Cyclopropyl Ketone Formation

In order to defer stereochemical questions we will consider first the photoreaction of 6,6-diphenyI-cycIohexa-2,S-dienone (6). Either direct or sensitized photolysis of compound (6) in aqueous dioxane follows the following course  

Since the phosphorescence emission from (6) (68.8 kcal/mole) is very similar in energy and vibrational structure to benzophenone, and has a short lifetime (O.S msec), it was proposed that the photorearrangement takes place via the /I - 7T triplet state. A Zimmerman-like mechanism is as follows for the formation of the cyclopropyl ketone (7) from dienone (6)  

Several questions should be asked about this mechanism (a) Is excited state bond formation [(8)- (9)] reasonable (b) Could the rearrangement and intersystem crossing take place simultaneously [(9) - (7) or even (8) - (7)] (c) If the ground state species (10) is formed, will it rearrange to (7)  

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In light of these results, the study of Rodgers and Hart<27) is particularly interesting. They found that as one increases substitution at C-3 and C-5, there is a greater stereospecificity in cyclopropyl ketone formation ... 

Formation of rearranged products in the solvolysis of homopropargyl systems need not involve triple-bond participation and vinyl cations in all instances. Ward and Sherman investigated the formolysis of 4-phenyl-1-butyn-l-yl brosylate, 57 (80). At 80°C in the presence of one equivalent of pyridine, they observed formation of phenyl cyclopropyl ketone, 58, and... 

When two equivalents of pyridine were added to the nmr sample and the probe heated to 80° C, the enol formate 61 decreased and phenyl cyclopropyl ketone 58 appeared at a rate approximately ten times faster than in the previous buffered system. The observation of intermediate 61 and the kinetic results, together with the observed induction periods, are consistent with the idea that some and perhaps all of the rearranged product ketone in the solvolysis of this system arises via double-bond participation in 61 rather than triple-bond participation and a vinyl cation (80). 

Zimmerman(24,a6> has provided strong circumstantial evidence that zwitterionic intermediates can be involved in formation of cyclopropyl ketones from dienones. His approach was to generate the dipolar species via ground state chemistry and show that these rearrange to the photoproduct ... 

Although not formally a type I cleavage process, /1-cleavage of cyclopropyl ketones to form propenyl ketones and/or epimerized cyclopropyl groups bears such a close similarity to a-cleavage that it should be discussed in combination with the latter. The first report of a reaction thought to occur by 0-cleavage was made by Pitts in 1954 for the formation of methyl propenyl ketone from methyl cyclopropyl ketone,<72)... 

Products from the photolysis of the cyclopropyl ketone (44) are dependent on the pH of the solvent.(42) In aqueous dioxane only the 2,3-diphenyl-phenol (45) is formed along with the photoacid (46). Bond cleavage at c takes place via both the singlet and triplet states, whereas bond cleavage at a with phenol formation takes place in the triplet state ... 

The Norrish-Yang reaction [20] is based on the photochemical excitation of ketones followed by an intramolecular hydrogen transfer with the formation of biradicals. Wessig and coworkers used this procedure to prepare functionalized cyclopropyl ketones as 5-75 from 5-72 (Scheme 5.15) [21]. The substrate employed con-... 

This type of cyclobutanone annelation is feasible with various dibromocyclopropanes. When diaryl ketones are used as electrophiles, the oxaspiropentane-cyclobutanone rearrangement occurs spontaneously, so that the cyclobutanone is obtained directly (equation 63)"° . When 1-bromo-l-lithiocyclopropanes are allowed to react with aldehydes, the formation of cyclopropyl ketones results" . 

Cycloadduct 212 is converted into the dihydrobenzofuran 213 when treated with boron trifluoride diethyl etherate in good yield <2000JA8155>. The formation of the dihydrobenzofuran proceeds by an initial ring opening followed by a subsequent dehydration and acid-catalyzed cyclopropyl ketone rearrangement (Equation 142). 

Where the carbon-carbon double bond is a part of an aromatic system, in general, cyclopropanation of diazoketones results in the formation of unstable cyclopropane adducts. For example, Saba140 has shown that in the intramolecular cyclopropanation of diazoketone 57 the norcaradiene ketone 58 can be detected by low-temperature NMR and can be trapped in a Diels Alder reaction with 4-phenyl-l,2,4-triazoline-3,5-dione (equation 69). In addition, Wenkert and Liu have isolated the stable norcaradiene 60 from the rhodium catalysed decomposition of diazoketone 59 (equation 70)105. Cyclopropyl ketones derived from intramolecular cyclopropanation of hetereoaromatic diazoketones are also known and two representative examples are shown in equations 71 and 72106. Rhodium(II) compounds are the most suitable catalysts for the cyclopropanation of aromatic diazoketones. 

In intermolecular PET processes, radical ions are formed either as close pairs or as free species from neutral molecules (Sch. 1) [2,6]. Most commonly, carbonyl compounds or related derivatives as for example enol ethers, cyclopropyl ketones, and siloxycyclopropanes are used for intramolecular cyclization reactions. With the exception of cycloadditions the ring-building key step is always an intramolecular bond formation. In PET... 

The efficient formation of dihalocyclopropanes could be extended to allyl alcohol adducts 74, which are oxidized to 75. The resulting ketones are very useful synthetic building blocks. Reaction with alkoxide, for instance, affords dihydrofuran derivatives 76 via alkoxysubstituted cyclopropyl ketones 43). This ring enlargement might be a purely thermal process (1,3-sigmatropic shift), but other mechanistic possibilities could also be conceived (cf. Scheme 2). 

Additional support for an alternative alkene first mechanism in these cyclisations came from the successful cyclisation of cyclopropyl ketone 26 with no observance of fragmentation products (Scheme 5.21).43 This suggests that a ketyl radical anion is not formed during the cyclisation and that reduction of the alkene leads to product formation. 

The relative yields of cyclized products increase greatly with the decreasing nucleophilicity (2a-c, 3 and 4 of Table 3) and with the increasing ionizing power of the solvent. Cyclobutanone derivatives (32) are usually obtained in much greater amounts than cyclopropyl ketones (33) but, when mercuric ions are added, formation of 33 is overwhelming. The effect of R in 31 on the product distribution is illustrated in cases 3b, 4a, 5a, 6a, and 7. 

Palladium diacetate catalyses the reaction of diazomethane with a(3-unsaturated ketones to give cyclopropyl ketones in high yields. Steroidal examples include formation of the products (89) and (90) from the corresponding enones.106... 

Oxa-di-TT-methane rearrangement A photochemical reaction of a P,y-unsaturated ketone to form a saturated a-cyclopropyl ketone. The rearrangement formally amounts to a 1,2-acyl shift and bond formation between the former a and y carbon atoms. 

Cyclopropyl ketone 222 (Scheme 55) was prepared to probe the mechanism of the cleavage reaction [39,40]. Isolation of 224 where the cyclopropyl ring is intact (Scheme 56) suggests cleavage proceeds via formation of radical 227 rather than ketyl radical anion 226, formed by single-electron transfer to the ketone carbonyl, as cyclopropylmethyl radical anions are known to undergo facile fragmentation. 

Homoconjugate additions of secondary amines to cyclopropyl ketones catalysed by acid have been reported as well as formation of certain 5,6-dihydro-4H-l,2-oxazines with hydroxylamine hydrochloride. Demuth and Mikhail have recently demonstrated that cyclopropanes of the tricyclo[3.3.0.0 ] octan-3-one type can be selectively converted to functionalized bicyclic compounds with different kinds of electrophilic/nucleophilic reagents (equation 41) the products have extensively been exploited for natural product synthesis ". ... 

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