Construction of Quaternary Stereogenic Centers via [2 + 2] Cycloaddition Reactions. Synthesis of Homochiral 4,4-Disubstituted 2-Azetidinones and Imine Substituent Effects on β-Lactam Formation

Abstract

A study on the asymmetric construction of quaternary stereogenic centers via [2 + 2] cycloaddition reaction of ketenes with ketimines is described. Reaction of achiral ketenes and chiral alpha-alkoxy ketone-derived imines resulted in formation of new beta-lactams as single diastereomers. The cycloaddition was extended to pyruvate imines, aralkyl ketone-derived imines, and dialkyl ketimines. In these cases the asymmetric induction was satisfactorily achieved using beta-silylalkanoyl ketenes and the Evans-Sjögren ketene. C,C-Bis (trimethylsilyl)methylamine ketimines derived from enolizable dialkyl ketones cleanly led to the corresponding C(4) disubstituted beta-lactams without deprotonation. Therefore, a general methodology for a convergent asymmetric synthesis of beta-lactams in which C(4) exists as a quaternary carbon is provided.

Asymmetric Synthesis and Antimicrobial Activity of Some New Mono and Bicyclic β-Lactams

“…A solution of phthalimidoacetyl chloride was slowly added at -10 o C to a solution of chiral Schiff base 5 and triethylamine in dry methylene chloride. This method of addition produced the cis β-lactam 6 as a single stereoisomer in 80% yield [13][14][15][16]. The expected cisconfiguration of 6 was confirmed by 1 H-NMR, which showed a characteristic coupling constant of about 5 Hz for the β-lactam protons [17][18].…”

Reactivity Enhancement for Chiral Dirhodium(II) Tetrakis(Carboxamidates)

“…Thus oxidative cleavage of the acetone ketal of d-mannitol, [7] followed by imine formation, afforded 3 which was then treated with zinc dust and ethyl bromodifluoroacetate [8] to produce 4 as a mixture of diastereoisomers whose ratio was dependent on R 1 (Bn, syn/anti = 4.7; p-MeOC 6 H 4 CH 2 , syn/anti = 4.0; Ph 2 CH, syn/anti = 2.0). Chromatographic separation of the syn-isomer, alcoholysis, oxidation, [9] and esterification produced the azetidin-2-one product 5 that was deprotected [10] to afford the desired ligand. The key to this synthesis was the success of the Reformatsky reaction (step d), for which the only deficiency was the stereoisomer ratio with imines whose R 1 substituent was removable at a later stage.…”

“…The syn to anti ratio was determined by 1 13 C NMR (62.5 MHz,CDCl 3 ): d = 159. 9,130.1,126.1,119.9 (t,J F,C = 292 Hz),114.1,110.5,74.8,66.3 (t, J F, C = 23.7 Hz),66.1,55.3,44.8 (t,J F,C = 2.8 Hz),26.5,24.9. asc.wiley-vch.de (4R)-1-(4'-Methoxylbenzyl)-3,3-difluoro-4-(isobutyloxycarbonyl)azetidin-2-one A solution of c-lactam 4 (7.6 g, 23.2 mmol) in 166 mL of 6 : 3 : 1 CH 2 Cl 2 /TFA/CH 3 OH (100 : 50 : 16 mL) was stirred at room temperature for 1 h (step e, Scheme 1). The solvent was evaporated under vacuum, and to the residue was added toluene (50 mL) which was evaporated to remove residual TFA.…”

From?-lactams to?- and?-amino acid derived peptides

“…The key step of this approach is the cycloaddition reaction of benzyloxyketene with a-alkoxyketone-derived imines 19 as readily available starting materials which possess the required structural subunit of the desired amino acid and, at the same time, provide chirality to the corresponding NCA precursors, Scheme 6. Using standard cycloaddition conditions we got the corresponding fi-lactams in good yields and, most notably, as single diastereomers (Palomo et al, 1997c). Subsequent removal of the benzyl protective group from the resulting cycloadducts, led to the ct-hydroxy fl-lactams 20.…”