Ilhyong Ryu

Carbonylation Reactions of Alkyl Iodides through the Interplay of Carbon Radicals and Pd Catalysts

Numerous methods for transition metal catalyzed carbonylation reactions have been established. Examples that start from aryl, vinyl, allyl, and benzyl halides to give the corresponding carboxylic acid derivatives have all been well documented. In contrast, the corresponding alkyl halides often encounter difficulty. This is inherent to the relatively slow oxidative addition step onto the metal center and subsequent β-hydride elimination which causes isomerization of the alkyl metal species. Radical carbonylation reactions can override such problems of reactivity; however, carbonylation coupled to iodine atom transfer (atom transfer carbonylation), though useful, often suffers from a slow iodine atom transfer step that affects the outcome of the reaction. We found that atom transfer carbonylation of primary, secondary, and tertiary alkyl iodides was efficiently accelerated by the addition of a palladium catalyst under light irradiation. Stereochemical studies support a mechanistic pathway based on the synergic interplay of radical and Pd-catalyzed reaction steps which ultimately lead to an acylpalladium species. The radical/Pd-combined reaction system has a wide range of applications, including the synthesis of carboxylic acid esters, lactones, amides, lactams, and unsymmetrical ketones such as alkyl alkynyl and alkyl aryl ketones. The design of unique multicomponent carbonylation reactions involving vicinal C-functionalization of alkenes, double and triple carbonylation reactions, in tandem with radical cyclization reactions, has also been achieved. Thus, the radical/Pd-combined strategy provides a solution to a longstanding problem of reactivity involving the carbonylation of alkyl halides. This novel methodology expands the breadth and utility of carbonylation chemistry over either the original radical carbonylation reactions or metal-catalyzed carbonylation reactions.

Ruthenium Hydride-Catalyzed Addition of Aldehydes to Dienes Leading to β,γ-Unsaturated Ketones

An efficient cross-addition reaction of dienes with aldehydes was developed by using RuHCl(CO)(PPh3)3 as a catalyst to give a wide variety of beta,gamma-unsaturated ketones, where a pi-allylruthenium species, derived from hydroruthenation of diene, may be involved as a key intermediate.

Iodine-catalyzed aziridination of alkenes using Chloramine-T as a nitrogen source

Abstract Iodine was found to be an efficient catalyst for the aziridination of alkenes utilizing Chloramine-T (N-chloro-N-sodio-p-toluenesulfonamide) as a nitrogen source. For example, when two equivalents of styrene were added to Chloramine-T in the presence of a catalytic amount of iodine in a 1 : 1 solvent mixture of acetonitrile and neutral buffer, the corresponding aziridine 1 was obtained in 91% yield. The reaction could be applied to other acyclic and cyclic alkenes such as 1-octene and cyclohexene. The aziridination of p-substituted styrene derivatives 2–5 with Chloramine-T showed that electron-rich alkenes reacted faster than electron-poor ones. Several Chloramine-T analogs were also examined and were found to give the corresponding aziridines 8–10 in only moderate yields.

Radical carboxylations of iodoalkanes and saturated alcohols using carbon monoxide

This review covers two radical carboxylation methods using carbon monoxide, both of which were developed by our group. The first method, atom transfer carbonylation, converts alkyl iodides into carboxylic acid esters or amides and the second method, remote carboxylation, converts saturated alcohols into δ-lactones. Both methods rely upon radical carbonylation chemistry to introduce carbon monoxide, but the key steps are conceptually different. The first method utilizes an atom transfer reaction from an alkyl iodide to an acyl radical leading to an acyl iodide and the latter employs a one-electron oxidation reaction to convert an acyl radical into an acyl cation. The iodine atom transfer carbonylation process is reversible and therefore highly inefficient unless it is performed in concert with an ionic system to shift the equilibrium in the direction of an acyl iodide. In the latter process, a 1,5-translocation scheme to shift the radical from oxygen to the δ-carbon is successfully coupled with the carbonylation–oxidation sequence. Carboxylations of alkyl halides by transition metal catalyzed methods are often problematic because of the inherent weakness of alkyl–metal bonds. Existing methods for carbonylative δ-lactone synthesis using transition metal catalysts are limited to unsaturated alcohols. Thus, these two radical carboxylation methods nicely complement existing transition metal catalyzed carboxylations.

Nitrogen atom transfer to alkenes utilizing Chloramine-T as a nitrogen source

Abstract Aziridination of alkenes proceeds successfully using Chloramine-T (N-chloro-N-sodio-p-toluenesulfonamide). When anhydrous Chloramine-T was added to an acetonitrile solution of alkenes in the presence of various CuCl catalysts and MS-5A, the corresponding aziridines were obtained in moderate to good yields.

Novel Asymmetric and Stereospecific Aziridination of Alkenes with a Chiral Nitridomanganese Complex

The addition of pyridine N-oxide is necessary to obtain high enantioselectivities in the asymmetric aziridination of styrene derivatives through transfer of a nitrogen atom from chiral, toluenesulfonic anhydride activated nitridomanganese complex 1 [Eq. (a)]. Remarkably, high stereospecificity was observed in all the aziridinations of trans- and cis-1,2-disubstituted alkenes. R1 =H, Me, nPr, iPr; R2 =H, Me; Ts=p-toluenesulfonyl.

Synthesis of Alkyl Alkynyl Ketones by Pd/Light-Induced Three-Component Coupling Reactions of Iodoalkanes, CO, and 1-Alkynes

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.

Spurring radical reactions of organic halides with tin hydride and TTMSS using microreactors.

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.

Sunlight photocatalyzed regioselective β-alkylation and acylation of cyclopentanones

Sunlight-induced direct regioselective β-alkylation of cyclopentanones with electron-deficient alkenes was accomplished by using tetrabutylammonium decatungstate (TBADT) as the catalyst. The regiochemistry can be rationalized by a polar transition state for an SH2 reaction. In the presence of CO, the reaction gave the three-component β-acylation product in good yield.

INITIATION OF TIN-MEDIATED RADICAL REACTIONS BY DIETHYLZINC-AIR

Abstract Diethylzinc-air system can serve as an initiator of tin hydride mediated radical reactions of organic halides.