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Thomas J J Müller

Publications and source records attributed to Thomas J J Müller.

14 recordsLinked to original sources
PubMed2006

Coupling-isomerization synthesis of chalcones.

The Sonogashira coupling of electron-deficient (hetero)aryl halides 1 and (hetero)aryl or alkenyl 1-propargyl alcohols 2 does not terminate at the stage of the expected internal propargyl alcohols, but rather gives rise to the formation of alpha,beta-unsaturated ketones 3 with a variety of acceptor substituents. This new domino reaction, a coupling-isomerization reaction (CIR), can be rationalized as a sequence of rapid Pd/Cu-catalyzed alkynylation followed by a slow amine-base-catalyzed propargyl alcohol-enone isomerization. Performing the CIR in deuterated protic solvents or with a selectively deuterated propargyl alcohol revealed that the base-catalyzed isomerization step proceeds through a formal 1,3-H shift with minimal H/D exchange with the surrounding solvent. Additionally, 19F NMR kinetic measurements on the isomerization step with the fluorinated propargyl alcohol 4 r support the mechanistic rationale.

Alkenes↗
PubMed2006

Coupling-isomerization-N,S-ketene acetal-addition sequences--a three-component approach to highly fluorescent pyrrolo[2,3-b]pyridines, [1,8]naphthyridines, and pyrido[2,3-b]azepines.

Annelated 2-amino pyridines such as pyrrolo[2,3-b]pyridines, [1,8]naphthyridines, and pyrido[2,3-b]azepines can be synthesized in moderate to good yields in a consecutive one-pot three-component process by a coupling-isomerization-enamine-addition-cyclocondensation sequence of an electron-poor (hetero)aryl halide, a terminal propargyl N-tosylamine, and an N,S-ketene acetal. After the coupling-isomerization sequence, a Diels-Alder reaction with inverse electron demand of the intermediate enimine and the N,S-ketene acetal and subsequent aromatization furnish annelated 2-amino pyridines 4 that were unambiguously characterized by numerous X-ray structure analyses. These heterocycles are highly fluorescent and partially pH sensitive, and their electronic structure was studied with spectroscopic and computational methods.

Journal Article↗
PubMed2005

A sequential palladium-catalyzed alder-ene-reductive amination reaction.

[reaction: see text]. Alkyne allyl alcohols are readily transformed into beta-amino ethyl alkylidene tetrahydrofurans or beta-amino ethyl alkylidene pyrrolidines in a Pd-catalyzed cycloisomerization-reductive amination sequence with remarkable chemoselectivity leaving benzyl groups and trisubstituted double bonds intact.

Journal Article↗
PubMed2005

A novel one-pot three-component synthesis of 3-halofurans and sequential Suzuki coupling.

A novel sequence of Sonogashira coupling and electrophilic addition to an ynone, with concomitant deprotection and cyclocondensation, opens a new one-pot synthesis of 3-halofurans; the method can be readily elaborated to a new sequential Sonogashira-addition-cyclocondensation-Suzuki reaction to furnish 2,3,5-trisubstituted furans in a one-pot fashion.

Crystallography, X-Ray↗
PubMed2003

Practical synthesis of iodo phenothiazines. A facile access to electrophore building blocks.

Bromine-lithium exchange of the mono- and dibromophenothiazines 1 and 3a regiospecifically furnishes upon electrophilic trapping with iodine the iodo- and diiodophenothiazines 2, 3b, and 3d in excellent yield. The 3-bromo-7-iodophenothiazine 3d can be submitted to regioselective and sequential Suzuki coupling reactions with phenothiazine mono- and bisboronates 4 and 5 and/or (hetero)aryl boronic acids to give the bromodiphenothiazine 6a, the dibromo terphenothiazine 7, and the (hetero)aryl-substituted phenothiazine dyads 6b-d in moderate to good yields.

Journal Article↗
PubMed2003

New entry to a three-component pyrimidine synthesis by TMS-Ynones via Sonogashira coupling.

[reaction: see text] TMS-ynones are versatile synthetic equivalents of beta-keto aldehydes and can be readily synthesized in an atom-economical fashion by coupling (het)aroyl chlorides and (TMS)-acetylene with only one equiv (!) of triethylamine under Sonogashira conditions. This mild ynone synthesis is also a suitable entry to 2,4-disubstituted pyrimidines in the sense of a one-pot three-component reaction, i.e., a coupling-addition-cyclocondensation sequence.

Journal Article↗
PubMed2003

Facile one-pot coupling-aminovinylation approach to push-pull chromophores: alkyne activation by sonogashira coupling.

A straightforward coupling-aminovinylation sequence of terminal alkynes 1, electron-deficient heteroaryl halides 2, and secondary amines 4 furnishes highly solvochromic push-pull chromophores 5 in good yields. Semiempirical calculations (PM3) suggest that the aminovinylation proceeds in a stepwise fashion through a zwitterionic intermediate with a final rate-determining intramolecular protonation. Crucial parameters for the success of the amine addition are the relative LUMO energies and the charge distribution at the beta-alkynyl carbon atom.

Journal Article↗
PubMed2003

Coupling-isomerization-coupling sequences switched on by propargyl alcohol-enone-isomerization.

The coupling-isomerization-reaction (CIR) of an electron-deficient halide 1 with 1-(p-bromo phenyl) propyne-1-ol (2) leads to an in-situ activation of the carbon-bromine bond towards oxidative addition and has been elaborated to a consecutive CIR-coupling sequence where subsequent palladium catalyzed coupling reactions such as Sonogashira, CIR, Heck, or Suzuki reactions allow a rapid construction of more complex frameworks in a one-pot reaction and in moderate to good yields.

Alcohols↗