Methylenecyclopropyl ketone

As a reductive cascade reaction with Sml2, treatment of methylenecyclopropyl ketone (310) with Sml2 in a mixture of HMPA and f-BuOH at 0 °C generates bicyclic alcohols (311a) and (311b) which are the skeleton of a natural product, paeonilactone, as shown in eq. 3.130. 

Curran s elegant approach to the natural products ( )-hypnophilin and ( )-coriolin is among the best examples of a Sml2-mediated sequence and consists of a 5-exo-trig cyclisation followed by a stereoselective 5-exo-dig cycli-sation in a radical-radical cascade (Chapter 7, Section 7.4).4 More recently, Kilburn employed a Sml2-mediated radical-radical sequence involving a methylenecyclopropyl ketone in the preparation of paeonilactone B.5,6 In... 

A related radical-radical sequence was used by Kilburn to access the tricyclic ether skeleton of the eudesmanes.7 It was found that Sml2 in THF-MeOH (4 1) gave the most efficient conversion of methylenecyclopropyl ketone 6 to tricycle 7 (Scheme 6.3). 

Palladium-catalyzed cycloisomerization of methylenecyclopropyl ketone 101 was affected by added salts [119]. When the reaction was performed in the presence of 2 equiv. of Nal, furan 102 was obtained exclusively. However, when the reaction was performed in the absence of Nal, 4//-pyran 103 was obtained (Scheme 2.67). 

Nucleophilic attack by a heteroatom, such as nitrogen and oxygen, in the reaction of alkynyl amines and alkynyl ethers (Section 27.2.1), alkynyl oxiranes and alkynyl aziridines (Section 27.2.2), propargylic esters (Section 27.2.3), alkynyl oximes (Section 27.2.4), and allenyl and methylenecyclopropyl ketones (Section 27.2.5), forming a carbon-heteroatom bond. 

Kilburn et at. determined that various methylenecyclopropyl ketones [33], ketals and aldehydes function as new precursors of six- or seven-membered carbocycles by a transformation from the cyclopropyl systems using Lewis acid catalysts [34]. The ring expansion reaction using TiCU predominantly gave the dichlorinating compounds however, the SnCU promoted reaction alternatively gave the corresponding monochloro-methylenecyclohexane derivatives (S cheme 10.13). 

It has also been established that the treatment of silyl-substituted methylenecyclopropyl ketone with SnCU leads to the corresponding tertiary alcohols having a six- or seven-membered ring (Scheme 10.14) [35]. 

A convenient, short-step synthesis of enantiomerically pure 2-methylenecyclopropyl-methanol has been achieved by treating optically pure epichlorohydrin with methylenephosphorane (equation 146)325. Vinyl ketones are cyclopropanated with ( )-1-... 

Direct metallation of methylenecyclopropane with butyllithium in THF affords meth-ylenecyclopropyllithium. This reacts with carbonyl electrophiles such as aldehydes, ketones and lactones by ring alkylation to give selectively 2-methylenecyclopropyl carbinols. No products of exo alkylation are isolated. Other bases such as r-BuOK and KH do not deprotonate methylenecyclopropane. Use of diethyl ether as the solvent, instead of THF, significantly reduced the rate of lithiation. Similar reaction of the lithium reagent with ethylene oxide gave 2-(2-methylenecyclopropyl)ethanol (equation 294) In the reaction with C-labeled ethylene oxide the addition of TMEDA to the reaction mixture is recommended. ... 

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