Hydrogenolytic cleavage

Hydrogenolytic cleavage of isoxazolines has also proved useful in preparation of -dihydroxy ketones and -hydroxy carboxylic acids (47). The isoxazolines were prepared by a [3 -1- 2] cycloaddition. 

The starting material could be synthesized from the corresponding known dibenzyl tetrapyrrole-dicarboxylate17 by hydrogenolytic cleavage of the benzyl esters followed by decarboxylative Clezy formylation.18... 

Basically, the cleavage of the C-O bond takes place through two mechanisms. The first mechanism (the hydrogenolytic cleavage) is a hydrogen-assisted bond-cleavage reaction, whereas the second mechanism is an ionic insertion of the metal into the C-O bond. The characteristic features of the two mechanisms are summarized in Table 4.1. 

On Pt and Pd, cleavage of the C-O bond results from a hydrogenolytic cleavage, whereas on Ni and Cu, an insertion mechanism occurs. The regiose-lectivity of the two mechanism is different. The less sterically hindered bond (b) is cleaved on Pt and Pd, whereas the more hindered bond (a) is cleaved on Ni and Cu (Scheme 4.62). 

Hydrogenolytic cleavage of the C-N bond takes place more easily than that of the C-C bond but with more difficulty than that of the C-O bond. Activation... 

It was found in the case of O-benzyl systems that palladium oxide is much more effective than palladium metal. No such effect was observed with the N-benzyl system.8 It is possible that the N-compounds can poison the electrophile metal ions, and the hydrogenolysis of the N-benzyl bond can take place only by the hydrogenolytic cleavage instead of the insertion mechanism. This is supported by the experimental finding that the product amine can inhibit the catalyst, and this can be minimized by buffering at a pH less than 4. 

The extremely high selectivity for tandem cycloaddition, the ease of manipulation of the nitroso acetals, and the release of the vinyl ether appendage in the hydrogenolytic cleavage constitute ideal features for asymmetric modifications of the cycloadditions with chiral vinyl ethers. As discussed in Section 8.3.2.1 (Inter [4+2]/inter [3+2] cycloadditions of nitroalkenes), the stereochemical course depends on the Lewis acids. The results are summarized in Scheme 8.38.179 The high levels and complementary selectivity with three chiral vinyl ethers and two kinds of Lewis acids (Ti- and Al-based Lewis acids) are presented in this scheme. 

Another important route to obtain organostannanes is the hydrogenolytic cleavage of tin-nitrogen bonds96,97. This reaction obeys the general scheme... 

Formation of eperezolid (92) proceeds via the catalytic hydrogenation of 88 to the deprotected intermediate (91), which is then acylated with ben-zyloxyacetyl chloride. Finally, the benzylic hydrogenolytic cleavage of this intermediate gives rise to the targeted compound eperezolid (92), as depicted in Scheme 18. 

Similarly, protecting groups susceptible to hydrogenolytical cleavage cannot be used in combination with prenyl moieties, as the unsaturated carbon—carbon bonds do not survive the cleavage conditions. 

Usually alcohols accompany aldehydes in reductions with lithium aluminum hydride [1104] or sodium bis 2-methoxyethoxy)aluminum hydride [544], or in hydrogenolytic cleavage of trifluoroacetylated amines [7772]. Thus terr-butyl ester of. -(. -trifluoroacetylprolyl)leucine was cleaved on treatment with sodium borohydride in ethanol to rerr-butyl ester of A7-prolylleucine (92% yield) and trifluoroethanol [7772]. During catalytic hydrogenations over copper chromite, alcohols sometimes accompany amines that are the main products [7775]. 

The formation of spirocyclopropanes from the reaction of diazodiphenylmethane and ( )-8-phenylmenthyl esters of acrylic acid and methyl fumarate occurred with a modest level of diastereofacial selectivity (136). In contrast, diastereoselectivities of 90 10 were achieved in the cycloadditions of diazo(trimethylsilyl)methane with acrylamides 65 derived from camphor sultam as the chiral auxiliary (137) (Scheme 8.16). Interestingly, the initial cycloadducts 66 afforded the nonconjugated A -pyrazolines 67 on protodesilylation the latter were converted into optically active azaproline derivatives 68. In a related manner, acrylamide 69 was converted into A -pyrazolines 70a,b (138). The major diastereoisomer 70a was used to synthesize indolizidine 71. The key step in this synthesis involves the hydrogenolytic cleavage of the pyrazoline ring. 

On acid-catalyzed glycosylation of 110 with the rhodinoside 111, the disaccharide 112 is formed. This, after hydrogenolytic cleavage of the benzyl ether gives the 2,3,6-trideoxy-4-0-[2,3,6-trideoxy-7V-trifluoracetyl-4-0-p-nitrobenzoyl -L-/yx o-hexopyra-nosyl]-L-/Areo-hexopyranose (113) in 20% yield. 

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