Ferrocenyl Migrations and Molecular Rearrangements

inorganics Review ReviewFerrocenyl Migrations and Molecular FerrocenylRearrangements: Migrations The Significance and Molecular of Electronic Rearrangements: The Significance of Electronic Charge Delocalization Michael J. McGlinchey Michael J. McGlinchey School of Chemistry, University College Dublin, D04 V1W8, Belfield, Dublin 4, Ireland; School of Chemistry, University College Dublin, D04 V1W8 Belfield, Dublin 4, Ireland; [email protected] [email protected] Received: 27 November 2020; Accepted: 9 December 2020; Published: 11 December 2020 Received: 27 November 2020; Accepted: 9 December 2020; Published: 11 December 2020 Abstract: The enhanced stabilization of a carbocationic site adjacent to a ferrocenyl moiety was Abstract:recognizedThe within enhanced a few stabilization years of the of adiscovery carbocationic of sandwich site adjacent compounds. to a ferrocenyl While moietya detailed was recognizedunderstanding within of athe few phenomenon years of the discovery was the of subject sandwich of compounds.some early debate, While a detailedresearchers understanding soon took ofadvantage the phenomenon of it to control was the the subject ease ofand some direction early debate, of a wide researchers range of soon molecular took advantage rearrangements. of it to control We, thehere ease, discuss and direction the progress of a wide in this range area of molecularfrom the pioneering rearrangements. studiesWe, of here, the discuss1960s, to the more progress recent in thisapplications area from in the chromatography pioneering studies and of analytical the 1960s, detection to more recenttechniques, applications and currently in chromatography in the realm and of analyticalbioactive organometallic detection techniques, complexes. and Several currently classic in the reactions realm of inv bioactiveolving ferrocenyl organometallic migrations, complexes. such Severalas the pinacol, classic reactionsWolff, Beckmann, involving ferrocenyland Curtius, migrations, are discussed, such asas thewell pinacol, as the Wolinfluenceff, Beckmann, of the andferrocenyl Curtius, substituent are discussed, on the as wellmechanisms as the influence of the Nazarov, of the ferrocenyl Meyer-Schuster, substituent benzoin on the, mechanismsand Stevens ofrearrangements. the Nazarov, The Meyer-Schuster, preparation an benzoin,d isomerizations and Stevens of ferrocenyl rearrangements.-stabilized The vinyl preparation cations and isomerizationsvinylcyclopropenes, of ferrocenyl-stabilized together with the vinyl specific cations cyclization and vinylcyclopropenes, of acetylcyclopenta togetherdienyl with-metal the specificderivatives cyclization to form of1,3,5 acetylcyclopentadienyl-metal-substituted benzenes, demonstrate derivatives the to versatility form 1,3,5-substituted and generality benzenes, of this demonstrateapproach. the versatility and generality of this approach. Keywords: metalmetal-stabilized-stabilized carbocations; reaction mechanisms; NMR; bioorganometallics 1. Introduction The ability ability of of the the ferrocenyl ferrocenyl moiety moiety to tostabilize stabilize an adjacent an adjacent carbocationic carbocationic cente centerr has long has been long beenattributed attributed to delocalization to delocalization of the of theelectron electron deficie deficiencyncy onto onto the the iron iron atom atom [1] [1.]. The The X-rayX-ray crystallographically established [2,3] [2,3] tendency of of the cationic α--carboncarbon atom to lean towards the metal as in 1, was originally interpreted inin terms of an overlap of the vacant 2p orbital on carbon with a filled filled 3 3dd orborbitalital of of suitable suitable symmetry symmetry on on iron iron [4] [4. Taking]. Taking a more a more extreme extreme view, view, one one could could regard regard the + thesystem system as a asneutral a neutral fulvene fulvene ligand ligand coordinated coordinated to a to [(C a5 [(CH5)Fe]5H5+)Fe] unit,unit, as depicted as depicted in 2 (Figure in 2 (Figure 1), but1), butthis thishas been has been criticized criticized based based on the on low the barrier low barrier to rotation to rotation about about the exocyclic the exocyclic bond bondin some in somecases cases[5,6]. [5,6]. + R R Fe R +Fe R 1 2 Figure 1. Delocalization of charge from the cationic α carbon onto the iron atom. Fortunately, a comprehensive overview of this, sometimes controversial, phenomenon has been presented by Gleiter, Bleiholder, and Rominger [7]. Nevertheless, it is this character of charge Inorganics 2020, 8, x; doi: FOR PEER REVIEW www.mdpi.com/journal/inorganics Inorganics 2020, 8, 68; doi:10.3390/inorganics8120068 www.mdpi.com/journal/inorganics Inorganics 2020, 8, x FOR PEER REVIEW 2 of 22 Inorganics 2020, 8, x FOR PEER REVIEW 2 of 22 Inorganics 2020, 8, 68 2 of 23 Fortunately, a comprehensive overview of this, sometimes controversial, phenomenon has been presented by Gleiter, Bleiholder, and Rominger [7]. Nevertheless, it is this character of charge delocalization that facilitates a number of molecular rearrangements or ferrocenyl migrations, as we delocalization that facilitates a number of molecular rearrangementsrearrangements or ferrocenyl migrations, as we shall attempt to demonstrate. shall attempt to demonstrate. 2. Ferrocenyl Ferrocenyl-Mediated-Mediated Carbocationic Rearrangements 2.1. Isomerizations of Secondary to Tertiary CarbocationsCarbocations Following pioneering studies by Cais [[8]8],, dissolution of ferrocenyl ferrocenyl-substituted-substituted alcoholsalcohols in 1 1 trifluoroacetic acid acid allowed allowed the the acquisition acquisition of well-resolved of well-resolvedH NMR 1H NMR spectra spectra by several by several other groupsother groups [9–11], and[9–11] revealed, and revealed the unusual the unusual stability stability of the of carbocations the carbocations so generated. so generated.Subsequently, Subsequently, in a in series a series of ground-breakingof ground-breaking papers, papers, Watts Watts and and his his group group reported reported the the rearrangement rearrangement behavior behavior of aof number a number of alkylferrocenylof alkylferrocenyl carbocations carbocations upon upon protonation protonation of theirof their precursor precursor alcohols alcohols [12 ].[12]. Typically, thethe quantitativequantitative conversionconversion ofof thethe ferrocenyl-stabilizedferrocenyl-stabilized secondary carbocationcarbocation 3 intointo itsits tertiary isomer isomer 44, ,is is in in accord accord with with the the accepted accepted hierarchy hierarchy of stable of stable carbocations. carbocations. At first At firstsight, sight, this thisappears appears to be to a be double a double shift shift rearrangement rearrangement whereby whereby an an alkyl alkyl migration migration to to form form the ββ-ferrocenyl-ferrocenyl cation 5 isis followedfollowed byby aa [[11,2,2]-hydrogen]-hydrogen shiftshift toto yieldyield thethe observedobserved product.product. However, thethe authorsauthors did not prefer this mechanism since the intermediate rearrangement product, 5, would undoubtedly be thermodynamically disfavored relative to the ferrocenyl-stabilizedferrocenyl-stabilized startingstarting cation 33.. Instead, they proposed that the initialinitial methylmethyl migrationmigration might proceed synchronously with the formation of a short-livedshort-lived spirospiro-diene-diene species species6 (depicted 6 (depicted in Scheme in Scheme1) which 1) couldwhich reopen could with reopen concomitant with concomitant hydrogen migration,hydrogen migration, thus generating thus thegenerating observed the final observed product fin [13al]. product In such a[13] scenario,. In such the a cationicscenario, charge the cationic would charge would be delocalized onto the metal in the transition state. The analogous rearrangement of+ becharge delocalized would be onto delocalized the metal inonto the the transition metal in state. the transition The analogous state. rearrangement The analogous of rearrangement [Fc–CH–CPh3 ]of, [Fc–CH–CPh3]+, 7, into +[Fc–CPh–CHPh2]+, 8, was also observed (Scheme 2), but in this case the 7[Fc, into–CH [Fc–CPh–CHPh–CPh3]+, 7, into2] [Fc, 8,– wasCPh also–CHPh observed2]+, 8, was (Scheme also2 ),observed but in this (Scheme case the 2), doubly-benzylic but in this case cation the doubly-benzylic cation+ [Fc–CHPh–CPh2]+, 9, might be a viable intermediate [14]. [Fc–CHPh–CPhdoubly-benzylic2 ]cation, 9, might [Fc–CHPh be a viable–CPh2 intermediate]+, 9, might be [ 14a viable]. intermediate [14]. Me Me Me Me Me Me Me Me OHMe + Me OH CF3CO2H + Fe H 3 2 Fe Me H Fe H Fe H Me H 3 Me + Fe Me + Fe Me Me 6 Me Me H 6 + H Me Me MeMe Me Me + Fe H Fe H Fe Me 5 4 5 4 Scheme 1. Rearrangement of 2° to 3° ferrocenyl trimethyl-carbocations. Scheme 1. Rearrangement of 22°◦ to 3° 3◦ ferrocenyl trimethyl trimethyl-carbocations.-carbocations. Ph Ph Ph Ph Ph Ph Ph + Ph H Ph + H Ph Ph Ph + Ph Ph Fe Ph + Fe H Fe H Fe H Fe Ph 7 9 8 SchemeScheme 2.2. Rearrangement of 22° to 33° ferrocenyl tri triphenyl-carbocations.phenyl-carbocations. Scheme 2. Rearrangement of 2°◦ to 3°◦ ferrocenyl triphenyl-carbocations. 2.2. Rearrangements of Vinyl and Allyl Cations 2.2. Rearrangements of Vinyl and Allyl Cations This work was elegantly extended to include the addition reactions of trityl cations to alkynylferrocenesThis work was to generate elegantly ferrocenyl-stabilized extended to include vinyl the carbocations, addition reactions10, that underwent of trityl cyclizationcations to alkynylferrocenes to generate ferrocenyl-stabilized vinyl carbocations, 10, that underwent

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