Schmidt Rearrangement Reactions with Alkyl Azides

Organic Azides Syntheses and Applications Edited by Stefan Erase and Klaus Banert 2010 John Wiley Sons, Ltd. ISBN 978-0-470-51998-1 

There were very few reports of Schmidt reactions involving alkyl azides for almost 40 years after Boyer s papers appeared. Some papers described sequences that resembled the bona fide Schmidt reaction in that azides ultimately afforded lactams, but were thermally enacted and mechanistically distinct from the classical Schmidt reaction (see Section 7.5). hi the early 1990s, a series of disclosures finally established synthetically useful versions of the Schmidt reaction using various kinds of alkyl azides as the key substrates. The following discussion of this chemistry will concentrate first on those reactions in which the electrophilic partner is a carbonyl group or carbonyl equivalent. Later sections will describe processes in which an alkyl azide attacks a carbocation derived from an alkene, alcohol, or a related precursor. Finally, the ways in which these reactions have been used to construct natural products or other compounds of interest will conclude this chapter. 

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Schmidt Rearrangement Reactions with Alkyl Azides... 

Schmidt Rearrangement Reactions with Alkyl Azides 201 Table 7.3 Reactions of hydroxyalkyl azides with ketones... 

Aube and co-workers have found that enolizable ketones react with benzyl azide in triflic acid to yield /V-(phenylamino)-methylated products [Eq. (5.354)]. The transformation is an aza-Mannich reaction interpreted with the involvement of the Mannich reagent A -phenyl iminium ion 295 formed in situ in a Schmidt rearrangement. Cyclic tertiary alcohols react with alkyl azides in triflic acid to yield N-alkylamines (296, 297)983 [Eq. (5.355)]. The Schmidt rearrangement was used to transform Merrifield resin into amino-polystyrene resin by reacting the azido derivative in excess triflic acid (CH2CI2, 0°C).984... 

In addition to the Beckmann reaction, the Schmidt rearrangement is used to generate M-alkylated lactams, too. Alkyl azides 231 react with the cyclic ketones (and aldehydes) in the presence of proton or Lewis acids. On running the inter-molecular reactions, in most cases symmetric ketals 230 have been converted... 

A tandem reaction sequence involving electrocyclization, azide capture, and Schmidt rearrangement is observed when certain cross-conjugated dienones and alkyl azides are treated with BE3 OEt2. ... 

Although the rearrangement of alkyl and aryl azides on treatment with acids, reaction (39), was discovered by Curtius , it is sometimes called a Schmidt reaction, although Schmidt did not work with these... 

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