Nature of intermediates in organo-SOMO catalysis of alpha-arylation of aldehydes.
ABSTRACT: The intramolecular alpha-arylation of aldehydes via organo-SOMO catalysis was investigated using density functional theory (B3LYP and M06-2X functionals). The geometries, spin densities, Mulliken charges, and molecular orbitals of the reacting enamine radical cations were analyzed, and the nature of the resulting cyclized radical cation intermediates was characterized. In agreement with experimental observations, the calculated 1,3-disubstituted aromatic system shows ortho selectivity, while the 1,3,4-trisubstituted systems show para, meta (instead of ortho, meta) selectivity. The selectivity change for the trisubstituted rings is attributed to a distortion of the ortho substituents in the ortho, meta cyclization transition structures that causes a destabilization of these isomers and therefore results in selectivity for the para, meta product.
Project description:The intramolecular alpha-arylation of aldehydes has been accomplished using singly occupied molecular orbital (SOMO) catalysis. Selective oxidation of chiral enamines (formed by the condensation of an aldehyde and a secondary amine catalyst) leads to the formation of a 3pi-electron radical species. These chiral SOMO-activated radical cations undergo enantioselective reaction with an array of pendent electron-rich aromatics and heterocycles thus efficiently providing cyclic alpha-aryl aldehyde products (10 examples: > or = 70% yield and > or = 90% ee). In accordance with our radical mechanism, when there is a choice between arylation at the ortho or para position of anisole substrates, we find that arylation proceeds selectively at the ortho position.
Project description:The first organocatalytic enantioselective radical polycyclization has been accomplished using singly occupied molecular orbital (SOMO) catalysis. The presented strategy relies on a selective single-electron oxidation of chiral enamines formed by condensation of polyenals with an imidazolidinone catalyst employing a suitable copper(II) oxidant. The reaction proceeds under mildly acidic conditions at room temperature and shows compatibility with an array of electron-poor as well as electron-rich functional groups. Upon termination by radical arylation followed by subsequent oxidation and rearomatization, a range of polycyclic aldehydes were accessed (12 examples, 54-77% yield, 85-93% ee). The enantioselective formation of up to six new carbocycles in a single catalyst-controlled cascade is described. Evidence for a radical-based cascade mechanism is indicated by a series of experimental results.
Project description:The intramolecular asymmetric cyclization of aldehydes has been accomplished using singly occupied molecular orbital (SOMO) catalysis. Selective oxidation of chiral enamines (formed by the condensation of an aldehyde and a secondary amine catalyst) leads to the formation of a 3?-electron radical species. These chiral SOMO-activated radical cations undergo enantioselective cyclization with an array of pendent allylsilanes thus efficiently providing a new approach to the construction of five-, six- and seven-membered carbocycles and heterocycles.
Project description:A new method to rapidly generate pyrrolidines via a SOMO-activated enantioselective (3 + 2) coupling of aldehydes and conjugated olefins has been accomplished. A radical-polar crossover mechanism is proposed wherein olefin addition to a transient enamine radical cation and oxidation of the resulting radical furnish a cationic intermediate which is vulnerable to nucleophilic addition of a tethered amine group. A range of olefins, including styrenes and dienes, are shown to provide stereochemically complex pyrrolidine products with high chemical efficiency and enantiocontrol.
Project description:A highly selective, radical-mediated (4 + 2) coupling reaction of aldehydes and conjugated olefins has been achieved through asymmetric SOMO-catalysis. A radical-polar crossover mechanism is proposed wherein olefin addition to a transient enamine radical cation and oxidation of the resulting radical furnishes a cation which is vulnerable to nucleophilic addition. A range of aromatic aldehydes are shown to couple with styrenes and dienes to provide cyclic products with high chemical efficiency, regioselectivity, and stereoselectivity.
Project description:Conventionally, the singly occupied molecular orbital (SOMO) of a radical species is considered to be the highest occupied molecular orbital (HOMO), but this is not the case always. In this study, we considered a number of radicals from smallest diatomic anion radicals such as superoxide anion radical to one-electron oxidized DNA related base radicals that show the SOMO is energetically lower than one or more doubly occupied molecular orbitals (MOs) (SOMO-HOMO level inversion). The electronic configurations are calculated employing the B3LYP/6-31++G** method, with the inclusion of aqueous phase via the integral equation formalism of the polarized continuum model solvation model. From the extensive study of the electronic configurations of radicals produced by one-electron oxidation or reduction of natural-DNA bases, bromine-, sulfur-, selenium-, and aza-substituted DNA bases, as well as 20 diatomic molecules, we highlight the following important findings: (i) SOMO-HOMO level inversion is a common phenomenon in radical species. (ii) The more localized spin density in ?-orbital on a single atom (carbon, nitrogen, oxygen, sulfur, or selenium), the greater the gap between HOMO and SOMO. (iii) In species with SOMO-HOMO level inversion, one-electron oxidation takes place from HOMO not from the SOMO, which produces a molecule in its triplet ground state. Oxidation of aqueous superoxide anion producing triplet molecular oxygen is one example of many. (iv) These results are for conventional radicals and in contrast with those reported for distonic radical anions in which SOMO-HOMO gaps are smaller for more localized radicals and the orbital inversions vanish in water. Our findings yield new insights into the properties of free radical systems.
Project description:Efficient C-H functionalization requires selectivity for specific C-H bonds. Progress has been made for directed aromatic substitution reactions to achieve ortho and meta selectivity, but a general strategy for para-selective C-H functionalization has remained elusive. Herein we introduce a previously unappreciated concept that enables nearly complete para selectivity. We propose that radicals with high electron affinity elicit arene-to-radical charge transfer in the transition state of radical addition, which is the factor primarily responsible for high positional selectivity. We demonstrate with a simple theoretical tool that the selectivity is predictable and show the utility of the concept through a direct synthesis of aryl piperazines. Our results contradict the notion, widely held by organic chemists, that radical aromatic substitution reactions are inherently unselective. The concept of radical substitution directed by charge transfer could serve as the basis for the development of new, highly selective C-H functionalization reactions.
Project description:A strategy for affecting ortho versus meta/para selectivity in Ir-catalyzed C-H borylations (CHBs) of phenols is described. From selectivity observations with ArylOBpin (pin = pinacolate), it is hypothesized that an electrostatic interaction between the partial negatively charged OBpin group and the partial positively charged bipyridine ligand of the catalyst favors ortho selectivity. Experimental and computational studies designed to test this hypothesis support it. From further computational work a second generation, in silico designed catalyst emerged, where replacing Bpin with Beg (eg = ethylene glycolate) was predicted to significantly improve ortho selectivity. Experimentally, reactions employing B2eg2 gave ortho selectivities > 99%. Adding triethylamine significantly improved conversions. This ligand-substrate electrostatic interaction provides a unique control element for selective C-H functionalization.
Project description:2,4-toluene diisocyanate (TDI) has been commonly used to bind molecules and polymers onto the surface of cellulose nanocrystals (CNCs). Such a process usually involves two steps: (1) the more reactive para-isocyanates (p-NCOs) of TDI are reacted with the surface hydroxyl groups of CNCs then (2) the ortho-isocyanates (o-NCOs) are reacted with certain desired molecules. During the first reaction, an ideal para/ortho selectivity could be impossible to achieve, as o-NCOs are not fully unreactive. Therefore, there is a need to better understand the reaction between CNCs and TDI towards a maximum para/ortho selectivity. For that goal, CNCs were reacted with TDI under varying temperatures (35-75 °C) and TDI/CNCs molar ratios (1-5). The amount of the reacted TDI was estimated using elemental analysis while the free o-NCO groups were quantified following the hydrolysis method of Abushammala. The results showed that temperature had a negative impact on para/ortho selectivity while TDI/CNCs molar ratio improved it. A maximum selectivity of 93% was achieved using a temperature of 35 °C and a molar ratio of 3. This is a three-fold improvement to that using the traditional reaction conditions (75 °C and molar ratio of 1).
Project description:Three new isomeric asymmetric diarylethenes with a naphthyl moiety and a formyl group at the para, meta or ortho position of the terminal benzene ring were synthesized. Their photochromism, fluorescent-switch, and electrochemical properties were investigated. Among these diarylethenes, the one with a formyl group at the ortho position of benzene displayed the largest molar absorption coefficients and fluorescence quantum yield. The cyclization quantum yields of these compounds increased in the order of para < ortho < meta, whereas their cycloreversion quantum yields decreased in the order of meta > para > ortho. Additionally, all of these diarylethenes functioned as effective fluorescent switches in both solution and PMMA films. Cyclic voltammograms proved that the formyl group and its position could effectively modulate the electrochemical behaviors of these diarylethene derivatives.