The use of “gaseous molecule surrogates,” which can produce gaseous compounds by chemical reactions or physical stimuli, has been attracting attention as a beneficial tool to realize safe and ...convenient organic synthesis. We have engaged in the development of novel surrogates of gaseous molecules, especially focusing on carbon monoxide (CO), and in their application to synthetic organic chemistry. This article describes our recent progress on the development of catalytic organic reactions utilizing gaseous molecule surrogates with high safety and practicality. Detailed mechanism of CO generation from phenyl formate as a CO surrogate has been elucidated both experimentally and theoretically, which led us to develop a series of Pd-catalyzed carbonylative reactions such as room-temperature alkoxycarbonylation and rapid fluorenone formation. We have also exploited the novel synthetic role of potassium metabisulfite as a sulfur dioxide (SO2) surrogate to selectively afford sulfur-containing compounds with various valences, based on achieving the selective formation of cyclic sulfonamides and sulfinamides, symmetrical sulfones, and symmetrical sulfides. It is noteworthy that newly developed modular synthesis-like reactions utilizing both CO and SO2 surrogates were safely conducted with ordinary glassware and were scalable to gram-scale production without any difficulties, indicating their potential use on facile derivatization in medicinal chemistry and on large-scale synthesis.
The use of toxic gas surrogates in organic reactions instead of the gas itself contributes to enhancing the safety, practicality, and efficiency of the reactions involved. Our efforts toward the ...creation of toxic gas surrogates and the development of a series of catalytic reactions using these surrogates are described. Improvements in substrate scope during the hydroesterification of alkenes using formates facilitated by the Ru–imidazole catalyst system provided the opportunity to discover that phenyl formate is a useful carbon monoxide (CO) surrogate for the generation of CO and phenol under weakly basic conditions. This discovery triggered the development of highly reactive but stable CO surrogates and a variety of Pd-catalyzed carbonylative transformations. N-Formylsaccharin facilitated the use of additional nucleophiles in carbonylation reactions that provided access to a variety of carbonyl compounds. Detailed experimental and theoretical mechanistic studies into the generation of CO from phenyl formate suggest that CO generation proceeds via a concerted E2 α-elimination. Furthermore, a known surrogate of sulfur dioxide was applied for the first time to the selective syntheses of cyclic sulfonamides and sulfinamides, confirming that the surrogate operates as an “S=O” source. Notably, the reactions described herein are scalable and can be performed without the use of external toxic gases and specialized reaction vessels; they are easy and simple to perform and demonstrate enormous potential for industrial application.
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•Recent progress on catalytic Heck carbonylations using carbon monoxide surrogates is summarized.•Two types of methods, in-situ and ex-situ methods, are described.•These are useful ...synthetic methods for preparation of various carbonyl compounds.
Ongoing efforts toward the development of carbon monoxide (CO) surrogates have changed the way in which carbonylative transformations are conducted. For synthesizing carboxylic acid derivatives, Heck carbonylation using CO surrogates in slight excess has become a more efficient and practical method than the conventional one using large excess of CO gas. To supply CO for the reaction, both in-situ and ex-situ methods has been considered. Herein, we summarize recent progress in catalytic Heck carbonylation using CO surrogates, including discussion of the mechanism for CO generation from recently developed CO surrogates.
A variety of cyclic sulfonamides and sulfinamides could be selectively synthesized under Pd catalysis using haloarenes bearing amino groups and a sulfur dioxide (SO2) surrogate. The amount of base ...was key in determining the selectivity. Mechanistic studies revealed that sulfinamides were initially formed via an unprecedented formal insertion of sulfur monoxide and were oxidized to sulfonamides in the presence of an iodide ion and DMSO.
N-Formylsaccharin, an easily accessible crystalline compound, has been employed as an efficient CO source in Pd-catalyzed fluorocarbonylation of aryl halides to afford the corresponding acyl ...fluorides in high yields. The reactions use a near-stoichiometric amount of the CO source (1.2 equiv) and tolerate diverse functional groups. The acyl fluorides obtained could be readily transformed into various carboxylic acid derivatives such as carboxylic acid, esters, thioesters, and amides in a one-pot procedure.
The high utility of 2,4,6-trichlorophenyl formate, a highly reactive and easily accessible crystalline CO surrogate, is demonstrated. The decarbonylation with NEt3 to generate CO proceeded rapidly at ...rt, thereby allowing external-CO-free Pd-catalyzed carbonylation of aryl/alkenyl halides and triflates. The high reactivity of the CO surrogate enabled carbonylation at rt and significantly reduced the quantities of formate to near-stoichiometric levels. The obtained trichlorophenyl esters can be readily converted to a variety of carboxylic acid derivatives in high yields.
Various cyclic carbonyl compounds were concisely synthesized by carbonylative cyclization of haloarenes bearing nucleophilic moieties under Pd catalysis. A broad substrate scope and a feasible ...large-scale synthesis clearly demonstrate the high applicability of the reaction as a general, user-friendly method for access to cyclic carbonyl compounds.
Herein, we present a safe and practical methodology for synthesizing symmetrical sulfides using iodoarenes and potassium metabisulfite (K2S2O5). While K2S2O5 is known as a convenient sulfur dioxide ...surrogate, here it acts as a divalent sulfur source, pioneering its potential utility. The reaction exhibits wide substrate generality in which even highly bulky substrates can be applied to afford sterically congested sulfides.
Background
Human gut microbiota is involved in host health and disease development. Investigations of age-related and sex-related alterations in gut microbiota are limited, and the association ...between stool consistency and gut microbiota has not been fully investigated. We investigated gut microbiota differences related to age, sex, and stool consistency in healthy Japanese subjects.
Methods
Two-hundred and seventy-seven healthy Japanese subjects aged 20–89 years were enrolled. Fecal samples were obtained to analyze the gut microbiome. We evaluated the association between stool consistency Bristol stool scale (BSS) and gut microbiota.
Results
Although there were significant differences in the microbial structure between males and females, the α-diversity of gut microbiota showed no difference between males and females or among age groups. There were significant increases in genera
Prevotella
,
Megamonas
,
Fusobacterium
, and
Megasphaera
and
Bifidobacterium
,
Ruminococcus
, and
Akkermansia
in males and females, respectively. The ratio of hard stools (BSS types 1 and 2) was higher in females; the ratio of loose stools (BSS type 6) was higher in males. No younger male had BSS type 1 or type 2.
Fusobacterium
in males was significantly higher in the loose consistency group, and
Oscillospira
was significantly higher in the hard consistency group in males;
Campylobacter
,
SMB53
, and
Turicibacter
were significantly higher in the hard consistency group in females.
Conclusions
Several changes in gut microbiota were associated with age and sex. Stool consistency and gut microbiota associations emphasized the importance of stool consistency assessments to understand intestinal function.
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