Staudinger asymmetric

Asymmetric synthesis of 3-amino (3-lactams via Staudinger ketene-imine cycloaddition reaction 98KGS1448. 

The Staudinger reaction [92], a [2 + 2]-cycloaddition of a ketene and a nucleophilic imine, usually proceeds by an initial imine attack on the ketene thus forming a zwitterionic enolate which subsequently cyclizes. This reaction is an expedient route to p-lactams, the core of numerous antibiotics (e.g., penicillins) and other biologically active molecules [93]. In contrast, for Lewis-base catalyzed asymmetric reactions, nonnucleophilic imines are required (to suppress a noncatalyzed background reaction), bearing, for example, an N-Ts [94] or -Boc-substituent [95]. 

Fig. 40 Formation of (3-lactams via asymmetric Staudinger-type reactions, catalyzed by 64c...

Lee EC, Hodous BL, Bergin E, Shih C, Fu GC (2005) Catalytic asymmetric Staudinger reactions to form P-lactams an unanticipated dependence of diastereoselectivity on the choice of the nitrogen substituent. J Am Chem Soc 127 11586-11587... 

Wilson and Pasternak reported the first asymmetric Staudinger reaction (Scheme 4) where the chiral phosphane (7) reacts with the racemic azide (8) to afford diastereomeric iminophosphoranes in different quantities, giving after hydrolysis an amine in slight enatiomeric excess. Separation of the racemate seems to be kinetically controlled, but needs optimization (90MI1). 

An alternative route starting from serine 73 or threonine 68 74 makes use of diethoxy-triphenylphosphorane. Attempts to asymmetrically synthesize (25)-aziridine-2-carboxylic acid (1) by treating a, 3-dibromopropanoates with chiral amines 75 or by the Staudinger reaction from oxirane-2-carboxylic acid ester 70,76 leads to optically impure products, whereas 3-alkyl derivatives of tert-butyl aziridine-2-carboxylates can be prepared with high cis-selectivity from a-halo ester enolates and jV-trimethylsilyl imines. 77 Moreover, when optically... 

The reaction of iV-benzyloxycarbonyl L-proline acid chlorides 134 with imine 135 in the presence of triethylamine, at room temperature, gave the corresponding spiro-(3-lactams 136, 137 as a 1 1 mixture of diastereoisomers, which were separated by column chromatography. The Staudinger reaction proceeds with complete stereoselectivity with a cis relative disposition of the pyrrolidine nitrogen and the phenyl group, but no asymmetric induction was observed. However, very... 

Thiruvazhi et al. [112] have shown interest in the area of (3-tum mimetics and the synthetic application of d- and L-proline for asymmetric synthesis of proline-derived spiro-(3-lactams. It has been shown that the asymmetric Staudinger reaction of optically active acid chloride of d- and L-proline with achiral imines is impossible due to the loss of stereochemistry at C-2. The authors have developed a strategy in which a chiral group at C-4 of the acid chloride of proline directs the stereoselectivity of the reaction and is sacrificed later to obtain optically active spiro-(3-lactams (Scheme 38). 

In 2002, the asymmetric synthesis of 3-substituted 3-hydroxy-p-lactams has been reported to be realized by metal-mediated l,3-butadien-2-ylation reactions between 1,4-dibromo-2-butyne and optically pure azetidine-2,3-diones [64]. This latter starting material was prepared via Staudinger reaction followed by sequential transesterification and Swem oxidation (Scheme 15), [65]. 

Reaction of D-phenylalanine ethyl ester with cinnamaldehyde has been reported to give a chiral Schiff base, that underwent an asymmetric Staudinger [2+2] cycloaddition reaction with phthalimidoacetyl chloride to give the monocyclic... 

This research group further carried out an asymmetric version of the solid-phase Staudinger reaction using a chiral auxiliary at C-3 for the generation of active carbacephems and other multicyclic (3-lactam. Thus, the homochiral (,S )-4... 

Asymmetric synthesis on solid support is crucial for the generation of combinatorial libraries of novel optically active carbacephems and other polycyclic p-lactam derivatives [44]. Solid-phase Staudinger reaction of the homochiral... 

The role of some chiral bifunctional amines and optically active cinchona alkaloid derivatives (Figure 3) as catalysts has been explored in catalytic asymmetric Staudinger reactions. Bicarbonate salts have been used as viable alternatives to... 

Different polyethylene glycol polymers were used in various papers and proved to be very reliable and useful for different classes of molecules their use for the synthesis of peptides [180, 181], of peptidomimetics [182] and of oligosaccharide libraries [183] was reported as the development and the use of a new PEG-linked traceless linker [184, 185], the selection of ligands for asymmetric Sharpless dihydroxylation [186-188], the use of PEG-linked triarylphosphines for LPCS requiring Mitsunobu or Staudinger conditions [189], the use of PEG-based supports to prepare a library of [l,4]oxazepine-7-ones [190] and the use of PEG-supported Schiff bases for the synthesis of a-substituted amino acids [191], Other examples of soluble polymers used for LPCS may include cellulose[192], polyacrylamide [193] polyvinyl alcohol [194, 195], various copolymers [196, 197] and NCPS [198-200]. Three excellent reviews [201-203] summarized the properties of PEG and other soluble polymers and their applications to the synthesis of peptides, oligonucleotides,... 

Polymer-bound P-lactams have been prepared via the ester enolate imine condensation route <02JOC8034>. On the other hand, an efficient asymmetric synthesis of 2-azetidinones was accomplished when chiral acid chlorides or chiral aldehydes were used in the polymer-supported Staudinger reaction <02TA905>. 

Palomo, C. Aizpurua, J. M. Ganboa, I. Oiarbide, M. Asymmetric Synthesis of P-Lactams by Staudinger Ketene-Imine Cycloaddition Reaction, Eur. J. Org. Chem. 1999, 3223-3235. 

Imines derived from optically active amines have also been used in asymmetric Staudinger syntheses of p-lactams. Georg et al. [32] employed O-acetylated galactosylamine as the chiral auxiliary for the synthesis of P-lactams. The reaction between imines 41 and aryloxyacetyl chlorides 42 in the presence of Et3N afforded c/ -configurated A -galactosyl-P-lactams 43 in diastereomeric ratios not exceeding 66 34 (Scheme 10.11). 

SCHEME 10.11 Asymmetric Staudinger preparation of P-lactams directed by sugar-derived chiral auxiliaries. 

Cossio, F P, Airieta, A, Lecea, B, Ugalde, J M, Chiral control in the Staudinger reaction between ketenes and imines. A theoretical SCF-MO study on asymmetric torquoselectivity, J. Am. Chem. Soc., 116, 2085-2093, 1994. 

Barton, D H R, Gateau-Oleska, A, Anaya-Mateos, J, Cleophax, J, Gero, S D, Chiaroni, A, Riche, C, Asymmetric synthesis of 1,3,4-trisubstituted and 3,4-disubstituted 2-azetidinones strategy based on use of D-glucosamines as a chiral auxiliary in the Staudinger reaction, J. Chem. Soc. Perkin. Trans. 1, 3211-3212, 1990. 

Cossio, F. P., Lecea, B., Cuevas, C., Mielgo, A., Palomo, C. A novel entry for the asymmetric Staudinger reaction experimental and computational studies on the formation of P-lactams through [2+2] cycloaddition reaction of ketenes to imines. An. Quim. 1993, 89, 119-122. 

Palonao, C., Aizpurua, J. M. Azetidinone frameworks as chiral templates via asymmetric Staudinger reaction. Trends in Organic Chemistry 1993, 4, 637-659. 

---