Tetrasubstituted 1,3-dienes synthesi

The Diels-Alder addition of the tetrasubstituted diene (126) to benzoquinone derivatives has led to a synthesis of kermesic acid (127) and related species, and the exocyclic sulphur-substituted diene (128) can be employed in the regioselec-tive construction of bicyclic systems/ ... 

Trost reported the synthesis of 1,4-dienes with ruthenium catalysis through regioselective carbometallation of alkynes with alkenes.51 Di- and trisubstituted olefins can also be obtained with arylboronic acids through an intermolecular process under rhodium,30 52 55 nickel,56 and palladium catalysis.57 Recently, Larock has reported an efficient palladium-catalyzed route for the preparation of tetrasubstituted olefins.58,59... 

Beccalli et al. reported a synthesis of carbazomycin B (261) by a Diels-Alder cycloaddition using the 3-vinylindole 831 as diene, analogous to Pindur s synthesis of 4-deoxycarbazomycin B (619). The required 3-vinylindole, (Z)-ethyl 3-[(l-ethoxy-carbonyloxy-2-methoxy)ethenyl]-2-(ethoxy-carbonyloxy)indole-l-carboxylate (831), was synthesized starting from indol-2(3H)one (830) (620). The Diels-Alder reaction of the diene 831 with dimethyl acetylene dicarboxylate (DMAD) (535) gave the tetrasubstituted carbazole 832. Compound 832 was transformed to the acid 833 by alkaline hydrolysis. Finally, reduction of 833 with Red-Al afforded carbazomycin B (261) (621) (Scheme 5.99). 

Various aspects of this reaction have been summarized by Kocienski.2 It is particularly useful for synthesis of disubstituted alkenes and conjugated dienes and trienes. It fails with some trisubstituted alkenes and most tetrasubstituted. alkenes because the precursors are unstable. One advantage of this route is that rra/is-alkenes are formed preferentially or exclusively. Yields are highest when the eliminated groups can adopt a /rons-coplanar arrangement. 

The Heck reaction of 1,3 -diene systems via 7r-allylpalladium is also useful. This cyclization, which forms very congested quaternary carbon centers involving the intramolecular insertion of di-, tri- and tetrasubstituted alkenes, is particularly useful for natural products synthesis. In the synthesis of morphine, bis-cyclization of the octahydroisoquninoline precursor 112 by the intramolecular Heck reaction proceeded using palladium trifluoroacetate and 1,2,2,6,6-pentamethylpiperidine (PMP). The insertion of the diene system forms the 7i-allylpalladium intermediate 113, which attacks the phenol intramolecularly to form the benzofuran ring 114. Based on this method, the elegant total syntheses of (—)- and (+)-dihydrocodeinone, and (—)- and (+)-morphine (115) have been achieved [50],... 

An N-l-diene-l-aza-1,3-butadiene was employed in a Diels-Alder reaction to synthesize the key intermediate, a tetrasubstituted pyridine, in the total synthesis of the pyridine-base natural product, piericidin (Scheme 53) <2005JA15704>. The concerted cyclization conditions were surprisingly mild, considering the steric demand of the dienophile and that the aromatization was not successful under a variety of basic conditions, but the Lewis acid cleanly affected the transformation. 

Pt(II) to the alkyne of the substrate likely triggers all these events. The cycloisomerization might undergo a metallacyclic intermediate that proceeds to eliminate /3-H. The formation of cyclopropanes is presumably succeeded via alkenyl platinum carbene followed by platina(IV)cyclobutane intermediates. The extension using formal metathesis of the enynes includes two transformations, the formation of 1,3-diene moieties and the stereoselective tetrasubstituted aUcene derivatives via O C allyl shift, both leading to diverse structural motifs and serving as the key step in the total synthesis of bioactive targets (Scheme 83). 

Cyclopentenones.1 One limitation to Jung s cyclopentenone synthesis (8, 178) is that tetrasubstituted alkenes react slowly, if at all, with this diene (1). An expedient is the use of a dienophile such as isobutenyl acetate (2), which does react, even if slowly, to give 3 as the major adduct. The adduct can be converted in several steps lo a cyclopentenone such as 4. The cyclopentenone 4 (R = />-tolyl) has been converted to /(-cuparenonc (5).2... 

The y, 5-double bond of a conjugated keto-diene may be selectively hydrogenated over catalysts, offering useful synthetic applications. Hydrogenation of dienone 16 affords 17 as an intermediate in the total synthesis of steroids. The disubstituted double bond is reduced more readily than the tetrasubstituted double bond in a nonpolar solvent to prevent participation of the carbonyl groups ... 

RCM of 1,8-dienes constitutes an efficient access to cycloheptenes since di-, tri-, and tetrasubstituted olefins could be elaborated in good yields with catalyst loading as low as 1 mol%. In this context, the highly demanding field of natural product synthesis constitutes an efficient test for the development of more active and... 

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