Hydrogenolysis acetals

The cleavage of the tricyclic structure such as the product presented in Eq. 8.83 leads to a linear aminopolyhydroxylated structure (Scheme 8.25).135 Two-step unfolding (silyl ether hydroxydesilylation/nitroso acetal hydrogenolysis) can be useful in the preparation of hydroxy-lated amino acids (Eq. 8.84). 

Synthesis of enantiomerically enriched 4-aminocyclohex-anones also has been achieved (Scheme 16.72). Reaction of dienophile (+)-365 with nitroalkene 38 affords nitronate 366 in 98% yield via an exo-(alkoxy)-transition structure. The [3 + 2] cycloaddition requires 110 °C to produce nitroso acetal 367 in 78% yield. To preserve the carbonyl moiety, the nitroso acetal hydrogenolysis must be closely monitored and stopped when both N—O bonds are cleaved ( 40min). Acetylation of the product affords 368 in 86% yield. 

Two tandem [4 -I- 2]/[3 -I- 2] cycloadditions were highlighted one involves nitroalkenes and the other 1,3,4-oxadia-zoles. However, this nomenclature is an oversimplification. The tandem processes involving cycloadditions of nitroalkenes do not really end after the [3 + 2] cycloaddition step. The nitroso acetal hydrogenolysis is almost always an inevitable component of the process, intimately connected to the cycloadditions with the common objective—to create polycyclic amines. Therefore, the more accurate name of such processes should be tandem [4 - - 2]/[3 - - 2]/hydrogenolysis. On the other hand, the tandem cycloaddition of 1,3,4-oxadiazoles involves an intervening extmsion of dinitrogen, which is a retro-[3 + 2] cycloaddition. Therefore, the more accurate name is tandem [4 -I- 2]/retro-[3 -I- 2]/[3 -I- 2] cycloaddition. 

The blocking and deblocking of carboxyl groups occurs by reactions similar to those described for hydroxyl and amino groups. The most important protected derivatives are /-butyl, benzyl, and methyl esters. These may be cleaved in this order by trifluoroacetic acid, hydrogenolysis, and strong acid or base (J.F.W. McOmie, 1973). 2,2,2-Trihaloethyl esters are cleaved electro-lytically (M.F. Semmelhack, 1972) or by zinc in acetic acid like the Tbeoc- and Tceoc-protected hydroxyl and amino groups. 

The 2,3-alkadienyl acetate 851 reacts with terminal alkynes to give the 2-alkynyl-1,3-diene derivative 852 without using Cul and a base. In the absence of other reactants, the terminal alkyne 853 is formed by an unusual elimination as an intermediate, which reacts further with 851 to give the dimer 854. Hydrogenolysis of 851 with formic acid affords the 2, 4-diene 855[524]. 

Unusual reducing properties can be obtained with borohydride derivatives formed in situ. A variety of reductions have been reported, including hydrogenolysis of carbonyls and alkylation of amines with sodium borohydride in carboxyHc acids such as acetic and trifluoroacetic (38), in which the acyloxyborohydride is the reducing agent. 

Many other polymerization processes have been patented, but only some of them appear to be developed or under development ia 1996. One large-scale process uses an acid montmorrillonite clay and acetic anhydride (209) another process uses strong perfiuorosulfonic acid reski catalysts (170,210). The polymerization product ia these processes is a poly(tetramethylene ether) with acetate end groups, which have to be removed by alkaline hydrolysis (211) or hydrogenolysis (212). If necessary, the product is then neutralized, eg, with phosphoric acid (213), and the salts removed by filtration. Instead of montmorrillonite clay, other acidic catalysts can be used, such as EuUer s earth or zeoHtes (214—216). 

One process (182) esterifi.es the acetic acid with ethanol (or methanol) and then converts the ester to alcohol by hydrogenolysis in the vapor phase over a copper—2inc catalyst. 

The best way to make pyrimidine in quantity is from 1,1,3,3-tetraethoxypropane (or other such acetal of malondialdehyde) and formamide, by either a continuous (58CB2832) or a batch process (57CB942). Other practical ways to make small amounts in the laboratory are thermal decarboxylation of pyrimidine-4,6-dicarboxylic acid (744), prepared by oxidation of 4,6-dimethylpyrimidine (59JCS525), or hydrogenolysis of 2,4-dichloropyrimidine over palladium-charcoal in the presence of magnesium oxide (53JCS1646). 

Picolyl ethers are prepared from their chlorides by a Williamson ether synthesis (68-83% yield). Some selectivity for primary versus secondary alcohols can be achieved (ratios = 4.3-4.6 1). They are cleaved electrolytically ( — 1.4 V, 0.5 M HBF4, MeOH, 70% yield). Since picolyl chlorides are unstable as the free base, they must be generated from the hydrochloride prior to use. These derivatives are relatively stable to acid (CF3CO2H, HF/anisole). Cleavage can also be effected by hydrogenolysis in acetic acid. ... 

A benzylidene acetal is a commonly used protective group for 1,2- and 1,3-diols. In the case of a 1,2,3-triol the 1,3-acetal is the preferred product. It has the advantage that it can be removed under neutral conditions by hydrogenolysis or by acid hydrolysis. Benzyl groups and isolated olefins have been hydrogenated in the presence of 1,3-benzylidene acetals. Benzylidene acetals of 1,2-diols are more susceptible to hydrogenolysis than are those of 1,3-diols. In fact, the former can be removed in the presence of the latter. A polymer-bound benzylidene acetal has also been prepared." ... 

Historically, simple Vz-alkyl ethers formed from a phenol and a halide or sulfate were cleaved under rather drastic conditions (e.g., refluxing HBr). New ether protective groups have been developed that are removed under much milder conditions (e.g., via nucleophilic displacement, hydrogenolysis of benzyl ethers, and mild acid hydrolysis of acetal-type ethers) that seldom affect other functional groups in a molecule. 

Over palladium this cleavage occurs in preference to the saturation of a 5,6-double bond. " The use of platinum in acetic acid allows saturation of the A -olefin in (36) without hydrogenolysis of the 22,23-dibromides. 

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