Ketene imines synthesis

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

Mermerian AH, Fu GC (2005) Nucleophile-catalyzed asymmetric acylations of silyl ketene imines application to the enantioselective synthesis of verapamil. Angew Chem Int Ed 44 949-952... 

Four-membered ring adducts from 2n + 2n cycloaddition of keten-imines to sulfur dioxide. Isolation of l,2-thiazetidin-3-one 1-oxides. jS-Sultames. Simple method for synthesis of substituted 1,2-thia-zetidin 1,1-dioxide. ... 

Reviews including aspects of P-lactam chemistry are ketene-imine cycloaddition reactions <98CHE1222>, radical cyclization processes <98MI169>, combinatorial synthesis <98AJC875>, electrophilic cyclization of unsaturated amides <98T13681> and theoretical studies on the synthesis of P-lactams <98MI245>. 

Carbacephalosporins The ketene-imine cyclization described above has been extended to a synthesis of a chiral carbacepham (4). This synthesis uses a dihy-droanisole group as the equivalent of a p-keto ester. Thus the azetidinone 1, obtained in 80% yield by the above route, was reduced and acylated in situ to provide 2. Ozonization followed by a rhodium-catalyzed cyclization of an a-diazo-P-keto ester provides 3, which is a useful intermediate to various substituted car-bacephams such as 4. 

In conclusion, the CAI activity of spiro-(3-lactams, their antiviral and antibacterial properties, their potential as efficient (3-tum nucleators and (3-tum mimetics, and their application as synthons for a,a-disubstituted (3-amino acids motivated synthetic and medicinal chemists to design novel spirocyclic (3-lactams. Several approaches to the stereoselective synthesis of spiro-(3-lactams have been described in this review. However, ketene-imine cycloaddition (Staudinger Reaction) shows much versatility for the access to diversely functionalized spiro-(3-lactams. In addition, we have developed a facile route to novel spiro-(3-lactams by using... 

Compared with the single-bond construction approach of (3-lactam synthesis, the ketene-imine cycloaddition, which includes carbenoid insertion and the Staudinger reaction, have been widely used [56, 65]. Due to the ready availability of both imines and ketenes, the Staudinger reaction has provided a useful and economical approach for the synthesis of (3-lactams. In addition, the ketene-imine cycloaddition is efficient, which constructs the (3-lactam four-member ring in just one-step... 

After examining the feasibility of an asymmetric [2 + 2] ketene-imine cycloaddition route and an asymmetric ester enolate-imine cyclocondensation route, we chose the latter route for the efficient asymmetric synthesis of (3/ ,4Sj-3-hydroxy-4-phenylazetidin-2-one and (2R,35)-/V-benzoyl-3-phenylisoserine. The cyclocondensation of the lithium enolate of (-)-(1 / ,2S)-2-phenyl-1 -cyclohexyltriiso-propylsiloxyacetate (5a P = (i-Pr)3Si (TIPS) and R = (-)-(lR,2S)-2-phenyl-1 -cyclohexyl) with A-trimethylsilylbenzaldimine (6a R1 = Ph) in THF at -78 °C gives (3/ ,4S)-3-triisopropylsiloxy-4-phenylazetidin-2-one (7a P = TIPS and R1 = Ph)... 

Based on their fluorination protocol, Cahard and co-workers have elaborated a convenient synthesis of a-fluoro-a-phenylglycin derivatives [18]. For example, upon reaction with reagent 24 racemic nitrile 23 was converted into the fluorinated derivative 25 with 94% enantiomeric excess. The corresponding ester derivatives of 23 gave rise to somewhat lower ees. This difference was contributed to the fact that a-lithiated nitriles can be in equilibrium with axial-chiral lithio ketene imines of low racemization barriers thus leading to a potential dynamic kinetic resolution. 

Fu has demonstrated that acetate anion attack on the silicon center of the silyl ketene acetal, as well as formation of an acyl pyridinium salt, contribute towards the promotion of these reactions [62]. Additionally, silyl ketene imines have also been shown to participate in analogous asymmetric C-acylation reactions to yield chiral quaternary nitriles, and this method was employed as a key step in the synthesis of verapamil [65]. 

An efficient use of triphosgene, as an acid activator, for the synthesis of substituted 2-azetidinones via ketene-imine cycloaddition reaction using various acids and imines has been achieved <02T2215>. Novel routes to monocyclic (3-lactams 13 and 14 through the photochemical decomposition of oxime oxalate amides <02CC2086> and a-oxoamides <02OL1443> have also been described. 

A convenient synthesis of thiazolo-fused 2-pyridones 41 has been developed <07JOC4917>. Thus, A2-thiazolines 39 undergo acyl ketene imine cyclocondensation with Meldrum s acid derivatives 38 to give the dihydro thiazolo-fused 2-pyridones 40, which transform to 41 via bromination-elimination process. Pyridones 41 are converted to the 2-substituted analogs 43 and the saturated products 42 by Heck coupling and conjugate addition, respectively. 

For a review of reactions of ketene imines, generated from carbene complexes by addition of isocyanides, see Ref. 3q and Aumann, R. In Organometallics in Organic Synthesis Aspects of a Modern Interdisciplinary Field de Meijere, A. tom Dieck, H., Eds. Springer-Verlag Berlin, Heidelberg, 1987, pp. 69-83. 

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. 

Ab initio calculations indicate that in the gas phase the reaction of ketene imine and formaldehyde is concerted hut asynchronous whereas in dichloromethane it is a two-step zwitterionic reaction. The 2 - - 2-cycloadditions of keteniminiinn triflates with imines yields 2-azetidiniminiinn salts with cis stereoselectivity. The intramolecular 2 + 2-cycloaddition of ketenimines with imines (24) provides a novel synthesis of azeto[2,l-h]quinazolines (25) (Scheme 9)." ... 

Borer, B C, Balogh, D W, An asymmetric synthesis of a 3-hydroxy-(3-lactam by ketene-imine cycloaddition utilization of chiral ketenes from carbohydrates. Tetrahedron Lett., 32, 1039-1040, 1991. 

Acid amide-triphenylphosphine dihalide adducts (4) have found wide application in organic synthesis. - Synthetic equivalents are adducts (5) from acid amides and triphenylphosphine/CCU, which are prepared in situ from the educts. - With these reagents the following transformations have been performed dehydration of amides or aldoximes to nitriles, preparation of isonitriles from secondary form-amides, preparation of imidoyl halides from amides or acylhydrazines and preparation of ketene imines from amides. Using polymer-supported triphenylphosphine the work-up procedure is much easier to achieve. Triphenylphosphine can be replaced by tris(dialkylamino)phosphines. - Instead of CCI4 hexa-chloroethane, hexabromoethane or l,l,2,2-tetrabromo-l,2-dichloroethane can be used " the adducts thus formed are assumed to be more effective than those from the triphenylphosphine/CCU system. 

Ecteinascidin (ET)-743 is a marine natural product that exhibits potent antitumor activity. R.M. Williams and coworkers developed an approach for the synthesis of the pentacyclic framework of the molecule. At an early stage in the synthesis, they used a ketene-imine cycloaddition utilizing a chiral A/-protected ketene derivative to control the stereoselectivity. Subsequently, the chiral auxiliary was removed and the intermediate 3-lactam was converted to the target structure. 

Palomo, C., Aizpurua, J. M. Asymmetric synthesis of 3-amino-P-laclams via Staudinger ketene-imine cycloaddition reaction. Chem. Met. Comp. (New York) (Translation of Khim. Geterot. Soed.) 1999, 34,1222-1236. 

Macias, A., Alonso, E., Del Pozo, C., Venturini, A., Gonzalez, J. Diastereoselective [2+2]-Cycloaddition Reactions of Unsymmetrical Cyclic Ketenes with Imines Synthesis of Modified Prolines and Theoretical Study of the Reaction Mechanism. J. Org. Chem. 2004, 69, 7004-7012. 

Jones, W. M., Grasley, M. H. Tetrahedron Lett. 1962, 927 cf. the synthesis of highly reactive ketene imines from ot-diazoamino compounds Arnold, B., Regitz, M. Angew. Chem. 91, 337 (1979) Angew. Chem. Int. Ed. Engl. 18, 320 (1979)... 

The Staudinger reaction, i.e. the [2+2] ketene-imine cycloaddition, is the most frequently employed procedure of synthesis of the azetidin-2-one nucleus. Base-promoted cyclization of suitable linear substrates is another frequently employed procedure. We wish to report the electrochemical methodologies of synthesis of P-lactams, according to both procedures, and the possible utilization of RTILs (as solvents and/or as parent of intermediates). 

Scheme 16.3 Synthesis of the azetidin-2-one nucleus via the Staudinger reaction the [2+2] ketene-imine cycloaddition...

Palomo C, Aizpurua JM, Ganboa 1, Oiarbide M (1999) Asymmetric synthesis of P-lactams by Staudinger ketene-imine cycloaddition reaction. Eur J Org Chem 1999 3223-3235... 

Solid-phase and combinatorial synthesis of 6-lactams using the Staudinger reaction has widely been studied. Carbohydrates as a chiral pool, however, were not employed except for one report [148]. The polymer supported-imines were employed to prepare several -lactams by enolate/imine condensation and ketene/imine cycloaddition (Scheme 46) [146]. The reactions carried out on the polymer-boimd imines showed a remarkable similarity to those in solution, both in terms of yield and stereoselectivity [54,55]. )S-Lactams were removed from the polymer by CAN oxidation [ 148]. 

The synthesis of optically active thiazolo[3,2-fl]pyridinones has been described. Chiral thiazolines 27, prepared from the condensation of imino ethers 25 with (R)-cysteine methyl ester 26, undergo a ketene-imine cycloaddition reaction with Meldrum s acid derivatives 28 to give thiazolo[3,2-a]pyridinones 29 in good yields <01JOC6756>. 

In a continuation of his studies on asymmetric P-lactam synthesis, Evans [42] utilized a,P-epoxyaldehydes 49a and 49b, prepared in two steps from achiral allylic alcohols via Sharpless asymmetric epoxidation and Swern oxidation, as chiral glyoxal synthons for the ketene-imine cycloaddition. Diastereosel-ection was excellent, ranging from 90 10 to 97 3 with overall yield of 50 up to 84% (for Schiff base formation and cycloaddition) after recrystallization or chromatographic purification of the major diastereomer. The sense of asymmetric induction correlated with that obtained in the analogous glyceraldehyde reaction, as established by periodic acid cleavage to aldehydes 51. 

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