Polysulfones as new organic catalysts

Even unsubstituted butadiene adds to sulfur dioxide in the hetero-Diels-Alder mode more rapidly than in the chelotropic mode. The sultine can be observed in equilibrium with the diene and the sulfur dioxide only at low temperature and in the presence of CF3COOH. Crystals of the 4,5-dialkyl-sultine resulting from the SO2 addition to 1,2-dimethylidenecyclohexane have been obtained at -60 °C and analyzed by X-ray diffraction. Quantum chemistry calculations have shown that hyperconjugative interactions within the sulfinyl moiety are responsible for the anomeric effects observed in sultines that prefer pseudo-chair conformations with pseudo-axial S=O bonds. Mixing of sulfur dioxide and methylidenecyclopentane leads to the formation of alternating copolymer poly(methydilenecyclopentane sulfone) and isomerization of methylidenecyclopentane to 1-methylcyclopentene. Polysulfones are known to equilibrate with radicals upon heating (ceiling temperature of polysulfone formation). These sulfonyl radicals can abstract a hydrogen atom from methylidenecyclopentane (and from other 2-alkylalk-1-enes) to give an allyl radical type intermediate and sulfinic acid. The intermediate allyl radical abstracts an hydrogen atom from sulfinic acid and gives isomerized product (1-methylcyclopentene). Diphenyldisulfone or solid polysulfones are mild and efficient organic catalysts for selective cleavage of methylprenyl (2,3-dimethylbut-2-en-1-yl), prenyl (3-methylbut-2-en-1-yl), and methallyl (2-methylallyl) ethers. Our reaction conditions are compatible with the presence of other protecting groups such as acetals, acetates, and allyl, benzyl, and TBDMS ethers. Exposure of 2,3-dimethylbut-2-en-1-yl and 3-methylbut-2-en1-yl ethers to diphenyldisulfone or solid polysulfones led to the formation of 2,3-dimethylbuta-1,3-diene and isoprene, respectively. 2-Methylallyl ethers undergo isomerization to 2-methylpropenyl ethers, which are easily hydrolyzed into the corresponding free alcohols and isobutyraldehyde. We discovered that (2-methoxyprop-2-en-1-yl) silyl sulfinates are very effective agents for the silylation of alcohols and oximes. (2-methoxyprop-2-en-1-yl) silyl sulfinates allow easy, efficient and fast silylation of primary, secondy and tertiary alcohols. The diols are monosilylated at low temperature with high regioselectivity and high yields.

Transition metal-catalyzed carbon-carbon cross-coupling reactions using sulfonyl derivatives

The goal of this thesis was to find conditions to form C-C double bond and single bond using sulfonyl derivativies, which are arising from the Vogel's oxyallylation cascades. In a second chapter, it is shown that 2-methylprop-2-ene-1-sulfonyl fluorides can be easily prepared via the ene reaction of methallylsilanes and SO2 followed by halogenosis (NCS, then KF). In the presence of a base, aldehydes and 2-methylprop-2-ene-1-sulfonyl fluorides give mixture of (1Z)- and (1E)-1-aryl-3-methylbutadienes. Their (Z)→(E) isomerization by classical means fails or leads to their polymerization. We have discovered that SO2 can isomerize 1-aryl-3-methyl-1,3-dienes at low temperature, without formation of sulfolenes (cheletropic addition/elimination). Preliminary mechanistic studies suggest that SO2 add to the 1,3-dienes forming 1,4-diradical intermediates that are responsible for the (Z)→(E) isomerizations. In the third chapter, we have shown that arenesulfonyl chlorides are versatile electrophilic reagents for C-C cross-coupling reactions. Arene-, arylmethane- and alk-2-ene-1-sulfonyl chlorides undergo desulfitative Stille, carbonylative Stille, Negishi and Suzuki-Miyaura cross-coupling reactions. In these reactions the reactivity order is ArI> ArSO2Cl> ArBr> ArCl. Similarly, desulfitative Sonogashira-Hagihara cross-couplings of arenesulfonyl chlorides with aryl- and alkylacetylenes can be catalyzed by Pd2(dba)3/P(t-Bu)3/CuI. New conditions have been found for the desulfitative Mizoroki-Heck arylation and trifluoromethylation of mono- and disubustituted olefins with arenesulfonyl and trifluoromethanesulfonyl chlorides. This procedure allows one to obtain (E)-1,2-disubstituted alkenes with high stereoselectivity and 1,1,2-disubstituted alkenes with high (E)/(Z) stereoselectivity. If phosphine- and base-free conditions are required, 1 mol% {RhCl(C2H4)2} catalyses the desulfitative cross-coupling reactions. On the contrary to what has been reported for RuCl2(PPh3)2 catalyzed coupling reactions with sulfonyl chlorides, the palladium and rhodium desulfitative Mizoroki-Heck coupling reactions are not inhibited by radical scavenging agents. Moreover, sulfones that are formed from the sulfonylation of alkenes at 60°C can theoretically be envisaged as intermediates in all cross-coupling reactions. However we have shown that they are not desulfitated at higher temperatures in the presence of the Pd or Rh-catalysts. Alk-2-ene-1-sulfonamides can also undergo desulfamylating cross-coupling reaction with Grignard reagents in the presence of a nickel catalyst. In the fouth chapter, we have evaluated the possibility that silyl sulfinates can be used as nucleophilic partners to form C-C bond. Our preliminary results indicate that their hypothesis should be explored further. In a fifth chapter, we have contributed to the development of an efficient one-pot, three component syntheses of sulfonamides and sulfonic esters. We have demonstrated that the ene-reaction of sulfur dioxide with enoxysilanes can be stereoselective under conditions of kinetic control. As others in our laboratory, we have shown that the hetero-Diels-Alder addition of sulfur dioxide to 1-oxy or 1,3-dioxy-1,3-dienes generates zwitterions that add to enoxysilanes or allylsilanes giving silyl sulfinates that can be converted in the same pot into polyfunctional sulfones, sulfonamides or sulfonic esters. Intramolecular S-allylation of intermediate silyl sulfinates has allowed one to prepare new tetrahydro-2H-thiocine derivatives. Our key contribution has been to use enantiomerically enriched amines which has allowed one to obtain enantiomerically enriched polyfunctional sulfonamides.

EPFL2005

Mechanistic Studies Related to Nickel-Catalyzed Alkyl-Alkyl Cross Coupling Reactions

Jan Breitenfeld

Cross-coupling reactions of non-activated alkyl halides are potentially useful chemical transformations. At the same time, however, they are challenging due to a series of unproductive side reactions. Recently, significant progress has been made to overcome these difficulties. With judicious choice of metal, ligands, and reaction conditions, the normally problematic β- H elimination can be suppressed. As a consequence, a number of examples of the successful coupling of non-activated alkyl halides have been demonstrated. The mechanistic understanding of such reactions is, in most cases, still primitive. In the majority of cases, the active catalysts are generated in situ and remain unidentified and unknown. This dissertation is devoted to mechanistic studies of alkyl-alkyl cross-coupling catalyzed by a well-defined nickel pincer complex [(MeNN2)Ni-Cl] (1; Nickamine). This complex showed excellent activity for the cross-coupling of unactivated alkyl halides. Moreover, several nickel alkyl complexes bearing β-hydrogen atoms have been isolated. These features offered a unique platform to carry out mechanistic studies to gain a better understanding of nickel-catalyzed crosscoupling reactions. Chapter one provides examples of palladium-, iron-, cobalt-, and nickel-catalyzed alkyl-alkyl cross-coupling reactions. In each case mechanistic details are discussed. At the end of the chapter cross-coupling reactions using Nickamine are presented. In chapter two the propensity of isolated nickel alkyl complexes to undergo -hydride elimination is explored. Isomerization and olefin exchange experiments show that -hydride elimination is kinetically viable but thermodynamically unfavorable in [(MeNN2)Ni-alkyl] complexes. The intermediacy of an [(MeNN2)Ni-H] (6) species was corroborated by trapping experiments. The alkyl complex [(MeNN2)Ni-propyl] catalyzes olefin isomerization reactions. In chapter three the aforementioned nickel(II) hydride complex 2 was synthesized by reaction of [(MeNN2)Ni-OMe] (10) with Ph2SiH2, and was characterized by NMR and IR spectroscopy, as well as X-ray crystallography. Complex 6 was unstable in solution, and decomposed via two reaction pathways. The first pathway was through intramolecular N-H reductive elimination to III give MeNN2H and Ni particles. The second pathway was intermolecular, giving H2, Ni particles, and a five-coordinate Ni(II) complex [(MeNN2)2Ni] (12) as the products. Compound 6 reacted with ethylene and acetone, forming [(MeNN2)Ni-Et] (2) and [(MeNN2)Ni-OiPr] (13), respectively. Complex 6 also reacted with alkyl halides, yielding nickel(II) halide complexes and alkanes. The reduction of alkyl halides was rendered catalytic, using 1 as catalyst, NaOiPr or NaOMe as base, and Ph2SiH2 or Me(EtO)2SiH as the hydride source. The catalysis appeared to operate via a radical mechanism. In chapter four a detailed mechanistic study of alkyl-alkyl Kumada coupling catalyzed by the preformed nickel(II) pincer complex 1 is reported. The coupling proceeds through a radical process, involving two nickel centers for the oxidative addition of alkyl halide. The catalysis is 2nd order in Grignard reagent, 1st order in catalyst, and 0th order in alkyl halide. A transient species, (MeNN2)Ni-Alkyl2, is identified as the key intermediate responsible for the activation of alkyl halide, the formation of which is the turnover-determining step of the catalysis. Finally, a catalytic cycle for Nickamine-catalyzed cross-coupling reactions was established. This dissertation elaborates the properties of nickel-alkyl and nickel-hydride complexes of the Nickamine system. It elucidates many mechanistic features of the alkyl-alkyl Kumada coupling reactions catalyzed by Nickamine, and establishes, for the first time, a bimetallic oxidative addition mechanism for nickel-catalyzed coupling reactions. The work significantly enhances the current understanding of cross-coupling reactions of alkyl halides.

EPFL2013

Transition metal-catalyzed carbon-carbon cross-coupling reactions using sulfonyl derivatives

EPFL2005

Mechanistic Studies Related to Nickel-Catalyzed Alkyl-Alkyl Cross Coupling Reactions

Jan Breitenfeld

EPFL2013