Total synthesis of (–)-dihydroprotolichesterinic acid via a diastereoselective conjugate addition, development of enantioselective halocyclization reactions, and progress towards the total synthesis of jiadifenolide

In an effort to develop a unified route to functionalized succinic acid derivatives, a new diastereoselective conjugate addition of monoorganocuprates, Li[RCuI], to a chiral fumarate was developed. The conjugate addition proceeded with good yields and a high degree of diastereoselectivity for a variety of alkyl and aryl nucleophiles. Application of this new methodology culminated in the shortest total synthesis of (–)-dihydroprotolichisterenic acid to date. The novel organocatalyst developed by the Martin group was applied to enantioselective iodolactonization reactions. Reaction conditions were optimized and the resulting halolactones were obtained in high yields and enantioselectivities for a number of olefinic acids. Of particular note is the disclosure of the first iodolactonization reactions forming a C–I bond at a stereogenic center. The utility of this catalyst was further extended to kinetic resolution reactions. Additionally, this catalyst was found to promote the first enantioselective halolactamization reaction with moderate enantioselectivity. Finally, the catalyst was modified in an effort to enhance the enantioselectivity and verify the proposed bifunctional nature of the catalyst. Lastly, an enantiospecific total synthesis of the neurotrophic sesquiterpenoid natural product (–)-jiadifenolide was progressed. The stereochemistry was introduced by the use of commercially available (+)-pulegone as the starting material. The first diastereoselective decarboxylative allylation on a cyclopentanone was developed A samarium diiodide mediated radical annulation was planned to forge two of the rings, and late stage oxidation manipulation could then lead to the completion of the synthesis.Chemistr

Synergistic O_3 + OH oxidation pathway to extremely low-volatility dimers revealed in β-pinene secondary organic aerosol

Dimeric compounds contribute significantly to the formation and growth of atmospheric secondary organic aerosol (SOA) derived from monoterpene oxidation. However, the mechanisms of dimer production, in particular the relevance of gas- vs. particle-phase chemistry, remain unclear. Here, through a combination of mass spectrometric, chromatographic, and synthetic techniques, we identify a suite of dimeric compounds (C_(15–19)H_(24–32)O_(5–11)) formed from concerted O3 and OH oxidation of β-pinene (i.e., accretion of O_3- and OH-derived products/intermediates). These dimers account for an appreciable fraction (5.9–25.4%) of the β-pinene SOA mass and are designated as extremely low-volatility organic compounds. Certain dimers, characterized as covalent dimer esters, are conclusively shown to form through heterogeneous chemistry, while evidence of dimer production via gas-phase reactions is also presented. The formation of dimers through synergistic O_3 + OH oxidation represents a potentially significant, heretofore-unidentified source of low-volatility monoterpene SOA. This reactivity also suggests that the current treatment of SOA formation as a sum of products originating from the isolated oxidation of individual precursors fails to accurately reflect the complexity of oxidation pathways at play in the real atmosphere. Accounting for the role of synergistic oxidation in ambient SOA formation could help to resolve the discrepancy between the measured atmospheric burden of SOA and that predicted by regional air quality and global climate models

Atmospheric autoxidation is increasingly important in urban and suburban North America

Gas-phase autoxidation—regenerative peroxy radical formation following intramolecular hydrogen shifts—is known to be important in the combustion of organic materials. The relevance of this chemistry in the oxidation of organics in the atmosphere has received less attention due, in part, to the lack of kinetic data at relevant temperatures. Here, we combine computational and experimental approaches to investigate the rate of autoxidation for organic peroxy radicals (RO_2) produced in the oxidation of a prototypical atmospheric pollutant, n-hexane. We find that the reaction rate depends critically on the molecular configuration of the RO_2 radical undergoing hydrogen transfer (H-shift). RO_2 H-shift rate coefficients via transition states involving six- and seven-membered rings (1,5 and 1,6 H-shifts, respectively) of α-OH hydrogens (HOC-H) formed in this system are of order 0.1 s^(−1) at 296 K, while the 1,4 H-shift is calculated to be orders of magnitude slower. Consistent with H-shift reactions over a substantial energetic barrier, we find that the rate coefficients of these reactions increase rapidly with temperature and exhibit a large, primary, kinetic isotope effect. The observed H-shift rate coefficients are sufficiently fast that, as a result of ongoing NO_x emission reductions, autoxidation is now competing with bimolecular chemistry even in the most polluted North American cities, particularly during summer afternoons when NO levels are low and temperatures are elevated

Synergistic O_3 + OH oxidation pathway to extremely low-volatility dimers revealed in β-pinene secondary organic aerosol

Dimeric compounds contribute significantly to the formation and growth of atmospheric secondary organic aerosol (SOA) derived from monoterpene oxidation. However, the mechanisms of dimer production, in particular the relevance of gas- vs. particle-phase chemistry, remain unclear. Here, through a combination of mass spectrometric, chromatographic, and synthetic techniques, we identify a suite of dimeric compounds (C_(15–19)H_(24–32)O_(5–11)) formed from concerted O3 and OH oxidation of β-pinene (i.e., accretion of O_3- and OH-derived products/intermediates). These dimers account for an appreciable fraction (5.9–25.4%) of the β-pinene SOA mass and are designated as extremely low-volatility organic compounds. Certain dimers, characterized as covalent dimer esters, are conclusively shown to form through heterogeneous chemistry, while evidence of dimer production via gas-phase reactions is also presented. The formation of dimers through synergistic O_3 + OH oxidation represents a potentially significant, heretofore-unidentified source of low-volatility monoterpene SOA. This reactivity also suggests that the current treatment of SOA formation as a sum of products originating from the isolated oxidation of individual precursors fails to accurately reflect the complexity of oxidation pathways at play in the real atmosphere. Accounting for the role of synergistic oxidation in ambient SOA formation could help to resolve the discrepancy between the measured atmospheric burden of SOA and that predicted by regional air quality and global climate models

Atmospheric autoxidation is increasingly important in urban and suburban North America

Gas-phase autoxidation—regenerative peroxy radical formation following intramolecular hydrogen shifts—is known to be important in the combustion of organic materials. The relevance of this chemistry in the oxidation of organics in the atmosphere has received less attention due, in part, to the lack of kinetic data at relevant temperatures. Here, we combine computational and experimental approaches to investigate the rate of autoxidation for organic peroxy radicals (RO_2) produced in the oxidation of a prototypical atmospheric pollutant, n-hexane. We find that the reaction rate depends critically on the molecular configuration of the RO_2 radical undergoing hydrogen transfer (H-shift). RO_2 H-shift rate coefficients via transition states involving six- and seven-membered rings (1,5 and 1,6 H-shifts, respectively) of α-OH hydrogens (HOC-H) formed in this system are of order 0.1 s^(−1) at 296 K, while the 1,4 H-shift is calculated to be orders of magnitude slower. Consistent with H-shift reactions over a substantial energetic barrier, we find that the rate coefficients of these reactions increase rapidly with temperature and exhibit a large, primary, kinetic isotope effect. The observed H-shift rate coefficients are sufficiently fast that, as a result of ongoing NO_x emission reductions, autoxidation is now competing with bimolecular chemistry even in the most polluted North American cities, particularly during summer afternoons when NO levels are low and temperatures are elevated

Intramolecular Hydrogen Shift Chemistry of Hydroperoxy-Substituted Peroxy Radicals

Gas-phase autoxidation – the sequential regeneration of peroxy radicals (RO_2) via intramolecular hydrogen shifts (H-shifts) followed by oxygen addition – leads to the formation of organic hydroperoxides. The atmospheric fate of these peroxides remains unclear, including the potential for further H-shift chemistry. Here, we report H-shift rate coefficients for a system of RO_2 with hydroperoxide functionality produced in the OH-initiated oxidation of 2-hydroperoxy-2-methylpentane. The initial RO_2 formed in this chemistry are unable to undergo α-OOH H-shift (HOOC–H) reactions. However, these RO_2 rapidly isomerize (>100 s^(–1) at 296 K) by H-shift of the hydroperoxy hydrogen (ROO–H) to produce a hydroperoxy-substituted RO_2 with an accessible α-OOH hydrogen. First order rate coefficients for the 1,5 H-shift of the α-OOH hydrogen are measured to be ∼0.04 s^(–1) (296 K) and ∼0.1 s^(–1) (318 K), within 50% of the rate coefficients calculated using multiconformer transition state theory. Reaction of the RO_2 with NO produces alkoxy radicals which also undergo rapid isomerization via 1,6 and 1,5 H-shift of the hydroperoxy hydrogen (ROO–H) to produce RO_2 with alcohol functionality. One of these hydroxy-substituted RO_2 exhibits a 1,5 α-OH (HOC–H) H-shift, measured to be ∼0.2 s^(–1) (296 K) and ∼0.6 s^(–1) (318 K), again in agreement with the calculated rates. Thus, the rapid shift of hydroperoxy hydrogens in alkoxy and peroxy radicals enables intramolecular reactions that would otherwise be inaccessible