Hyung Yoon

Additive Effects in the Palladium-Catalyzed Carboiodination of Chiral N-Allyl Carboxamides†

The use of Pd catalysis as a means to synthesize organic halides has recently received increased attention. Among the reported methods is the Pd-catalyzed carboiodination, which uses extremely bulky ligands to facilitate carbon-halogen reductive elimination from Pd(II) as the key catalytic step. When approaching substrates exhibiting low stereoselectivity, catalyst troubleshooting becomes difficult as there are few ligands known to promote the key reductive elimination. Herein, we present our finding that tertiary amines act as weakly coordinating ligands which significantly enhance diastereoselectivity in the Pd/QPhos-catalyzed carboiodination of chiral N-allyl carboxamides. This methodology allows efficient access to enantioenriched and densely functionalized dihydroisoquinolinones, and has been applied toward the asymmetric formal synthesis of (+)-corynoline.

Rh-Catalyzed Domino Addition–Enolate Arylation: Generation of 3-Substituted Oxindoles via a Rh(lll) Intermediate

A Rh-catalyzed domino conjugate addition-arylation sequence via a Rh(III) intermediate is reported. This process involving a proposed intramolecular oxidative addition of a rhodium enolate was utilized to achieve the synthesis of 3-substituted oxindole derivatives in moderate to excellent yields.

Diastereoselective Palladium-Catalyzed Arylcyanation/Heteroarylcyanation of Enantioenriched N-Allylcarboxamides

A diastereoselective Pd-catalyzed arylcyanation/heteroarylcyanation of chiral N-allylcarboxamides using Zn(CN)2 as the cyanide source is reported. Nitrile-containing dihydroisoquinolinone products are obtained in good to excellent yields with up to >95:5 dr and with full preseveration of enantioenrichment. By circumventing a difficult nucleophilic cyanation of a hindered neopentyl iodide, this approach represents an improvement to the previously reported formal synthesis of (+)-corynoline.

Palladium‐Catalyzed Spirocyclization through C−H Activation and Regioselective Alkyne Insertion

A Pd-catalyzed spirocyclization involving a sequential carbopalladation, intramolecular C-H activation, and a highly regioselective alkyne insertion to afford spirooxindoles and spirodihydrobenzofurans has been achieved. The spirocyclic products were generated in good to excellent yields with complete regiocontrol in a readily scalable procedure.

Carboiodination Catalyzed by Nickel

A novel nickel-catalyzed cycloisomerization reaction forming a new carbon-carbon bond while preserving the carbon-halogen bond has been developed. A cheap and readily available Ni-catalyst is employed to generate nitrogen containing heterocycles in good to excellent yields and the procedure is readily scalable. The more readily available aryl bromides were also cyclized with the addition of potassium iodide to generate the respective alkyl iodides. A rare dual ligand system employing a bisphosphine and bisphosphine monoxide was used to achieve enantioenriched products.

Enantioselective Rhodium-Catalyzed α-Allylation of Aldehydes

Significance: The α-functionalization of aldehydes via the formation of the corresponding enolates remains a challenge in modern synthetic chemistry. The high propensity for aldehydes to undergo competing side-reactions under basic conditions, in addition to the difficulties associated with the control of the enolate geometry in acyclic systems limit their application in stereoselective transformations. In the present work, Wright and Evans present a highly enantioselective rhodiumcatalyzed allylic alkylation of α-alkyl benzylic aldehydes. Comment: The reaction of α-alkyl benzylic aldehydes with allyl benzoate was catalyzed by a chiral rhodium-complex in the presence of LiHMDS as a base and DMPU as deaggregating reagent. The corresponding aldehydes, bearing a stereogenic quaternary center in the α-position, were obtained in moderate to good yields and enantioselectivities. The choice of the base and of the deaggregating agent was crucial for the stereochemical outcome of the reaction. Several derivatizations of the resulting products were carried out to illustrate the synthetic utility of these compounds. No examples of allylation of α,α-dialkyl aldehydes were reported. Selected examples: 15 examples 61–83% yield 77–94% ee CHO R2

Zinc-Catalyzed Asymmetric Mannich Reaction Forming β-Amino Ketones

Significance: The asymmetric formation of allcarbon quaternary stereocenters in an efficient and atom economical manner has been of interest for decades. Trost and co-workers are able to display a highly asymmetric Mannich reaction forming β-amino ketones bearing a quaternary carbon stereocenter, utilizing the Zn-ProPhenol catalytic system previously prepared in the group. Comment: The zinc-catalyzed Mannich reaction forming β-amino ketones proceeded in excellent yield, diastereoand enantioselctivity. The reaction tolerated a wide range of functional groups including heteroaromatics, seven-membered rings, and sterically encumbered imines. The two-point binding of the Boc-imine to the catalyst, as seen in the proposed transition state, explains the stereochemical outcome of the reaction. Selected examples: OH N N Ph HO Ph Ph OH Ph

Rhodium-Catalyzed Asymmetric Arylation of Diarylmethylamines

Significance: Triarylmethanes are an important class of compounds that are useful in medicinal chemistry and materials science. Reports on their asymmetric synthesis include cross-coupling (B. L. H. Taylor et al. Angew. Chem. Int. Ed. 2013, 51, 7790), selective oxidation (B. F. Shi et al. Angew. Chem. Int. Ed. 2008, 47, 4882) and Friedel– Crafts reaction (M.-H. Zhuo et al. Org. Lett. 2014, 16, 1096). The authors report a rhodium-catalyzed 1,4-addition strategy of an o-quinone methide generated in situ for the synthesis of chiral triarylmethanes. Comment: A variety of triarylmethanes were generated using this strategy. Substitution of all three aryl groups were tolerated well, giving good to excellent enantioselectivities. One limitation was noted: the enantioselectivity was reduced for substrates with ortho-substitution on Ar1. The final products could also be deoxygenated through triflation followed by palladium-catalyzed hydrogenolysis. Selected examples: Ar1 N OH