Barton reactions

Misslitz, A. de Meijere, Methoden Org. Chem. (Houben-Weyl), 1990, Vol. E19b, p. 675-680. 

Nitrous acid esters 1 can be converted to 3-nitroso alcohols 2 by irradiation with ultraviolet light. This conversion is called the Barton reaction.  

Upon the irradiation the nitrous acid ester 1 decomposes to give nitrous oxide (NO) and an alkoxy radical species 3. The latter further reacts by an intramolecular hydrogen abstraction via a cyclic, six-membered transition state 4 to give an intermediate carbon radical species 5, which then reacts with the nitrous oxide to yield the 3-nitroso alcohol 2  

There is quite some evidence for a mechanism as formulated above,especially for the six-membered transition state—the Barton reaction is observed only with starting materials of appropriate structure and geometry, while the photolysis of nitrite esters in general seldom leads to useful products formed by fragmentation, disproportionation or unselective intermolecular hydrogen abstraction. 

The photolysis of 1-octyl nitrite 6 yields 4-nitroso-l-octanol 8 in 45% yield, via cyclic transition state 7—the formation of regioisomeric nitroso alcohols is not observed  

Irradiation at wavelength greater than 330 nm, causes homolytic cleavage of O—NO bond of the nitrite to nitric oxide and alkoxy radical. 

The nitric oxide and alkoxy radical formed on photolysis can undergo one of the following reactions  

By the Barton reaction a methyl group in the 5-position to an Hydroxyl group can be oxidized to a —CHO group. 

Like Norrish type I reaction, the intermolecular 1, 5-hydrogen transfer to alkoxy radical involves a six memhered cyclic transition state structure, as demonstrated by the photolysis of series of co-phenylalkyl nitrites. 

The propyl and pentyl nitrites are expected to transfer a benzylic hydrogen to the alkoxy radical through a five- and a seven-membered cyclic transition state but only 1, 5-Hydrogen transfer is observed. 

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Baeyer-Villager oxidation, 10, 151, 433 Bamford-Stevens reaction, 402 Barton reaction, 253 Beckmann rearrangement, 140 Benzilic acid rearrangement, 418, 435 3 -Benzoyloxy-7-methylenecholest-5-ene, 60 Benzylmagnesium chloride, 64 3-Benzyloxycholesta-3,5-diene, 342... 

The Barton reaction is usually carried out by irradiation of a nitrite ester 1 dissolved in a hydroxyl-free solvent under nitrogen atmosphere. Possible side-reactions can be decomposition reactions and intermolecular reactions sometimes the disproportionation may even predominate ... 

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. ... 

The Hofmann-Loeffler-Freytag reaction has been described with A-chloro-as well as A-bromoamines—the former however usually give better yields. A-chlorinated primary amines react well in the presence of Fe-(II) ions. Just like the Barton reaction, the Hofmann-Loeffler-Freytag reaction has been applied mainly in steroid chemistry. An interesting example from alkaloid chemistry is the synthesis of nicotine 12 by Loeffler ... 

A radical approach to asymmetnc iildol synthesis, which is based on the radical addition of a chiral hydroxyalkyl radical equivalent to a tutroalkene, has been reported, as shown in Eq 4 93 The radical precursor is prepared from the corresponding carboxyhc acid by the Barton reaction, which has been used for synthesis of new fi-lactams ... 

Scheme 19. Nitrite ester photolysis the Barton reaction.

Scheme 21. The Barton reaction in Magnus s synthesis of grandisol (117).

Another related reaction is the Barton reaction, by which a methyl group in the 0 position to an OH group can be oxidized to a CHO group. The alcohol is first converted to the nitrite ester. Photolysis of the nitrite results in conversion of the nitrite group to the OH group and nitrosation of the methyl group. Hydrolysis of the oxime tautomer gives the aldehyde, for example,... 

Imidazole-A-thionocarboxylates (also called thiocarbonylimidazolides ) are intermediates in a convenient radical-induced deoxygenation of primary and secondary alcohols with tributylstannane (Barton reaction).[1],[2]... 

Other synthetic applications of the Barton reaction in the steroid field follow[Pg.263]

Photolysis of 2-propylnitrite, in which intramolecular hydrogen abstraction cannot occur via a six-membered transition state, results in a 30% yield of 2-propanone. As we shall see, this intramolecular hydrogen abstraction has been extensively applied to steroid syntheses by D. H. R. Barton and hence is commonly referred to as the Barton reaction. 

Radical migration of hydrogen is also known, though only over longer distances than 1,2-shifts, e.g. a 1,5-shift to oxygen via a 6-membered cyclic T.S. in the photolysis of the nitrite ester (129)—an example of the Barton reaction ... 

Nitro-aldols, which are readily available (see Henry reaction Section 3.1), are converted into olefins via conversion of the hydroxyl group to the corresponding phenyl thiocarbonate ester and treatment with tin radical.158 The yield was not reported. Because the radical deoxygenation via thiocarbonate (Barton reaction) proceeds in good yield, the elimination of Eq. 7.115 might be good choice for olefin synthesis.159... 

The photochemical cleavage of organic nitrites 224), also known as Barton reaction, has been widely utilized in the steroid field. The mechanistic sequence as described in (2.14) consists of ... 

An alternative method in the synthesis of alkaloids, photochemical rearrangement of endocyclic nitrones into bicyclic lactams has drawn special attention. Analyses of photochemical rearrangement and application of modified conditions of the Barton reaction testify to the comparability of results obtained in these approaches (Scheme 2.89) (460). 

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