Schmidt reactions intermolecular

Intermolecular Schmidt reactions of alkyl azides and hydroxyalkyl azides with cycloketones in the presence of a Lewis acid, lead to formation of iV-alkyl lactams and A-hydroxyalkyl lactams respectively in good yield. The synthesis of chiral lactams by an asymmetric Schmidt reaction has also been reported. ... 

Imines react with alkynes to give pyrroles (equation 29). " A related transformation of azides has been reported by the group of Toste to afford pyrroles by an acetylenic Schmidt reaction (equation 30). " In an intermolecular-related addition, gold triazolates are obtained. The intramolecnlar hydroamination of trichloroacetimidates derived from propar-gyl and homopropargyl alcohols also proceeds with cationic An(I) as catalysts. ... 

Under the conditions of the Schmidt reaction the azide group in (81) was captured intermolecularly by a carbocation, producing an aminodiazonium ion intermediate which subsequently rearranged yielding indolizidine 167B (82) <93JA10183>. 

Somewhat similar results are obtained with a Hojfman reaction on polyacrylamide [279]. A Schmidt reaction on poly (acrylic acid) also yields mixed results [250]. When it is run in acetic acid, the intermolecular reactions appear to predominate over the intramolecular ones. Also, the products formed in acetic acid have higher nitrogen content that those formed in dioxane [250]. The NMR spectra show presence of some acid anhydride groups. This has an additional effect of lowering the yield. 

The acid-promoted intermolecular Schmidt reaction has been developed, though with moderate success rScheme Indeed, several products can be isolated depending on the allq l azides used and the nature of the acid. Generally, cyclohexanones and related cyclic ketones can generate the traditional Schmidt adduct 11 in the presence of T1C14, whereas a Mannich... 

Scheme 4.6 Intermolecular Schmidt reactions using hydroxyalkyl azides.

Scheme 4.17 Intermolecular Diels-Alder/Schmidt reaction sequence with enones.

Ketones generally fail to react with alkyl azides under standard Schmidt conditions. However, when these reactions are conducted in the presence of Lewis acid instead of the protic conditions used in the standard Schmidt reactions, the intermolecular Schmidt reactions can be carried out in moderate to good yields. Titanium(IV) chloride (> 1.0 equiv) in dichloromethane is the best reagent for effecting this type of reactions. The best substrates include the sterically unhindered ketones, especially cyclohexanones. This transformation is sensitive to steric effects, and even the a-substituted ketones may lead to poor yields and require long reaction time. The intermolecular Schmidt reaction with alkyl azides is still limited to a small range of cyclic ketones. For example, cyclopentanones do not react well with alkyl azides. 

Aube and collaborators reported an expeditious total synthesis of ( )-stenine in only nine steps and 14% overall yield through a cascade intermolecular Diels-Alder reaction/intramolecular Schmidt reaction sequence (Scheme 13.17) [20]. The cascade sequence allowed the construction of the BCD ring system of the natural product in one step, and the routine was also the shortest one among all the completed synthetic strategies so far. 

Scheme 13.17 Total synthesis of ( )-stenine (117) by using cascade intermolecular Diels-Alder reaction/intramolecular Schmidt reaction sequence.

Following the introduction of the intramolecular azido-Schmidt reaction, it was reported that potent Lewis acids such as TiCL were found to facilitate certain intermolecular... 

Scheme 7.23 Intermolecular Schmidt reactions of alkyl azides with carbocations...

The examples of ex situ steady-state X-ray photodiffraction utihzed to follow the photodimerizations of olefin bonds in a single-crystal-to-single-crystal (or nearly so) manner are ubiquitous in the chemical literature. The interest of sohd-state chemists in this reaction dates back to the work of Cohen and Schmidt [30, 31], and it has become much of a guinea pig in organic solid-state photochemistry. In 1993, Enkelmann and collaborators published two seminal papers in the Journal of the American Chemical Society [32] and in Angewandte Chemie [33], where they presented a series of structures of a-tra s-cinnamic acid crystals reacted to various extents. These reports laid the way for a plethora of later studies on the olefin photodimerization reaction. The convenience of the high conversion and the simple mechanism, combined with the relatively small structural perturbation that it requires, has turned this reaction into a very useful tool to probe intermolecular... 

The above properties (a and b) are interpreted by Cohen and Schmidt (21) on the basis of a detailed crystallographic study of photochromic and thermochromic anils. They conclude that photochromic crystals involve structures in which the central portion of adjacent molecules are essentially isolated from one another, so that, to a first approximation the energetics are that of an isolated molecule. On the other hand, when the alignment of the molecular dipoles is such as to give strong intermolecular interactions then the transition to the quinoid form requires much less energy and can occur thermally. For crystals in which thermochromism occurs, the photochemical isomerization is still possible but the reverse reaction is so rapid that no buildup of color is observed. In fact, fluorescence measurements on the thermochromic 5 -chlorosalicylidene-aniline (Fig. 5) indicate that photochemical isomerization precedes the luminescence process via the photochromic route ... 

Scheme 4.S Schmidt versus Mannich pathways in intermolecular reactions.

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