Diene synthesis from aldehydes

Danishefsky et al. were probably the first to observe that lanthanide complexes can catalyze the cycloaddition reaction of aldehydes with activated dienes [24]. The reaction of benzaldehyde la with activated conjugated dienes such as 2d was found to be catalyzed by Eu(hfc)3 16 giving up to 58% ee (Scheme 4.16). The ee of the cycloaddition products for other substrates was in the range 20-40% with 1 mol% loading of 16. Catalyst 16 has also been used for diastereoselective cycloaddition reactions using chiral 0-menthoxy-activated dienes derived from (-)-menthol, giving up to 84% de [24b,c] it has also been used for the synthesis of optically pure saccharides. 

The total synthesis of palytoxin (1) is a landmark scientific achievement. It not only extended the frontiers of target-oriented synthesis in terms of the size and complexity of the molecules, but also led to new discoveries and developments in the areas of synthetic methodology and conformational analysis. Among the most useful synthetic developments to emerge from this synthesis include the refinement of the NiCh/CrC -mediated coupling reaction between iodoolefins and aldehydes, the improvements and modifications of Suzuki s palladium-catalyzed diene synthesis, and the synthesis of A-acyl vinylogous ureas. 

Terminal allenes.1 A synthesis of 1,2-dienes (3) from an aldehyde or a ketone involves addition of ethynylmagnesium bromide followed by reaction of the adduct with methyl chloroformate. The product, a 3-methoxycarbonyloxy-l-alkyne (2), can be reduced to an allene by transfer hydrogenolysis with ammonium formate catalyzed by a zero-valent palladium complex of 1 and a trialkylphosphine. The choice of solvent is also important. Best results are obtained with THF at 20-30° or with DMF at 70°. 

The synthetic value of this reaction has been enhanced by the development of a wide range of methodologies for glycal synthesis from 0-acylatcd glycosyl halides1 or from noncarbohydrate precursors. By use of the Lewis acid-catalyzed diene-aldehyde cyclocondensation reaction, glycals of natural and non-natural sugars can be obtained (Scheme 4).31... 

Note, too, the mild conditions used for the formation of the diisopropyl acetal 552 from aldehyde 55,1 again without p-elimination. Another example comes from a synthesis of Arachidonic Add in which a key step was the mild hydrolysis of a diisopropyl acetal under conditions that do not provoke rearrangement of the p,y-double bond into conjugation with the aldehyde function.118 The method has been applied to the synthesis of a number of natural (Z,Z)-skipped 1,4-dienes.119... 

The development of the synthesis of peptides on solid supports has also had a strong impact on other areas of organic synthesis. From the very beginning, some research groups tried, with some success, to export the idea from peptide synthesis to, for instance, the monoalkylation and monoacylation of carboxylic acids,the synthesis of aldehydes and ketones, or to the use of resin-bound dienes or dienophiles to trap reactive intermediates.PI This pioneering work has been fundamental to the much more recent explosion of combinatorial chemistry on solid supports. Synthesis on solid supports has also found application in the synthesis of oligonucleotides, PI oligosaccharides,PI peptide-DNA hybrids,P°l and peptide nucleic acids (PNAs).P l... 

These adducts were thought to occur via attack of the first excited singlet state of propanal on the diene. Evidence from subsequent studies point to the fact that it is likely the excited singlet state of the aldehyde that is responsible for the Patemo-Biichi reaction with 1,3-dienes. This comes from a number of sources and includes evidence from a number of studies . The synthesis of ( )-6-nonen-l-ol, a component of the sex pheromone of the Mediterranean fruit fiy, applied this process as the first step. Hydrogenation and metal catalyzed [2 + 2] cycloreversion gave 165, which was then easily converted to the target by reduction (Scheme 37). 

In a continuation of their studies on the Claisen-Cope rearrangement, Thomas etal have utilised this procedure in the synthesis of torreyaland dendro-lasin. Thus, pyrolysis of the ether (20), derived from the reaction of 3-furyl-methanol with l-ethoxy-2-methylbuta-1,3-diene, gave the aldehyde (21). This, on reduction to the corresponding alcohol and further treatment with the above diene, yielded torreyal (22, R = CHO) which could be converted to dendrolasin... 

In the synthesis of zincophorin, two cyclocondensation reactions are also used. In the first cyclocondensation reaction, trimethylsilyloxy diene (14) reacts with aldehyde (193) using anhydrous MgBr2 as the catalyst to give the anti-ACF pyrone (194) in 80% yield (Scheme 53). The syn.anti ratio in this reaction is 7 1. After a series of standard manipulations aldehyde (19< ) is obtained. In the second cyclocondensation reaction, anti-CF pyrone (197) results from reaction of the (4 )-r-butyidimethylsilyloxy diene (195) with aldehyde (19< ) under BF3-OEt2 catalysis (197) and its syn-CF isomers are obtained in a ratio of 4 1 and overall yield of 68%. The anti-CF aldol product is purified and cyclized to anti-CF pyrone (197) in benzene using pyridinium p-toluenesulfonate as a catalyst. Pyrone (197) converted into zincophorin (198) by a sequence of steps shown in Scheme 52. 

A study comparing, under a range of conditions, diene synthesis by the two alternative Wittig routes, allylic ylide-saturated aldehyde (route 1) and reactive ylide-a,P-unsaturated aldehyde (route 2), has been reported. 9 por the system chosen (Scheme 2) the reactive ylide-a,P-unsaturated aldehyde route is clearly preferred in that the stereochemistry of the new double bond can be controlled more easily and there is little or no isomerisation of the double bond already present in the aldehyde. A route to symmetrically substituted polyenes containing an odd or even number of double bonds has been reported (Scheme 3).20 The Wittig reactions of ylides derived from... 

The first total synthesis of Neu5Ac from non-carbohydrate precursor has been reported by Danishefsky et al. in 1988, who used a hetero Diels-Alder reaction between a diene and an aldehyde to establish the pyranoid ring [135] (Scheme 48). 

Stereospecific heterodiene synthesis with l,3-dien-2-amines Tetrahydro-4-pyrones from aldehydes... 

Michael addition with j -acoxyketones, and 2-acoxynitro compounds, diene synthesis with 2-acoxynitro compounds s. 17, 814 a, -Ethyleneketones from aldehydes GHO GH G GOR... 

This conversion of thioacetals into vinyl sulfides was applied to a C-C connective synthesis of 2-phenylthio-1,3-butadienes from aldehydes (eq 47). The key elimination step converts cyclobu-tanone thioacetal intermediates into 1-phenylthiocyclobutenes that undergo electrocycUc ring opening to deliver dienes. 

Shibahara F, Bower JF, Krische MJ (2008) Diene hydroacylation from the alcohol or aldehyde oxidation level via ruthenium-catalyzed C-C bond-forming transfer hydrogenation synthesis of p, y-unsaturated ketones. J Am Chem Soc 130 14120-14122... 

Among nonmetal chiral complexes, chiral oxazaborolidines have been found effective in many D-A reactions. The adduct obtained from the D-A reactions of 5-benzyloxymethyl-l,3-cyclopentadiene 98a with a-bromoacrolein in the presence of catalyst 98 (S-tryptophan-derived oxazaboroUdine) is an important intermediate in the synthesis of prostaglandins. The aldehyde group of the dienophile is bound to the catalyst by coordination with boron by Lewis interaction and the Lewis complex is stabilized by H-bonding. The upper face of the aldehyde is shielded by indole moiety of the catalyst. The benzyloxymethyl substituent of the cyclopentadiene produces a steric differentiation on the two faces of cyclopentadiene ring resulting the approach of the diene preferably from one face. 

A regioselective synthesis of 1,4-dienes (69) from a,/3,7,5-unsaturated ketones, e.g. (68), proceeds in excellent yield on alkylation with organolithium reagents followed by reduction with lithium in liquid ammonia. The reaction is not successful with the corresponding aldehydes and the lithamide reduction product must be quenched with ethanol or t-butyl alcohol rather than with conventional protic sources such as ammonium chloride. Where applicable, the 1,4-diene is formed as a mixture of the E- and Z-stereoisomers at the newly developed double bond. 

A new stereocontrolled diene synthesis via a palladium-catalysed decarboxy-lative elimination of the adducts from a,jS-unsaturated aldehydes and carboxylate enolate has been reported and applied to the synthesis of insect pheromones and to regiospecifically substituted cyclohexadienes (Scheme 32). ... 

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