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Ring Expansion of Cyclobutylmethylcarbenium Ions to Cyclopentane Or Cyclopentene Derivatives and Metal-Promoted Analogous Rearrangements

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Ring Expansion of Cyclobutylmethylcarbenium Ions to Cyclopentane Or Cyclopentene Derivatives and Metal-Promoted Analogous Rearrangements Ring expansion of cyclobutylmethylcarbenium ions to cyclopentane or cyclopentene derivatives and metal-promoted analogous rearrangements Erika Leemans, Matthias D‟hooghe, Norbert De Kimpe* Department of Sustainable Organic Chemistry and Technology, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, B-9000 Ghent, Belgium *[email protected] Table of Contents 1 Introduction ........................................................................................................................ 2 2 Ring expansion of cyclobutylmethylcarbenium ions through activation of a carbon- carbon double bond .................................................................................................................... 5 2.1 Acid-promoted activation of alkenylcyclobutanes ...................................................... 7 2.1.1 Pinene rearrangement ........................................................................................... 7 2.1.2 Ring expansion of vinylcyclobutanes (different from pinene) ............................. 9 2.1.3 Semipinacol rearrangement of 1-vinylcyclobutanols ......................................... 17 2.2 Halogen/selenium cation-promoted activation .......................................................... 23 2.3 Metal-promoted activation ........................................................................................ 27 2.3.1 Mercury-promoted activation ............................................................................. 27 2.3.2 Palladium-promoted activation .......................................................................... 28 2.3.3 Thallium-promoted activation ............................................................................ 41 2.4 Conjugated double bond (1,3-dienyl group) activation ............................................. 43 3 Ring expansion of cyclobutylmethylcarbenium ions through activation of an allene ..... 44 3.1 Acid-promoted activation .......................................................................................... 44 3.2 Metal-promoted activation ........................................................................................ 45 3.2.1 Palladium-promoted activation .......................................................................... 45 3.2.2 Ruthenium- or gold-promoted activation ........................................................... 49 4 Ring expansion of cyclobutylmethylcarbenium ions through activation of an alkynyl substituent ................................................................................................................................. 51 4.1 Palladium-promoted activation .................................................................................. 52 4.2 Ruthenium-promoted activation ................................................................................ 55 4.3 Gold-promoted activation .......................................................................................... 57 5 Ring expansion of cyclobutylmethylcarbenium ions through activation of a carbonyl group ......................................................................................................................................... 59 5.1 Direct activation ........................................................................................................ 60 5.2 Special cases .............................................................................................................. 76 6 Formation of cyclobutylmethylcarbenium ions through expulsion of a leaving group ... 79 6.1 A halogen atom as leaving group .............................................................................. 79 6.1.1 Cyclobutylmethyl chlorides ............................................................................... 79 6.1.2 Cyclobutylmethyl bromides ............................................................................... 84 6.1.3 Cyclobutylmethyl iodides .................................................................................. 89 6.2 N2 as leaving group .................................................................................................... 98 6.2.1 Via azide addition across methylenecyclobutanes ............................................. 98 6.2.2 Semipinacol rearrangement .............................................................................. 100 6.3 An activated nitro group as leaving group ............................................................... 117 6.4 An activated hydroxy group as leaving group ......................................................... 118 1 6.4.1 Cyclopentane/Cyclopentene synthesis ............................................................. 118 6.4.2 Pinacol rearrangement (cyclopentanone synthesis) ......................................... 127 6.4.3 A mesyloxy group as leaving group ................................................................. 132 6.4.4 A tosyloxy group as leaving group .................................................................. 134 6.5 An ether moiety as leaving group ............................................................................ 138 6.5.1 An alkoxy or aryloxy group as leaving group .................................................. 138 6.5.2 Ring opening of an epoxide as driving force for the ring expansion reaction . 147 6.5.3 Ring opening of an activated tetrahydrofuran ring as driving force for the ring expansion reaction .......................................................................................................... 151 6.5.4 A special case ................................................................................................... 153 6.6 An alkyl- or arylthio group as leaving group .......................................................... 153 6.7 An alkyl- or arylselenyl group as leaving group ..................................................... 158 6.8 Sulfone, sulfoxide and selenoxide groups as leaving group .................................... 160 6.8.1 A sulfone group as leaving group .................................................................... 161 6.8.2 A sulfoxide as leaving group ............................................................................ 162 6.8.3 A selenoxide as leaving group ......................................................................... 165 7 Miscellanous ................................................................................................................... 166 8 Concluding Remarks ...................................................................................................... 174 9 References ...................................................................................................................... 175 1 Introduction The synthesis of five-membered carbocycles remains an important task within the design of functionalized target compounds bearing a cyclopentane unit.1 Ring enlargement reactions are commonly used to access five-membered ring systems. Many of these methodologies utilize ring strain in consort with the generation of a positive charge on a carbon atom adjacent to a four-membered ring as a driving force for the ring expansion reaction.2 In this way, the cyclobutylmethylcarbenium ion 1 can rearrange smoothly under mild conditions to provide the cyclopentylcarbenium ion 2 (Scheme 1).3 1 2 Scheme 1 2 The ring enlargement of cyclobutanes to five-membered rings is associated with a release of 20 kcal/mol (ring strain energy). In contrast, the relief of strain associated with C3 to C4 and 4 C5 to C6 enlargements is less pronounced, but the activation barrier for 1,2-shifts is higher in cyclobutanes than in cyclopentanes or cyclohexanes.5 In addition to experimental work, theoretical studies on cyclobutylmethyl and cyclopentylcarbenium ions have been performed in the past.6 Some of the classical methods applied to ring homologation by a one carbon atom are the Demjanov,7 the Tiffeneau-Demjanov,7 the Wagner-Meerwein8 and the pinacol rearrangement.9 Well-known ring homologation methods which incorporate a heteroatom into the ring are the Baeyer-Villiger reaction (oxygen)10 and the Beckmann rearrangement (nitrogen).11 Cyclobutanones are readily available derivatives of cyclobutanes.12 The chemical reactivity of cyclobutanones is considerably different from that of cyclic ketones with larger rings due to the ring strain of ca. 25 kcal/mol. Information regarding the influence of the ring strain on regio-, chemo- and stereoselective transformations of four-membered ring ketones is of particular importance.13 Cyclobutanones can be constructed through a variety of methods14 and may be further functionalized by means of Grignard reactions,12 aldol reactions of cyclobutanone enolates with aldehydes,15 and many other reactions to offer a convenient four- carbon ring substrate for further ring enlargement reactions. Enantioselective reactions involving deprotonations, alkylations, reductions, and other functionalization reactions of the carbonyl group of cyclobutanones represent practical approaches to optically enriched cyclobutanes starting from racemates.16 The interest in cyclopentanes and cyclopentanones stems from their presence in a wide variety of natural products. Their structures characterize the core of different classes of substances like steroids and sesquiterpenes, but also 3 jasmones,17 pyrethroids and prostaglandins.18 Substituted cyclopentenones are found in various naturally occurring, biologically active compounds, like pentenomycins.19 In 1988, Bellus and Ernst
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