Alkynes are one of the most important building blocks in organic synthesis and serve as synthons for a wide range of chemical transformations. Among them, in particular, hetero-substituted alkynes, which are polarized molecules due to their electronic nature, can be employed in reactions that require high levels of regio- and stereoselectivity. The development of transformations of this interesting type of alkynes has gained significant progress in the past few decades. However, owing to their importance in organic synthesis, new synthetic applications and reaction modes remain in high demand.

In this thesis, a series of interesting transformations of hetero-substituted alkynes are described, including [3+2] cycloaddition of electron-rich alkynes, geminal hydrogenation and hydroboration...[ Read more ]

Alkynes are one of the most important building blocks in organic synthesis and serve as synthons for a wide range of chemical transformations. Among them, in particular, hetero-substituted alkynes, which are polarized molecules due to their electronic nature, can be employed in reactions that require high levels of regio- and stereoselectivity. The development of transformations of this interesting type of alkynes has gained significant progress in the past few decades. However, owing to their importance in organic synthesis, new synthetic applications and reaction modes remain in high demand.

In this thesis, a series of interesting transformations of hetero-substituted alkynes are described, including [3+2] cycloaddition of electron-rich alkynes, geminal hydrogenation and hydroboration of silyl alkynes, and hydroboration and hydrosilylation of ynones. These results are discussed in detail in the following chapters.

In chapter 1, a highly efficient and regioselective ruthenium-catalyzed AAC of internal seleno-alkynes is described. With the proper choice of the [Cp*RuCl₂]_n catalyst, a wide range of seleno-alkynes smoothly reacted with various azides, especially those carbohydrate and amino acid derivatives, to afford fully-substituted 5-seleno-1,2,3-triazoles in high efficiency. The successful reaction under air atmosphere in water and the efficient cleavage of C−Se bond in the seleno-substituted triazoles both represented promising applications for bioorthogonal reactions.

In chapter 2, a catalytic regiodivergent [3+2] cycloaddition of nitrile oxides with alkynes is described. The innate reactivity of nitrile oxides typically utilizes the oxygen as the nucleophilic motif and the carbon as the electrophilic center. However, the use of ruthenium catalyst could override the inherent polarity of nitrile oxides and completely reverse the regioselectivity. With the proper choice of the cationic [CpRu(MeCN)₃]PF₆ catalyst, a diverse range of internal thioalkynes or ynol ethers participated smoothly in the mild intermolecular cycloaddition reactions to provide the 3,4,5-trisubstituted isoxazoles bearing a 4-sufenyl or 4-alkoxyl group with moderate to excellent efficiency respectively. In addition to electron-rich alkynes, complete switch of regioselectivity was also observed for electron-deficient alkynes.

In chapter 3, a geminal semi-hydrogenation of 1-silyl alkynes featuring silyl migration is described, which provides new access to the useful terminal vinylsilanes. This process also presents a new mode of reactivity of silyl alkynes. With the proper choice of the cationic [CpRu(MeCN)₃]PF₆ catalyst and a suitable silyl group, both aryl- and alkyl-substituted silyl alkynes can participate in this highly efficient gem-selective process. Furthermore, dedicated condition optimization also allowed switching of selectivity from gem to trans by using different conditions, including the suitable silyl group, additive and H₂ pressure. Some carefully designed control experiments on the mechanism revealed that the formation of the gem-H₂ Ru-carbene might be the key intermediate in both gem- and trans-addition reactions, rather than the Ru-vinylidene intermediate.

In chapter 4, an unusual 1,1-hydroboration for 1-silyl alkynes is described. It is the first demonstration of gem-(H,B) addition to an alkyne triple bond. With the superior [CpRu(MeCN)₃]PF₆ catalyst, a range of silyl alkynes and HBpin reacted efficiently under mild conditions to form various synthetically useful silyl vinyl boronates with exclusive stereoselectivity and good functional group compatibility. An extension to germanyl alkynes as well as the hydrosilylation of alkynyl boronates toward the same type products was also achieved. Mechanistically, this process features a new pathway featuring gem- (H,B) addition to form the unprecedented key intermediate α-boryl-α-silyl Ru-carbene followed by silyl migration. Control experiments and DFT calculations provided important insights into the mechanism, which excluded the involvement of metal vinylidene intermediate. This study represents a new step forward not only for alkyne hydroboration, but also for other geminal alkyne additions.

In Chapter 5, a highly stereoselective Ru-catalyzed formation of vinylogous enolates through ynone hydroboration and hydrosilylation is introduced. Conventional methods for the synthesis of vinylogous enolates suffer from poor chemo- or stereocontrol. Herein, with the proper choice of Ru-catalysts, a range of γ-silyl ynones were smoothly transformed into the corresponding vinylogous enolates with high regio- and stereoselectivity and moderate to high efficiency. Mechanistically, an unconventional formal 1,3-addition mode was proposed for hydroboration, and a β-regioselective syn-addition followed with 1,5-silyl migration is responsible to the formation of silyl vinylogous enolates. This study not only provides a new synthetic tool for the highly chemo- and stereoselective formation of vinylogous enolates, but also opens up a new synthetic avenue for ynone hydrometallation.