A Chiral, Oxidatively Cleavable Auxiliary in β-Lactam Synthesis - Double Diastereocontrol with p-Methoxyphenethyl-Substituted Imines

Abstract

A new chiral, oxidatively removable auxiliary for the Staudinger reaction is presented. When diazo ketones 1-3 prepared from suitably protected amino acids reacted with p-methoxyphenethyl (PMPE)-substituted imines, the corresponding trans-substituted b-lactams 7 and 8a-h were formed. With the (S)-configured imine 5, an improvement of the selectivities is observed in comparison with achiral p-methoxybenzyl (PMB)-substituted imines by double stereoselection; consequently, the ratio of isomers decreased with the (R)-imine 4. The auxiliary could be removed with cerium ammonium nitrate (CAN).

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 resulting solution was cooled to 0°C under an ice-water bath. Ceric ammonium nitrate (18.1 g, 33.2 mmol) was added to the mixture which was stirred at the same temperature for 1 h. [10] The solution was allowed to warm to room temperature, and stirring was continued for another 3 h. The reaction mixture was extracted with ethyl acetate (2´200 mL). The combined organic layer was washed with water (30 mL) and brine (50 mL), dried over anhydrous MgSO 4 , and the solvent was evaporated under reduced pressure.…”

“…The resulting aqueous solution was extracted with dichloromethane (3´50 mL), the organic layers were combined and dried (MgSO 4 ), and the solvent was removed under vacuum to yield a yellow oil which was subjected to silica gel column chromatography [EtOAc : hexanes (3 : 2) as eluent]. The title compound was isolated as a yellow oil which was a mixture of diastereoisomers; yield: 5.22 g (94%); 1 H NMR (600 MHz, CDCl 3 ) syn-isomer: = 5.31 (ddd,J = 52,10,8 Hz,1 H),4.19 (dd,J = 16,6 (5S)-2,2-Dimethyl-7,7-difluoro-8-oxo-1-aza-3-oxabicyclo[3.3.0]octane Prepared as described for the monofluorination procedure using the 2,2-dimethyl-7-fluoro-8-oxo-1-aza-3-oxabicyclo[3.3.0]octane (4.95 g, 28.6 mmol), column chromatography [chloroform : EtOAc (4 : 1) as eluent] afforded the title compound as a white solid; yield: 4.37 g (80%) mp 35±37°C (from ethyl acetate/light petroleum); [a] D 28 = +89.2 (c 0.85, CHCl 3 ); IR (film): m = 1732 cm ±1 ; 1 H NMR (500 MHz, CDCl 3 ):…”

Recent advances in CAN mediated reactions in organic synthesis

“…162 Removal of PMPE group from b-lactam 166 was achieved by using CAN in acetonitrile. 163 Tomioka et al have reported a CAN mediated oxidative removal of N-PMP (p-methoxy phenyl) group. 164 …”

Unanticipated products from reductive and oxidative cleavages of 1‐substituted 3,3‐diphenyl‐1′‐methylspiro[azetidine‐2,3′‐indoline]‐2′,4‐diones

“…The N ‐dearylation (4‐methoxyphenyl group) and N ‐dealkylation ( bis ‐4‐anisylmethyl group, 4‐methoxyphenethyl group) of 2‐azetidinones by oxidative cleavage on treatment with well known oxidizing agent Ce(IV) ammonium nitrate (CAN) are well‐known reactions [30–34]. This reaction opens up room for a wide variety of transformation on the 2‐azetidinone ring.…”