Cyclopropyl furans

Analysis of triene structures in leukotrienes or the dienes in the HETEs reveals in all cases that a cis,trans dienes (partial structure) is commonly shared. The Merck Frosst group has recently described a methodology for the delivery of cis,trans dienes in the synthesis of various HETEs. Scheme 2.9 depicts the basic route whereby a-diazoketones 25 react, via a carbenoid species, with furan to produce an unstable cyclopropyl furan intermediate 26. This reaction is efficiently... 

Transformation of pyridazine 1-oxides and their methyl derivatives into cyclopropyl ketones and/or substituted furans can also occur (Scheme 14). 

Replacement of the ethanolamine head group is also well tolerated. Substitution with a cyclopropyl (243) [37], allyl (244) or propargyl group (245) [164] all led to an increase in binding affinity compared to AEA. Replacement of the head group with aromatics is also allowed. The phenyl derivative (246) retains affinity at the CBi receptor [37], whereas the 2-substituted A-methyl pyrrole (247) has a 2-fold improved affinity compared to AEA [167]. Interestingly, the 3-substituted furan derivative (23) that has micromolar affinity for the AEA transporter (see above) does not bind to the CBi receptor, but has good affinity for the CB2 receptor [167]. These results are summarised in Table 6.20. 

Another example of Au-catalyzed was reported using alkynyl cyclopropyl ketones as a starting material. Trisubstituted furans were given in high yields under mild condition via a domino reaction process and an example is given below <06AG(I)6704>. 

A related synthesis of highly substituted furans was reported by Schmalz and Zhang from cyclopropyl alkynyl ketones. The reaction scope included a great variety of nucleophiles such as several alcohols, indole or even acetic acid [140]. 

Similarly, carbinols 237 are converted to dienes 238 having two benzenethio substituents (Scheme 11)101). Here again starting materials are dichloro-cyclopropyl ketones 235 (cf. Scheme 5), which can be transformed to the desired dithioacetals 236 by treatment with sodium benzene thiolate. Cyclopropanes 236 are ring opened to P,y-unsaturated ketones 240, y-oxothioesters 241, or for R1 = H expanded to furan derivative 239102 t03>. 

As demonstrated below, a Lewis acid-mediated reaction was utilized in the synthesis of dihydro[b furan-based chromen-2-one derivatives from l-cyclopropyl-2-arylethanones and allenic esters <070L4017>. The TiCh-catalyzed anti-Markovnikov hydration of alkynes, followed by a copper-catalyzed O-arylation was applied to the synthesis of 2-substituted benzo[6]furan <07JOC6149>. In addition, benzo[6]furan-based heterocycles could be made from chloromethylcoumarins <07SL1951>, substituted cyclopropanes <07AGE1726>, as well as benzyne and styrene oxide <07SL1308>. On the other hand, DBU-mediated dehydroiodination of 2-iodomethyl-2,3-dihydrobenzo[6]furans was also useful in the synthesis of 2-methylbenzo[Z>]furans <07TL6628>. 

Depending upon reaction conditions, the Pd-catalysed isomerisation of alkylidene cyclopropyl ketones can lead to furans or pyrans. In acetone and in the absence of added salts, proximal bond cleavage occurs exclusively and 4//-pyrans are formed <03AG(E)183>. The 4//-pyran unit has been spiro-linked into the indanoparacyclophanes <03T1739>. 

Ethen (Z)-2-Acetoxy-l-cyclopropyl-EI5/1, 112 [5,6-H2 —2H-pyran + Ac2OJ Furan... 

Ethen 1 -Cyclopropyl-1 -morpholino-E15/1, 616 (Keton + Amin) Furan 3-(2-Cyan-ethyl)-3,4-... 

Change of solvent to benzene also yields these dimers which are accompanied by the adducts (78) and the furan (79). The adducts (78) are formed via a hydrogen abstraction pathway. The photochemical isomerization of the spirocyclopropane derivatives (80) affords the carbazole derivatives (81). This reaction involves ring-opening of a cyclopropyl bond followed by cyclization of the resultant biradical. An oxidative step must also be operative. 

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 corresponding ring contractions of furans normally give cyclopropenyl products, but in some cases a cyclopropyl product is isolated. Hence, photolysis of 2-cyanofuran gave a mixture of stereoisomers of 3-alkoxy-2-formylcyclopropane-l-carbonitrile (14). ... 

Conversion of -chloro amide 8 by sodium metal in diethyl ether in the presence of chlorotrimethylsilane at 0 C smoothly afforded l-[l-(trimethylsiloxy)cyclopropyl]piperidine (5) in high yield. Reaction of this silyl derivative with tetrabutylammonium fluoride in tetrahydro-furan yielded the corresponding hydroxyamine 9. These preparations of 5 and 9 serve as short, inexpensive ways of forming cyclopropanone equivalents. 

The —C = C— functionality remains intact In 1986, results from a systematic study revealed that successful, selective debenzylation of substrates containing a variety of functional groups could be achieved with 2.2 equiv. calcium (Tab. 4.1) [12]. These groups include benzene, furan, and cyclopropyl rings allyhc, furfuryl, cyclo-propyalkoxyl, and tert-butyldimethlysilyl ethers and the C = C triple bond. 

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