The Direct Metalation and Subsequent Functionalization of Trifluoromethyl‐Substituted Pyridines and Quinolines

Schlosser, Manfred; Marull, Marc

doi:10.1002/ejoc.200390216

Cited by 69 publications

(48 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…When the aryne was set free in the presence of a threefold excess of tert-butyllithium, nucleophilic addition of the latter occurred. Upon neutralization, (5-tert-butyl-2-chlorophenyl)trimethylsilane (11) and, upon protodesilylation, 1-tert-butyl-4-chlorobenzene (12) were both obtained in 73 % yield, respectively. The latter product was separately prepared from the commercial 1-bromo-4-tert-butylbenzene by consecutive halogen/metal permutation and chlorination with 1,1,2-trichloro-1,2,2-trifluoroethane.…”

mentioning

confidence: 99%

meta‐ Rather than ortho‐Directed Metalations: Buttressing Effects Prejudicing the Proton Abstraction from (2,6‐Dihalophenyl)silanes

2005

Self Cite

View full text Add to dashboard Cite

(2,6-Dichlorophenyl)trimethyl-and -triethylsilane exhibit untypical reactivity patterns toward strong bases. When treated at -100°C with lithium 2,2,6,6-tetramethylpiperidide, they give rise to two, with sec-or tert-butyllithium even three, different organometallic intermediates which can be intercepted with standard electrophiles. The trialkylsilyl group intervenes in two respects. Exerting steric pressure on the neighboring chlorine atoms, it facilitates the permutational displacement of one of them against lithium, a side reaction which occurs whenever alkyllithium compounds are employed. At the same time it impedes the attack of hydrogen When applying the "toolbox" methods [1] to the regioexhaustive functionalization of 1,3-difluorobenzene [2] and 1,3-dichlorobenzene [3] we made an unexpected discovery. (2,6-Dichlorophenyl)trimethylsilane and (2,6-dichlorophenyl)triethylsilane underwent hydrogen/metal permutation ("metalation") at the 5-rather than the 4-position or, in other words, meta rather than ortho to the activating halogen. However, the yields of the trapping products, the 3,5-dichloro-4-(trialkylsilyl)benzoic acids (60-70 %), ranged far below our expectations, no matter whether sec-butyllithium or lithium 2,2,6,6-tetramethylpiperidide (LITMP) were employed as the base in tetrahydrofuran at -75°C. When (2,6-dibromophenyl)triethylsilane served as the substrate, 3,5-dibromo-4-(triethylsilyl)benzoic acid (2) was isolated in an even lower yield of only 52 %. We worried whether we might have missed a regioisomer or any other by-product derived from the dichlorinated or dibrominated starting materials. The reaction was therefore repeated under systematic variation of some key parameters and the resulting mixtures were carefully examined by gas chromatography. At -100°C in tetrahydrofuran, LITMP promoted mainly a bromine/lithium permutation and only to a minor extent remote deprotonation as evidenced by the formation of 39 % of 3-bromo-2-(triethylsilyl)benzoic acid (1) and 8 % of 3,5-dibromo-4-(triethylsilyl)benzoic acid (2). The relative atoms by the base in the immediate vicinity of the halogens due to relay transmission of steric hindrance. As a consequence, deprotonation occurs preferentially or exclusively at the 5-("meta") rather than the 4-("ortho")position. 4-Lithiated species, generated as by-products or separately by permutational halogen/metal interconversion, eliminate lithium chloride at -75°C to set free didehydrobenzenes ("arynes") which are trapped by their aryllithium precursors.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005) amounts of 1 and 2 were inverted to 11 % vs. 61 % and 5.6 % vs. 70 %, respectively, when LITMP was employed in the presence of N,N,NЈ,NЈЈ,NЈЈ-pentamethyldiethylenetriamine (PMDTA) alone or in the additional presence of potassium tert-butoxide. The latter "Faigl mix" [4] gave the dibromo acid 2 exclusively when the reaction was performed at -125°C in tetrahydrofuran or diethyl ether (15 and 4.1 %

show abstract

mentioning

confidence: 99%

meta‐ Rather than ortho‐Directed Metalations: Buttressing Effects Prejudicing the Proton Abstraction from (2,6‐Dihalophenyl)silanes

2005

Self Cite

View full text Add to dashboard Cite

show abstract

“…[8] Experimental Section Generalities: Abbreviations and laboratory routines have been explained in previous publications from this laboratory. [9][10][11][12] The stationary phases of the gas chromatography columns used in the present work are encoded as BGB-2.5 (= 2.5 % of diphenylpolysiloxane and 97.5 % of dimethylpolysiloxane), Bentone (= 50 % of dimethyloctadecylammonium bentonite and 50 % of didecylphthalate), DB-1701 (= 14 % of cyanopropylphenylpolysiloxane + 86 % of dimethylpolysiloxane); DB-FFAP (= polyethylene glycol) and DB-WAX (= acid modified polyethylene glycol).…”

Section: Resultsmentioning

confidence: 99%

The Kinetic Acidity of Oligofluorobenzenes Correlated with Their Gas Phase Deprotonation Energies

Schlosser¹,

Marzi²

2005

Chemistry A European J

Self Cite

View full text Add to dashboard Cite

The relative reactivities of fluorobenzene, all di-, tri-, and tetrafluorobenzenes and pentafluorobenzene toward sec-butyllithium have been assessed in tetrahydrofuran at -100 degrees C. At this temperature no subsequent transmetalation reactions take place but those compromise the outcome of the competition experiments if the latter are conducted at -75 degrees C. The rates determined at -100 degrees C reflect the basicity differences between the naked (oligo)fluorophenyl anions to the extent of 10 %.

show abstract

“…[9][10][11] Unless specified otherwise, the 1 H and 13 C NMR spectra were recorded at 300 and 75 MHz, respectively, of samples dissolved in deuteriochloroform. …”

Section: Methodsmentioning

confidence: 99%

Trifluoromethyl‐Substituted Phenylsilanes: The Regiochemical Course of Their Metalation Dictated by Buttressing Effects

Schlosser

Heiss

Leroux³

2006

Eur J Org Chem

Self Cite

View full text Add to dashboard Cite

Triethyl [(2-trifluoromethyl)phenyl]silane reacts with the superbasic LIC-KOR mixture of butyllithium and potassium tert-butoxide exclusively at the 4-position ("meta-metalation") and not at all at the 3-position ("ortho-metalation"). Two further substrates which simultaneously contain two trifluoromethyl groups, triethyl[2,4-and 2,5-bis(trifluoromethyl)phenyl]silane, undergo deprotonation at the 5-and

show abstract

The Direct Metalation and Subsequent Functionalization of Trifluoromethyl‐Substituted Pyridines and Quinolines

Cited by 69 publications

References 36 publications

meta‐ Rather than ortho‐Directed Metalations: Buttressing Effects Prejudicing the Proton Abstraction from (2,6‐Dihalophenyl)silanes

meta‐ Rather than ortho‐Directed Metalations: Buttressing Effects Prejudicing the Proton Abstraction from (2,6‐Dihalophenyl)silanes

The Kinetic Acidity of Oligofluorobenzenes Correlated with Their Gas Phase Deprotonation Energies

Trifluoromethyl‐Substituted Phenylsilanes: The Regiochemical Course of Their Metalation Dictated by Buttressing Effects

Contact Info

Product

Resources

About