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Aminocarbonylation of alkenyl iodides with CO and amines proceeded under heating to produce α,β-unsaturated amides in good yields (23 examples, 71% average yield). This catalyst-free method exhibited good functional-group tolerance, and open a straightforward access to functionalized acrylamides, as illustrated by the synthesis of Ilepcimide. A hybrid radical/ionic mechanism involving chain electron transfer is proposed for this transformation.

Tetrabutylammonium decatungstate (TBADT)-photocatalyzed C–H functionalization of alkylpyridines was investigated. Unlike alkylbenzene counterparts, alkylation of α-C–H bonds did not proceed for the reaction of 2- and 4-alkylpyridines and reluctantly proceeded for 3-alkylpyridines, which allow site-selective C(sp3)–H functionalization at nonbenzylic positions. The observed nonbenzylic site selectivities are rationalized by the polar inductive effects of pyridyl groups in the SH2 transition states. Consecutive γ-functionalization and α-bromofunctionalization were successfully carried out in selected cases.

A radical-chain addition of allyl bromides to aryl alkenes, vinyl ester, and vinyl phthalimide was studied in which elusive β-bromoalkyl radicals were trapped efficiently to give 5-bromo-1-pentenes in good to high yields (16 examples). A subsequent carbonylative radical cyclization with AIBN/Bu3SnH/CO was successful in giving the corresponding 3,5-disubstituted cyclohexanone derivatives in moderate yields. Synthesis of a piperidine ring was also successful by subsequent reaction with primary amine.

A carbonylative Mizoroki-Heck reaction using alkyl iodides was achieved with a Pd/photoirradiation system using DBU as a base. In this reaction, alkyl radicals were formed from alkyl iodides via single-electron transfer (SET) and then underwent a sequential addition to CO and alkenes to give β-keto radicals. It is proposed that DBU would abstract a proton α to carbonyl to form radical anions, giving α,β-unsaturated ketones via SET.

A Cossy 5-exo-dig photocyclization of organohalides (X = Br, I) onto a C-C triple bond was studied using a flow photomicroreactor, which proceeded in a minute order of residence time. A deuterium labeling study supported the nonchain radical mechanism proposed by the Cossy group, in which a hydrogen source originates from a triethylamine cation radical. Scalable flow synthesis using a larger volume of flow reactor was also successful, providing 4 g of the product in high yield.

Tetrabutylammonium decatungstate (TBADT)-photocatalyzed C-H functionalization of alkylpyridines was investigated. Unlike alkylbenzene counterparts, alkylation of α-C-H bonds did not proceed for the reaction of 2- and 4-alkylpyridines and reluctantly proceeded for 3-alkylpyridines, which allow site-selective C(sp

The generation of, and subsequent reactions with, 1-silyl-substituted organolithiums with CO was carried out using serially connected flow microreactors. The flow system proved to be quite useful for the carbonylation of silyl-substituted organolithiums under slightly pressurized conditions of CO, which was created conveniently by the use of a back-pressure regulator. This flow system, coupled with heating, accelerated the carbonylation reaction of 1-silyl-substituted organolithiums and allowed the stable silyl-substituted alkyllithium, 1,3-disilylallyllithium, which was not effective in a batch-flask reaction under a CO atmosphere, to participate in an efficient carbonylation reaction.

Tetrabutylammonium decatungstate (TBADT) accelerated the addition of C-H bonds to the N═N double bond of diisopropyl azodicarboxylate (DIAD) under irradiation conditions. The photoinduced three-component coupling between cyclic alkanes, CO, and DIAD was also achieved to give the corresponding acyl hydrazides.

The regioselective radical bromoallylation of allenes proceeded efficiently in the presence of AIBN as a radical initiator to give 2-bromo-substituted 1,5-dienes in excellent yields. The addition of a bromine radical took place regioselectively onto the central carbon of allenes generating a stable allyl radical, which underwent addition/β-fragmentation reactions with allylbromides. The products could be further functionalized by Pd-catalyzed coupling reactions.

Tin-free radical/ionic hydroxymethylation of secondary and tertiary alkyl iodides proceeded efficiently in the presence of tetrabutylammonium borohydride as the hydrogen source under atmospheric pressure of CO in conjunction with photoirradiation using black light. Two possible mechanisms were proposed, both of which involve hybrid radical/ionic processes.

Highly efficient thermal radical carboaminoxylations of various olefins by using the novel alkoxyamine A to give adducts of type B are described. It is reported that these radical addition reactions can be performed in a microflow reaction system. As compared to conventional batch reaction setup, significantly higher yields are obtained by running carboaminoxylations using the microflow system under analogous conditions.

Tributyltin hydride-mediated radical reactions of organic halides were successfully carried out in a continuous flow system using a microreactor. The reactions proceeded within a very short period of time, coupled with quickly decomposing radical initiators such as V-65 and V-70. The continuous flow reaction system was applied to gram scale synthesis of a key intermediate for furofuran lignans.

β- or γ-Site-selective C–H alkylation of aliphatic nitriles has been achieved using a decatungstate salt as the photocatalyst. The observed site selectivity was justified by a radical polar effect in transition states for hydrogen abstraction.

[reaction: see text] The PdCl2(PPh3)2-catalyzed Sonogashira coupling reaction, in good to high yields, was performed in an ionic liquid ([BMIm][PF6]) in the absence of a copper salt. The use of an ionic liquid allows for the facile separation and recycling of the catalyst. The application of the above reaction in a microflow system in conjunction with an IMM micromixer was also successful.

An efficient approach to the synthesis of fluorenones via the rhodium-catalyzed intramolecular acylation of biarylcarboxylic acids was developed. Using this procedure, fluorenones with various substituents can be synthesized in good to high yields. This work marks the first recorded use of catalytic intramolecular acylation to synthesize fluorenones.

We have developed an expedient method for the synthesis of polycyclic compounds from propargyl acetates or vinyl allenes involving up to three Au(I)-catalyzed elemental steps: 3,3-rearrangement, metalla-Nazarov reaction, and electrophilic cyclopropanation. The reaction proceeds under very mild conditions and in short times. The mechanism has been studied by DFT computations.

Carbonylation reactions, such as Heck, Sonogashira, and radical carbonylations, were successfully carried out in a "two-chamber reactor" where carbon monoxide was produced ex situ by the Morgan reaction (dehydration of formic acid by sulfuric acid). By a subsequent application in a microflow system using a "tube-in-tube" reactor where gas-permeable Teflon AF2400 was used as the inner tube, it is demonstrated that formic acid/sulfuric acid can be employed concomitantly with an amine base such as triethylamine in the Heck aminocarbonylation of aryl iodide.

Rhodium-catalyzed intramolecular C–H arylation of 2-aryloxybenzoic acids proceeded accompanied by decarbonylation to give dibenzofuran derivatives in high yields. The present reaction is widely applicable to substrates bearing various functionalities.

Under photoirradiation conditions using a xenon light, and in the presence of PdCl(2)(PPh(3))(2) as a catalyst, four-component coupling reactions comprising of α-substituted iodoalkanes, alkenes, carbon monoxide, and alcohols proceeded smoothly to give functionalized esters in good yields. When alkenyl alcohols were used as acceptor alkenes, three-component coupling reactions accompanied by intramolecular esterification proceeded to give lactones in good yields. The present reaction system represents the vicinal C-functionalization of alkenes.

Under photoirradiation conditions using xenon light, in the presence of a catalytic amount of PdCl(2)(PPh(3))(2) with triethylamine as a base, a three-component coupling reaction of iodoalkanes, carbon monoxide, and terminal alkynes proceeded to give alkyl alkynyl ketones in good yields.

The cross-coupling reaction of alpha,beta-unsaturated aldehydes with primary alcohols to give 2-hydroxymethyl ketones was achieved using RuHCl(CO)(PPh(3))(3) as a catalyst. This atom-economical reaction is likely to proceed via the hydroruthenation of alpha,beta-unsaturated aldehydes followed by an aldol reaction of the resultant enolates with aldehydes to give alpha-formylated ketones, which undergo transfer hydrogenation with primary alcohols leading to alpha-hydroxymethyl ketones. The reduction step can generate aldehydes, participating in the next catalytic cycle.

Tin-free Giese reaction and the related radical carbonylation process proceeded efficiently in the presence of sodium cyanoborohydride and tetrabutylammonium cyanoborohydride. The reaction took place chemoselectively at the carbon−iodine bond but not at the carbon−bromine and carbon−chlorine bonds. The iodine atom transfer followed by hydride reduction of the resulting carbon−iodine bond is proposed as a possible mechanism.

Ruthenium catalyzes a carbonylative [3+2+1] cycloaddition, using silylacetylenes, alpha,beta-unsaturated ketones, and CO as the starting materials, providing the new method for the synthesis of tetrasubstituted alpha-pyrones. In this reaction, the carbonyl group and alpha-carbon of vinyl ketones are incorporated as a three-atom assembling unit. [reaction: see text].

[reaction: see text] Catalytic [2 + 2 + 1 + 1] cocyclization reaction of an alkyne, an alkene, and two molecules of carbon monoxide, leading to functionalized hydroquinones, was studied. Using [Cp*RuCl2]2 as a catalyst, we found that a variety of electron-deficient alkenes, such as alpha,beta-unsaturated ketones, esters, amides, and nitriles, can be employed as an alkene coupling partner to give the corresponding hydroquinones.