Use of substituted 1,3-Dienes

Ftinguelli, A. Taticchi, Dienes in the Diels-Alder Reaction, J. Wiley and Sons, New York-Chichester (1990) 

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Useful 1,3-dienyhnagnesinm species can be generated throngh an awfi-vinyhnagnesia-tion of 2-butyn-l-ol (Scheme 28). The resnltant organomagnesinm species 49 is allowed to react with electrophiles, such as iodine, aldehydes and ketones, to furnish a range of substituted 1,3-dienes 50 in reasonable overall yields (Scheme 28) . ... 

Metal-mediated cyclizations that rely on the initial complexation of an alkene or alkyne around a low oxidation state metal center are often sensitive to the presence of additional substituents (particularly electron-donating substituents), and relatively more stringent reaction conditions are often required for successful cychzation. This effect was noted in the Ni-catalyzed formal [4 -I- 4] cycloaddition reactions developed by Wender and Tebbe and is apparent when one compares the reported facility of Pd-catalyzed linear dimerization of 1,3-butadiene versus that of substituted 1,3-dienes. Similarly, the initial attempts at Pd-catalyzed cyclization of bisdiene 70a (Scheme 22) were rather disappointing. Using 0.05 equiv of [Pd(OAc)2/3 PhjP] (THF, 65 °C, 12 h), only a small... 

Hydrosilylation of alkyl-substituted 1,3-dienes 46g-46j in the presence of a ferrocenylmonophosphine-palladium catalyst also proceeded with high regioselectivity to give the corresponding 1,4-addition products with moderate enantioselectivity (entries 13-16).52 62 Enantioselectivity was improved by using ligands 37f and 37g (entries 17 and 18).57a... 

Contrasting results are obtained for the peralkylated disilanes RMe2SiSi-Me2R (R = Me, "Bu, Bu), which yield only trace amounts of the 1,4-addition products under the same reaction conditions. Attempts to increase double silylation yields by use of other platinum or palladium catalyst precursors under carbon monoxide pressure or inert atmosphere were also unsuccessful for these peralkylated disilanes. Additionally, the reaction of tetramethyl-l,2-divinyldisilane results in conversion to an intractable product mixture, with no incorporation of the 1,3-diene. Phenyl-substituted disilanes are also effective reagents in the Pt(dba)2-catalyzed double silylation of phenylacetylene, but again, the alkylated disilanes and the vinyl-substituted disilane do not give double silylation products. 

In their pioneering work on the catalytic carbopalladation reaction of 1,2-heptadiene with phenyl iodide in the presence of a suitable base, Shimizu and Tsuji observed the formation of the corresponding substituted 1,3-dienes 62 via a / -hydride elimination from the 7z>allyl intermediate 61 [61]. Based on these observations, a three-component Heck-Diels-Alder cascade process has been developed by Grigg and co-workers [73]. A wide variety of aryl and heteroaryl iodides were used for the intermolecular reaction with dimethylallene to afford the corresponding 1,3-dienes. These subsequently react in situ with N-methylmaleimide to give the bicyclic adducts 63 (Scheme 8.30). 

Additions to l,3-dienes6 (12, 367-368 14, 249-250 15, 245). This reaction can be used to effect intramolecular cyclization of cyclic 1,3-dienes substituted by a suitable nitrogen nucleophile. Thus reaction of the amido diene 1 with lithium acetate catalyzed by Pd(OAc)2 (with benzoquinone as reoxidant) provides the ds-fused heterocycle cis-2, in which the acetoxy group is cis to the ring fusion, formed by an overall trans-1,4-oxyamidation of the diene system. Addition of a trace of LiCl improves the yield and results in an overall cis- 1,4-oxyamidation (equation I). Acetamides and carbamates can also be used in place of amides. 1,4-Chloroamidation can also be effected by use of 2 equiv. of LiCl. 

In Table XIII we have summarized the results obtained by codimerization of various substituted 1,3-dienes with butadiene. In all cases the highest yields were obtained using the nickel-tri(o-phenylphenyl)phosphite catalyst. 

Nickel-catalyzed cyclization of a 1,3-diene side chain of the substituted pyrrolidones yields a precursor to the indolizidine alkaloid (—)-elaeokanine C (Equation 86) <1997TL3931>. Other metal-catalyzed reactions include the Rh-induced in situ carbene generation and subsequent cyclization onto the heteroatom to yield piperidines <1997T16565, 1997JOC67>. Pauson-Khand cyclizations have also been used (Equation 87) <1997T6611>. 

Fig. 15.22. Diels-Alder reactions with normal electron demand reactivity increase by the use of donor-substituted 1,3-dienes (Do refers to a donor substituent).

In general, the telomerization reaction is defined as the dimerization of two molecules of a 1,3-diene in the presence of an appropriate nucleophile HX to yield substituted octadienes [216,217]. This reaction allows us to assemble simple starting materials in a 100% atom efficiency [218] and to easily prepare useful intermediates in the total synthesis of natural products [219,220] and industrial precursors [221], In light of numerous studies, the mechanism of the palladium-catalyzed telomerization reaction is well understood [222,223]. It is accepted that one strongly bound and sterically hindered ligand on the metal center is desirable to generate highly active species, characteristics fulfilled by (NHC)-Pd(O) complexes. 

Diels-Alder cycloadditions of carbonyl compounds with aldehydes and ketones provide a powerful method for synthesis of 5,6-dihydropyrans, which are useful synthons for a variety of purposes. This methodology was slow to develop since early work indicated that simple carbonyl compounds react poorly with most alkyl and aryl substituted 1,3-dienes. However, with the understanding that [4 + 2] cycloadditions are facilitated by Lewis acid catalysts and high pressure, along with the recent availability of highly reactive oxygenated dienes, this chemistry has been increasingly exploited in total synthesis. 

One of the more obvious synthetic uses of cyclobutenes which has already been mentioned is for the preparation of specifically substituted 1,3-dienes, often to be used in subsequent [4 -t- 2] cycloaddition reactions. 

The allylic chloride offers a useful dual control of stereoselectivity in the allylic substitution since the chloride can be replaced with either retention (via a Pd(0)-catalyzed reaction) or inversion (via a nornial 8 2 reaction or a Cu(I)-catalyzed reaction). This was used in cyclic systems to obtain stereoselective cis- and rra72.s-annulation reactions [86,87]. The reaction starts with the transformation of cyclohexa-1,3-diene to cis- and trans-62 via chloroacetate 58 (Scheme 8-21) [78,88]. Subsequent transformation of cis- and trans-62 to cis- and trans-63, respectively, followed by an intramolecular palladium-catalyzed allylic substitution (syn) afforded the cis- and franj-annulated products [86]. 

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