Biomedical subjects
Publications and source records attributed to Max Malacria.
5-En-1-yn-3-ol substrates bearing a free hydroxyl group or an acyl group are highly versatile partners for PtCl2-catalyzed cycloisomerizations. Electrophilic activation of the alkyne moiety triggers at wish a hydride or an O-acyl migration yielding at the end to regioisomeric keto derivatives. The efficient preparation of Sabina ketone, an important monoterpene precursor, has been worked out.
[reaction: see text] The first examples of totally chemo- and regioselective formal intermolecular cobalt(I)-catalyzed [2 + 2 + 2] cyclizations of three different alkynes are reported. The use of disposable silylated tethers in the sequence cyclization followed by the displacement of the silicon group led to polysubstituted arenes as a unique cycloadduct in high yields.
[reaction: see text] Various ene-tosylynamides react with platinum(II) chloride and lead to bicyclic nitrogenated heterocycles. This unprecedented and easily operated process can be coupled with a hydrolysis of the intermediate cyclic tosylenamides in a one-pot transformation, which provides cyclobutanones.
The PtCl2-catalyzed cycloisomerization of allenyne systems has been examined. This process is a highly versatile tool for obtaining products that cannot be attainable with other metals. Simple adjustment of the allene or alkyne substitution can direct the reactivity in a selective manner and give birth to important carbocyclic frameworks (hydrindenes, cyclic vinylallenes, and trienes).
[reaction: see text] A new class of N-substituted radical has been studied. Obtained from the corresponding chlorides, beta-lactamido N-sulfonyl radicals were allylated and added onto electron-rich olefins. It has been shown that the radicals do not undergo desulfonylation and are electrophilic in nature.
Reaction of sulfonamides with iodosobenzene leads to phenyliodinanes. A new catalysis reaction of the decomposition of these products in the presence of sulfoxides that allows the smooth synthesis of sulfoximines has been evidenced and studied: copper(II) salts were used to prepare compounds 4 a-j and 5 b, d, f, j, k from the corresponding, easily prepared, sulfoxides. The reactions proceed with retention of configuration at the sulfur center, and copper(II) triflate is the best candidate for the catalyst for the imination. Switching from sulfonamides to sulfinamides in the preparation of the starting iodinanes completely alters the reaction pathway: iodinanes are no longer accessible, and sulfonimidates 7 a-j are obtained instead. This behavior can be rationalized by the increase in pK(a) brought about by the removal of one oxygen atom from the sulfur center. Sulfonimidates are interesting molecules with varied applications. Optimization of their one-pot synthesis has been achieved by carrying out the reaction in acetonitrile. The stereochemical study has shown that the transformation proceeds with global retention of the configuration at the sulfur center, albeit with erosion of the enantiomeric purity. A model accounting for this outcome is proposed. In addition, the presence of oxidized sulfonamide by-products has been explained, and this latter pathway becomes the sole one when alcohol is replaced by water. Good yields of the oxidized products are obtained.
A radical cascade involving a 5-exo-dig cyclization followed by a 6-endo-trig radical trapping transforms ynamides into heterogeneous polycyclic compounds in good yields. This leads interestingly to the formation of isoindols, isoindolinones, and pyridoisoindolones. [reaction: see text]
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A series of 2-silylbut-2-ene-1,4-diol derivatives 2 bearing different substituents on the silicon atom have been prepared and tested in palladium-catalyzed alkylations with dimethyl malonate. Totally chemo- and stereoselective, these high yielding reactions are strongly influenced by the presence of the silicon group on the allyl moiety. The preparation and reactivity of two analogues 9 where the silyl group is replaced by a tert-butyl group were also examined. Their difference of reactivity toward the nucleophile can be ascribed to the ability of the silicon group to stabilize a beta-carbocation. Indeed, both steric and electronic factors are responsible for this behavior.
[reaction: see text] A new and efficient procedure for the preparation of unsymmetrical silaketals via a three-step protocol without isolation of the intermediates is presented. The unsymmetrical silyl ethers and silanes can also be readily obtained via this sequence of reactions.
We recently discovered that a linear multifunctional trimethylsilylacetylene (TMSA) compound forms long-range and highly stable self-assembled monolayers (SAMs) on reconstructed Au(111). To better understand the interactions governing self-assembly in this new system, we synthesized a series of homologue organosilanes and performed scanning tunneling microscopy (STM) measurements at the Au(111)/n-tetradecane interface. The four TMSA-terminated linear silanes that we synthesized self-assemble in similar ways on gold, with the molecules standing upright on the surface. In contrast, compounds with a slightly modified terminal group but the same polyunsaturated linear chain above the TMSA head do not self-assemble. In particular, substituting a methyl group of TMSA with a more bulky one prevents self-assembly. Removing the C triple bond C triple bond of TMSA or substituting the Si atom by a C atom also hinders self-assembly. Finally, substituting one methyl group of TMSA by a hydrogen atom induces self-assembly but in a different geometry, with the molecules lying flat on the gold surface in a quasi-epitaxy mode. Our molecular approach demonstrates the key role played by the TMSA head in self-assembly, its origin being twofold: 1) the TMSA layers are commensurate to the Au(111) adlattice along the <112> direction, and 2) the C triple bond C triple bond of TMSA activates the Si atom and induces the creation of a surface Si-Au chemical bond. The highly stable TMSA-based SAMs appear then as promising materials for applications in surface modification.
[reaction: see text] Various allylic and propargylic amines bearing a protecting group (PG) have been employed in N-silyl-tethered radical cyclizations. The resulting silapyrrolidine adducts could be smoothly oxidized, creating access to gamma-amino alcohols. The silylation, radical cyclization, and oxidation reactions could be consolidated in a one-pot process.
Variously substituted linear enediynes phosphines oxides possessing the double bond at either the terminal or internal position and with the phosphine oxide appended onto the alkyne or the alkene terminus have been prepared. Their cobalt(I)-mediated cyclizations produce the eta(4)-complexed tricyclic compounds in high yields. The endo/exo selectivity depends on both the position of the phosphine oxide on the enediyne and the position of the double bond in the tether. With chiral phosphine oxides, a certain degree of induction was observed, and depending on the substituents on the phosphorus atom, the diastereoselectivity can reach 74%. Up to now, it is the highest level reported for such a cyclization in which a stereogenic center is created. Regarding all of our results, two reaction pathways involving an initial coordination of the cobalt moiety on the chelating site of the substituent have been suggested to explain the observed selectivities.
Sulfonimidates were prepared from sulfinamides and iodosobenzene in a very mild one-pot procedure in good to excellent yields. This reaction allows quick and efficient access to a class of molecules of important synthetic as well as biological and industrial interest. [reaction: see text]
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We report on the formation of self-assembled monolayers of 13-(trimethylsilyl)-1-tridecene-6,12-diyne [C13H17-Si(CH3)3], an organosilane derivative with a linear polyunsaturated chain, on Au(111) substrates. Molecular resolution STM images recorded at the liquid-solid interface between gold and tetradecane reveal a long-range and densely packed hexagonal lattice with a ( radical3 x radical3)R30 degrees -like structure commensurate against gold adlattice.
[reaction: see text] A new and efficient sequence of two consecutive cyclizations, a cobalt(I)-mediated [2 + 2 + 2] cyclotrimerization and a Diels-Alder reaction, is proposed to allow the formation of the ABC core of the taxoids in 65% overall yield, starting from an acyclic polyunsaturated precursor.