Tiffeneau-Demjanov rearrangements

Selectivity in rearrangement reactions is affected by the electronic nature of both the group that migrates and the group that is left behind. But there is more Stereochemistry is important too. The outcome of diazotization and semipinacol rearrangement (Tiffeneau-Demjanov rearrangement) of this amino-alcohol depends entirely on the diaster eoisomer you start with. There are four diastereoisomers, and we have drawn each one in the only conformation it can reasonably adopt, with the f-butyl group equatorial. 

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

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 ... 

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 stabilization of the intermediate as a carhenium - oxonium ion in the diazotization of P-amino alcohols (Tiffeneau-Demjanov rearrangement) is responsible for the formation of 4-bromo-5,5-dimethylbicyclo[2.1.1]hexane-l-carbaldehyde (30) in the reaction of l-amino-4-bromo-7,7-dimethylbicyclo[2.2.1]heptan-2-ol with nitric acid.96... 

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.

Similar results were obtained on application of the related Tiffeneau-Demjanov reaction. This semipi-nacol-type reaction, an extension of the Demjanov rearrangement, involves the rearrangement of a diazonium ion (25 Scheme 7), which is generated by the diazotization of the corresponding amino alcohol (24).The amino alcohol is obtained from the ketone by reduction of a nitrome ane adduct (23a), cyanohydrin (23b) or trimethylsilyl cyanohydrin (23c). This procedure allows for a controlled addition-rearrangement sequence in cases where the use of diazomethane is complicated by the further reaction of the product ketone. 

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

Semipinacol rearrangements of diazonium salts derived from 2-amino alcohols are sometimes called TIffeneau-DemJanov rearrangements. 

---