1,3-Butadienes, stereoselective synthesis

Similarly, cycloaddition of the cyclohexenone-like dienophile 40 with 2-tri-methylsilyloxy-1,3-butadiene (41) allowed [7] the regio- and stereoselective synthesis of tetracyclic compound 42, in high yield (Equation 5.5). 

The seco-phenanthroindolizidine alkaloid septicine has been synthesized by a nitrone route. A cycloaddition of 1-pyrroline 1-oxide with 2,3-bis-(3,4-dimethoxyphenyl)butadiene gives two stereoisomeric isoxazolidines, one of which is converted into ( ) septicine.10 ( )-Tylophorine and 5-coniceine have been prepared by a new route that makes use of an intramolecular imino-Diels-Alder reaction.11 A stereoselective synthesis of 3,5-dialkyl-indolizidines has been applied to the synthesis of a stereoisomer of the trail pheromone of the Pharaoh ant and to a stereoisomer of gephyrotoxin 223.12 A stereoselective total synthesis of ( )-perhydrogephyrotoxin (21)13 and a simple synthesis of ( )-gephyran14 have been reported. 

Thioxanthenes are not only valuable synthetic intermediates [1], they also find considerable interest in pharmaceutical research [2] and as dyes for numerous applications [3]. Only few methods are known for the stereoselective synthesis of S-heterocycles [4], Sequential transformations are a powerful strategy in organic synthesis frequently allowing the synthesis of complex molecules in a single synthetic operation [5]. It was anticipated that 4-silyloxy-l-benzothiopyrylium-salts 1 [6], which represent double-activated 4-thiochromanones, can be used for the stereoselective synthesis of aimulated thiochromanones 3 by reaction with 2-silyloxy-l,3-butadienes 2 [7]. 

Although the cross-reductive coupling between different activated olefins could also afford the formation of stereosiomeric (threo and erythro) products, no study has been reported so far. However, it was reported that acrylates gave almost predominantly the corresponding rrawj-unsaturated carboxylic acids (V) by reduction in the presence of butadiene [Eq. (5)] [55]. This reaction may be valuable from the aspect of stereoselective synthesis. 

Nickel and Grignard catalyzed stereoselective synthesis of cis and trans 2-alkyl-vinylcyclopentanes from telemerization of butadiene. Cyclization (ene reaction) of unsaturated allyl Grignard reagents, see also Feldman (see 1st edition). 

As well as [2 + 2], [4 + 4] and [4 + 4 + 4] products, the cyclodimerization of conjugated dienes also yields [4 + 2] cycloadducts47Thus, butadiene gives 4-vinyleyelohexene, ci.v-1,2-divinyl-cyclobutane and 1,5-cyclooctadiene. The influence of the catalyst and reaction conditions on the product distribution has been carefully investigated50- 53. Efforts towards asymmetric induction have concentrated on the stereoselective synthesis of 4-vinylcyclohexene as the sole chiral product. 

A similar rearrangement was used in a stereoselective synthesis of (if, )-3,7-dimethyT2,6-deca-diene-l,10-diol (pheromone of the queen butterfly) in six steps from gcraniol (Table 3, entry 16)310. Use of 2-methoxy-l,3-butadienes and related compounds (e.g., unsaturated acetals311) allows an iterative Claisen rearrangement by reduction of the resulting enone28,309. 

Table24.13 Stereoselective synthesis of 2-[(trimethylsilyl) methyl]-l,3-butadienes [18] ...

Table 24.14 (continued) Stereoselective synthesis of terminal 1,3-butadienes [19a] ... 

Sulfur substituted 1,3-butadienes are valuable synthons, particularly in Diels-Alder reactions, where they impart an added level of reactivity and regioselec-tivity [35]. Pearson et al [36] have reported the stereoselective synthesis of 2-(phenylthio)-1,3-butadiene by the protocol delineated in Scheme 24.12. 

Control of the diastereochemistry of the DA reaction by means of a chiral center in the substrate is a versatile and reliable mean for stereoselective synthesis of six-membered ring derivatives with multistereogenic centers. A reaction of fu-marate having two chiral auxiliaries with 2-methyl-l,3-butadiene afforded virtually complete stereocontrol in titanium-promoted DA reaction to give an optically active cydohexene derivative [147] (Scheme 14.58). 

After separation by preparative GC, (162 a) was treated with osmium tetroxide and acid to afford brevicomin. Catalytic dimerization and carbonylation of butadiene by Byrom et al. (121), followed by reduction, epoxidation, and hydrolysis gave the alkenediol (166), which was cyclized catalytically to e /o-brevicomin (Scheme 33). A stereoselective synthesis of optically active (li ,7JR)-(+)-exo-brevicomin (150) from (2S,3S)-D-(—)-tartaric acid (167) has been achieved by Mori (122) (Scheme 34). 

Cycloaddition involves the combination of two molecules in such a way that a new ring is formed. The principles of conservation of orbital symmetry also apply to concerted cycloaddition reactions and to the reverse, concerted fragmentation of one molecule into two or more smaller components (cycloreversion). The most important cycloaddition reaction from the point of view of synthesis is the Diels-Alder reaction. This reaction has been the object of extensive theoretical and mechanistic study, as well as synthetic application. The Diels-Alder reaction is the addition of an alkene to a diene to form a cyclohexene. It is called a [47t + 27c]-cycloaddition reaction because four tc electrons from the diene and the two n electrons from the alkene (which is called the dienophile) are directly involved in the bonding change. For most systems, the reactivity pattern, regioselectivity, and stereoselectivity are consistent with describing the reaction as a concerted process. In particular, the reaction is a stereospecific syn (suprafacial) addition with respect to both the alkene and the diene. This stereospecificity has been demonstrated with many substituted dienes and alkenes and also holds for the simplest possible example of the reaction, that of ethylene with butadiene ... 

Enantiomerically pure 1-sulfinyl-l,3-butadienes 577 are efficient chiral dienes providing the corresponding Diels-Alder products with high stereoselectivity. However, their use in asymmetric synthesis is limited to highly reactive... 

The trans/cis ratio of the product must, therefore, be determined at an earlier reaction stage and most probably by the ratio of species 27a and 27b. Steric or electronic factors affecting this ratio will influence the trans/cis ratio of the resulting 1,4-hexadiene. The phosphine and the cocatalyst effect on the stereoselectivity can thus be interpreted in terms of their influence on the mode of butadiene coordination. Some earlier work on the stereospecific synthesis of polybutadiene by Ni catalyst can be adopted to explain the effect observed here, because the intermediates that control the stereospecificity of the polymerization should be essen-... 

Mechanisms have been proposed to explain stereoselectivity in 1,3-diene polymerizations, but these processes are less understood than the polymerization of ethylene and 1-alkenes [Peluso et al., 1997]. The ability to obtain cis 1,4-, trans 1,4-, and st 1,2-polymers from 1,3-butadiene, each in very high stereoregularity, hy using different initiators has great practical utility for polymer synthesis even if it is not well understood why a particular initiator gives a particular stereoregular polymer. 

Avalos et al. has reported the microwave-assisted synthesis of tetrazine derivatives by a hetero Diels-Alder reaction of homochiral 1,2-diaza-l,3-butadienes with diethyl azodicarboxylate (Scheme 3.40)65. Under conventional conditions, reactions could be performed in benzene solution at room temperature. However, under microwave heating conditions, the reaction was significantly accelerated (by a factor of 1000) when carried out solvent free. The observed stereoselectivity was identical for the hetero Diels-Alder reaction under both microwave-heated and conventional conditions. 

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