Intramolecular Schmidt rearrangement

The obtained spiro keto esters 2-181 could be converted into 2-183, employing among other transformations an intramolecular Schmidt rearrangement [101] of the azido ketones 2-182. 

Nitrones derived from 2-azabicyclo[5.3.0]decane give quinolizidine compounds by photochemical Beckmann rearrangement which implies simultaneous ring expansion and ring contraction reactions. Intramolecular Schmidt reactions in 2(4-azidobutyl)-cyclopentanones also give quinolizidinone derivatives by ring expansion. Examples of both types of reactions are given in Sections 12.01.11.1 and 12.01.11.3, respectively. 

The intramolecularity of the migration step in the Schmidt rearrangements has been convincingly demonstrated by showing the retention of chirality of the migrating group.166... 

Treatment of 2,3 Cpoxy-l-amines with Lewis acid induces a rearrangement to aziridinium ions that react efficiently with a nucleophiles to give functionalized hydroxy sulfides or hydroxy amines (Equation 23) <1997SL11>. Under the influence of ethylaluminium chloride, an epoxide tethered to an azide undergoes Lewis acid-assisted cyclization followed by an intramolecular Schmidt reaction and subsequent in situ reduction of the intermediate iminium species upon addition of sodium borohydride (Scheme 8). This protocol was used as a key step in a novel synthesis of indolizidine alkaloids of pharmaceutical interest <20030L583, 2004JOC3093>. 

The total synthesis of (+)-sparteine (85) was achieved from 2,5-norbomadione 84 in 15 steps. The key steps in the synthesis were the two ring expansion reactions, one involving an intramolecular Schmidt reaction and the other a variant of the photo-Beckmann rearrangement ring-... 

The intramolecular Schmidt reactions of azido tertiary benzylic and propargylic alcohols 32 lead to l-azabicyclo[5.3.0]decanes or 1-azabicyclo[4.3.0]decanes (indolizidines) 36 without formation of the products derived from cation rearrangement. However, simple tertiary alcohols such as 37 undergo cation rearrangement prior to cyclization to give a mixture of regioisomeric indolizidines. 

Thiazolidine rings are normally easy to prepare but this year a new reaction has appeared in which the ring system was produced during a thermally-induced intramolecular eliminative rearrangement. The azido-enones (364) were heated to 140 C leading to a mixture of the products (365) and (366) in equal proportions. The authors have determined that an intramolecular acid-catalysed Schmidt reaction is not involved, and have proposed the triazoline (367) as a reasonable intermediate. They have also shown that in certain cases rearrangement coupled with desulphurization provides a completely regioselective method for conversion of 2-cycloalkenones to the ene lactams (368). 

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