Demjanov-Tiffeneau ring expansion

The formation of diazonium salts from aromatic primary amines by reaction with nitrous acid undoubtedly involves the intermediate formation of V-nitroso compounds. The Demjanov and Tiffeneau-Demjanov ring expansions also involve V-nitroso compounds [2]. Some V-nitroso compounds have been used as sources of free radicals and as blowing agents. 

P. A. S. Smith, D. R. Baer, The Demjanov and Tiffeneau-Demjanov Ring Expansions, Org. React. 1960,... 

The elaboration of ketone 144 by cycloaddition of ketene to cyclopentadiene has been known for some time.218- The Tiffeneau-Demjanov ring expansion of 144 was first described by Roberts and Gorham in 1952219 and the use of diazomethane to achieve the same objective clarified by Paquette in 1974.126-> Under both sets of conditions the 1-keto derivative predominates, the more so in the first instance. 

Tiffeneau-Demjanov ring expansion. Rearrangement of (i-amino alcohols on diazotization with nitrous acid to give ring-expanded carbonyl compounds. 

Vogel has applied the Tiffeneau-Demjanov ring-expansion reaction to convert oxabicyclo[2.2.1] substrates into oxabicyclo[3.2.1] compounds [91]. The reduction of nitrile 4 a generates 84 which, under deamination conditions, yielded 85, Eq. 64. Because 4a can be obtained in enantiomerically pure form, this constitutes a enantioselective synthesis for oxabicyclo[3.2.1] substrate 85. 

Table 3 Products from Tiffeneau-Demjanov ring expansion of 3-oxo-steroid...

Tiffeneau-Demjanov ring-expansion of an androstan-16-one leads selectively to the D-homo-17-one. Migration of C-15 through a favourable chair-like... 

Conflicting reports relating to the products obtained from the Tiffeneau-Demjanov ring-expansion of 5a-cholestan-3-one have appeared. G.Lc. analysis has failed to reveal the presence of the A-homo-3-ketone, although it has been detected by o.r.d. and c.d. measurements. The pure A-homo-4-ketone has now been obtained via solvolysis of the dibromocarbene adduct (309) of 3-methoxy-cholest-2-ene to afford the unsaturated halogenoketone (310) which was then reduced to the 4-one. In a similar manner, 3-acetoxycholest-3-ene afforded the isomeric unsaturated halogenoketone (311) which on reduction produced A-homo-5a-cholestan-3-one. 

Tiffeneau-Demjanov ring-expansion of 6jff-acetoxy-5a-cholestan-3-one has been used to prepare the corresponding A-homo-4-ketone methylene insertion with diazomethane led to A-bis- and -tris-homocholestanones as the only isolated products. 

Enones can be reduced to the saturated ketones with triethylsilane and Wilkinson s catalysis62 (equation 54). Interestingly, the same product was prepared via a Tiffeneau-Demjanov ring expansion wherein trimethylsilyl cyanide was used (equation 55). The selective reduction of the double bond of enones can also be carried out with diphenylsilane in the presence of palladium(O) or palladium(II) and zinc chloride63 (equation 56), or more effectively with phenylsilane and molybdenum hexacarbonyl64 (equation 57). This latter reagent was also used to reduce the double bond of a,/ -unsaturated esters, amides and nitriles. 

This reaction is related to the Wagner-Meerwein Rearrangement, Demjanov Rearrangement, Tiffeneau-Demjanov Ring Expansion and Retropinacol Rearrangement involving carbocation intermediates. 

An improved preparation of p-aminomethyl alcohols from ketones has been developed using trimethylsilyl cyanide followed by lithium aluminium hydride reduction. It is particularly useful for ocp-unsaturated ketones and for relatively hindered ketones, and should make the Tiffeneau-Demjanov ring-expansion procedure more attractive. ... 

Homoadamantanone is also obtained from the Tiffeneau-Demjanov, 01> 102) and diazomethane 103> 1041 homologations of adamantanone 67> 69 These ring expansions enable easy access to homoadamantane (36) and a variety of 4-mono and 4,5-disubstituted homoadamantanes. Some of this chemistry is summarized in Scheme 12. 

Fig. 11.19. Ring expansion of cyclic ketones via the Tiffeneau-Demjanov rearrangement. The first step consists of the additions of HCN or nitromethane, respectively, to form either the cyanohydrin or the /i-nitroalcohol, respectively. The vicinal amino alcohol A is formed in the next step by reduction with LiAIII4. The Tiffeneau-Demjanov rearrangement starts after diazotation with the dediazotation.

The use of Lewis acids for the diazomethane and diazoethane homologations of a series of Ce-Cu ketones has been reported to reduce the amount of epoxide formation, although as the ring size increases the amount of unreacted starting material increases (Scheme 12). The expansion of 2-allylcyclohexa-none with diazomethane in the presence of AlCh proceeds with migration of the less-subsdtut bond, in contrast to the Tiffeneau-Demjanov expansion of 2-methyl- and 2-isopropyl-cyclohexanone wherein the alkyl-substituted bond migrates preferentially (Scheme 13). - ... 

The stereochemistry of cyclic primary amines or aminoalcohols dramatically influences the product distribution of their respective Demjanov and Tiffeneau-Demjanov rearrangements. P. Vogel and co-workers have studied the ring-expansion of 2-aminomethyl-7-oxabicyclo[2.2.1]heptane derivatives upon treatment with nitrous acid. Some of their findings are shown below. ... 

The homologation of ketones by the addition of diazoalkanes complements the Tiffeneau-Demjanov rearrangement. Epoxide formation is a side reaction which can be minimized if polar aprotic solvents are avoided (Scheme 7). Rearrangement i.e. homologation) is maximized in ether solvents or by Lewis acid catalysis. The reaction is most effective in the ring expansion of cyclic ketones. 

Apparently contradictory results in the Tiffeneau-Demjanov expansion of ring have been only partially clarified from separate study of the epimeric 3-aminomethyl-3-ols (491) derived from 5a-cholestan-3-one, 17j5-hydroxy-5a-androstan-3-one, and the related trans-2-decalyl derivatives. The three reported products, the A-homo-3-one (492), A-homo-4-one (493), and the oxiran (494), are formed in differing proportions (Table 3). The same products arise from reaction between the 3-oxo-steroids and diazomethane it is clear from... 

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