2-Bromo-1,3-butadienes are demonstrated to be effective substrates for tandem Diels–Alder/transition metal cross-coupling reaction sequences. Intermolecular cycloaddition of a 2-bromo-1,3-diene with activated dienophiles proceeded under Lewis acid catalysis in generally high yields with good to excellent endo diastereoselectivity. The resulting vinyl bromide cycloadducts underwent subsequent Stille and Suzuki cross-couplings under standard conditions in good yields. Both the Diels–Alder and cross-coupling steps were highly tolerant of a range of functionalities and protecting groups. The use of the bromine substituent as both a cycloaddition directing group and cross-coupling nucleofuge avoids extra steps required to install and remove the more commonly used silyl enol ethers and enol sulfonates for each transformation and gives full control of the alkene regiochemistry throughout the reaction sequence. The 2-bromo-1,3-dienes were conveniently prepared in three steps from readily available aldehydes and established as hydrolytically stable and practical synthetic intermediates.

The template-directed synthesis of RNAp layed an important role in the transition from prebiotic chemistry to the beginnings of RNAb ased life,b ut the mechanism of RNA copying chemistry is incompletely understood. We measured the kinetics of template copying with as et of primers with modified 3'-nucleotides and determined the crystal structures of these modified nucleotides in the context of ap rimer/ template/substrate-analog complex. pH-rate profiles and solvent isotope effects show that deprotonation of the primer 3'hydroxyl occurs prior to the rate limiting step,the attackofthe alkoxide on the activated phosphate of the incoming nucleotide.T he analogs with a 3 Er ibose conformation show the fastest formation of 3'-5' phosphodiester bonds.Among those derivatives,t he reaction rate is strongly correlated with the electronegativity of the 2'-substituent. We interpret our results in terms of differences in steric bulk and charge distribution in the ground vs.t ransition states.

Asymmetric access to α-hydroxy-1,4-diketones has been achieved by direct ene coupling of silyl enol ethers with glyoxal electrophiles, mediated by a chiral N,N′-dioxide–nickel(II) complex catalyst. Successful union of a polyketide silyl enol ether with an α-quaternary glyoxal, generated by dioxirane oxidation of an α-diazo ketone, models a proposed C5–C6 disconnection of the polyketide and spirocyclic imine domains of the marine natural product, portimine.