Fragmentation cyclopropyl ketone

Kuwajima employed the fragmentation of cyclopropyl ketone 21 to introduce the Cl 9-methyl group in an approach to the anti-cancer natural product paclitaxel (Taxol) treatment of 21 with Sml2 gave enol 22 in quantitative yield (Scheme 4.12).22... 

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. 

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. 

Photocyclisation of 8-alkoxy-l,2,3,4-tetrahydro-l-naphthalenones and 4-alkoxy-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-ones gives naphtho[l, 8-bc]furans and cyclohepta[cd]benzofurans respectively, and conformational and substituent effects of 1,5-biradicals in the cyclisation process are discussed." " The same authors also describe substituent effects on the photocyclisation of ethyl 2-(8-oxo-5,6,7,8-tetrahydro-l-naphthyloxy)acetates and ethyl 2-(5-oxo-6,7,8,9-tet-rahydro-5H-benzocyclohepten-4-yloxy)acetates to give naphtho[l,8-bc]furans and cyclohepta[c,d]benzofurans respectively." Also reported are cyclisations involving photogenerated radical cations of unsaturated silyl enol ethers, fragmentation cyclisations of unsaturated ot-cyclopropyl ketones which occur by photoelectron transfer and give polycyclics, and kinetic and theoretical studies of [2+3] cycloadditions of nitrile ylids. These reactions have been studied mechanistically and their synthetic potential investigated. 

The cyclopropyl ketone system in 3a,7,7-trimethyloctahydrocyclopropa[c]inden-2-one (26, thujopsene) was converted to the 3-methyl ketone fragment 27 upon reduction with lithium. ... 

Two groups have reported syntheses of the bicyclo[3.2.1]octane ring system found in certain tetracyclic diterpenes in which the key step is an intramolecular carbenoid insertion reaction. Thus decomposition of the diazoketone (4) in the presence of copper(II) sulfate gives the cyclopropyl ketone (5) in 48% yield. Acid hydrolysis of the acetal grouping is accompanied by concomitant fragmentation to the substituted bicyclo[3.2.1]octanone derivative (6).3... 

Related to the epoxy ketones are cyclopropyl ketones, whose ketyls can also fragment under reductive conditions afforded by Smli [98]. Ring expansions have been developed based upon these observations [99], and yields and selectivities can be high when the cleavage is stereoelectronically favored (Eqs. 88, 89). As shown by the results depicted in Eq. (88), the ring expansion can be accompanied by y9-elimination of appropriately situated leaving groups. 

The catalytic system based on Cu(0Ac)2-H20 and ligand L8 in combination with PhSiH3 as a hydride source also proved efficient in the reduction of aryl- and heteroaryl cycloaUcyl ketones (Scheme 11) [23]. The substrate scope was probed employing different size cycloalkyl groups along with variation of the aromatic or heteroaromatic fragment. Cyclopropyl derivatives proved particularly difficult ... 

Obtained in two steps from methyl cyclopropyl ketone PCI5 fragmentation followed by iodide displacement. 

Triethylamine as the electron donor was also used by Mattay and co-workers in tandem fragmentation cyclization reactions of a-cyclopropylketones. The initial electron transfer on the ketone moiety is followed by the fast cyclopropyl-carbinyl-homoallyl rearrangement, yielding a distonic radical anion. With an appropriate unsaturated side chain within the molecule both annealated and spi-rocyclic ring systems are accessable in moderate yields (Scheme 41) [62]. 

Corey s method20 relies on metal exchange with the bromocyclopropane 69 prepared by carbene addition. The extra stabilisation of cyclopropyl anions (chapter 8) makes both this lithium derivative and the ylid 63 more easily handled. Addition to aldehydes or ketones gives mixtures of adducts 70 [it turns out that none of the stereochemistry of 69 or 70 matters] which fragment under Lewis acid catalysis to give the thioacetal 71. Careful hydrolysis releases the 3,4-enal -72, the product of a homoaldol reaction with an aldehyde homoenolate and RCHO and a difficult compound to make as the double bond moves into conjugation very easily. 

A further extension of the cyclopropyl fragmentation method involves entrapment of the initially formed radical by a suitable radical acceptor [100]. This radical cascade has facilitated the efficient synthesis of spirocyclic ketones (Eq. 90). 

Scheme 14. Diyl fragmentation of cyclopropyl aldehydes and ketones...

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