Carta manuscrita de Paco (Manchester) a Pere Pascual comentant diversos aspectes de beques i del GIFT

Highly active bifunctional iminophosphorane catalysts have been applied to the organocatalytic ring-opening polymerization (ROP) of l-lactide (LA), δ-valerolactone (VL), and ε-caprolactone (CL). LA polymerization using catalyst <b>2</b> at 1 mol % loading rapidly gave poly­(LA) in full conversion and with excellent control over the molecular weight distribution. VL and CL were polymerized under the control of catalyst <b>3</b> at 5 mol % loading. Poly­(VL) was obtained in high conversion and with very good control over the molecular weight distribution. The catalyst system was suitable for the formation of short lengths of poly­(CL), with good control over the molecular weight distribution. The formation of block copolymers by sequential monomer addition and the use of macroinitiators such as monomethoxy-terminated poly­(ethylene glycol) (mPEG) were also demonstrated using the catalyst system. Control experiments using nonbifunctional <i>N</i>-alkyl iminophosphorane <b>5</b> demonstrated the roles of both components of the bifunctional catalyst in the ROP reaction. Notably, the bifunctional iminophosphorane catalysts are moisture-stable and nonhygroscopic, enabling the assembly of ROP reactions on the open bench

Enantioselective Construction of the ABCDE Pentacyclic Core of the <i>Strychnos</i> Alkaloids

An efficient enantioselective 12-step synthesis of the ABCDE pentacyclic core of the <i>Strychnos</i> alkaloids is described. A key feature of this approach is an organocatalyzed enantioselective desymmetrization to generate the morphan core in high ee and dr. After palladium-catalyzed installation of the indole moiety, a subsequent 5-<i>exo</i>-trig dearomatizing atom transfer radical cyclization was developed to construct the C-ring. Following a series of functional group interconversions, the pentacyclic amine core was obtained with all the relevant architecture including five stereocenters pertaining to the <i>Strychnos</i> alkaloids

One-Pot Catalytic Enantioselective Synthesis of Tetrahydropyridines via a Nitro-Mannich/Hydroamination Cascade

The highly enantioselective preparation of synthetically useful tetrahydropyridine derivatives employing a one-pot nitro-Mannich/hydroamination cascade is reported. This approach utilizes an asymmetric organocatalytic nitro-Mannich reaction followed by a gold-catalyzed alkyne hydroamination/isomerization sequence that yields the desired tetrahydropyridines in good yields and high diastereo- and enantioselectivities

Bifunctional Iminophosphorane Organocatalysts for Enantioselective Synthesis: Application to the Ketimine Nitro-Mannich Reaction

The design, synthesis, and development of a new class of modular, strongly basic, and tunable bifunctional Brønsted base/H-bond-donor organocatalysts are reported. These catalysts incorporate a triaryliminophosphorane as the Brønsted basic moiety and are readily synthesized via a last step Staudinger reaction of a chiral organoazide and a triarylphosphine. Their application to the first general enantioselective organocatalytic nitro-Mannich reaction of nitromethane to unactivated ketone-derived imines allows the enantioselective construction of β-nitroamines possessing a fully substituted carbon atom. The reaction is amenable to multigram scale-up, and the products are useful for the synthesis of enantiopure 1,2-diamine and α-amino acid derivatives

Total Synthesis of Manzamine A and Related Alkaloids

Total syntheses of three structurally complex marine natural products, manzamine A, ircinol A, and ircinal A, are reported. The route pivoted on the construction of a late-stage protecting-group-free pentacyclic enol triflate coupling partner, from which all three family members were accessed divergently via palladium-catalyzed reactions. The rapid synthesis of this key pentacyclic enol triflate was achieved by a highly convergent union of five fragments through a stereoselective Michael addition, a three-component nitro-Mannich lactamization cascade, an unprecedented and highly stereoselective reductive nitro-Mannich cyclization cascade, a stereoselective organometallic addition, and a <i>Z</i>-selective alkene ring-closing metathesis. Altogether this chemistry has allowed the shortest synthetic route to date for manzamine A (18-step longest linear sequence) via a late-stage diversification point that is ideal for future manzamine A analogue synthesis

Total Synthesis of Manzamine A and Related Alkaloids

Total syntheses of three structurally complex marine natural products, manzamine A, ircinol A, and ircinal A, are reported. The route pivoted on the construction of a late-stage protecting-group-free pentacyclic enol triflate coupling partner, from which all three family members were accessed divergently via palladium-catalyzed reactions. The rapid synthesis of this key pentacyclic enol triflate was achieved by a highly convergent union of five fragments through a stereoselective Michael addition, a three-component nitro-Mannich lactamization cascade, an unprecedented and highly stereoselective reductive nitro-Mannich cyclization cascade, a stereoselective organometallic addition, and a <i>Z</i>-selective alkene ring-closing metathesis. Altogether this chemistry has allowed the shortest synthetic route to date for manzamine A (18-step longest linear sequence) via a late-stage diversification point that is ideal for future manzamine A analogue synthesis

The synthesis and decomposition behaviour of methylpalladium (II) N-heterocyclic carbene complexes

This thesis describes the synthesis of methylpalladium(II) complexes bearing various N-heterocyclic carbene (NHC) ligands. The decomposition behaviour of a subset of these complexes is also studied. The catalytic performance of methylpalladium(II) complexes bearing NHC ligands of similar steric bulk but varying basicities was assessed. Palladium(II) complexes bearing two large NHCs were found to be inactive in the Heck reaction of 4-bromoacetophenone and n-butyl acrylate, while methylpalladium(II) carbene dimers bearing bridging halide groups were found to be active pre-catalysts. Ligand basicity was shown, in some cases, to dramatically influence catalytic activity. In addition, the catalytic activity of [Pd(NHC)Me(PP)J13F4-type complexes was assessed. Such complexes were also found to be inactive

Alkali Base-Initiated Michael Addition/Alkyne Carbocyclization Cascades

A new cascade reaction involving an intramolecular Michael addition followed by an alkyne carbocyclization is presented. The reaction is promoted by a substoichiometric amount of KHMDS and represents one of the rare examples where the carbocyclization of an unactivated alkyne is mediated by an alkali metal base, under mild conditions. The reaction allows the generation of functionally dense, stereochemically defined, tricyclic structures possessing three adjacent stereocenters in good yields and with high stereoselectivity

Dual Amine and Palladium Catalysis in Diastereo- and Enantioselective Allene Carbocyclization Reactions

A pyrrolidine and Pd catalyzed diastereoselective carbocyclization of aldehyde and ketone-linked allenes has been developed. The cooperative organo/metal-catalyzed cyclization reaction, which presumably proceeds via an enamine intermediate, is efficient and broad in scope. Also, it has been extended to a catalytic asymmetric variant using diarylprolinol-based organocatalysts to afford substituted cyclopentane and pyrrolidine reaction products in up to 82% ee

Gold and BINOL-Phosphoric Acid Catalyzed Enantioselective Hydroamination/<i>N</i>‑Sulfonyliminium Cyclization Cascade

A highly enantioselective hydroamination/<i>N</i>-sulfonyliminium cyclization cascade is reported using a combination of gold(I) and chiral phosphoric acid catalysts. An initial 5-<i>exo</i>-dig hydroamination and a subsequent phosphoric acid catalyzed cyclization process provide access to complex sulfonamide scaffolds in excellent yield and high enantiocontrol. The method can be extended to lactam derivatives, with excellent yields and enantiomeric excesses of up to 93% ee