Ketenes cyclopropanones

Addition to ketenes,35 When a cold (—78°) methylene chloride solution of diazomethane is added to an excess of ketene, cyclopropanone can be identified as the product by various spectral properties and chemical reactions. In the same way,... 

Materials. Ketene was synthesized as described by Andreades and Carlson ( ) from diketene. Diazomethane was synthesized from N-methyl-N-nitroso-pi-toluenesulfonamide as outlined by Hudlicky (10). A typical synthesis of cyclopropanone involved the slow addition of 400 mL of a 1.0 M diethyl ether solution diazomethane to a 2-3-fold molar excess of ketene at -78°C. This synthesis was based on the... 

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. 

Since the ketene will copolymerize with cyclopropanone, excess ketene was removed by addition of 3A molecular sieves followed by evacuation at 1 mm Hg for 2-3 hours at -70°C. The amount of ketene was monitored by FTIR analysis. Ketene has a distinct strong absorption between 2130 and 2150 cm-1 (5,6). The solution FTIR spectrum of cyclopropanone in Figure 1 was taken before ketene removal. 

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. 

Figure 4.8 The ketene acetale 187 is the expected product of [3+2]-cycloaddition of methylene cyclopropanone ketal to Qo-...

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). 

The most common reaction involving this type of cycloaddition is the reaction of ketenes with diazoalkanes (Houben-Weyl, Vol. 4/4, pp 406-408) which proceed via cyclopropanone intermediates. This type of reaction finds limited use due to nonregioselective formation of substituted cyclobutanones as mixtures. 

In situ ring enlargement of intermediate cyclopropanones to silyl- and germyl-substituted cyclobutanones was achieved by treatment of silyl- and germyl-substituted ketenes 12 with an excess of diazomethane.129,130... 

Addition of a second mole gives bicyclopropyl derivatives.1025 1,4 addition is rare but has been reported in certain cases.1026 Carbene adds to ketene to give cyclopropanone.1027... 

To avoid destructive side reactions, cyclopropanones have to be prepared at low temperatures in the absence of nucleophiles. A good example is the synthesis of cyclopropanone itself from ketene and diazomethane (see Section 16-4 A) ... 

A versatile synthesis of cyclopropanones and closely related derivatives is provided by the diazoalkane-ketene reaction as shown in Scheme 2. Using this method, the parent ketone 2>3> and alkyl-substituted cyclopropanones 1()) have been prepared in yields of 60—90% based upon the concentration of diazoalkaneb) (Table 2). The reaction is rapid at Dry Ice-acetone temperatures and is accompanied by evolution of nitrogen. Although most cyclopropanones are not isolable, dilute solutions of 3 (0.5—0.8 M) may be stored at — 78 °C for several days or at room temperature in the presence of suitable stabilizing agents.15) The hydrate and hemiketal derivatives are readily prepared by the addition of water or alcohols to the solutions of. .2>8>5)... 

The Simmons-Smith reagent also adds to ketene acetals forming cyclopropanone acetals, as shown in the formation of 1,1-dimethoxy-2,2-dimethylcyclopropane (8) from l,l-dimethoxy-2,2-dimethylethyl-ene.17) Similarly, with methylene iodide, ketene o-xylylene acetal (9) affords the corresponding cyclopropanone derivative (JO) (70%).24)... 

Cyclopropanone acetals may also be prepared by the addition of other one-carbon species to ketene acetals as shown in Table 3. Thus, McElvain and Weyna have synthesized several cyclopropanone deriv-... 

Schollkopf and co-workers have synthesized a number of cyclopropanone acetals by the addition of various sulfur- and oxygen-containing carbenes to ketene diethylacetals (Table 3).26>27> Similarly, cyclopropanone dithioacetals may be prepared by the addition of the Ws-thiomethyl and Ws-thiobenzylcarbenes 12a, b to olefins.29) However, cyclopropanone acetal formation by this method requires double bonds with considerable electron enrichment and the yields are generally low. With unsubstituted olefins such as cyclohexene, the carbenes 12 a, b tend to form dimeric and trimeric products such as 13 and 14, instead of the double bond addition products. 

The polymerization of cyclopropanone is initiated °) by traces of water and is inhibited 15> by moisture scavengers such as acetyl chloride. The terminal groups are apparently hemiketal units since a,co-diacetoxy-poly(oxycyclopropylidenes) 85 are isolated from a mixture of cyclopropanone hydrate, diazomethane and excess ketene. 80>... 

Cyclopropanone hemiacetals and hydrate react with ketene to form acetoxy derivatives, e.g. 86 and 87, respectively. 5 15>80) As shown in Scheme 14, the diacetoxy compound 87 may also be obtained from the reaction of cyclopropanone with acetic acid and excess ketene. 83>... 

Presumably, 1-acetoxycyclopropanol (88) is the intermediate in this reaction as well as that between the hydrate and ketene. 80> Although 88 has not been isolated in the above cases, it may be prepared from acetic acid and cyclopropanone and reacts with ketene to give 87. 5>15>... 

The reaction of cyclopropanone with hydrogen chloride affords the chlorohydrin 90 (65%). 5 15) Acetylation of 90 with ketene gives the expected acetoxy compound 91 (34%) while the addition of methanol to a methylene chloride solution of 90 affords cyclopropanone methyl hemiketal (100%). The latter reaction illustrates the use of 91 as an in situ source of cyclopropanone. 

Similarly, photolysis of the cyclobutane-1,3-diones 19—21 produces varying amounts of ethylenes, ketenes and polymers in addition to carbon monoxide and the cyclopropanone, as was shown in Scheme 4, Section 2.3. 10>81)... 

Cyclobutanones may be prepared in a one-step procedure, i.e., without isolating the intermediate cyclopropanone, simply by adding the ketene to excess diazoalkane. 97>98) That cyclopropanones are intermediates has been established by carbon-14 labeling studies "> and... 

In accord with their unusually high reactivity, cyclopropanones may undergo various types of cycloaddition reactions. In addition to Diels-Alder type addition with conjugated dienes (4+3- 7 cycloadditions), substituted cyclopropanones also react with aldehydes forming dioxo-lanes (3 +2->-5), and with ketenes yielding (3-lactones (2 +2- 4).118>... 

Cyclopropanone ethyl hemiacetal was first synthesized by the reaction of ketene and diazomethane 1n ether at -78°C in the presence of ethanol.4 The yield is low (43%) and the reaction 1s hazardous, especially when a large-scale reaction is required. The method described in this procedure for the preparation of cyclopropanone ethyl hemiacetal from ethyl 3-chloropropanoate... 

Other, less stable cyclopropanones, such as the 2,2-dimethyl compound, can be made by carbene addition (Chapter 40) to ketenes. This compound did the Favorskii reaction with methoxide in methanol the only product came from the expected loss of the less unstable carbanion. This will, of course, be general-acid-catalysed by methanol as no free carbanion can be released into an alcoholic solvent. 

We note that the cyclopropanation of ketene to form cyclopropanone, isoelectronically and otherwise formally related to the cyclopropanation of allene to form methylenecyclopropane, has an altogether different enthalpy of reaction. This value is (63 4) kJmoT favoring ketene and is credible in terms of considerable resonance stabilization of the type CH2=C=0 CH2—C=0 and of a 3-atom n system that includes the double bond and the appropriate, antisymmetric (i.e. difference) combination of the oxygen lone pairs. Further documentation of the stabilization of ketene is seen by comparing the energetics of the hydrogenation reaction... 

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. 

Semiaminal (567) reacted with nucleophiles generally by a replacement of the hydroxy group Only few exceptions were known. For example, reaction of 567 with ketene or isocyanates caused acylation and displacement of the secondary amino moiety (equation 147) cyclopropanone (84) could be detected spectroscopically in one case. A similar removal of the amino function by tosyl isocyanate (571) was observed with 570, but here compound 574 was isolated in 47% yield (equation 148). 574 resulted from a subsequent addition of the initially formed products 572 and 573 . Steric reasons led to the sequence 570 - 574 the diastereomeric endo-morpholino semiaminal reacted with 571 by displacement of the exo-hydroxy group. 

A significant advance in the study of cyclopropanones resulted from studies by the Turro and the de Boer groups on the formation of cyclopropanones in solution by the reaction of ketenes with diazoalkanes. These investigators found that it is possible to store the parent ketone only for short periods at low temperature because of its unusual reactivity and propensity for polymerization. Subsequent work has shown that cyclopropanone seems to show chemical behavior similar to that of ketene. Thus, it is attacked by nucleophilic species such as water, alcohol and amines and reacts rapidly with itself to form... 

Because of their instability, cyclopropanones have been isolated in only a few cases, and methods for preparing the pure ketones are very limited. Among these are the addition of diazoalkanes to ketenes at low temperature ", potassium t-butoxide elimination of highly substituted a-bromoketones , photochemical decarbonylation of cyclobutane-1,3-diones " and ring-closure of 1,3-dihalo ketones Other methods exist for formation... 

By far the most useful method for making cyclopropanones has involved the addition of diazoalkanes to ketenes, a reaction which was first explored by Turro and Hammond and by de Boer and coworkers . The cyclopropanone formed (Scheme 1) is immediately trapped by the addition of a nucleophile such as water, an alcohol or carboxylic acid. Turro found that although cyclopropanone itself is not isolable, a dilute solution of this ketone (0.5-0.8 M) may be stored at — 78°C for several days. 

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