Jenkins, Tracy J.,1966- (1994) Geminal acylation of ketones, methodology, and applications to natural product syntheses. Doctoral (PhD) thesis, Memorial University of Newfoundland.
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Kuwajima et al. reported that the Lewis acid-catalysed reaction of a ketal with 1,2-bis(trimethylsilyloxy)cyclobutene (1) followed by rearrangement of the resulting cyclobutanone derivative with trifluoroacetic acid can provide a 2,2-disubstituted 1,3-cyclopentanedione in a reasonable yield. White this transformation has been improved by several groups, we now report, contrary to the literature, the analogous reaction between ketones and 1 occurs. For many substrates addition of a small amount of water to the reaction medium after completion of the first step assisted the subsequent rearrangement to the product, such that reversion of the intermediate to the starting ketone became an insignificant process. Yields were best with cyclohexanones (>90%), but steric hindrance and the presence of conjugated double bonds reduced yields considerably. This new spiro-annulation procedure has been applied to model studies towards the syntheses of fredericamycin A and a [4.3.3]-propellane. -- Model studies towards fredericamycin A began with 1-indanone. Geminal acylation with 1 followed by dehydrogenation provided the key enedione, spiro[3-cyclopentene-1,r-indan]-2,5-dione (83), which had established the key spiro center required for fredericamycin A. Our efforts concentrated on the condensation of 83 with 5,7-dimethoxy-1 (3H)~ isobenzofuranone (143). In an alternative approach, a Diels-Alder cyclization between the xylylene precursor, 3,4-bis(dibromomethyl)-1-methoxybenzene (114) and 83 was developed. -- Our studies towards the synthesis of propellanes was based on a novei intramolecular geminal acylation of a bis(trimethylsilyloxy)- cyclononene moiety (175). We had hoped that 175 could be prepared from diethyl 5-(1\3'-dioxocyclopentane)-4-methyl-1,9-nonanedioate (174), however geminal acylation of diethyl 4-methyl-5-(1,3-dioxolan-2- yl)nonanedioate (173) with 1 provided 174 in only trace amounts. As reported from our studies on the geminal acylation of ketals and ketones with 1 we attributed this lack of reactivity to the methyl substituent. Our second approach concentrated on a symmetrical bis(trimethylsilyloxy)- nonene compound. Double Grignard addition of the organomagnesium compound derived from 5-bromo-1-pentene to an ester gave 1,10- undecadien-6-ol (177), which established the carbon skeleton required for the nonene structure. Oxidation to 1,10-undecadien-6-one (179), followed by geminal acylation with 1 afforded 2,2-bis(4'- pentenyl)cyclopentane-1,3-dione (181). Conversion of the terminal double bonds of 181 into esters gave the nonene precursor, dimethyl 5-(1',3'- dioxocyclopentane)nonane-1,9-dioate (185). Unfortunately, our attempts to effect the acyloin condensation (diester 18£i to nonene species) and the subsequent intramolecular geminal acylation were not successful.
|Item Type:||Thesis (Doctoral (PhD))|
|Additional Information:||Bibliography: leaves 177-182|
|Department(s):||Science, Faculty of > Chemistry|
|Library of Congress Subject Heading:||Ketones; Acylation; Propellanes--Synthesis|
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