Cyclopropanones reactions with diazomethane

Acetoxycyclopropan-l-ol is a storable source of cyclopropanone. Reaction with diazomethane yielded cyclobutanone (11) and methyl aeetate via a low equilibrium concentration of free cyclopropanone.128... 

Mono- and bis(trimethylsilyl)-substituted cyclopropanones 15 are stable enough to be isolated. Reaction with diazomethane,131 trimethylsilyldiazomethane131 and diazoacetic acid es-ters 130 131 yielded mono-, bis- and tris(trimethylsilyl)-subslitutcd cyclobutanones 16 and 17. In all cases, the regio- and stereochemistry arc in accord with the general rules given. 

Cyclobutanones may be prepared without isolating the intermediate cyclopropanone by adding the ketene to excess diazoalkane (-78°C, 30 min) . The intermediacy of cyclopropanones in this process has been shown by C-labeling studies and by comparison of the product distributions in the diazoalkane-ketene with the corresponding diazoalkane-cyclopropanone reactions. When the cyclopropanone precursor is un-symmetrically substituted, the reaction with diazomethane leads to a mixture of cyclobutanones . 

For monocyclic and many fused bicyclic ketones the general order of reactivity of3>4>6>7 5 has been observed in the reaction with diazomethane and derivatives. Cyclopropanones react smoothly with diazomethane and diazoethane in the absence of catalysts to form cyclobutanones (equations 1 and 2). ... 

Reaction with Diazomethane to Form Silylated Cyclopropanes and Cyclohutanones. The reaction of (1) and diazomethane results in a mixture of products. Treatment of equimolar amounts of (1) with diazomethane at — 130°C leads to (trimethylsilyl)cyclopropanone in moderate yield (eq 12). The product obtained can then react with a second equivalent of diazomethane upon warming to — 78°C, resulting in ring expansion to a mixture of 2- and 3-(trimethylsilyl)cyclobutanones. Alternatively, these isomeric products may be obtained directly with 2 equiv of diazomethane. Treatment of the isomeric (trimethylsilyl)cyclobutanone mixture with methanol makes it possible to obtain pure 3-substituted isomer in 84% yield. This 3-(trimethylsilyl)cyclobutanone derivative can also be formed by a more elaborate route via the regioselective [2 + 2] addition of dichloroketene to trimethylsilylacetylene followed by hydrogenation and reductive removal of the two chlorine atoms. trimethylsilyidiazomethane has also been reported to react with (1) to form bis-silyl substituted cyclopropanones. ... 

Cyclopropanone Synthesis. The literature procedures (jj,6) for the synthesis of cyclopropanone utilize the reaction of a 2-3 fold excess of ketene with diazomethane at -78°C as shown in Equation 5. 

The transition metal-catalyzed cyclopropanation of alkenes is one of the most efficient methods for the preparation of cyclopropanes. In 1959 Dull and Abend reported [617] their finding that treatment of ketene diethylacetal with diazomethane in the presence of catalytic amounts of copper(I) bromide leads to the formation of cyclopropanone diethylacetal. The same year Wittig described the cyclopropanation of cyclohexene with diazomethane and zinc(II) iodide [494]. Since then many variations and improvements of this reaction have been reported. Today a large number of transition metal complexes are known which react with diazoalkanes or other carbene precursors to yield intermediates capable of cyclopropanating olefins (Figure 3.32). However, from the commonly used catalysts of this type (rhodium(II) or palladium(II) carboxylates, copper salts) no carbene complexes have yet been identified spectroscopically. 

Ketenes rarely produce [3+ 2]-cycloaddition products with diazo compounds. The reaction possibilities are complex, and nitrogen-free products are often obtained (5). Formation of a cyclopropanone represents one possibihty. Along these lines, the synthesis of (Z)-2,3-bis(trialkylsilyl)cyclopropanones and (Z)-2-trialkylsilyl-3-(triethylgermyl)cyclopropanones from diazo(trialkylsilyl)methanes and appropriate silyl- or germylketenes has been reported (256,257). It was found that subsequent reaction of the cyclopropanone with the diazoalkane was not a problem, in contrast to the reaction of diazomethane with the same ketenes. The high cycloaddition reactivity of diazomethylenephosphoranes also extends to heterocumulenes. The compound R2P(C1)=C=N2 (R = N(/-Pr)2) reacts with CS2, PhNCO and PhNCS to give the corresponding 1,2,3-triazole derivative (60). 

Reactions of cyclopropanones with nucleophiles frequently lead to ring enlargement reactions since the formation of four-membered rings from the reactive intermediates is accompanied by a considerable reduction in strain energy. Thus, 2 reacts with diazomethane to form cyclobutanone96>, with hydrazoic acid to form (3-lactam 76,89) and, under special conditions, with amines and hydroxyl amine derivatives to form N-sub-stituted (3-lactams 87> (Scheme 24). 

The bicyclic product 59 proved not to be derived from diazo ketone 58. It may arise from the reaction of diazenyl ketene intermediate 53 with diazomethane via the postulated 2-[2-methyl-2-(phenyldiazenyl)propyl] cyclopropanone intermediate 60 and its subsequent isomerization to the bicyclic product 59 (Scheme 14). The formation of the diazenyl ketene intermediate 53 has been made plausible by carrying out the reaction in the presence of an excess of isobutyl alcohol to afford isobutyl 3-methyl-3-[(E)-phenyldiazenyl]butanoate (61) in a competing addition. 

Homologiauion. The rea nt catalyzes the reaction of ketene acetals with diazomethane to give cyclopropanone acetals ... 

Ketene allowed to react at-145° with diazomethane in a solventless liq. phase cyclopropanone. Y ca. 90%. - Reactivity at cryogenic temp, increases with increasing ring strain. F. products and reactions s. E. F. Rothgery, R. J. Holt, and H. A. McGee, Jr., Am. Soc. 97, 4971 (1975). 

The utility of cyclopropanones as synthetic intermediates has hitherto been limited by their low accessibility. It has now been shown that a very convenient precursor of cyclopropanone is 1-acetoxycyclopropanol, the acetate group being readily replaced by various nucleophiles (e.g. CN, N3, NRj, OR, SR) via a low equilibrium concentration of the ketone. The existence of this equilibrium was demonstrated by treatment with diazomethane, giving cyclobutanone and methyl acetate. Similarly, the OH group of 1-dimethylaminocyclopropanol is readily replaced by all common nucleophiles via an S l reaction with (487) as intermediate. ... 

In the reaction of ketene with diazomethane, cyclopropanone is initially formed, which reacts with another equivalent of diazomethane to give cyclobutanone ". Diazoketones react with ketenes by addition to the diazo compound. The cycloadduct eliminates nitrogen to produce butenolides. However, the ketocarbene 370, generated from... 

Similarly, cyclopropanones have not been found among the products from the reaction of ethyl diazoacetate with dimethylketene or diphenylketene although cyclopropanone intermediates may be involved (see Section 4.1.5).20) Attempts to prepare the cyclic thioketal 5C) by the addition of diazomethane to the trithiane 6 were also unsuccessful.21)... 

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