Cycloaddition ketene-imine

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

These building blocks can be obtained either by the Miller cyclization of (5-hydroxy-ct-amino acids or by the Staudinger reaction7 ([2+2] ketene-imine cycloaddition). The procedure reported here follows the second route and has the advantages of being diastereospecific and to proceed in high yield. For a large scale preparation, the harmful and toxic N-methylhydrazine can be replaced by N,N-dlmethyl-1,3-propanediamine. Further transformations of the key intermediate have been reported elsewhere.7 9... 

In an analogous late-stage arylation approach, terminal alkyne 31 was envisioned as a versatile intermediate. Slow addition of 4-pentynoyl chloride to imine 3 and (n-Bu)3N at reflux (efficient condenser, 100°C, 12 h, 1 1 toluene heptane) afforded only trace amounts of 31. Reaction of 4-pentynoyl chloride with triethylamine in methylene chloride under preformed ketene conditions ( 78°C, 1 h), followed by addition of 3 and warming to — 10°C over 4 h, afforded a complex mixture of products. Since high-yield preparation of 31 remained elusive, access to internal alkynyl analogs (type 33) was accomplished by preassembly of the appropriate arylalkynyl acid substrate for the ketene-imine cycloaddition reaction (Scheme 13.9). 

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>. 

Keywords Biological activity Cholesterol absorption inhibitors Ketene-imine cycloaddition Spiroazetidin-2-ones Spiro-(3-lactams Synthetic intermediates (3-Lactamase inhibitors... 

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... 

Ketene-imine cycloaddition reactions of ethoxycarbonyl(phenylthio)ketene with various imines and subsequent desulfurization reactions have been reported in 2006 to synthesize 3-ethoxycarbonyl (3-lactam derivatives [108]. 

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)... 

The past decade has witnessed considerable interest in solvent-free ketene-imine cycloaddition reactions employing microwave irradiation (Equation 203) C1995TL213, 1996TL6989, 1997H(44)405, 2005JOC334, 2005IJB2093>,... 

An approach to obtain racemic 7-ACA and its 7-epimer has been achieved employing a Staudinger-Bose ketene-imine cycloaddition to form the /3-lactam ring <1996T7691> (Scheme 18). Reaction of azidoacetyl chloride and thiazine 75 in the presence of 7-Pr2NEt afforded azidocephem 76 in 38% yield. Compound 76 was reduced to amine... 

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 rather intriguing route that both forms bond b as well as the annulated ring in a single step is outlined in Equation (2) <2005SL2370>. The starting azetidinone 12 is prepared by a ketene-imine cycloaddition. Treatment of 12 with methanolic HCl at reflux provides the aziridino-7-lactone 13 in excellent yield. 

THEOCHEM), in press. Electrostatic Solvent Effect on the Ketene—Imine Cycloaddition Reaction. 

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. 

VII. Methylseleno-Promoted Ketene-Imine Cycloaddition Reaction. 30... 

A new methylseleno-promoted ketene-imine cycloaddition reaction between 151 and 152 (86JOC4737) gave the bicyclic product 153 in an extremely high stereoselective fashion and in fairly good yield (36-92%) (Scheme 27). 

The reaction between methoxyacetyl chloride and (4/ )-155 or (4/ )-157 gave the corresponding bicyclic product in a moderate yield [58% in (4/ )-155] or in a very poor yield [5% in (4/ )-157] (compared to the 81% yield of 153a). Thus, a methylseleno substituent on the imine moiety promoted this ketene-imine cycloaddition reaction. 

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. 

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. 

Georg, G. I., Ravikumar, V. T. Stereocontrolled ketene-imine cycloaddition reactions. Org. Chem. fi-Lactams 993, 295-368. 

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. 

Sordo, J. A., Gonzalez, J., Sordo, T. L. An ab initio study on the mechanism of the ketene-imine cycloaddition reaction. J. Am. Chem. Soc. 

In a similar manner, enantiopure l-f-Boc-3-TIPSO-4-CF3-P-lactam 14 was synthesized from benzyloxyacetyl chloride/triethylamine and (V-PMP-CF3-aldimine through [2+2] ketene-imine cycloaddition, enzymatic optical resolution (PS Amano lipase at... 

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... 

The reaction of ester enolates with imines is a general method for the preparation of /5-lactams. This reaction is clearly not a concerted cycloaddition. The enolate adds to the imine generating an arnido ester intermediate. This intermediate, which is usually not isolated, cyclizes to give the /3-lactam. Since this subject has been recently reviewed81, only the stereochemical aspects of this reaction will be discussed here. In this reaction there are four possible sites for the chiral auxiliary. As in ketene imine cycloadditions, stereogenic centers can be introduced into the substituent on the imine carbon (R1), the substituent on the imine nitrogen (R2) or the substituent on the acyl portion of the ester (R3). There is a fourth possibility in these cycloadditions since the stereogenic center can also be introduced into the alkyl portion of the ester (R4), In some cases /r K-/ -lactams are obtained exclusively, while in other cases, mixtures of cis- and trans-isomers are isolated. 

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