reactions involving cyclic dienes. In these cases, two different stereoisomers can be formed endo and exo. 

The symmetrical dienyne 58a was converted to a fused bicyclo [4.3.0] ring in 95% yield [17] (Eq. 27). With substrate 58c containing an unsymmetrical diene tether, two different products, 59c and 59c, were obtained in a ratio of 1 to 1 (Eq. 28). The reaction course in the formation of the different bicyclic rings is shown in Scheme 8. This dienyne metathesis is also catalyzed by tungsten or molybdenum complex 62 or 63 (Fig. 1), and a dienyne bearing terminal alkyne 58b could be cyclized to give 59b in 97% yield. 

Hydrolysis of zirconacyclopentadienes provides, in a stereocontrolled manner, 1,2,3,4-tetrasubstituted dienes 13. In particular, unsymmetrical diene derivatives 14 can be prepared by this method (Eq. 2.10) [14]. 

Other calculations were aimed at predicting the reactivity of some bicyclic 5-6 systems. For instance, the rare [l,4,2]diazaphospholo[4,5- ]pyridine 22 (Scheme 2) was examined for its reactivity (C=P bond) toward dienes in cycloaddition reactions <2005T10521>. The results of density functional theory (DFT) calculations were in good agreement with the experimentally obtained regioselectivity when using unsymmetrical dienes. 

Vinylidenecycloalkanones 125 undergo cycloadditions with 1,3-dienes in the presence of a Lewis acid catalyst to give spirocyclic dienones 126 [107]. Good regio- and stereoselectivities were observed for unsymmetrical dienes. 

The homo-coupling reaction of 1,1-dimethylallene proceeds at -50 °C to give a symmetrically substituted diene in good yield (Scheme 16.99) [105], In sharp contrast, the reaction of a monosubstituted allene proceeds via a titanabicycle to give an unsymmetrical diene. 

In the Diels-Alder reaction between an unsymmetrical diene and dienophile, up to eight stereoisomers can be formed (March, 1992a). It is known that the regioselectivity of the Diels-Alder reaction can be biased so that only the four ori/io-adducts are produced (Fig. 21) through increasing the electron-withdrawing character of the substituent on the dienophile (Danishefsky and Hershenson, 1979). However, stereochemical control of the Diels-Alder reaction to yield the disfavoured exo-products in enantiomerically pure form has proved to be very difficult. 

The regiochemistry of the addition of nitrosoarenes to unsymmetrical dienes has been discussed90. 

You may think that is the end of the problem but, since we have an unsymmetrical diene, it is also necessary to consider protonation of the other double bond. Protonation on C-4 also gives a favourable resonance-stabilized allylic carbocation, this time with primary and secondary limiting structures. Protonation on C-3 gives an unfavourable primary carbocation with no resonance stabilization. Since the products formed are related to initial protonation at C-1, it is apparent that, despite the stability associated with an allylic cation, a tertiary limiting structure is formed in preference to that with a secondary limiting structure. 

Photochemical [2 + 2] cycloadditions followed by vinylcyclobutane to cyclohexene rearrangements often yield the same products as the thermal Diels-Alder reactions. Strongly directing substituents on unsymmetrical dienes, however, may lead to constitutionally different isomers depending on the reaction path.19 21... 

Dihydropyrans and tetrahydropyrans add on alkenes when irradiated but some of the products are unstable. 3,3-Dimethylpyran-2,4-dione (664) and an unsymmetrical diene such as 2-methylprop-l-ene (665) give regiospecifically a 1 1 mixture of cis- and frans-fused pyran-4-one (666) (73T1317). Tetrahydropyran (667) does not undergo photoaddition unless a sensitizer such as benzophenone is present, but then it reacts with diethyl maleate (668) (67T3193). 

The insertion of 1,3-dienes into a ir-allylpalladium complex is believed to proceed via an intermediate in which the metal is complexed to the less hindered double bond of an unsymmetrical diene, followed by an electrocyclic rearrangement which links the more substituted allyl terminus with the more substituted alkene (equation 77).246-251 Electron-withdrawing substituents on the ir-allyl fragment generally increase the rate of insertion,248 whereas substituents on the diene generally slow the rate.268... 

In addition to the stereoisomers, already discussed, unsymmetrical dienes like piperylene 2.129 or isoprene 2.133 and unsymmetrical dienophiles like methyl acrylate 2.130 give two adducts, depending upon the orientation of the two substituents in the product. The selectivity for the formation of one... 

The asymmetric dihydroxylation of dienes has been examined, originally with the use of NMO as the cooxidant for osmium [56a] and, more recently, with potassium ferricyanide as the cooxidant [56b], Tetraols are the main product of the reaction when NMO is used, but with K3Fe(CN)6, ene-diols are produced with excellent regioselectivity. The example of dihydroxylation of trans.trans-1,4-diphenyl-1,3-butadiene is included in Table 6D.3 (entry 21). One double bond of this diene is hydroxylated in 84% yield with 99% ee when the amounts of K3Fe(CN)6 and K2C03 are limited to 1.5 equiv. each. Unsymmetrical dienes are also dihydroxy-lated with excellent regioselectivity. In these dienes, preference is shown for (a) a bans over a cis olefin, (b) the terminal olefin in a,p,y,8-unsaturated esters, and (c) the more highly substituted olefin [56b],... 

Regioisomerism in azide additions is also evident in unsymmetrical dienes with two unequally strained double bonds.89,92,144 Reaction occurs preferentially at the angle-strained double bond,25,81,89-92 and two isomeric exo-monotriazoline adducts are obtained.81,93 The ratios of the triazoline isomers from the reaction of phenyl azide and bicycloocta-2,6-diene, as deduced from their NMR spectra, indicate that the major isomer is the one that results from the terminal azido nitrogen attacking the olefinic carbon more removed from the unreactive double bond (Scheme 10).92 Similar reactions... 

Very few mechanistic studies have appeared on this subject and Houk group has studied the hetero-Diels-Alder reaction between thioformaldehyde and butadiene475, using ab initio calculations, to show that the reaction is concerted and nearly synchronous. In the case of unsymmetrical dienes, several rules are known to establish the regiochemistry of the cycloadducts1 471. 

Activated alkyl halides react with sodium thiosulfate to form the Bunte salts 438 which, on treatment with base, generate thiocarbonyl compounds <1984CC922>. Trapping with 1,3-dienes affords 3,6-dihydro-2-//-thiopyrans in satisfactory yields and in a one-pot reaction, although with unsymmetrical dienes the regio and diastereo selectivities are not good (Scheme 143) <1996JOC4725>. 

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