Cyclopropyl ketones synthesis

Ketone, 9-anthryl methyl, 30,1 cyclopropyl methyl, 31, 74 Ketone synthesis, 33, 84... 

Scheme 5.15. Photochemical synthesis of functionalized cyclopropyl ketones.

Ketone, 9-anthryl methyl, 30,1 CYCLOPROPYL METHYL, 31, 74 1-HYDROXYCYCLOHEXYL methyl, 35,1 PHENYL 3-PYRIDYL, 37, 6 Ketone synthesis, 33, 84 Kies extraction apparatus, 37, 30... 

Another example of the superiority of the alkoxy group as a directing group was reported by Johnson in his synthesis of enantiomericaUy pure cyclopropyl ketones after auxiliary cleavage (equation 56). In that case, the product resulting from a sulfoximine directed cyclopropanation was never observed. 

Intermolecular cyclopropanation of diazoketones is an effective method in organic synthesis. Wenkert and coworkers have applied this methodology to the synthesis of a substantial number of cyclopropane adducts 2868, 2969 and 307° which are synthetic intermediates in the preparation of natural products (equations 41—43). Copper catalysts were chosen for these transformations. Another interesting application of intermolecular cyclopropanation is to be found in Daniewski s total synthesis of an aromatic steroid. Palladium(II) acetate catalysed decomposition of 4-bromo-l-diazo-2-butanone in the presence of m-methoxystyrene was used to give the cyclopropyl ketone 31 which was a key intermediate in the total synthesis (equation 44)71. 

Intramolecular cyclopropanation of diazoketones to furnish [3.1.0] and [4.1.0] bicyclic systems are the most common and effective reactions in this category. Two recent examples are shown in equations 48 and 49. The bicyclic ketone 34 has been used in the synthesis of polycyclic cyclobutane derivatives77, whereas ketone 35 is the key intermediate in the total synthesis of ( )-cyclolaurene78. When the olefinic double bond is attached to, or is part of, a ring system, the cyclopropanation process also works well. Copper oxide catalysed decomposition of diazoketone 36 produces the strained tricyclic ketone 37 in 86% yield (equation 50)79. In another case, in which the cyclopropanation of diazoketone 38 gave stereospecifically the cyclopropyl ketone 39, copper sulphate catalysis was used. The cyclopropyl ketone 39 is the key intermediate in the total synthesis of ( )-albene 40 (equation 51). ... 

The intramolecular cyclopropanation of appropriate y,(5-unsaturated a-diazoketones following a stereoselective catalytic reduction of the cyclopropyl ketone group provides a useful approach in diterpenoid synthesis. Some examples of the use of the cyclopropanation-reductive cleavage approach in synthesis are shown in equations 67 and 68l0f103. 

A methodology developed for the synthesis of cyclopropyl ketones from THFs (51) has been shown to suffer from stereochemical leakage resulting from the unexpected cleavage of a benzoate ester by potassium r-butoxide and the subsequent participation of the resulting hydroxyl group in the adjacent substitution reactions.90 This prob- lem has been solved, however, by the discovery of a simpler, more direct cascade reaction for the synthesis of single enantiomers of cyclopropanes with predictable stereochemistry.90 The mechanism of the reactions has been discussed. 

The thiophene can be considered a four-carbon synthon via reductive desulfurization with Raney nickel. A strategy using the thiophene as a lynch-pin for the construction of complex building blocks was utilized in a total synthesis of the cytotoxic sponge metabolite haliclamine A <02JOC6474>. Thienyl cyclopropyl ketone (108) was elaborated into 109. Reduction of 109 with Raney Ni gave 110 which was taken on to haliclamine A. 

The ate complexes prepared from 4-tosyloxy-l-butyne and trialkylboranes also provides a selective synthesis of cyclopropyl ketones and homopropargylic alcohols simply by changing the reaction temperature (Eq. 53)... 

Two examples that show selectivity in synthetic applications are the synthesis of cycloheptanone (19),7 which involves ring expansion via a [1,5] hydrogen shift, and the synthesis of sarkomycin (20 Scheme 5). 7 In both of these protocols, the intermediate cyclopropyl ketone or vinylcyclopropane system could be rearranged to dihydrofurans or cyclopentenes respectively by the appropriate adjustments in the experimental conditions. ... 

Schoberlh and Hanack have reported a simple synthesis of cyclopropylacetylene (11) from methyl cyclopropyl ketone (9), The ketone is converted into the dichloride (10) by treatment with purified phosphorus pentachloride in carbon tetrachloride, and this is then dehydrohalogenated with potassium r-buioxide in DMSO. 

This reagent is used as a Lewis acid catalyst for the intramolecular addition of diazo ketones to alkenes [130], The direct synthesis of bicyclo[3.2.1]octenones from the appropriate diazoketones using BF3 Et20 (Eq. 76) is superior to the copper-catalyzed thermal decomposition of the diazo ketone to a cyclopropyl ketone and subsequent acid-catalyzed cleavage [131]. 

A stereoselective Li-NHs reduction of a cyclopentenone has been employed in two different syntheses of the cytotoxic sesquiterpene coriolin (69 Scheme 2). In one synthesis, tricyclic ketone (70) was reduced stereoselectively to alcohol (71) using Li-NHs-methanol. In the second synthesis, tetracyclic enone (72) was converted in a single step to (71). This reduction proceeds by initial cleavage of the cyclopropyl ketone unit of (72) to give ketone (70), which is then reduced to (71). 

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 ". ... 

The cyclopropyl ketone displayed in equation 47—accessible from norbornadiene and formaldehyde via the Prins reaction—can serve as a versatile starting material for the synthesis of prostaglandins , pseudoguainolides " and steroidsStereochemical aspects of HBr addition to cyclopropyl ketones have been studied . 

Further activation and functionality is introduced to cyclopropyl ketones or esters by an additional hydroxymethyl substituent or its equivalent. On this basis, a synthesis of a-methylene y-butyrolactones has been performed (equation 52). ... 

Additional applications of this intriguing method to create polyquinanes include synthesis of hirsutene, modhephen, and silphinene employing acid-induced or reductive cleavage of a vinylcyclopropane and opening of a cyclopropyl ketone with a... 

---