Demjanov-Tiffeneau ring

An interesting feature of Scheme 10.17 is that the cyclopentane ring is formed in the final step by a Tiffeneau-Demjanov-type ring contraction (Section 8.6). The... 

Asymmetrically substituted rings can expand in two ways to give position isomers, the proportions of which can usually be rationalised by conformational considerations as to which ring bond is suitably placed for migration (however, see reaction 15). Demjanov-Tiffeneau reactions can be applied to bicyclics (reaction 15)... 

When a cyclic /3-amino alcohol—e.g. 1—is treated with nitrous acid, a deamination reaction can take place, to give a carbenium ion species 2, which in turn can undergo a rearrangement and subsequent loss of a proton to yield a ring-enlarged cyclic ketone 3. This reaction is called the Tiffeneau-Demjanov reactionit is of wider scope than the original Demjanov reaction ... 

Various side-reactions may be observed with the Demjanov reaction the Tiffeneau-Demjanov reaction usually gives better yields of the ring-enlarged product. 

This reaction has been used to form ring-expanded cyclic ketones, a procedure known as the Tiffeneau-Demjanov reaction 1... 

Treatment of 4,4-dimethyl-2-phenyl-l,3-thiazole-5(4//)-thione with ethyl diazoacetate gives, among other products, ethyl 1,3-thiazine carboxylate (179) (99). The formation of 179 has been rationalized by an acid-catalyzed addition of ethyl diazoacetate to the thiocarbonyl ylide 177 to first give intermediate 178, which undergoes a subsequent ring enlargement reaction via a Tiffeneau-Demjanov rearrangement. 

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. 

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. 

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

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 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. 

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). - ... 

Table 1 Ring Expnasion of Bridged Bicyclic Ketones with Diazoalkanes or Tiffeneau-Demjanov Rearrangement... 

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. ... 

---