Cyclopropanones reactions

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... 

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 . 

There are several mechanistically related ring expansion reactions of cyclopropanones which lead to /3-lactams. The conversion of cyclopropanone to /3-lactam (174) via the cyclopropanolamine (173) (75JOC1505) is just one modification, but it illustrates the strategy of this type of approach (73TL4855, 69JA2375) which has been applied to the synthesis of 3-amino-nocardicinic acid (81JOC2999). 

In the initial step " the a-halo ketone 1 is deprotonated by the base at the a -carbon to give the carbanion 4, which then undergoes a ring-closure reaction by an intramolecular substitution to give the cyclopropanone derivative 2. The halogen substituent functions as the leaving group ... 

We have investigated the reaction of NH phosphinous amides with diphenyl-cyclopropanone. The products were unequivocally identified as the corresponding p-phosphinyl carboxamides 27 resulting from the hydrolysis of a presumed heterocyclic intermediate (Scheme 28) These results await publication. 

There is evidence that the rearrangement involves cyclopropanones or their open 1,3-dipolar equivalents as reaction intermediates.86... 

It has been found that the bromo ketones 10-7a-c can rearrange by either the cyclopropanone or the semibenzilic mechanism, depending on the size of the ring and the reaction conditions. Suggest two experiments that would permit you to distinguish between the two mechanisms under a given set of circumstances. 

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 formation of a cyclopropanone derivative (originally determined by the isolation of degradation products from this unstable species) stimulated considerable interest in this reaction. Tetramethylcyclopropanone, however, cannot be isolated from the reaction mixture under normal photolysis conditions even with the use of an inert solvent. That it is indeed formed as an initial product of a-cleavage results from various trapping experiments in which chemical agents present in the reaction mixture were used to produce stable derivatives of the cyclopropanone [see equation (4.65)]. 

Reaction of cis-2,3-bis(trimethylsilyl)cyclopropanone with p-ketophosphorus ylide gives 2-trimethylsilyl-3-trimethylsilylmethyl-5-methylfuran and 2-methyl-4-trimethyl-silylmethylfuran in a ratio of 77 23 <00TL3399>. y-Hydroxyketal 72 undergoes acidic decomposition to afford the corresponding furan derivatives <00CEJ2887>. 

Reactions with cyclopropene.11 Lithium organocuprates react with the cyclo-propenone ketal 1 (12, 152-154) to form a copper species (a) that behaves as an enolate of a cyclopropanone. Thus it reacts with alkyl halides to form cis-2,3-disubstituted derivatives of 1. 

Product distribution in the reaction of 4 with furan depends on the reaction conditions as well as on the oxy group of the acetal substrates 4a-c. The diverse products formed in the reaction of 4a-c with furan are rationalized by the reaction pathways illustrated in Scheme 13. All products arise from nucleophilic addition of furan to alkylideneallyl cation intermediate 5M (5S), which is generated by acid-mediated ring opening of cyclopropanone acetals 4a-c (Scheme 5). The [4 + 3] cycloadduct 23 is simply formed via 27, and the furanyl... 

The reaction of allenes with peracids and other oxygen transfer reagents such as dimethyldioxirane (DM DO) or hydrogen peroxide proceeds via allene oxide intermediates (Scheme 17.17). The allene oxide moiety is a versatile functionality. It encompasses the structural features of an epoxide, an olefin and an enol ether. These reactive intermediates may then isomerize to cyclopropanones, react with nucleophiles to give functionalized ketones or participate in a second epoxidation reaction to give spirodioxides, which can react further with a nucleophile to give hydroxy ketones. 

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. 

The mechanism of the novel transformation of a-nitro- to a-hydroxy-ketones has been probed. The reaction, which proceeds under basic aqueous conditions, requires that the Q -nitro substrate be CH-acidic in the a -position, and that it be readily depro-tonated under the conditions employed. NO2 -OH exchange occurs with retention of configuration, with the hydroxyl oxygen being predominantly derived from the solvent. A mechanism involving neighbouring-group participation, via a Favorskii-like cyclopropanone intermediate, is proposed. 

A double 5n2 reaction, which proceeds via a Favorskii-like cyclopropanone intermediate, has been proposed to account for the novel stereoretentive replacement of NO2 by OH on reaction of a-nitro ketones (which must bear an acidic hydrogen at the O -position) with aqueous base. ... 

However, the hemiaminal 17 is unstable as a free base and readily undergoes exchange reactions. Since the hydroxy moiety of 17 is more easily displaced than the amine moiety, a highly reactive cyclopropyliminium salt 18 is formed, which then reacts with weak nucleophiles such as ethanol, to give e. g., 19. Otherwise in water solution 17 can also probably eliminate ammonia to form the highly reactive cyclopropanone 20, which is in equilibrium with its hydrate 21 and hemi-acetal 22, Eq. (8) [20]. It has been reported that hydrate 21 is also a potent inhibitor of ALDH [20,21]. 

It has been suggested that the inhibition of ALDH by AGP 17 starts with an interaction between the amino group of 17 and the cysteinyl thiolate side chain of the enzyme to form a modified holoenzyme, or that the enzymic reaction may either proceed through the cyclopropanone 20 yielding 24 a or through the imi-nium ion 18, yielding the modified enzyme 24b [17]. Thus, the covalent he-mithioacetal 24a or hemithioaminal enzyme derivatives 24b rapidly accumulate in the enzyme microenvironment and lead to the observed activity loss, Eq. (9) [21]. 

Due to their physiological importance, considerable efforts are currently devoted towards the total synthesis of 2,3-methanoamino acids (ACCs). The parent compound ACC 71 has been readily prepared from acrolein, through the base-induced (K2CO3) cyclization of 2-amino-4-chlorobutyronitrile [96] or from one-pot Strecker reaction of cyclopropanone hemiacetal [97]. 

There is considerable evidence that the rearrangement involves cyclopropanones and/or the 1,3-dipolar isomers of cyclopropanone as reaction intermediates.39... 

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