Polymer Endgroup Control Through a Trifunctional Cobalt-Mediated Radical Polymerization: New Avenues for Synthesising Protein Conjugates

Cobalt-mediated radical polymerisations (CMRPs) have been initiated by the radical decarboxylation of tetrachlorophthalimide activated esters. This allows for the controlled radical polymerisation of both activated and less activated monomers across a broad temperature range with a single cobalt species, with incorporation of polymer endgroups derived from simple carboxylic acids derivatives and termination with an organozinc reagent. This method has been applied to the synthesis of a water-soluble protein/polymer conjugate, demonstrating the first example of CMRP in protein conjugation.

Total Synthesis of Endolides A and B

The total synthesis of endolides A and B has been achieved in a concise and highly stereoselective fashion (12 steps; 16.2 and 16.0% overall yield, respectively). Key features of the route include a modified Negishi coupling between 3-bromofuran and an organozinc reagent derived from an iodoalanine derivative for the synthesis of a 3-(3-furyl)alanine derivative, and a judicious choice of reaction conditions to overcome the conformational constraints placed by converting a linear peptide into the corresponding macrocycle.

Synthesis of 5-Substituted 2-Pyrrolidinones by Coupling of Organozinc Reagents with Cyclic N-Acyliminium Ions

A coupling reaction between cyclic N-acyliminium ions with organozinc reagents is described. The cyclic N-acyliminium ions, generated in situ from N-substituted-5-hydroxy-2-pyrrolidinones by treatment with boron trifluoride–diethyl ether complex or titanium tetrachloride, are trapped by the organozinc reagent, which is formed from an alkyl bromide in the presence of zinc in the same reaction medium. The N-substituted-5-allyl-2-pyrrolidinones generated using this method serve as versatile intermediates for the synthesis of azabicyclic systems with indolizidine and pyrroloazepinolizidine cores.

Ultrasound-Assisted Metal-Mediated Method for the Formation of Tetrahydro-3,3′-Disubstituted Biscoumarins

A new method for faster and simple preparation of 3,3′,4,4′-tetrahydro-3,3′-disubstituted-4,4′-biscoumarins with participation of an organozinc reagent is reported. The reaction is promoted by ultrasound irradiation and it offers a simple experimental setup and excellent reproducibility of the results. Moreover, homodimers were isolated in yields of 45–92%. The dimerization conditions are applicable to coumarins with electron-withdrawing groups at third position.

Practical tetrafluoroethylene fragment installation through a coupling reaction of (1,1,2,2-tetrafluorobut-3-en-1-yl)zinc bromide with various electrophiles

(1,1,2,2-Tetrafluorobut-3-en-1-yl)zinc bromide was prepared by insertion of the zinc–silver couple into the CF2–Br bond of commercially available 4-bromo-3,3,4,4-tetrafluorobut-1-ene in DMF at 0 °C for 0.5 h, The resultant polyfluorinated zinc reagent was found to be thermally stable at ambient temperature and storable for at least 1.5 years in the refrigerator. This CF2CF2-containing organozinc reagent could be easily transmetallated to copper species, which underwent cross-coupling reactions with various aromatic iodides or acyl chlorides to produce a broad range of CF2CF2-containing organic molecules in good-to-excellent yields. Therefore, the zinc reagent could become a new and practical synthetic tool for producing functional molecules with a CF2CF2 fragment.

Dimerization of Benzyl and Allyl Halides via Photoredox-Mediated Disproportionation of Organozinc Reagents

Benzyl and allyl halides undergo homocoupling when treated with zinc in the presence of a catalytic amount of a cationic iridium(III) complex under irradiation with 400 nm light-emitting diodes. The reaction proceeds through the intermediate formation of an organozinc reagent, which disproportionates to a free radical and elemental zinc under photoredox conditions.