Titanocene(III)-catalyzed formation of indolines and azaindolines

Reductive cyclization of epoxides tethered to substituted anilines and aminopyridines in the presence of 3 mol % of titanocene dichloride and stoichiometric manganese metal promotes a radical annulation to form 3,3-disubstituted indolines and azaindolines.     

Mechanism of gold(I)-catalyzed rearrangements of acetylenic amine-N-oxides: computational investigations lead to a new mechanism confirmed by experiment

Quantum mechanical studies of the mechanism of gold-catalyzed rearrangements of acetylenic amine-N-oxides to piperidinones or azepanones have revealed a new mechanism involving a concerted heteroretroene reaction, formally a 1,5 hydrogen shift from the N-alkyl groups to the vinyl position of a gold-coordinated methyleneisoxazolidinium or methyleneoxazinanium. Density functional calculations (B3LYP, B3LYP-D3) on the heteroretroene mechanism reproduce experimental regioselectivities and provide an explanation as to why the hydrogen is transferred from the smaller amine substituent. In support of the proposed mechanism, new experimental investigations show that the hydrogen shift is concerted and that gold carbenes are not involved as reaction intermediates.     

Bromination of (phosphine)gold(I) bromide complexes: stoichiometry and structure of products

The course of the oxidative addition of elemental bromine to complexes of the type (L)AuBr is strongly influenced by the nature of the tertiary phosphine ligand L. Standard square planar gold(III) complexes (L)AuBr3 are obtained not only with L = PMe3 but also with P((I)Pro)3 for which the oxidative addition fails in the corresponding iodine system. Excess bromine is integrated into crystals of the products with the stoichiometry [(Me3P)AuBr3].(Br2) and {[(iPro)3P]AuBr3}.(Br2). Of the series of iodine analogues, an intercalate [(Me3P)AuI3]2.(I2) has been structurally characterized. [((t)Bu)3P]AuBr undergoes ligand redistribution upon treatment with bromine to give a complex reaction mixture, from which {[(tBu)3P]2Au}+(Br3)-.(Br2) could be crystallized. It contains polymeric anions [(Br5)-]n as zig-zag chains. [(o-Tol)3P]AuBr is readily brominated to give [(o-Tol)3P]AuBr3. Contrary to the situation in the gold(I) complex with its linear PAuBr unit, the square planar structure of the PAuBr3 unit causes steric hindering of the rotation of the tolyl groups about the P-C bonds as demonstrated by solution NMR studies. (The corresponding reaction with iodine is known to give only polyiodides with the oxidation state of the gold atom unchanged.) The even more severe congestion in [(Mes)3P]AuBr prevents oxidative addition not only of iodine but also of bromine. With the latter, P-Au cleavage occurs instead affording [(Mes)3PBr]+[AuBr4]-.     

A combined mechanistic and computational study of the gold(I)-catalyzed formation of substituted indenes

Substituted indenes can be prepared after a sequence [1,3] O-acyl shift-hydroarylation-[1,3] O-acyl shift. Each step is catalyzed by a cationic NHC-Gold(I) species generated in situ after reaction between [(IPr)AuOH] and HBF(4)·OEt(2). This interesting silver-free way is fully supported by a computational study justifying the formation of each intermediate.     

An efficient approach to fused indolines via a copper(I)-catalyzed reaction of sulfonyl azide with 2-ethynylaryl methylenecyclopropane

A cascade reaction of 2-ethynylaryl methylenecyclopropane with sulfonyl azide catalyzed by copper(I) iodide under mild conditions is described, which provides a novel and efficient route for the generation of fused indolines.     

Mechanism of the gold(I)-catalyzed Rautenstrauch rearrangement: a center-to-helix-to-center chirality transfer

The mechanism of the stereospecific gold(I)-catalyzed Rautenstrauch rearrangement of (E)-1-ethynyl-2-methyl-but-2-en-yl acetate to 3,4-dimethyl-cyclopent-2-enone has been computationally addressed using DFT (B3LYP/6-31G, SDD for Au). Our results indicate that the bond formation event follows the Au(I)-induced acetyl transfer to the vicinal alkyne and that it is the helicity of the pentadienyl cation intermediate which keeps memory of the chiral information. The fidelity of the center-to-helix-to-center chirality transfer requires that the rates of helix interconversion and pivaloyl rotation are slower than the cyclization, as calculations predict.     

Mechanistic analysis of gold(I)-catalyzed intramolecular allene hydroalkoxylation reveals an off-cycle bis(gold) vinyl species and reversible C-O bond formation

Mechanistic investigation of gold(I)-catalyzed intramolecular allene hydroalkoxylation established a mechanism involving rapid and reversible C-O bond formation followed by turnover-limiting protodeauration from a mono(gold) vinyl complex. This on-cycle pathway competes with catalyst aggregation and formation of an off-cycle bis(gold) vinyl complex.     

Divergent outcomes of gold(I)-catalyzed indole additions to 3,3-disubstituted cyclopropenes

Depending on the conditions employed, gold(I)-catalyzed addition of indoles to 3,3-disubstituted cyclopropenes can be controlled to yield either 3-(E)-vinylindoles (3) or bis-indolylalkanes (4). If the cyclopropene substituents are sterically bulky, unprecedented gold-catalyzed oxidation under air occurs to yield bis-indolylalkene (5) and epoxide (6) at room temperature.     

Stereoselective synthesis of vinylsilanes by a gold(I)-catalyzed acetylenic sila-cope rearrangement

Cationic tri-tert-butylphosphinegold(I) serves as a catalyst in the sila-Cope rearrangement of acetylenic allylsilanes. When phenol is employed as a nucleophile, the reaction allows for the stereoselective synthesis of vinylsilanes. Alternatively, use of methanol as a nucleophile leads to cyclic vinylsilanes, which can be viewed as latent vinylsilanes that are revealed on treatment with a mild Lewis acid. Thus, both of these reagents serve as useful reagents for stereoselective synthesis of trisubstituted olefins through transition-metal-catalyzed cross-coupling reactions.     

Epoc group: transformable protecting group with gold(iii)-catalyzed fluorene formation

This study presents the novel concept of a transformable protecting group, which changes its properties through structural transformation. Based on this concept, we developed a 2-(2-ethynylphenyl)-2-(5-methylfuran-2-yl)-ethoxycarbonyl (Epoc) group. The Epoc group was transformed into an Fmoc-like structure with gold(iii)-catalyzed fluorene formation and was removable under Fmoc-like mild basic conditions post-transformation even though it was originally stable under strongly basic conditions. As an application for organic synthesis, the Epoc group provides the novel orthogonality of gold(iii)-labile protecting groups in solid-phase peptide synthesis. In addition, the high turnover number of fluorene formation in aqueous media is suggestive of the applicability of the Epoc group to biological systems.

A protecting group removable with gold(iii)-catalyzed fluorene formation and the subsequent addition of piperidine was developed.     

Synthesis of functionalized pyrroles via gold(I)-catalyzed aza-Claisen-type rearrangement

Gold(I)-catalyzed cyclization of pentenynyl allyl tosylamides allows the rapid construction of functionalized pyrroles. The concerted aza-Claisen-type mechanism induces a complete selectivity of the process and allows the easy formation of quaternary centers.     

Synthesis of functionalized furans via gold(I)-catalyzed Claisen-type rearrangement

Gold(I)-catalyzed cyclization of pentenynyl allyl ethers allows the rapid construction of functionalized furans. The concerted oxy-Claisen-type mechanism induces a complete selectivity of the process and allows the easy formation of quaternary centers.     

Synthesis of 2-cyclopentenones by gold(I)-catalyzed Rautenstrauch rearrangement

The rearrangement of 1-ethynyl-2-propenyl pivaloates to cyclopentenones catalyzed by cationic triphenylphosphinegold(I) complexes is described. The reaction tolerates both alkyl and aryl substitution at the acetylenic and olefinic positions. Importantly, the gold(I)-catalyzed rearrangement of enantioenriched propargyl pivaloates proceeds with excellent chirality transfer, thus providing a practical method for the enantioselective synthesis of cyclopentenones.     

(Triphenyl phosphite)gold(I)-catalyzed intermolecular hydroamination of alkenes and 1,3-dienes

Intermolecular addition of different sulfonamides to alkenes and conjugated dienes can be carried out using a low loading of (triphenyl phosphite)gold(I) chloride and silver triflate as a catalytic mixture. The reaction can be performed under conventional thermal or microwave conditions and at rt in the case of dienes. Terminal alkenes undergo regioselective hydroamination at the internal carbon atom and dienes at the less substituted double bond.     

Pd(II)-catalyzed enantioselective oxidative tandem cyclization reactions. Synthesis of indolines through C-N and C-C bond formation

We have developed an efficient Pd(II)-catalyzed enantioselective oxidative tandem cyclization strategy using molecular oxygen as a green oxidant for the double 5-exo-trig cyclizations of N-(2-allylaryl) amides to afford a variety of indolines in good yields without the formation of undesired monocyclization products. By employing Pd(TFA)2/(-)-sparteine as the chiral catalyst, we obtained tandem cyclization products with high enantioselectivity (up to 91% ee).     

Gold(I)-catalyzed stereoselective formation of functionalized 2,5-dihydrofurans

[reaction: see text] A study concerning the gold(I)-catalyzed rearrangement of butynediol monobenzoates into functionalized 2,5-dihydrofurans is described. The mild reaction conditions employed allow the efficient and rapid stereoselective synthesis of a variety of 2,5-dihydrofurans via a sequence of two gold(I)-catalyzed isomerization steps.     

Assembly of digitoxin by gold(I)-catalyzed glycosidation of glycosyl o-alkynylbenzoates

Digitoxin, a clinically important cardiac trisaccharide, was assembled efficiently from digitoxigenin and 3,4-di-O-tert-butyldiphenylsilyl-d-digitoxosyl o-cyclopropylethynylbenzoate in 9 steps and 52% overall yield via alternate glycosylation and protecting group manipulation. The present synthesis showcases the advantage of the gold(I)-catalyzed glycosylation protocol in the synthesis of glycoconjugates containing acid-labile 2-deoxysugar linkages.