Asymmetric synthesis of 34--substituted β-lactams via chiral norephedrine-derived oxazolidines.

Chiral-Auxiliary-Controlled Diastereoselective Epoxidations

“…Another example is the diastereoselective oxidation of the chiral norephedrine-derived oxazolidines 9 (Scheme 8), which may be readily prepared on a large scale from the commercially available norephedrine 1S,2R-enantiomer. 40 As shown, the a,b-unsaturated aldehyde 9 is oxi-dized by potassium chlorite in aqueous THF to give the corresponding epoxy acid in 90% overall yield as the single 2R,3R-isomer (de value >96% by 1 H NMR spectroscopy). Based on this efficacious method, Gennari et al reported an attractive diastereo-and enantioselective synthesis of the functionalized cis-configured b-lactam described in section 4.…”

“…40 As shown, the a,b-unsaturated aldehyde 9 is oxidized by potassium chlorite in aqueous THF to give the corresponding epoxy acid in 90% overall yield as the single 2R,3R-isomer (de value >96% by 1 H NMR spectroscopy). Based on this efficacious method, Gennari et al…”

“…73 For this purpose, Gennari et al 40 have described a diastereoselective synthesis of such functionalized cis-disubstituted b-lactams, which is based on the use of norephedrine-derived oxazolidines as chiral auxiliary. The sequence started with the optically pure epoxy acid, prepared from the a,b-unsaturated aldehyde (see Scheme 8 in subsection 2.2), which was treated with Me 2 CuLi in Et 2 O-THF to give regioselectively and stereoselectively (>98%) the corresponding anti-a-methyl-bhydroxy acid in 70% yield of isolated product.…”

The Use of N‐Boc‐1,3‐Oxazolidines as Chiral Auxiliaries in Asymmetric Synthesis

“…Scheme 2 This pioneering work showed that protection of the nitrogen in the oxazolidines with an electron-withdrawing group allowed purification by flash chromatography, thereby es-tablishing their utility as chiral inductors in asymmetric synthesis. This work was rapidly followed by the publication of other efficient stereoselective transformations of alkenyl moieties adjacent to a N-acyl-or N-tosyl-oxazolidine heterocycle, such as cuprate, [11] Grignard, and lithium acetylide [12] conjugated additions, epoxidation, [13] Michael addition of alkoxides, [14] radical cyclizations, [15] cyclopropanation, [16] hydrogenation, [17] 1,3-dipolar cycloadditions, [18] and intramolecular DielsϪAlder reactions. [19] The problems discussed in the Introduction were to a large extent solved at this stage, since the introduction of an electron-withdrawing group on the nitrogen of the heterocycle allowed the stereoselective synthesis of the cis-2,4 isomer with excellent diastereoisomeric excesses, [12] this cis isomer being favored both kinetically and thermodynamically.…”

Monocarboxylates of 3‐Methylidene‐β‐lactams: Synthesis and unusual oxidative rearrangement into a spiro[azetidine‐3,3′‐pyrrolidine] derivative

“…2 kcal/mol between the (E)-and (2)-isomers, they may explain the preferred formation of the (E)-isomers. From the reaction of 7b or 7c with H,O, in alkali [6], t-BuOOH [7], or KOCl [8], we always isolated one single crystalline product, which obviously was not an oxirane. Its structure 8, a spiro[azetidine-3,3'-pyrrolidine]-2,5'-dione, is established by MS and spectroscopic data.…”