Sang Young Yun

Alkane C–H Insertion by Aryne Intermediates with a Silver Catalyst

Arynes generated directly from alkyne building blocks in the presence of silver catalysts effectively activate primary, secondary, and tertiary alkane C-H bonds. This C-H insertion requires only a catalytic amount of silver complex and modest heating compared to harsh conditions and extra promoters including directing groups, oxidants, and bases in typical transition-metal-based C-H bond functionalizations. Preliminary mechanistic studies suggest that the C-H bond-breaking and new bond-forming events take place in a concerted manner, rendering a formal 1,2-addition of C-H bond across the π-bond of arynes.

Alder-Ene Reactions of Arynes

Efficient Alder-ene reactions of various arynes generated directly from bis-1,3-diynes are described. The reactivity of ene donors with different tethers was examined under thermal and metal-catalyzed conditions, which indicates that both the formation of aryne intermediates and their ene reactions are less sensitive to the catalyst than to the structural features of the substrates.

Stereoelectronic Effect for the Selectivity in C-H Insertion of Alkylidene Carbenes and Its Application to the Synthesis of Platensimycin

A systematic study of C-H insertion reactions with variously substituted and conformationally constrained substrates was carried out. High selectivity in the insertion between two competing C-H bonds caused by a strong stereoelectronic effect of an oxygen substituent was achieved. This regioselective C-H insertion reaction was employed as a platform to develop a concise asymmetric synthesis of platensimycin.

Regioselectivity in the nucleophile trapping of arynes: the electronic and steric effects of nucleophiles and substituents.

The regioselectivity in nucleophile trapping is investigated with arynes generated directly from bis-1,3-diynes. The regioselectivity is profoundly influenced by not only the nature of nucleophiles but also the substituents on the arynes, which is the consequence of both the unfavorable steric interaction between the incoming nucleophile and the nearby substituent and the inherent electronic bias induced by different substituents on the arynes.

Total Synthesis of (−)‐Dactylolide

The development of an approach leading to the total synthesis of dactylolide is described. The key features of this route include a catalytic asymmetric allylation, a diastereoselective pyran annulation, and a Horner−Wadsworth−Emmons macrocyclization.

Hydroarylation of arynes catalyzed by silver for biaryl synthesis

A new biaryl synthesis via silver-catalyzed hydroarylation of arynes from acyclic building blocks with unactivated arenes in intra- and intermolecular manners has been developed. The previously observed Diels-Alder reactions of arynes with arene were not observed under the current silver-catalyzed conditions. Deuterium scrambling and DFT calculations suggest a stepwise electrophilic aromatic substitution mechanism through the formation of a Wheland-type intermediate followed by a water-catalyzed proton transfer in the final step of the hydroarylation.

Structure and Reactivity of Alkynyl Ruthenium Alkylidenes

The isolation and structural characterization of alkynyl Ru-alkylidene species has been elusive owing to their rapid metallotropic shift and fast turnover. The enyne ring-closing metathesis and relay metathesis provides the platform to form a variety of alkynyl Ru-alkylidene species possessing a sterically and electronically different substituent on the carbenic carbon, which allowed their regio-controlled trapping and structural characterization.

Selectivity control in alkylidene carbene-mediated C-H insertion and allene formation.

Regioselectivity of alkylidene carbene-mediated C-H insertion was explored utilizing electronic, conformational, steric, and stereoelectronic effects. Relying on these factors, highly regio- and chemoselective carbene insertion reaction of C-H bonds in different environments could be obtained. The observed selectivity clearly indicates that an electronic effect plays a more important role than steric effect. In general, C-H bonds in conformationally rigid cyclic environments are less reactive than those in acyclic systems toward carbene insertion, and in this situation, a competing intermolecular reaction between alkylidene carbene and trimethylsilyldiazomethane led to the formation of allenylsilanes. The formation of allenylsilane becomes more favorable as the concentration of reaction becomes higher, as well as the C-H bonds undergoing insertion becomes electronically and conformationally deactivated.

Initiation and Termination Mode of Enyne Cross-Metathesis and Metallotropic [1,3]-Shift Controlled by Remote Substituents

The cross-metathesis of terminal alkyne and alkene using Ru-based Grubbs catalyst generally undergoes alpha-insertion. In this study, excellent control over alpha- and beta-insertion of ruthenium alkylidene into terminal alkynes has been achieved by using a substituent at a remote site from the reaction center. While the origin of this regioselectivity of insertion and metallotropic shift remains to be established, the trend indicates that the alpha-insertion with a concomitant metallotropic shift is favored with small substituents whereas the beta-insertion without a metallotropic shift is favored with bulky substituents such as tert-butyl and trialkyl silyl groups.

Structure and reactivity of alkyne-chelated ruthenium alkylidene complexes.

The isolation and structural characterization of alkyne-bound Ru alkylidene complexes has been elusive. However, a sequential enyne ring-closing metathesis of a diyne moiety and metallotropic [1,3]-shift followed by a second enyne ring-closing metathesis allowed the formation of a highly stable alkyne-chelated ruthenium complex. The full characterization of this complex was realized by NMR spectroscopy and X-ray crystallography.