Diels-Alder reaction masked functionality

Many other examples of synthetic equivalent groups have been developed. For example, in Chapter 6 we discussed the use of diene and dienophiles with masked functionality in the Diels-Alder reaction. It should be recognized that there is no absolute difference between what is termed a reagent and a synthetic equivalent group. For example, we think of potassium cyanide as a reagent, but the cyanide ion is a nucleophilic equivalent of a carboxy group. This reactivity is evident in the classical preparation of carboxylic acids from alkyl halides via nitrile intermediates. 

The synthetic utility of the Diels-Alder reaction can be significantly expanded by the use of dienophiles that contain masked functionality and are the synthetic equivalents of unreactive or inaccessible species (see Section 13.2 for a more complete discussion of the concept of synthetic equivalents). For example, a-chloroacrylonitrile shows satisfactory reactivity as a dienophile. The a-chloronitrile functionality in the adduct can be hydrolyzed to a carbonyl group. Thus, a-chloroacrylonitrile can function as the equivalent of ketene,... 

Molecular electrostatic potentials have been used to explain the regioselectivity exhibited in the Diels-Alder cycloaddition reactions between 1-trimethylsilyloxy-butadiene and the quinones 5-formyl-8-methyl-1,4-naphthoquinone, 5-methoxy-7-methyl-1,4-phenanthrenequinone, and 5,6,7-trimethyl-1,4-phenanthrenequinone.128 The intramolecular Diels-Alder reaction of masked o-benzoquinones (123) with a variety of dienes provides adducts (124) which rearrange to functionalized ris-decal ins (125) with complete stereocontrol of up to five stereocentres. This methodology ... 

Recently, the reaction of masked ortho-benzoquinone [92] with C60 was tested [93]. The [4+2] cycloaddition reaction of such electron-deficient dienes with fullerenes resulted in the formation of highly functionalized bicyclo [2.2.2] octenone-fused fullerenes. The reactants were generated in situ by the oxidation of the readily available 2-methoxy phenols with hypervalent iodine agents. For the several different masked ortho-benzoquinones that were tested, it was found that the yield of the cycloadducts depends on the nature of the starting materials and the reaction conditions. Other Diels-Alder reactions of such electron-deficient dienes with electron-poor fullerenes involved tropones [94], 1,3-butadienes substituted with electron-withdrawing groups [95], and 2-pyrone [96]. 

The efficiency of the intramolecular Diels-Alder reactions of furan has been described in several reviews, including an excellent treatise by Lipshutz. Steric factors, rather than electronic or solvent effects, appear to have the greatest influence on the outcome of the cycloaddition [1,19,20]. Electronically-disfavored cycloadditions can be brought about by creative functional group modifications. Thus, an electron-deficient furan, such as one bearing an a-keto group, can be masked and induced to undergo cycloaddition, as shown in Eq.8 [21]. 

The hetero Diels-Alder reaction (909 —> 910) produces a 5 1 mixture of diastereomers from which cis-910 is isolated by flash chromatography (95% optically pure). Reduction of the ketone carbonyl followed by methanolysis furnishes the axial glycoside 911. The furan heterocycle behaves as a masked carboxylic acid function that can be liberated by oxidation with ruthenium tetraoxide. The conversion of 911 to 912 requires 13 steps. 

This review will concentrate on ways in which functionality can be assembled around the sulfolene nucleus, to provide useful masked diene precursors for Diels-Alder reactions. We therefore make only brief mention of ways in which SO2 has been added to dienes. Such reactions are used mainly to prepare simple sulfolenes, or to mask existing dienes [113]. 

After masking of the alkyne function by a dicobalthexacarbonyl complex, RCM was used to cyclize the diene 573 (Scheme 9.15). Then, decomplexation enabled a Diels-Alder reaction with the disiloxydiene 575, ensued by elimination of isobutylene. Two hydroxy groups of the resorcylic macrolide (576) obtained were protected and the TBS-ether was cleaved. Thus, dehydration with concluding deprotection of all alcohol functions furnished aigialomycin D (482), in an overall yield of 8%. 

The Diels-Alder reactions of masked o-benzoquinones (MOBs) with [60] fullerene afforded novel and highly functionalized bicyclo-[2.2.2]-octenone-fused [60]fullerene derivatives... 

The high-pressure Diels-Alder reaction of ketones with 1-methoxybutadiene yields the masked a,/3-unsaturated aldehyde (30). ° Under similar conditions, the highly functionalized cyclohexene (31) may be obtained [equation (6)]."°... 

The 1,5-dicarbonyl functionality is also represented by 2-alkoxy-3,4-dihydro-2H-pyrans (e.g., 162, a masked 5-ketoaldehyde), which are obtained by hetero-DiELS-ALDER reaction of enones and vinyl ethers (c p. 315). On treatment with hydroxylamine, they afford pyridines (e.g., 163) ... 

The synthetic utility of the Diels-Alder reaction can be significantly expanded by the use of dienophiles that contain masked functionality and are the synthetic equivalent of unreactive or inaccessible species. For example, a-chloroacrylonitrile... 

A successful method for preparation of an isoquinuclidene related to 203 based on Diels-Alder reaction between dihydropyridine 131 and a ketene equivalent was developed. This approach involving preparation and zwit-terionic amino-Claisen rearrangement of the isoquinuclidene 203 to form the enone 202 followed by subsequent E-ring elaboration and Wenkert cycliza-tion ultimately culminated in a formal synthesis of deserpidine (3) (Scheme 3.32) (44). Mariano and his coworkers found that Diels-Alder reaction of the N-trichloroethoxycarbonyl-l,2-dihydropyridine (209) and the masked ketene equivalent, 210, reacted to afford the isoquinuclidene 211 as an epimeric mixture of 7-cyano-7- acetoxy isomers. The a-cyanoacetate functionality in... 

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