Pablo Mauleón

Formal Regiocontrolled Hydroboration of Unbiased Internal Alkynes via Borylation/Allylic Alkylation of Terminal Alkynes

In accessing trisubstituted vinyl boronates from terminal alkynes, a propargyl directing (2-pyridyl)sulfonyl group allows terminal alkynes to undergo Cu-catalyzed B2(pin)2-borylation and subsequent Cu-catalyzed allylic alkylation with Grignard reagents without affecting the pinacolboronate moiety, thereby formally enabling a highly stereo- and regiocontrolled access to hydroboration products of unbiased dialkyl internal alkynes.

Cu-catalyzed silylation of alkynes: a traceless 2-pyridylsulfonyl controller allows access to either regioisomer on demand.

The Cu-catalyzed silylation of terminal and internal alkynes bearing a 2-pyridyl sulfonyl group (SO2Py) at the propargylic position affords a breadth of vinyl silanes in good yields and with excellent regio- and stereocontrol under mild conditions. The directing SO2Py group is essential in terms of reaction efficiency and chemoselectivity. Importantly, this group also provides the ability to reverse the regiochemical outcome of the reaction, opening the access to either regioisomer without modification of the starting substrate by virtue of an in situ base-promoted alkyne to allene equilibration which takes place prior to the silylcupration process. Furthermore, removal of the directing SO2Py allows for further elaboration of the silylation products. In particular, a one-pot tandem alkyne silylation/allylic substitution sequence, in which both steps are catalyzed by the same Cu species, opens up a new approach for the access to either formal hydrosilylation regioisomer of unsymmetrical aliphatic-substituted internal alkynes from propargyl sulfones.

Sulfenylphosphinoferrocenes: Novel planar chiral ligands in enantioselective catalysis

Structurally well-defined transition-metal complexes of 1-phosphino-2-sulfenylferrocene (Fesulphos ligands) act as highly efficient catalysts in a variety of mechanistically different transformations. Excellent enantioselectivities were achieved in Pd-catalyzed allylic substitutions, desymmetrization of meso-heterobicyclic alkenes by Pd-catalyzed addition of dialkylzinc reagents, Pd-catalyzed Diels-Alder reaction of cyclopentadiene with N-acryloyl oxazolidinones, and in Cu-catalyzed formal aza-Diels-Alder reaction of Danishefsky diene to N-sulfonyl aldimines.

Enantioselective construction of stereogenic quaternary centres via Rh-catalyzed asymmetric addition of alkenylboronic acids to α,β-unsaturated pyridylsulfones

The highly enantioselective construction of all-carbon quaternary stereogenic centres via Rh-catalyzed Chiraphos-mediated conjugate addition of alkenylboronic acids to β,β-disubstituted α,β-unsaturated 2-pyridylsulfones is described.

Gold-Catalyzed Intermolecular Enantioselective [2+2] Cycloadditions of Sulfonylallenamides and Styrenes

The development of synthetic methods for the enantioselective construction of stereogenic centers remains one of the fundamental goals of our discipline. Of these methods, those that involve cycloaddition reactions are particularly useful, owing to their elevated atom economy and to the fact that they frequently generate more than one stereogenic center in a single reaction step. In general, [2 + 2] cycloadditions rank amongst the more challenging because of the elevated ring strain in the reaction products. Thus, it is not surprising that few efficient catalytic asymmetric versions of this class have been developed to date. Metal catalysts have emerged as powerful tools for the enantioselective cycloisomerization of alkenes, alkynes, and allenes. Among them, gold(I) based catalysts were once believed to be incapable of efficiently transferring chiral information from ligand to substrate because of their two-coordinate linear geometry, which places the substrate around 5 away from the chiral ligand. However, researchers have found ingenious ways to overcome this restriction, and today gold(I) catalysts are powerful tools to create cycles in an enantioselective fashion. In spite of the growing number of reports on gold(I)-catalyzed cycloadditions, the vast majority of them describe cycloisomerization processes (and hence intramolecular). With a few notable exceptions, examples of gold(I)-catalyzed intermolecular asymmetric transformations are still scarce. In late 2012, Gonz lez and co-workers reported in Angewandte Chemie on the enantioselective catalytic [2+2]-cycloaddition of sulfonyl allenamides and a variety of styrenes in an intermolecular fashion. This transformation nicely ascribes to the general reactivity observed between allenes and nucleophilic olefins, which is depicted in Scheme 1: upon coordination of a p-acidic transition metal to the allene, this moiety is “activated”, or in other words, its electrophilicity is enhanced. In the presence of a nucleophilic double bond, two new carbon–carbon bonds are formed between the two fragments in a stepwise process with the participation of carbocation intermediate. Previous results by Toste and co-workers demonstrated that this reactivity pattern was observed in the reaction of allenenes to form cyclobutenes in an intramolecular fashion. Using chiral dinuclear gold(I)-biarylphosphine complexes as catalysts, the enantioselective [2+2]-cycloaddition intramolecular cycloaddition of allenes and a variety of styryl groups was achieved (Scheme 2, top). In this context, the Gonz lez research team steps up to the intermolecular challenge, and describes that cyclobutane carbon frameworks can be obtained in high yields and very good optical purities upon treatment of mixtures of allenamides and styrenes with several gold(I)-phosphoramidite complexes (at 70 8C and after just one hour in dichloromethane, see Scheme 2, bottom). The relevance of this achievement is highlighted by two factors: 1) the number of examples that describe gold-catalyzed intermolecular transformations, as mentioned above, is still relatively low; and 2) the extended period of research time (five years) that took to move from intramolecular to intermolecular. The transformation fulfills all the fundamental requirements of the ideal catalytic asymmetric reaction: perfect atom economy, mild reaction conditions, good functional group tolerance, high reactivity, and good stereo-, regio-, and enantioselectivity. Other notable features of the report are the preparation of a number of synScheme 1. General reactivity between allenes and nucleophilic double bonds under gold catalysis.

Pyridylidene-Mediated Dihydrogen Activation Coupled with Catalytic Imine Reduction†

In recent years, dihydrogen activation at non-metallic centers has received increasing attention. A system in which dihydrogen is trapped by a pyridylidene intermediate that is generated from a pyridinium salt and a base is now reported. The dihydropyridine formed in this process can act as reducing agent towards organic electrophiles. By coupling the hydrogen-activation step with subsequent hydride transfer from the dihydropyridine to an imine, a catalytic process was established. Treatment of the N-phenylimine of phenyl trifluoromethyl ketone with 5-20 mol% of N-mesityl-3,5-bis(2,6-dimethylphenyl)pyridinium triflate and 0.3-1.0 equivalents of LiN(SiMe3)2 under 50 bar of hydrogen gas resulted in high conversion into the corresponding amine.

Corrigendum: Pyridylidene‐Mediated Dihydrogen Activation Coupled with Catalytic Imine Reduction

DOI: 10.1002/anie.201503233 Upon further studies of the imine reduction shown in Table 1, it was found that the control experiment in entry 5 could not be reproduced.[1] In contrast to the earlier result, which had shown no reaction, repetition of this experiment under carefully controlled conditions using freshly prepared LiHDMS solution revealed that imine 20 was reduced to the corresponding amine in a purely base-mediated process. This finding casts doubt on the mechanism postulated in Scheme 7 in the original publication, which involves hydride transfer from dihydropyridine 18 to imine 20. Additional studies, which included deuteration experiments,[1] demonstrated that two independent parallel reactions occur under the conditions listed in Table 1, namely a base-mediated reduction of pyridinium salt 16 via a pyridylidene intermediate (as formulated in Scheme 4) and a purely baseinduced hydrogenation of imine 20. On the other hand, no evidence for the postulated hydride transfer from dihydropyridine 18 to imine 20 could be obtained. Accordingly, the mechanistic conclusions concerning the observed imine reduction have to be revised as shown here in Scheme 7, which replaces the original Scheme. Although dihydropyridine 18 is a potential hydride donor, it does not act as a reducing agent under the conditions listed in Table 1. On the other hand, the unexpected finding that imine 20 reacts with H2 in a solely base-induced process opens up new ways towards transition-metal-free hydrogenation. The scope and mechanism of this base-mediated imine reduction are currently under investigation.