Barton functionalization transform

The required nitrite esters 1 can easily be obtained by reaction of an appropriate alcohol with nitrosyl chloride (NOCl). The 3-nitroso alcohols 2 formed by the Barton reaction are useful intermediates for further synthetic transformations, and might for example be converted into carbonyl compounds or amines. The most important application for the Barton reaction is its use for the transformation of a non-activated C-H group into a functional group. This has for example been applied for the functionalisation of the non-activated methyl groups C-18 and C-19 in the synthesis of certain steroids. ... 

Carbon-centered radicals generated by Barton s thiohydroxamate method can also participate in ring-forming reactions (see Scheme 26).52b,s3 For example, irradiation of 129 results in the formation of compound 130 (82% yield). The outcome of this transformation is reminiscent of Stork s elegant radical cyclization/trapping processes (see Schemes 7 and 8), in that/botn alkene carbon atoms have become functionalized. / I... 

The substitution of a functional group for a hydrogen atom is a very important transformation in synthetic organic chemistry. Barton et al. [10] developed various radical chain defunctionalization reactions using dialkylphosphonates... 

BARTON, NAKANISHI, METH-COHN Comprehensive Natural Products Chemistry BARTON OLLIS Comprehensive Organic Chemistry KATRITZKY REES Comprehensive Heterocyclic Chemistry I CD-Rom KATRITZKY, REES SCRIVEN Comprehensive Heterocyclic Chemistry II KATRITZKY, METH-COHN REES Comprehensive Organic Functional Group Transformations... 

Barton, Nakanishi Meth-Cohn Comprehensive Natural Products Chemistry Katritzky, Meth-Cohn Rees Comprehensive Organic Functional Group Transformations Katritzky, Rees Scriven Comprehensive Heterocyclic Chemistry II Sainsbury Rodd s Chemistry of Carbon Compounds... 

Sequences in which addition precedes cyclization are not as straightforward to conduct as the reverse however, they are very important because a net annulation results (that is, a new ring is formed by the union of two acyclic precursors in one experimental step). The intermediate radical is differentiated from the other radicals provided that the cyclization reaction is rapid, but it can be difficult to differentiate the initial radical from the final radical. As illustrated in Scheme 57, this is particularly true in the tin hydride method because many different types of radicals react with tin hydride at similar rates. Reaction of (69) under standard radical addition conditions produces (70), which results from a sequence of addition/cy-clization/addition.233 That the last C—C bond is formed actually results from a lack of selectivity the initial and final radicals are not differentiated and they must undergo the same reaction. Of course, this lack of selectivity is of no consequence if the product contains the desired skeleton and the needed functionality for subsequent transformations. Such sequences are very useful for forming three carbon-carbon bonds, and they can also be conducted by Barton s thiohydroxamate method.234 Structural modifications are required to differentiate the initial and final radicals, and, as illustrated by the conversion of (71) to (72), phenyl groups can provide the needed differentiation (probably by retarding the rate of addition more than they retard the rate of hydrogen abstraction). Clive has demonstrated that phenyl-substituted vinyl radicals also provide the needed selectivity, as illustrated by the second example in Scheme 57.233... 

Among the numerous applications of this reaction reported over four decades, some typical examples of the functionalization are outlined in Schemes 3 to 10. Thus, Scheme 3 outlines the well-known Barton transformation of corticosterone acetate nitrite into aldosterone acetate oxime which, with nitrous acid, gives aldosterone 12-acetate [4]. The yield of 18-oxime is, however, rather low (21 %), since attack by the 11/3-alkoxyl radical on C-19 competes with the desired attack on C-18. Incorporation of the 1,2-double bond into the nitrite prevented undesired C-19 attack by the radical and a far better yield (47 %) of 18-oxime was achieved [5] (Scheme 4). This example may indicate that the Barton reaction is sensitive to... 

Barton [26] suggested that one may use a Fourier transform formula to convert the intensity modulation into an image function, (r) ... 

Remote functionalization of the angular methyl group in santonin derivatives has also been accomplished using the Barton reaction. For example a key step in the previously reported synthesis of the norsesquiterpenoid rishitin (450) from tetrahydro-a-santonin (443) involves photochemical transformation of the nitrite ester (447) to the oxime (448) (c/. Scheme 46). Rishitin (450) is a well known antifungal phytoalexin produced by diseased potato tubers and recent studies... 

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