Photocycloaddition of S,S-Dioxo-benzothiophene-2-methanol, Reactivity in the Solid State and in Solution: Mechanistic Studies and Diastereoselective Formation of Cyclobutyl Rings

Abstract

The formation of cyclobutane rings is a promising strategy in the development of potential drugs and/or synthetic intermediates, typically challenging to obtain due to their constrained nature. In this work, the [2 + 2] photocycloaddition reaction of S,S-dioxobenzothiophene-2-methanol was explored in microcrystalline powders and its outcome was compared to that observed in solution. It was found that the molecular constraints inherited within the crystal lattice provide an optimal environment that leads to photodimer 4 as the major product in ca. 9.6:0.4 diastereomeric ratios with conversions >95%. The photoreaction was analyzed via X-ray, displaying a crystalline-to-amorphous transformation and showing that units of monomer 2 align to generate the corresponding dimer with a syn-head-to-tail regio-and diastereoselectivity. This result contrasted with that obtained in solution, where the diastereomeric ratio varied as a function of the excited state that is generated, to yield mixtures of dimers 4 and 5 (anti-head-to-tail), or exclusively 5 in the tripletsensitized photoreaction, in the presence of benzophenone. Density functional theory was used to elucidate a plausible detailed mechanism for the phototransformation, which aided in justifying the results that led to the corresponding dimers. X-ray crystallography allowed us to establish the stereochemical assignment of the obtained cyclobutyl rings. Thus, the use of solidstate or solution photochemistry can be used to gain control of diastereo-and regioselectivities in the formation of this important moiety.

Modification at the C2′-O-Position with 2-Methylbenzothiophene Induces Unique Structural Changes and Thermal Transitions on Duplexes of RNA and DNA

“…Regarding proposed step 3, temperature- and salt-dependent transitions are known, and an A- to Z-form duplex transition was recorded in a temperature dependent manner, where the Z-form was generated at 45 °C using high monovalent cation concentrations (NaClO 4 , up to 6 M). 23 Transitions that are similar to those reported here are not common; however, something similar, albeit less intense, was reported with DNA containing pyrene units at the nucleobase. 49 All studies describing such arrays do not exhibit the stabilization observed in this work, presumably because the salt concentration was increased substantially herein.…”

“…In regards to the observed transition, and given the gathered information, we are proposing a model where (1) the benzothiophene units may interact with each other, stronger in higher monocation content, and the nucleobase interactions (base pair H-bonding or π–π stacking) are disrupted; (2) upon heating, the abnormal base pair H-bonding interactions show signs that disruption/breakage starts to occur; (3) the hydrophobic benzothiophene rings aid to maintain the structure in place and allow for another internal H-bond rearrangement (much like a duplex transition, A- to Z-form) into a more thermodynamically stable structure, resulting in optimal nucleobase interactions; and (4) increased temperatures lead to denaturation of the duplex. Regarding proposed step 3, temperature- and salt-dependent transitions are known, and an A- to Z-form duplex transition was recorded in a temperature dependent manner, where the Z-form was generated at 45 °C using high monovalent cation concentrations (NaClO 4 , up to 6 M) . Transitions that are similar to those reported here are not common; however, something similar, albeit less intense, was reported with DNA containing pyrene units at the nucleobase .…”

“…Alkylation of the uridyl nucleoside resulted in lower yields, where the formation of suspensions was typically observed, and adjusting the concentration or temperature did not lead to enhanced yields. Bromination of benzothiophene methyl alcohol was achieved via an Appel reaction following a known procedure . Deprotection in the presence of HF yielded diol R3 in good yields, which was tritylated under standard conditions to afford nucleosides R4 .…”

“…Bromination of benzothiophene methyl alcohol was achieved via an Appel reaction following a known procedure. 23 Deprotection in the presence of HF yielded diol R3 in good yields, which was tritylated under standard conditions to afford nucleosides R4 . Subsequent phosphytilation, under standard conditions afforded their corresponding phosphoramidites ( R5 ).…”

Photomechanical Luminescence from Through‐Space Conjugated AIEgens

“…[6] However, these reactions were only performed in solutions. Resendiz et al [7] reported the photodimerization of BTO derivatives in the solid-sate and elucidated the impact of reaction conditions on the structures of the photodimers. In comparison with the BTO derivatives reported by Resendiz et al, P-BTO has a bulky phenyl substitute.…”