Photocatalytic synthesis of allylic trifluoromethyl substituted styrene derivatives in batch and flow.

A cobalt-catalyzed photochemical synthesis of allylic trifluoromethanes from styrene derivatives using 2,2,2-trifluoroethyl iodide is described. The method complements existing approaches, providing an alternative bond construction strategy to access these compounds. The process may be conducted in continuous mode in a novel photochemical flow reactor, resulting in a notable productivity increase.

Iridium-catalyzed enantioselective allylic vinylation.

The first example of Ir-catalyzed asymmetric substitution reaction with vinyl trifluoroborates is described. The direct reaction between branched, racemic allylic alcohols and potassium alkenyltrifluoroborates proceeded with high site selectivity and excellent enantioselectivity (up to 99%) mediated by an Ir-(P,olefin) complex. This method allows rapid access to various 1,4-dienes or trienes including the biologically active natural products (-)-nyasol and (-)-hinokiresinol.

Iridium-catalyzed enantioselective polyene cyclization.

A highly enantioselective polycyclization method has been developed using the combination of Lewis acid activation with iridium-catalyzed allylic substitution. This strategy relies on direct use of branched, racemic allylic alcohols and furnishes a diverse and unique set of carbo- and heteropolycyclic ring systems in good yields and ≥99% ee.

Total synthesis and stereochemical revision of the chlorinated sesquiterpene (±)-gomerone c.

Revised: the total synthesis of gomerone C results in revision of the stereochemical assignment at C3. The synthetic strategy relies on a late-stage Conia-ene reaction, which efficiently forms the bicyclo[3.2.

Cyclohexyne cycloinsertion in the divergent synthesis of guanacastepenes.

The guanacastepenes are a family of 15 diterpenes that share a common 5-6-7 tricyclic core, which is decorated with quaternary centers, unsaturation, hydroxyl and carbonyl groups. Some of these natural products show interesting antimicrobial potency. Their collective structural and biological features have stirred up vibrant activity among organic chemists.

Direct identification of ligand-receptor interactions on living cells and tissues.

Many cellular responses are triggered by proteins, drugs or pathogens binding to cell-surface receptors, but it can be challenging to identify which receptors are bound by a given ligand. Here we describe TRICEPS, a chemoproteomic reagent with three moieties--one that binds ligands containing an amino group, a second that binds glycosylated receptors on living cells and a biotin tag for purifying the receptor peptides for identification by quantitative mass spectrometry. We validated this ligand-based, receptor-capture (LRC) technology using insulin, transferrin, apelin, epidermal growth factor, the therapeutic antibody trastuzumab and two DARPins targeting ErbB2.

pH-Independent transfer hydrogenation in water: catalytic, enantioselective reduction of β-keto esters.

A pH-independent asymmetric transfer hydrogenation of β-keto esters in water with formic acid/sodium formate is described. The reaction is conducted open to air and gives access to β-hydroxy esters in excellent yields and selectivities.

Enantioselective allylic thioetherification: the effect of phosphoric acid diester on iridium-catalyzed enantioconvergent transformations.

You'll take the high road and I'll take the low road: Enantioenriched allylic thioethers have been synthesized from chiral racemic allylic alcohols. The combination of an Ir-(P,alkene) complex and dibutyl phosphoric acid are required to attain high selectivities. Mechanistic studies uncover an enantioconvergent transformation in which substrate enantiomers react along different pathways to give the same product (see scheme; cod=1,5-cyclooctadiene).

Preparation of trifluoromethyl-substituted aziridines with in situ generated CF3CHN2.

Direct access to trifluoromethyl-substituted aziridines through the use of a protocol in which trifluoromethyl diazomethane is generated in situ and subsequently undergoes addition to activated imines is reported.

Iron-catalyzed cyclopropanation in 6 M KOH with in situ generation of diazomethane.

Diazomethane is a common and versatile reagent in organic synthesis whose broader use is generally impeded by its explosiveness and toxicity. Here we report that a simple iron porphyrin complex catalyzes the cyclopropanation of styrenes, enynes, and dienes under the demanding conditions [aqueous 6 molar potassium hydroxide (KOH) solution, open to air] necessary for the in situ generation of diazomethane from a water-soluble diazald derivative. A biphasic reaction medium arising from the immiscibility of the olefin substrates with water appears essential to the overall efficiency of the process.

Arynes and cyclohexyne in natural product synthesis.

This Minireview highlights recent advances in the field of aryne and cyclohexyne chemistry that have allowed the extraordinary reactivity of these entities to be harnessed during the course of natural product syntheses. The syntheses presented rely on the use of these reactive species in chemoselective transformations and follow unprecedented synthetic strategies that are inspiring for the practitioners of synthetic organic chemistry.

Total synthesis and stereochemical reassignment of (±)-indoxamycin B.

Revised version: the first total synthesis of indoxamycin B leads to a stereochemical reassignment of the natural product. The synthetic route features an efficient carboannulation sequence to rapidly access the dihydroindenone system. Moreover, a series of Au(I)-catalyzed transformations served in the construction of the sterically congested core framework.

Total synthesis of (-)-dendrobine.

Cascading to alkaloids: an 18-step total synthesis of (-)-dendrobine is based on a reaction cascade with a key amine group. The amine is the initiator of the cascade and provides an efficient method for installing the stereocenters at C11 and C3. The overall transformation occurs stereoselectively only when the conversion is carried out without the isolation of intermediates.

Total synthesis of bafilomycin A1.

A convergent synthesis of bafilomycin A(1), a potent inhibitor of V-type ATPases, is presented. The synthesis relies on the zinc triflate mediated diastereoselective addition of a complex enyne to a sensitive aldehyde as the key fragment coupling. A ruthenium-catalyzed trans-reduction of the resulting propargylic enyne efficiently installs the required C10-C13 trans,trans-diene subunit, implementing an alternative strategy to traditional palladium-catalyzed cross-coupling strategies.

Direct, enantioselective iridium-catalyzed allylic amination of racemic allylic alcohols.

The direct route: iridium-catalyzed direct conversion of branched allylic alcohols into enantioenriched branched primary allylic amines is highly regio- and enantioselective.

Expanding the azaspiro[3.3]heptane family: synthesis of novel highly functionalized building blocks.

The preparation of versatile azaspiro[3.3]heptanes carrying multiple exit vectors is disclosed. Expedient synthetic routes enable the straightforward access to these novel modules that are expected to have significance in drug discovery and design.

Expedient preparation of trifluoromethyl-substituted benzofuranols.

Direct access to 3-trifluoromethyl-substituted benzofuranols is presented. The products are obtained in good yields from commercially available salicylaldehydes by using in situ generated trifluoromethyl diazomethane and boron trifluoride as an activator. As shown in a representative example, the products can be transformed into the corresponding trifluoromethyl-substituted benzofurans.

Synthesis of novel azaspiro[3.4]octanes as multifunctional modules in drug discovery.

Step-economic and scalable syntheses of novel thia-azaspiro[3.4]octanes are reported. These spirocycles and some related intermediates can serve as uncharted multifunctional modules for drug discovery chemistry.

Towards the synthesis of massadine: a unified strategy for the stereoselective synthesis of the carbocyclic C,D-ring subunit.

Massadine is a hexacyclic marine natural product, which belongs to the family of pyrrole-imidazole alkaloids. Herein, we describe a unified approach to the C,D-ring subunit of this sponge metabolite based on the exploitation of a norbornene scaffold for the stereocontrolled construction of massadine's carbon skeleton. Highlights of the sequence presented include the application of a stereospecific norbornyl rearrangement for facile introduction of an oxygen at the C7-position within the norbornene nucleus, a highly regioselective and end group differentiating ozonolytic scission of a C-C double bond, and an oxidative decarboxylation reaction for the installation of the hindered secondary C2-alcohol function.