Acyl thiohydroxamates

In more recent studies, the Barton group has shown that 0-acyl thiohydroxamates (thiohydroxamate esters) are convenient sources of alkyl radicals.490,51,52 Barton s thiohydroxamate ester chemistry is mild and easily executed, and the intermediate organic radicals are amenable to a wide variety of useful transformations. A thiohydroxamate ester of the type 125 (see Scheme 23) can be formed... 

The procedure described here allows for a convenient and efficient preparation in very high yields of large quantities of bromides from carboxylic acids containing an olefinic functionality. The Hunsdiecker reaction is traditionally accomplished by treating anhydrous silver carboxylates with bromine or iodine.2 Heavy metal salts such as mercury,3 lead,4 and thallium5 have also been used successfully as well as tert-butyl hypoiodite.6 The major disadvantages associated with the above methods, such as use of heavy metal salts and non-tolerance towards olefins, has led to the development of a more versatile method using O-acyl thiohydroxamates.7 8 The O-... 

An alternative method is the deoxygenation of the anomeric carboxylic acid 52, producing 55 [27], The functionalized precursor, in particular the O-acyl-thiohydroxamate ester 54, which is formed in situ after exposure of the carboxylic acid 52 to the salt 53, is decarboxylated by the Barton method. 

As an example in the furanose series, the sodium salt of commercial 2,3 4,6-di-0-isopropylidene-2-keto-a-L-gulonic acid222 was treated with oxalyl chloride, and then with 95. Heating the resultant 0-acyl thiohydroxamate to reflux in... 

The formation and photochemical decomposition of an o-acyl thiohydroxamate 65, Scheme 22, which is readily... 

The elements with a lone pair of electrons and very rich redox chemistry, have certainly been well exploited in ionic reactions. We decided to study the radical chain reactions based on acyl derivatives of thiohydroxamates and incorporating compounds of group V or VI elements in a unique fashion. In these very highly disciplined and efficient chain reactions (if properly designed and administered) the basic concept is one of valence shell expansion.11 The general philosophy of this series of reactions developed by us is depicted in Scheme 31. A simple illustration of this concept is the use of sulfur dioxide as a radical trap in conjunction with an o-acyl thiohydroxamate leading to the formation of S-pyridyl alkylthiosulfonates 117.84 For practical reasons this reaction is carried out at —10 °C in a mixture of dichloromethane and liquid S02. The sulfur atom undergoes a valence shell expansion from S(IV) to S(VI). 

A second, more versatile, method involves the O-acyl thiohydroxamates. These compounds are generally prepared by reaction of acyl chlorides with the commercial sodium salt (1) of 2-mercapto-pyridine A(-oxide (equation 6 X = Cl). Use of mixed anhydrides formed by reaction of the carboxylic acid with isobutyl chloroformate (equation 6 X = OCC>2CH2CHMe2) renders the procedure compatible with unprotected indoles, phenols, secondary and, presumably, tertiary alcohols. An alternative mode of preparation of the 0-acyl thlohydroxamates involves the s t (2) in reaction with the carboxylic acid (equation 7). 

The free radical chain reaction of 0-acyl thiohydroxamates with a tertiary thiol (r-butyl, triethylmethyl or more recently t-dodecyl) is by far the most wide-ranging reductive decarboxylation method describe to date7 A wide variety of functional groups, including aldehydes, ketones, esters, amides, isolated and conjugated double bonds, are tolerated. Representative examples are given in equations (10) and (11). ... 

A mild, but indirect, approach to oxidative decarboxylation involves a modification of the 0-acyl thiohydroxamate decarboxylative rearrangement (Section 5.4.6.1). An 0-acyl selenohydroxamate is photolyzed to give a noralkyl-2-pyridyl selenide which, after ozonolysis to the selenoxide, undergoes syn elimination to the alkene (equation IS). 

The photolytic or thermal decomposition of 0-acyl thiohydroxamates in halogen donor solvents such as tetrachloromethane or bromotrichloromethane constitutes the most wide-ranging and generally iplic-... 

The reaction of 0-acyl thiohydroxamates with tris(phenylthio)phosphorus, initiated by adventitious oxygen at room temperature, leads in the first instance to alkylbis(phenylthio)phosphines (Scheme 2) by a chain mechanism. Combination of the latter with the disulfide by product affords a phosphotus(V) species which on woik-up gives a]kylbis(phenylduo)phosphonates (Scheme 2 and equation 38) widh moderate to good yields. lliis reaction sequence provides a convenient meduxl for die overall transformation of a carboxylic acid into a readily hydrolyzable ester of the analogous phosphonic acid. 

A more efficient and general procedure once again involves the <7-acyl thiohydroxamates. Decomposition in the presence of triplet oxygen, and r-butyl thiol as hydrogen donor, provides norelkyl hydroperox-... 

In an alternative sequence, 0-acyl thiohydroxamates are reacted with tris(phenylthio)antimony to give the corresponding alkylbis(phenylthio)antimony compound. On admission of air Ais latter species undergoes oxygen insertion and rearrangement. Finely, hydrolysis provides the alcohol (Scheme 3 and equation 44). 

Hexenyl radicals cyclize to cyclopentylmethyl radicals (see Volume 4, Chapter 4.2). Thus radical decarboxylation of 6-heptenoic acids, by whatever means, usually results in die formation of five-mem-v beied rings. Although this fact had been appreciated previously it is only recendy, widi the advent of the 0-acyl thiohydroxamates, that it has been exploited from a syndietic point of view. An example is provided by the synthesis of bicyclo[4.3.0]proline derivatives from aspartic acid carried out by the Barton group (equation 51). It will be noted that activation of die C—C double bond acting as a radical trap is not necessary in these intramolecular reactions. 

Radical addition to C—C triple bonds is also possible with the 0-acyl thiohydroxamate methodology. As with addition to C—C double bonds (vide supra), the triple bond must be either terminal and activated with an electron-withdrawing group (equation 52) or doubly activated if intemal. ... 

The simple photolytic or thermal decomposition of 0-acyl thiohydroxamates in benzene or pyridine as solvent yields the product of decarboxylative rearrangement, and not alkylbenzenes or alkylpyridines. However, photolysis in dichioromethane in the presence of protonated heteroaromatic bases results in the formation of alkylated heterocycles in good yield, as illustrated in equation (57). The great advantage of this latter method lies in the fact that the base to be alkylated is not used as the reaction solvent, which evidently permits the use of a much wider range of bases as trapping agents. 

The Barton decarboxylation involves the preparation of O-acyl thiohydroxamates A from acid chlorides and sodium salt of N-hydroxy-2-thiopyridine (2.44), which undergoes... 

A wide variety of thiophilic radicals induce fragmentation of O-acyl thiohydroxamates by addition to the thiocarbonyl group, and in doing so generate carboxyl radicals (Scheme 1). After decarboxylation the... 

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