Development and Application of a Peroxyl Radical Clock Approach for Measuring Both Hydrogen-Atom Transfer and Peroxyl Radical Addition Rate Constants.

The rate-determining step in free radical lipid peroxidation is the propagation of the peroxyl radical, where generally two types of reactions occur: (a) hydrogen-atom transfer (HAT) from a donor to the peroxyl radical; (b) peroxyl radical addition (PRA) to a "C═C" double bond. Peroxyl radical clocks have been used to determine the rate constants of HAT reactions (kH), but no radical clock is available to measure the rate constants of PRA reactions (kadd). In this work, we modified the analytical approach on the linoleate-based peroxyl radical clock to enable the simultaneous measurement of both kH and kadd. Compared to the original approach, this new approach involves the use of a strong reducing agent, LiAlH4, to completely reduce both HAT and PRA-derived products and the relative quantitation of total linoleate oxidation products with or without reduction. The new approach was then applied to measuring the kH and kadd values for several series of organic substrates, including para- and meta-substituted styrenes, substituted conjugated dienes, and cyclic alkenes. Furthermore, the kH and kadd values for a variety of biologically important lipids were determined for the first time, including conjugated fatty acids, sterols, coenzyme Q10, and lipophilic vitamins, such as vitamins D3 and A.

Catalyst-Controlled Regioselective Chlorination of Phenols and Anilines through a Lewis Basic Selenoether Catalyst.

We report a highly efficient ortho-selective electrophilic chlorination of phenols utilizing a Lewis basic selenoether catalyst. The selenoether catalyst resulted in comparable selectivities to our previously reported bis-thiourea ortho-selective catalyst, with a catalyst loading as low as 1%. The new catalytic system also allowed us to extend this chemistry to obtain excellent ortho-selectivities for unprotected anilines. The selectivities of this reaction are up to >20:1 ortho/para, while the innate selectivities for phenols and anilines are approximately 1:4 ortho/para. A series of preliminary studies revealed that the substrates require a hydrogen-bonding moiety for selectivity.

Towards a Catalytic Atroposelective Synthesis of Diaryl Ethers via C(sp 2)-H Alkylation Using Nitroalkanes.

Herein we report studies towards a small molecule catalytic approach to access atropisomeric diaryl ethers that proceeds via a C(sp 2)-H alkylation using nitroalkanes as the alkyl source. A quaternary ammonium salt derived from quinine containing a sterically hindered urea at the C-9 position was found to effect atroposelective C(sp 2)-H alkylation with moderate to good enantioselectivities across several naphthoquinone-containing diaryl ethers. Products can then be isolated in greater than 95:5 er after one round of trituration. For several substrates that were evaluated we observed a 'nitroethylated' product in similar yields and selectivities.

The Catalyst-Controlled Regiodivergent Chlorination of Phenols.

Different catalysts are demonstrated to overcome or augment a substrate's innate regioselectivity. Nagasawa's bis-thiourea catalyst was found to overcome the innate para-selectivity of electrophilic phenol chlorination, yielding ortho-chlorinated phenols that are not readily obtainable via canonical electrophilic chlorinations. Conversely, a phosphine sulfide derived from 2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (BINAP) was found to enhance the innate para-preference of phenol chlorination.