Cycloadditions ketenes, imines

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... 

Scheme 29 describes a plausible mechanism for the formation of the products which fit the observed coulometric (n 0.45 F/mol) and preparative results. The intramolecular cyclization process involves a dimerization between a radical cation 52a and the ketene imine 52 to form the intermediate radical cation 52b which then cyclizes to the radical 52c which can abstract a hydrogen atom leading to 54 or can be further oxidized and transformed through a cyclization and deprotonation reaction to 53 which involves 1 F/mol. However, it seems that the [2 -1- 3]-cycloaddition between the parent compound 52 and the cation 52d giving rise to 55 is the fastest reaction as compared with the intramolecular cyclization of 52d to 53. This can also explain the low consumption of electricity. 

Density functional and semiempirical AMI molecular orbital calculations have been used to investigate substituent effects on site selectivity in heterocumulene-hetero-diene4 + 2-cycloadditions between ketene imines and acroleins.The new and novel heterocumulenes a, /3-unsaturated thioaldehyde S -oxides (97) behave as both diene... 

The cascade ketene imine [2 + 2] cycloaddition and palladium catalyzed cyclization is a convenient route to furoazepine 98 (X = O) with the fused )S-lactam... 

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). 

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. ... 

Cycloaddition reactions were also carried out using l,2-bis(trifluoromethyl)-fumaronitrile (137,138,191,192). Seven-membered cychc ketene imines (186-188) could actually be isolated in good yields from the reactions with 69,... 

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>. 

A number of cycloadditions of imines or imino compounds with a variety of alkenes, including allenes (88HCA1025), vinyl ethers (88TL547), methyl acrylate (86ZOR636), ketene acetals (87JOC365) and electrophilic alkenes (85T1953), afford functionalized azetidines. 

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)... 

Trifluoromethyl-P-lactam 63 was prepared in racemic form via a ketene-imine [2 + 2] cycloaddition, following previously published methods81 with modifications.46 The subsequent oxidative cleavage of PMP, acylation of NH with (f-Boc)20, hydrogenolysis over Pd/C, and protection as 1-ethoxyethyl ether gave N-f-Boc-P-lactam 63 in good overall yield (Scheme 13). 

The formal [2+2]-cycloaddition of imines to ketenes forms P-lactams. 

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. 

Another common method for the synthesis of 2-azetidinones is the cycloaddition of imines with ketenes, which is known as the Staudinger reaction . Although commonly described as a [2 + 2]... 

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. 

The multipole expansion model has seen use in the examination of solvation effects on both reaction coordinates and conformational equilibria, including the isomerization of push-pull ethylenes o (e,g., nitroenamines), the ketene-imine [2-f 2]-cycloaddition to form p-lactam,24i and the Diels-Alder reaction.242,243 Again, only the ENP terms are considered in general. 

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

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