Unraveling The Reaction Mechanisms Of Selected Photolabile Protecting Groups And Photoinduced Quinone Methide Compounds

By controlling the bond cleavage under light irradiation,a photolabile protecting group（PPG）can easily and precisely release the target molecule.The photodeprotection of PPGs in a high temporal and spatial resolution often occurs under mild conditions.There has been great interest in the design and optimization of a range of PPGs due to their wide applications in organic synthesis and biomedicine.The aromatic carbonyl compounds were found to be suitable PPGs for their excellent photosensitivity,which can reduce the dependence on strong light.This alleviates the cell damage caused during the application in vivo.Anthraquinone（AQ）compounds,as popular PPG platforms of aromatic carbonyl compounds,are used to protect carboxylic acids and carbonyl.AQ-PPGs have acceptable water solubility and high photodeprotection efficiency,which makes them potentially useful in biological systems.By introducing the photochromic molecules to the PPG platform designed as a versatile and novel release-and-report system can accurately reflect where and when the photodeprotection occurs.The molecule combining the diarylethene class of photoswitches and the the dialkoxybenzoin PPG（PC-PPG）enable efficient deprotection of carboxylic acids.Quinone methides（QMs）,as important reactive intermediates in the chemistry and photochemistry of phenols,are widely used in lignin biosynthesis and cancer therapy.Much attention has been devoted to the development of methods to generate QMs photochemically,since this provides temporal and spatial control over their formation in mild conditions.However,due to the lack of information describing intermediates,the photodeprotection mechanisms of AQ-PPGs and PC-PPG,as well the formation mechanisms of QMs are unclear.In this paper,femtosecond time-resolved transient absorption spectroscopy,nanosecond time-resolved transient absorption spectroscopy and nanosecond time-resolved resonance Raman spectroscopy will be utilized to directly detect electron transition spectra,Raman spectra,and kinetic information for the intermediates and transient species generated during the photoreaction process.After that,density functional theory computations were performed to help the interpretation of the experimental spectra and construct the reaction potential energy surface to promote the clarification of the reaction mechanisms of AQ-PPGs,PC-PPG,and photogenerated QM.In chapter 1,the backgrounds of photochemistry,dominant families of PPGs and corresponding photodeprotection mechanisms,the most important methods for the photogeneration of QM,time-resolved spectroscopy and density functional theory computations calculation were briefly summarized.In chapter 2,First,photodeprotection mechanism of 2-（1’-hydroxy）-anthraquinone-protected p-methoxybenzoic acid（Aqe-PPG）and solvent effect on the photodeprotection reaction were explored.It has been found that in aprotic organic solvents such as acetonitrile（ACN）only the triplet state species was seen,whereas a hydrogen atom transfer（HAT）reaction took place in isopropanol（IPA）to yield the aromatic ketyl radical species for Aqe-PPG.In protic solvent methanol（Me OH）and Me OH-H₂O,Aqe-PPG underwent HAT and a proton transfer process sequentially to accomplish the release of the leaving group.Photodeprotection is more favourable in the Me OH-H₂O due to the stronger proton mediation ability of the water molecules.Second,photodeprotection mechanism of anthraquinon-2-ylethyl-1′,2′-diol protected carbonyl compound（Aqe-diol-PPG）was studied.It was shown that the triplet state of Aqe-diol-PPG underwent a proton-coupled electron transfer process to form a xylylene intermediate.After the C–O bond cleavage,a diradical intermediate was generated,which further released the protected benzaldehyde with the by-product Aqe-diol.A comparison work suggested that Aqe-diol underwent a further photoredox reaction in aqueous solutions.Third,the photodeprotection mechanism of photochromic diarylethylene function attached photocage dimethoxybenzoin platform（PC-PPG）was explored.The photodeprotection proceeded with competition between cyclizations initiated by two different configurations of the singlet excited state of PC-PPG to generate acetic acid and ring-closed isomer of a diarylethene.In chapter 3,First,photoreactions of 4′-chloro-2-hydroxybiphenyl in ACN and ACN-H₂O were investigated.4′-chloro-2-hydroxybiphenyl went through a singlet excited state intramolecular proton transfer（ESIPT）to generate QM in ACN but behaved differently in ACN-H₂O,where a concerted asynchronous HCl elimination occurred to form a biradical intermediate,followed by HAT form ACN to produce ACN adduct.The hydrogen bond formed with water molecules promotes HCl elimination,while this is disfavored for ESIPT,making 4′-Cl extrusion the predominant process in ACN-H₂O solutions.Second,the formation mechanism of QM from 4-（2′-hydroxyphenyl）pyridine was studied.In ACN,the singlet excited state species with the cis-form underwent a thermodynamically favorable and ultrafast ESIPT to produce the singlet excited state QM.In ACN-H₂O,singlet excited state of 4-（2′-hydroxyphenyl）pyridine interacted with water molecules to form a solvated species,which induced water-assisted ESPT to the pyridine nitrogen to generate the singlet excited state QM in a concerted asynchronous manner that was initiated by deprotonation of the phenolic OH.The mechanistic work presented in this paper will provide insight to design and development of improved and versatile molecular and will also help in the better application of PPGs and QMs in organic synthesis and biochemistry.