We have developed a protocol for a Pd(0)‐catalyzed dearomative syn 1,2‐diarylation of indoles using readily available boroxines (dehydrated boronic acids) as coupling partners. This reaction proceeds ...efficiently using PtBu3 as the ligand to divergently access to fused indolines while minimizing the extent of direct Suzuki coupling. The scope of the reaction is remarkably broad and all products are obtained as single diastereomers in moderate to excellent yields. We have also compiled data which parallels the steric and electronic properties of both substrate and boroxine with the propensity to undergo the desired dearomative process over direct Suzuki coupling.
In‐dole zone: N‐Benzoyl indoles can be dearomatized by a fully syn‐selective Pd(0)‐catalyzed intramolecular diarylation using aryl and vinyl boroxines as coupling partners (see scheme). This operationally simple method provides an easy and highly divergent access to complex indoline‐containing tetracyclic products.
Herein, we report a convenient and broadly applicable strategy for the difluoromethylation of aryl bromides by metallaphotoredox catalysis. Bromodifluoromethane, a simple and commercially available ...alkyl halide, is harnessed as an effective source of difluoromethyl radical by silyl‐radical‐mediated halogen ion. The merger of this fluoroalkyl electrophile activation pathway with a dual nickel/photoredox catalytic platform enables the difluoromethylation of a diverse array of aryl and heteroaryl bromides under mild conditions. The utility of this procedure is showcased in the late‐stage functionalization of several drug analogues.
Bromodifluoromethane, a commercial alkyl halide, was harnessed as an effective source of difluoromethyl radical by silyl‐radical‐mediated halogen ion. The merger of this fluoroalkyl electrophile activation pathway with a dual nickel/photoredox catalytic platform enables the difluoromethylation of a diverse array of (hetero)aryl bromides under mild conditions.
The Mills reaction and cyclization of readily available 2‐aminobenzyl alcohols and nitrosobenzenes using thionyl bromide provided 2H‐indazoles in up to 88 % yields. In the metal‐free process, acetic ...acid played a crucial role for the both Mills reaction and cyclization. A brominated 2H‐indazole could also be obtained through the one‐pot sequence.
Heterocycles: The Mills reaction and cyclization of readily available 2‐aminobenzyl alcohols and nitrosobenzenes using thionyl bromide provided 2H‐indazoles in up to 88 % yields (see scheme). In the metal‐free process, acetic acid played a crucial role for the both Mills reaction and cyclization. A brominated 2H‐indazole could also be obtained through the one‐pot sequence.
Cyanosilylation of carbonyl compounds provides protected cyanohydrins, which can be converted into many kinds of compounds such as amino alcohols, amides, esters, and carboxylic acids. In particular, ...the use of trimethylsilyl cyanide as the sole carbon source can avoid the need for more toxic inorganic cyanides. In this paper, we describe an electrochemically initiated cyanosilylation of carbonyl compounds and its application to a microflow reactor. Furthermore, to identify suitable reaction conditions, which reflect considerations beyond simply a high yield, we demonstrate machine learning-assisted optimization. Machine learning can be used to adjust the current and flow rate at the same time and identify the conditions needed to achieve the best productivity.
Design of a suitable photoswitchable chiral cation-binding cage for the synthesis of optically active aminals was established using the azobenzene-BINOL hybrid oligoethylene glycol (ABOEG) through ...E/Z isomerization of the azobenzene unit. Under photoirradiation, both the catalytic activity and enantioselectivity of the generating (Z)-ABOEG are enhanced, in contrast to that of (E)-ABOEG, which can be attributed to the geometrically distinct coordination behavior between the metal cation and the oligoethylene glycols.
Azo-crown ether-based photoswitching chiral phase transfer catalysts have been developed to control the catalytic activity by photoirradiation. Azobenzene binaphthyl crown ether (ABCE) can switch its ...reactivity and selectivity through structural transformation of the crown ether moiety induced by E/Z photoisomerization of azobenzene. (Z)-ABCE promoted enantioselective alkylation of the glycine Schiff base to afford chiral amino acid derivatives in good yields with high enantiomer ratios. In contrast, (E)-ABCE hindered the reaction progress under the same conditions.
Bayesian optimization (BO)-assisted screening was applied to identify improved reaction conditions toward a hundred-gram scale-up synthesis of 2,3,7,8-tetrathiaspiro4.4nonane (
), a key synthetic ...intermediate of 2,2-bis(mercaptomethyl)propane-1,3-dithiol tetramercaptan pentaerythritol. Starting from the initial training set (ITS) consisting of six trials sampled by random screening for BO, suitable parameters were predicted (78% conversion yield of spiro-dithiolane
) within seven experiments. Moreover, BO-assisted screening with the ITS selected by Latin hypercube sampling (LHS) further improved the yield of
to 89% within the eight trials. The established conditions were confirmed to be satisfactory for a hundred grams scale-up synthesis of
.
Echolocating bats prey upon small moving insects in the dark using sophisticated sonar techniques. The direction and directivity pattern of the ultrasound broadcast of these bats are important ...factors that affect their acoustical field of view, allowing us to investigate how the bats control their acoustic attention (pulse direction) for advanced flight maneuvers. The purpose of this study was to understand the behavioral strategies of acoustical sensing of wild Japanese house bats Pipistrellus abramus in three-dimensional (3D) space during consecutive capture flights. The results showed that when the bats successively captured multiple airborne insects in short time intervals (less than 1.5 s), they maintained not only the immediate prey but also the subsequent one simultaneously within the beam widths of the emitted pulses in both horizontal and vertical planes before capturing the immediate one. This suggests that echolocating bats maintain multiple prey within their acoustical field of view by a single sensing using a wide directional beam while approaching the immediate prey, instead of frequently shifting acoustic attention between multiple prey. We also numerically simulated the bats' flight trajectories when approaching two prey successively to investigate the relationship between the acoustical field of view and the prey direction for effective consecutive captures. This simulation demonstrated that acoustically viewing both the immediate and the subsequent prey simultaneously increases the success rate of capturing both prey, which is considered to be one of the basic axes of efficient route planning for consecutive capture flight. The bat's wide sonar beam can incidentally cover multiple prey while the bat forages in an area where the prey density is high. Our findings suggest that the bats then keep future targets within their acoustical field of view for effective foraging. In addition, in both the experimental results and the numerical simulations, the acoustic sensing and flights of the bats showed narrower vertical ranges than horizontal ranges. This suggests that the bats control their acoustic sensing according to different schemes in the horizontal and vertical planes according to their surroundings. These findings suggest that echolocating bats coordinate their control of the acoustical field of view and flight for consecutive captures in 3D space during natural foraging.
The electrochemical synthesis of hetero7helicenes including pyrrole and furan rings has been established. A single electrochemical operation led to an oxidative heterocoupling and dehydrative ...cyclization sequence to afford oxaza7helicenes in 50–86% yields with 45–77% Faradic efficiencies. Their derivatization and chiroptical properties were also investigated.
A stereoselective synthetic route to chiral C3‐spirooxindole‐ and C2‐spiropseudoindoxyl‐pyrrolidines was accomplished by an enantioselective organocatalyzed Pictet‐Spengler reaction of tryptamines ...and isotryptamines followed by a diastereoselective oxidative rearrangement using eco‐friendly oxidants (i. e., NaOCl ⋅ 5H2O and Oxone®). This sequential reaction enables rapid access to chiral C3‐spirooxindole‐ and C2‐spiropseudoindoxyl‐pyrrolidines in a one‐pot process. A Wnt signaling inhibitory assay of the prepared enantioenriched spiro compounds demonstrated that they exhibited moderate activities.
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