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...[
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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*RuCl
2]
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]PF
6
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]PF
6 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 H
2 pressure. Some carefully designed control experiments on the
mechanism revealed that the formation of the gem-H
2 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]PF
6 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.
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