The photochemical alkylation and reduction of heteroarenes.

The functionalization of heteroarenes has been integral to the structural diversification of medicinally active molecules such as quinolines, pyridines, and phenanthridines. Electron-deficient heteroarenes are electronically compatible to react with relatively nucleophilic free radicals such as hydroxyalkyl. However, the radical functionalization of such heteroarenes has been marked by the use of transition-metal catalyzed processes that require initiators and stoichiometric oxidants. Herein, we describe the photochemical alkylation of quinolines, pyridines and phenanthridines, where through direct excitation of the protonated heterocycle, alcohols and ethers, such as methanol and THF, can serve as alkylating agents. We also report the discovery of a photochemical reduction of these heteroarenes using only iPrOH and HCl. Mechanistic studies to elucidate the underlying mechanism of these transformations, and preliminary results on catalytic methylations are also reported.

Direct alkylation of heteroarenes with unactivated bromoalkanes using photoredox gold catalysis.

Although visible light photoredox catalysis has emerged as a powerful tool for the construction of C-C bonds, common catalysts and/or their photoexcited states suffer from low redox potentials, limiting their applicability to alkyl radical generation from substrates with activated carbon-halogen bonds. Radicals derived from these activated compounds, being highly electrophilic or stabilized, do not undergo efficient addition to heteroarenes. Herein we describe the photocatalytic generation of nucleophilic alkyl radicals from unactivated bromoalkanes as part of a universal and efficient cross-coupling strategy for the direct alkylation of heteroarenes using a dimeric gold(i) photoredox catalyst, [Au2(bis(diphenylphosphino)methane)2]Cl2. The method proves to be efficient for alkylation of arenes under mild conditions in the absence of directing groups.

Theoretical and experimental determination of the effects governing the transannular Diels-Alder reaction of trans-trans-cis systems with or without activation of the dienophile.

A thorough study of the transannular Diels-Alder (TADA) reaction of trans-trans-cis macrocyclic trienes was carried out. It led to a better understanding of various parameters that govern the TADA reaction in particular and the Diels-Alder reaction in general. Thus, carbonyl activation of the dienophile and substitution of the diene are discussed, as well as the presence of substituents on the macrocycle and their respective effects at the transition-state level.

Total synthesis of (+)-arteanniun M using the tandem oxy-Cope/ene reaction.

[see reaction]. The first total synthesis of (+)-arteannuin M was accomplished using the tandem oxy-Cope/transannular ene reaction as the key step to construct the bicyclic core of the natural product. The tandem reaction proceeded with high diastereo- and enantiomeric excess.

Tandem oxy-Cope/transannular ene reaction of 1,2-divinylcyclohexanols

[reaction: see text] The syntheses via tandem oxy-Cope/transannular ene reaction of 1,2-divinylcyclohexanols to bi- and tricyclic skeletons are described. This strategy generates a rapid method for the preparation of advanced polycyclic intermediates with high diastereoselectivity.

Synthesis and biological evaluation of analogs of the marine toxin polycavernoside A.

Second generation analogs of polycavemoside A (2) possessing a side chain at C-15 different from that of the natural toxin have been synthesized. The in vivo toxicities of these new compounds (expressed as the minimal lethal dose) have been evaluated in mice (ip) and compared to 2, its aglycone (8), and polycavemoside B (9). The bioactivity profile of enynene 5 is particularly notable.