Diels-Alder/Wittig olefination

Figure 1.4 Scheme of cobalt-catalyzed Diels-Alder/Wittig olefination reaction. (Reproduced with permission from Ref [37. )... 

A concise synthesis of substituted stUbenes from propargylic phosphonium salts by a cobalt-catalyzed Diels-Alder/Wittig olefination reaction has been described (Figure 1.4) [37]. It was shown that the cobalt(I)Diels-Alder reaction of propargylic phosphonium salts and alkyne-fimctionalized phosphonium salts with 1,3-dienes led to dihydroaromatic phosphonium salt intermediates that were directly used in a one-pot Wittig-type olefination reaction with aldehydes. Subsequent oxidation led to styrene- and stUbene-type products with the formation of three new carbon-carbon bonds. The reaction gives predominantly the Econfigured products. 

Wittig olefination of 2-nitro-Z-cinnamaldehyde (1300) with the phosphonium bromide 1301 led to the diene 1302. The Diels-Alder cycloaddition of 1302 with maleimide (1303), followed by dehydrogenation with DDQ, afforded the phthali-mide 1304. Double deoxygenation of 1304 with triphenylphosphine (PPhs) in collidine gave O-methylarcyiiaflavin B (1305). Finally, heating of 1305 with molten pyridine hydrochloride led to arcyriaflavin B (346) (759) (Scheme 5.215). 

The asymmetric total synthesis of the natural enantiomer (—)-nakadomarin A was completed by Nishida et al. in 2004 (Scheme 8.12) [82]. Diels-Alder reaction between siloxydiene 173 and chiral dienophile 172 (prepared from L-serine in 10 steps [83]) gave the highly functionalized key intermediate hydroisoquinoline 174, which was subjected to Luche reduction, cyclization, and HCl treatment to furnish the tricyclic intermediate 175. Compound 175 was converted to 177 via ozonolysis cleavage of ring B followed by recyclization of the unstable bisaldehyde to a five-membered ring by aldol condensation. The Z-olefin 178 was obtained from Wittig reaction of 177, and was further converted to furan 180 via peroxide 179. The... 

The products of the Diels-Alder reactions of aminosiloxy dienes are versatile synthetic intermediates, as they can be subjected to reduction, Wittig olefination, or... 

Diels-Alder addn. with, 280-281, 297 synthesis, 80, 280-281 Bicyclo[4.2.0]octa-l,3,5-triene-7,8-dione benzene synthesis from, 78 Wittig olefination, 32-33 Bi-2,4-cyclopentadien-l-yl, 335-336 Bilayer lipid membrane (BLM), 350-351 Bitines, 10,23 dihydro-21//- porphyrins from, 349... 

Other examples of scale-up involved a triphenylphosphine-free one-pot Wittig olefination, a one-step three-component synthesis of imidazo annulated pyridine and a metal-catalyzed Suzuki coupling. Kappe and co-workers also recently transferred conditions for reactions originally performed on a small scale with a mono-modal system, to scale-up by parallel synthesis in a multimodal batch reactor [13]. Typically, the scale-up was 100-fold, from 1 mmol examples included Biginelli condensations, Heck and Negishi couplings, and Diels-Alder cycloadditions with gaseous reactants. 

Synthetic routes to vinylpyrroles and vinyl indoles continue to be of interest because of their potential as Diels-Alder dienes. Work by Settambolo and coworkers demonstrated that 3-acyl-l-p-toluenesulfonylpyrroles can be converted to 3-vinylpyrroles by standard methods such as Wittig olefination or organometallic addition followed by dehydration. <94G173> The tosyl group can be removed by alkaline hydrolysis. 

Syntheses of 4,5-Unsaturated Cyclic Compounds - Swem oxidation of methyl 2,3,4-tri-C>-acetyl-a-D-glucopyranoside followed by base-induced elimination of acetic acid afforded unsaturated aldehyde 33. Further transformation of the aldehyde group into a methylene unit by way of a Wittig olefination and replacement of the acyl groups with benzyls or methyls yielded 34 which underwent a Diels-Alder reaction (the acyl protected variant of 34 was unreac-tive) with 2-methoxycarbonyl-p-benzoquinone, followed by acid-catalysed double... 

Reviews have appeared on the use of the Wittig reaction in industrial practice, the Claisen rearrangement, synthetic applications of the retro-Diels-Alder reaction, organo-palladium intermediates for the alkylation and arylation of olefins, the Prins reaction to give 1,3-dienes, and intramolecular [4 + 2] (Diels-Alder) and [3 + 2] cycloadditions.An interesting discussion of the regiospecificity of the Diels-Alder reaction in terms of frontier orbital overlap favours the Woodward-Katz concept. Useful alkyne and polyene coupling reactions are described in reviews on the chemistry of vitamin the synthesis of insect sex... 

Following this historical precedent, a sulfone was readily appended onto the diene system of 37, affording 38 in 91 % yield (Scheme 7). One should note that in this transformation both isomers obtained from the prior Wittig olefination were employed, resulting in the mixture of stereoisomers at C-9 in 38. Based on the assumption that eventual thermal extrusion of SO2 from either diastereomer would provide the requisite trans-substituted olefin in the diene desired for Diels—Alder reaction, this lack of selectivity was not deemed problematic. However, the pressing issue at this juncture remained the generation of the quinone. Fortunately, with the diene now protected, oxidative demethylation smoothly furnished 39 in 79 % yield with concomitant TBS deprotection. 

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