Schmidt reaction stereoselectivity

The Schmidt reaction of a simple cyclic ketone yields lactams with the ring expanded, while the intramolecular Schmidt reaction of cyclic ketone with an azido group at the side chain leads to the formation of bicyclic lactams with nitrogen at the position of fusion. It is interesting that the reaction between a cyclic ketone and 2-azido ethanol can form either a lactam or a lactone by means of the treatment with a different base, in which the lactam is formed when the reaction system is treated with KOH, whereas lactone is generated when NaHCOs is used as the base. Especially, the reaction between 4-ferf-butylcyclohexanone and 3-azido-2-methyl-2-phenylpropanol gives lactam in 19 1 stereoselectivity. ... 

Zhang and Tu employed the intramolecular Schmidt reaction as a key step in their total synthesis of ( )-maistemonine (6) and ( )-stemonamide (7) [7]. Treatment of 2,2-disubstituted cyclohexadione 4 with TiC provided the desired bicyclic amide 5 containing the central perhydroazaazulene ring system. The remarkable stereoselectivity was accounted for by invoking the preferred conformation B over A, the latter suffering from repulsive steric interaction between the allyl and the alkynyl substituents (Scheme 4.2). 

Borzilleri RM, Zheng X, Schmidt RJ, Johnson JA, Kim S-H, DiMarco JD, Fairchild CR, Gougoutas JZ, Lee FYF, Long BH, Vite GD. (2000) A novel application of a pd(0)-catalyzed nucleophilic substitution reaction to the regio- and stereoselective synthesis of lactam analogues of the epothilone natural products. J Am Chem Soc 122 8890-8897. 

Movassaghi M, Schmidt MA (2005) N- Ielcrocyclic carbene-catalyzed amida-tion of unactivated esters with amino alcohols. Org Lett 7 2453-2456 Nair V, Vellalath S, Poonoth M, Mohan R, Suresh E (2006a) N- Ielcrocyclic carbene catalyzed reaction of enals and 1,2-dicarbonyl compounds stereoselective synthesis of spiro y-butyrolactones. Org Lett 8 507-509 Nair V, Vellalath S, Poonoth M, Suresh E (2006b) V-Heterocyclic carbene-catalyzed reaction of chalcones and enals via homoenolate an efficient synthesis of 1,3,4-trisubstituted cyclopentenes. J Am Chem Soc 128 8736-8737... 

In the second reported synthesis IS) (Scheme 3) racemic A-benzoyl-meroquinene (42 R = H) was obtained from hexahydroisoquinolone 34. The cis vinyl and acetic acid side chains were formed by a sequence of reactions including stereoselective hydrogenation, Schmidt rearrangement, and pyrolytic JV-nitrosolactam fragmentation. 

Historical perspective C. H. Heathcock, Comp. Org. Syn. 2, 133-179 (1991). General review T. Mukaiyama, Org. React. 28,203-331 (1982). Application of lithium and magnesium enolates C. H. Heathcock, Comp. Org. Syn. 2, 181-238 (1991) of boron enolates B. M. Kim etal, ibid. 239-275 of transition metal enolates I. Paterson, ibid. 301-319. Stereoselective reactions of ester and thioester enolates M. Braun, H. Sacha, J. Prakt. Chem. 335,653-668 (1993). Review of asymmetric methodology A. S. Franklin, I. Paterson, Contemp. Org. Syn. 1,317-338 (1994). Cf. Claisen-Schmidt Condensation Henry Reaction Ivanov Reaction Knoevenagel Condensation Reformatskv Reaction Robinson Annulation. 

Schmidt et al. reported an effect of a crown ether on the glycosylation of mannofuranose. Scheme 4 shows an example of stereoselective coupling of mannofuranose 2,3 5,6-di-O-isopropylidene acetal (6) with primary triflate (7) in the presence of NaH [5, 6]. The coupling reaction in the absence of the crown ether afforded only P-glycosides (9). Mannofuranose is different from ribofuranose in having two endo hydroxyl groups at the 2,3-positions. Thus mannofuranose could be a better ligand for complex formation. In particular, the P anion preferentially forms a complex... 

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