A Time‐Resolved Spectroscopic Study of the Bichromophoric Phototrigger 3′,5′‐Dimethoxybenzoin Diethyl Phosphate: Interaction Between the Two Chromophores Determines the Reaction Pathway

Abstract

3',5'-Dimethoxybenzoin (DMB) is a bichromophoric system that has widespread application as a highly efficient photoremovable protecting group (PRPG) for the release of diverse functional groups. The photodeprotection of DMB phototriggers is remarkably clean, and is accompanied by the formation of a biologically benign cyclization product, 3',5'-dimethoxybenzofuran (DMBF). The underlying mechanism of the DMB deprotection and cyclization has, however, until now remained unclear. Femtosecond transient absorption (fs-TA) spectroscopy and nanosecond time-resolved resonance Raman (ns-TR(3)) spectroscopy were employed to detect the transient species directly, and examine the dynamic transformations involved in the primary photoreactions for DMB diethyl phosphate (DMBDP) in acetonitrile (CH(3)CN). To assess the electronic character and the role played by the individual sub-chromophore, that is, the benzoyl, and the di-meta-methoxybenzylic moieties, for the DMBDP deprotection, comparative fs-TA measurements were also carried out for the reference compounds diethyl phosphate acetophenone (DPAP), and 3',5'-dimethoxybenzylic diethyl phosphate (DMBnDP) in the same solvent. Comparison of the fs-TA spectra reveals that the photoexcited DMBDP exhibits distinctly different spectral character and dynamic evolution from those of the reference compounds. This fact, combined with the related steady-state spectral and density functional theoretical results, strongly suggests the presence in DMBDP of a significant interaction between the two sub-chromophores, and that this interaction plays a governing role in determining the nature of the photoexcitation and the reaction channel of the subsequent photophysical and photochemical transformations. The ns-TR(3) results and their correlation with the fs-TA spectra and dynamics provide evidence for a novel concerted deprotection-cyclization mechanism for DMBDP in CH(3)CN. By monitoring the direct generation of the transient DMBF product, the cyclization time constant was determined unequivocally to be approximately 1 ns. This indicates that there is little relevance for the long-lived intermediates (>10 ns) in giving the DMBF product, and excludes the stepwise mechanism proposed in the literature as the major pathway for the DMB cyclization reaction. This work provides important new insights into the origin of the 3',5'-dimethoxy substitution effect for the DMB photodeprotection. It also helps to clarify the many different views presented in previous mechanistic studies of the DMB PRPGs. In addition to this, our fs-TA results on the reference compound DMBnDP in CH(3)CN provide the first direct observation (to the best of our knowledge) showing the predominance of a prompt (approximately 2 ps) heterolytic bond cleavage after photoexcitation of meta-methoxybenzylic compounds. This provides insight into the long-term controversies about the photoinitiated dissociation mode of related substituted benzylic compounds.

Reporting the Release of Caged Species by a Combination of Two Sequential Photoreactions, a Molecular Switch, and One Color of Light

“…Our results for compound 1 are consistent with the formation of its triplet excited state and the comparable cationic species A . A recent study on the 3′,5′‐dimethoxybenzoin photocage suggested that the photochemical pathway involving this cyclohexadienyl cation structure played only a minor role and a faster process could be the predominant pathway 52. Due to the limitations of our equipment, we were not able to observe any other intermediates prior to generating the proposed cyclohexadienyl cation structure ( A ).…”

Di-cysteine S,S-tetrazine: A potential ultra-fast photochemical trigger to explore the early events of peptide/protein folding

“…The initial ultrafast bleach of the parent carbonyl at 1753 cm −1 (Figure 4D) further suggests that the carbonyl is involved in a transient interaction with the tetrazine ring that quickly removes that carbonyl double bond absorption out of the spectral range, akin to the processes of ring formation observed in dimethoxybenzoin photochemistry. [42–44] The vibrational frequency shifts of the ester carbonyl are not seen, only the populations of the initial and recovered states are observed. Another possible interpretation is that the new CO absorption band of the intermediate state might be anomalously wide and comparable with the noise.…”

Photoremovable chiral auxiliary

“…Phillips and his coworkers recently confirmed this observation and established the dominant reaction pathway. [16][17][18] The presence of a stereogenic center in a PPG is generally considered a disadvantage. A pair of enantiomers of the benzoin group creates a mixture of diastereomers when the leaving group is chiral.…”