Schmidt reactions asymmetric

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. ... 

Figure 2.6 Claisen-Schmidt condensation-asymmetric epoxidation reactions over nanocrystalline aerogelpre pared AP-MgO catalysts.

Choudary, B.M. Kantam, M.L. Ranganath, K.V.S. Mahendar, K. Sreedhar, B. Bifunctional nanocrystalline MgO for chiral epoxy ketones via Claisen-Schmidt condensation-asymmetric epoxi-dation reactions. J. Am. Chem. Soc. 2004,126, 3396-3397. 

The Schmidt reaction is closely related to the Beckmann reaction (equation 34). Acyclic and cyclic ketones are transformed to amides and lactams by treatment with hydrogen azide. With bridged bi-cyclic ketones, the regioselectivity of the migration is opposite to the direction of the Beckmann reaction. The Schmidt reaction has been applied to asymmetric synthesis starting from optically active a,a-dialkylated -keto esters. High chemical and optical yields have been obtained (equation 35). ... 

Gracias, V., Milligan, G. L., Aube, J. Efficient Nitrogen Ring-Expansion Process Facilitated by in Situ Hemiketal Formation. An Asymmetric Schmidt Reaction. J. Am. Chem. Soc. 1995, 117, 8047-8048. 

CLAISEN-SCHMIDT CONDENSATION-ASYMMETRIC EPOXIDATION REACTIONS... 

Variation 4 Asymmetric Schmidt Reaction of Ketones with Hydroxyalkyl Azides (Aube )... 

Scheme 7.15 Asymmetric Schmidt reactions with a monosubstituted hydroxyalkyl azide...

Scheme 7.18 Role of cation-n interactions in asymmetric Schmidt reactions...

Rudy H, Cramer KE (1939) Uber den oxydativen Abbau des alloxan-2-dimethylatino anils zu 1-methyl benzimidazol. Chem Ber A 72(4) 728-744 Sahasrabudhe K, Gracias V, Furness K, Smith BT, Katz CE, Reddy DS, Aube J (2003) Asymmetric Schmidt reaction of hydroxyalkyl azides with ketones. J Am Chem Soc 125 (26) 7914-7922. doi 10.1021/ja0348896... 

Wrohleski A, Sahasrabudhe K, Aube J. Asymmetric total synthesis of dendrobatid alkaloids preparation of indolizi-dine 25 IF and its 3-desmethyl analogue using an intramolecular Schmidt reaction strategy. J. Am. Chem. Soc. 2004 126(17) 5475-5481. 

Penzien, K. and G. M. J. Schmidt (1969). Reactions in chiral crystals - an absolute asymmetric synthesis. Angew. Chem. Int. Ed. Engl, 8, 608. 

The dendrobatid alkaloid 251F 213 (Figure 12.4) was isolated from the skin exudates of a Columbian dendrobatid poison frog, Minyobates bombetes [105]. The asymmetric total synthesis of this molecule has been reported by Aube and co-workers [106], The synthesis featured a Noyori-type three-component reaction to access an advanced bicyclopentenone intermediate, and also included a tandem ROM/RCM reaction sequence and a Schmidt rearrangement as key steps. 

Penzien and Schmidt reported the first absolute asymmetric transformation in a chiral crystal. [10] They showed that enone 4,4 -dimethylchalcone 1, although being achiral itself, crystallizes spontaneously in the chiral space group P2 2 2 (Scheme 1). When single crystals of this material are treated with bromine vapor in a gas-solid reaction, the chiral dibromide 2 is produced in 6-25% ee. In this elegant experiment, it is the reaction medium, the chiral crystal lattice, that provides the asymmetric influence favoring the formation of one product enantiomer over the other, and the chemist has merely provided a non-chiral solvent (ethyl acetate) for the crystallization and a nonchiral reagent (bromine) for the reaction. 

Chiral crystals generated from non-chiral molecules have served as reactants for the performance of so-called absolute asymmetric synthesis. The chiral environments of such crystals exert asymmetric induction in photochemical, thermal and heterogeneous reactions [41]. Early reports on successful absolute asymmetric synthesis include the y-ray-induced isotactic polymerization of frans-frans-l,3-pentadiene in an all-frans perhydropheny-lene crystal by Farina et al. [42] and the gas-solid asymmetric bromination ofpjp -chmethyl chalcone, yielding the chiral dibromo compound, by Penzien and Schmidt [43]. These studies were followed by the 2n + 2n photodimerization reactions of non-chiral dienes, resulting in the formation of chiral cyclobutanes [44-48]. In recent years more than a dozen such syntheses have been reported. They include unimolecular di- r-methane rearrangements and the Nourish Type II photoreactions [49] of an achiral oxo- [50] and athio-amide [51] into optically active /Mactams, photo-isomerization of alkyl-cobalt complexes [52], asymmetric synthesis of two-component molecular crystals composed from achiral molecules [53] and, more recently, the conversion of non-chiral aldehydes into homochiral alcohols [54,55]. 

A fruitful approach to obtain asymmetric polymer synthesis was proposed by Overberger (126) who suggested that propagation could be influenced and optically active polymers could be synthesized by using optically active gegen-ions. Schmidt and Schuerch (127) followed up this suggestion and used boron trifluoride in conjunction with asymmetric Lewis bases (1-a-methyl benzyl alcohol, tosyl L-valine, camphor) to polymerize certain cyclic olefins. However, in spite of careful work and various modifications in reaction conditions, no optical activity was obtained in the polymers in this first attempt to test this ingenious hypothesis. 

The first use of crystals to achieve asymmetric induction in a chemical reaction was reported by Penzien and Schmidt in 1969 [3]. In what the authors termed an absolute asymmetric synthesis because it occurs in the absence of any external source of optical activity, Penzien and Schmidt showed that the achiral compound 4,4 -dimethylchalcone 1 crystallizes spontaneously from ethyl acetate in the chiral space group P2i2121, and when enantiomorphously pure... 

The use of Al(III) complexes as catalysts in Lewis acid mediated reactions has been known for years. However, recent years have witnessed interesting developments in this area with the use of ingeiuously designed neutral tri-coordinate Al(lll) chelates. Representative examples involving such chelates as catalysts include (1) asymmetric acyl halide-aldehyde cyclocondensations, " (2) asymmetric Meerwein-Schmidt-Ponndorf-Verley reduction of prochiral ketones, (3) aldol transfer reactions and (4) asymmetric rearrangement of a-amino aldehydes to access optically active a-hydroxy ketones. It is important to point out that, in most cases, the use of a chelating ligand appears critical for effective catalytic activity and enantioselectivity. 

---