2-Cycloheptenone synthesis

A synthesis of the 11-aryl-1 l-aza[5.3.1 ]propellan-2-one 29 was accomplished by the intermolecular cycloaddition of the cycloheptenone 26 with an aryl azide. The... 

Organometallic methods, with the possible exception of those involving the stoichiometric generation of enolates and other stabilized carbanionic species 140], have seldom been used in carbohydrate chemistry for the synthesis of cyclohexane and cyclopentane derivatives. The present discussion will not cover these areas. The earliest of the examples using a catalytic transition metal appears in the work of Trost and Runge [41], who reported the Pd-catalyzed transformation of the mannose-derived intermediate 22 to the functionalized cyclopentane 23 in 98% yield (Scheme 10). Under a different set of conditions, the same substrate gives a cycloheptenone 24. Other related reactions are the catalytic versions of the Ferrier protocol for the conversion of methylene sugars to cyclohexanones (see Chap. 26) [40,42,43]. 

A sequence of conventional transformations allowed cyclopropane bicycle 326 to be prepared which was quickly enlarged to cycloheptenone 327 by treatment with iron trichloride in DMF and subsequent dehydrochlorination. Ketone 327 represented the branching point of the synthesis due to its masked symmetric nature. In fact, when the azido group was installed on Ci and a carbonyl group was put in on C5... 

Several syntheses of 1-hydroxymethylpyrrolizidines have been reported. Borch and Ho1 have utilized a reductive cyclization method for their synthesis of ( )-isoretronecanol (6) and ( )-trachelanthamidine (7). The cycloheptenone ester (1), prepared by a novel route (Scheme 1), was reductively aminated to give a mixture of the diastereoisomeric amino-esters (2) and (3) in 48% yield. These esters could not be separated. Oxidative cleavage of the double bond of the esters, followed by reductive cyclization, gave a 35% yield of the pyrrolizidine esters (4) and (5). Separation of these compounds was achieved by preparative t.l.c., and a final reduction step afforded the racemic alkaloids (6) and (7). The second reductive amination process was stereoselective, because reduction of the unseparated ester mixture (4) and (5) gave a 1 2 ratio (g.l.c.) of the 1-hydroxymethylpyrrolizidines. 

The resulting stereoisomeric (6R, 85)-cycloheptenone 31 is used for the synthesis of (-i-)-scopadulcic acid A 32 as an enantiodivergent approach. 

Reductive cyclization has been used in a novel, recent synthesis of the alkaloids ( )-isoretronecanol (22) and ( )-trachelanthamidine (23) by Borch and Ho. Condensation of the dianion derived from methyl acetoacetate with Z-l,4-dichlorobut-2-ene, followed by cyclization with sodium meth-oxide yielded the cycloheptenone ester intermediate (32) (Scheme 2). Reductive amination of this ketoester with sodium cyanoborohydride and ammonium nitrate gave a mixture of the diastereoisomeric aminoesters 33 and 34. Oxidation with osmium tetroxide and periodate, followed by reductive cyclization, again using sodium cyanoborohydride, gave the two pyrrolizidine esters 35 and 36 in a ratio of 1 2 [gas-liquid chromatography (GLC) analysis]. The esters were separated by preparative layer chromatography, and lithium aluminum hydride reduction of the individual esters gave the two pyrrolizidine alkaloids 22 and 23. 

Functionalised nucleophiles normally need to be protected, as in the synthesis of the bicyclic enone 67 which requires the addition of a d3 reagent to cycloheptenone 69. The Me2S complex of the Cu(I) derivative of 70 fills this role deprotection and cyclisation being accomplished in acid solution.28 This synthesis also illustrates that tandem Michael-aldol sequences of this kind with an intramolecular aldol are perfectly satisfactory. 

Grieco and coworkers have utilized intramolecular aldolization of keto aldehydes to form seven-mem-bered rings. In a synthesis of ( )-helenalin, keto aldehyde (54) was cyclized to aldol (55 equation 1In a later modification of the basic approach, keto aldehyde (56) was cyclized to cycloheptenone (57 equation 113).The success of these cyclizations is related to the fact that the normally preferred five-membered ring closure would yield a strained rnzns-fused bicyclo[3.3.0]octene system. 

ETHENYL-4-METHOXYCYCLOBUTENE-l,2-DIONE. This procedure also provides a convenient method for the preparation of DIMETHYL SQUARATE, an important intermediate. The synthesis of (lR, 6S, 7S )-4-(tert-BUTYLDIMETHYLSILOXY)-6-(TRIMETHYLSILYL)BICYCLO-[5.4.0JUNDEC-4-EN-2-ONE is representative of a general protocol for the construction of cycloheptenones by a [3 + 4] annulation. The method features the addition of a lithium enolate to an acryloyl silane to give a 1,2-adduct that undergoes a novel sequence of a concerted Brook rearrange-ment/cyclopropanation and an anionic oxy-Cope rearrangement. 

Cycloadditions. Cycloheptenones are prepared from 1-alkenylcyclopropane derivatives via a [5 -(- 2]cycloaddition. Improvement of stereoselectivity (retention) by the use of [Rh(CO)2Cl]2 is recognized. A synthesis of (-l-)-aphanamol I has been realized based on such a cycloaddition involving an allenic double bond as the two-carbon component. ... 

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