Trisubstituted 1,3-butadienes

Trisubstituted 1,3-butadienes are afforded by Ni-phosphine-catalysed coupling of the corresponding tellurobutadienes with Grignard reagents. ... 

The surprising selectivity in the formation of 4 and 5 is apparently due to thermodynamic control (rapid equilibration via the 1,3-boratropic shift). Structures 4 and 5 are also the most reactive of those that are present at equilibrium, and consequently reactions with aldehydes are very selective. The homoallylic alcohol products are useful intermediates in stereoselective syntheses of trisubstituted butadienes via acid- or base-catalyzed Peterson eliminations. 

With trisubstituted benzoquinones and use of the cationic oxazaborolidinium catalyst B, 2-[tra-(isopropyl)silyloxy]-l,3-butadiene reacts at the monosubstituted quinone double bond. The reactions exhibit high regioselectivity and more than 95% e.e. With 2-mono- and 2,3-disubstimted quinones, reaction occurs at the unsubstituted double bond. The regiochemistry is directed by coordination to the catalyst at the more basic carbonyl oxygen. 

Type III (no homodimerization) Acrylonitrile," protected 3° allylamines" Vinyl trialkoxysilanes, vinyl siloxanes 1,1-Disubstituted olefins, " non-bulky trisubstituted olefms, vinyl phosphonates, " vinyl phosphine oxides,phenyl vinyl sulfone, acrylonitrile, 4° allylic carbons (all alkyl substituents), protected 3° allylic alcohols, 7,Aolefm of 2-subst. 1.3- butadienes, 7,Aolefin of electronically deactivated 1.3- butadienes ... 

Type IV (spectators to CM) 1,1-Disubstituted olefms " 1,1-Disubstituted olefms, disub. o ,/ -unsaturated carbonyls, 4° allylic carbon-containing olefins, perfluorinated alkane olefins, 3° allylamines (protected)" Vinyl nitro olefins, protected trisubstituted allyl alcohols, a,/ -olefin of 2-subst. 1.3- butadienes, a,/ -olefm of electronically deactivated 1.3- butadienes ... 

Trisubstituted X -phosphorins or X -phosphorins can be isolated unchanged even after long periods of irradiation when oxygen is excluded. Stade discovered that cyclic phosphinic acid esters 208 a-c which contain a cyclic butadiene (1.3)-moiety, photochemically rearrange smoothly to the tricyclic compounds 214 a-c. 

New possibilities in hetero-Diels-Alder condensation have been opened by the introduction of highly active l-methoxy-3-trimethylsilyloxy-, 4-benzoyIoxy-l-methoxy-3-trimethylsilyloxy-, and 2-acetoxy-l-alkoxy-3-trimethylsilyloxy-l,3-butadienes ( Danishefsky dienes, 5). These compounds readily react under atmospheric pressure, in the presence of Lewis acids, with normal aldehydes (e.g., acetaldehyde, benzaldehyde, furfural) to furnish 2,3-disubstituted or 2,3,5-trisubstituted derivatives of 2,3-dihydro-4H-pyran-4-one 7 capable of readily functionalizing to sugars (Scheme 5) [26]. This approach... 

Several cycloaddition reactions of 2,5-dihydrothiophene derivatives have been reported. Compounds possessing an enamine system undergo [2 + 2] cycloaddition with acetylene-dicarboxylic ester (Scheme 215) (77AHC(2l)253). Diels-Alder addition of the 2,5-di-hydrothiophene-3-carboxylic ester (557) with butadiene, followed by desulfurization, leads to the trisubstituted cyclohexane (558) (B-74MI31404). 

The metallacyclic compounds react with protic reagents to yield the corresponding substituted 1,3-butadienes and the iodination reactions give the 1,4-diiodo 1,3-butadiene derivatives (Scheme 122). Reactions with different unsaturated organic molecules have also been investigated. They catalyze the cyclotrimerization of a range of alkynes. Terminal alkynes with small substituents produce the 1,2,4-trisubstituted benzene, preferentially, in an exothermic reaction. The more bulky substrates BuTl CH and Me3SiC=CH react more slowly and only the symmetrical 1,3,5-isomer is produced (Scheme 122).174... 

The synthesis of such eight-membered rings by the nickel-catalysed dimerisation of butadienes, is used here with 2-methylbutadiene. The regio-selectivity and stereo-specificity of the hydro-boration of symmetrical 124 are as expected for a trisubstituted alkene. Conversion of the alcohol 125 into a good leaving group 126 made it reactive enough to carry out electrophilic addition on the other alkene. In aqueous solution, the final nucleophile was water and the product a mixture of diastereoisomers of the tertiary alcohol 127. 

The reaction of nitrone 101 with such olefins 5 as propylene, n-hexene, allyl alcohol, styrene, acrylic acid, methyl acrylate, acrylonitrile, and butadiene are all regiospecific to give S-substituted isoxazolidines of type l.77 The reaction with olefins 6 seems to be regio- and stereo-specific thus, nitrone 101 and methyl methacrylate give cycloadduct lilt as the sole product.77 Similarly, 101 and 1 -methyl-1-phenylethylene gives adduct Hit.77 In the reactions with olefins 7 or 8, the stereospecificity is more evident.77,78 The isoxazolidine obtained is always one of the two possible epimers. The reaction of nitrone 101 with trisubstituted olefins is highly stereoselective.64 Some results are summarized in Table III. 

Hetero-Diels-Alder reactions involving A -phenethyl-(2-pyridylmethylene)imine as the dienophile have been reported." A Cr complex 77 is useful for the synthesis of trisubstituted tetrahydro-4-pyranones, whereas a (salen)Cr(III) complex is involved in those reaction with l-amino-3-siloxy-l,3-butadienes." ... 

Zhang and Widenhoefer have reported a highly regio- anddiastereo-selective method for the intermolecular hydroalkoxylation of aUenes with alcohols [108]. As an example, reaction of 1-phenyl-l,2-butadiene with 2-phenyl-l-ethanol catalyzed by a 1.1 mixture of (IPr)AuCl [IPr = l,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene] and AgOTf in toluene at room temperature led to isolation of ( )-(3-phenethoxy-l-butenyl)benzene in 96% yield as a single regio- and stereo-isomer (Eq. (12.38)). The protocol was effective for primary and secondary alcohols and for monosubstituted, 1,1- and 1,3-disubstituted, trisubstituted, and tetrasubstituted allenes. Transfer of moiety to the newly formed tetrahedral stereocenter in the y o oxy ation of axially chiral 1,3-disubstituted allenes ranged from 0 to 81%, epen ing on the nature of the allene and the concentration of the alcohol. 

Additionally, Pd-catalyzed cross-coupling reactions were explored in pyridines synthesis also. In 2007, a multicomponent sequential process for the synthesis of trisubstituted pyridines was reported [59]. The reaction involves the formation of an enamine by Pd-catalyzed amination of an alkenyl bromide, formation of a 2-aza-1,3-butadiene by Pd-catalyzed cross-coupling of a trimethylsilylimine with an alkenyl bromide, and Lewis acid (Yb(OTf)3 (20mol%)) catalyzed cycloaddition between the enamine and the azadiene. Moderate yields can be achieved (Scheme 3.26). A zinc-mediated tandem reaction of nitriles... 

The terpenes a- and 6-myrcene are classical examples of substrates controlled by factor (ii). In these polyenes the relative reactivity of the nonconjugated C=C double bond (di- versus trisubstituted) controls the first reaction event. 6-Myrcene, a monoterpene triene with a trisubstituted nonconjugated double bond, undergoes preferentially the ene reaction with subsequent [4 + 2]-cycloaddition,whereas a-myrcene 57 solely reacts in a [4 + 2]-mode to give the endoperoxide 58. Alkoxy-substituted 1,3-dienes, which cannot undergo ene reaction, have been shown to be excellent substrates for [2 + 2]-cycloaddi-tion. The l,4-di-t-butoxy-l,3-butadienes were the first substrates that showed nonstereoselective [2 + 2]-cycloaddition reactions. Formation of the endoperoxide 60 was observed only from the ,Z-isomer 59, which indicates a pronounced activation effect by the alkoxy groups for dioxetane formation. 

---