Alkyne functionalization is a hot topic in organic synthesis since the products could be utilized in diverse transformations. The main themes of this thesis work are: (a) development of a new phosphine ligand for the copper(I)-catalyzed hydroboration of internal alkynes and its subsequent reactions; and (b) use of the gold(I)-catalyzed Meyer–Shuster rearrangement in the synthesis of the C19–C30 bis-tetrahydrofuran (bis-THF) fragment of iriomoteolide-13a. A brief introduction is given in Chapter 1, focusing on the most recent progress in the development and application of copper(I)-catalyzed hydroboration of internal alkynes and gold(I)-catalyzed Meyer–Schuster rearrangement of propargylic alcohols. It is followed by an illustration of the research topics to be explored in this t...[ Read more ]

Alkyne functionalization is a hot topic in organic synthesis since the products could be utilized in diverse transformations. The main themes of this thesis work are: (a) development of a new phosphine ligand for the copper(I)-catalyzed hydroboration of internal alkynes and its subsequent reactions; and (b) use of the gold(I)-catalyzed Meyer–Shuster rearrangement in the synthesis of the C19–C30 bis-tetrahydrofuran (bis-THF) fragment of iriomoteolide-13a. A brief introduction is given in Chapter 1, focusing on the most recent progress in the development and application of copper(I)-catalyzed hydroboration of internal alkynes and gold(I)-catalyzed Meyer–Schuster rearrangement of propargylic alcohols. It is followed by an illustration of the research topics to be explored in this thesis work.

Internal alkynes without a strong steric or electronic bias are the challenging substrates for the copper-catalyzed hydroboration. Presented in Chapter 2 are the results on extending our group's aromatic amide-derived phosphines (Aphos) to the copper-catalyzed hydroboration of unsymmetrical internal alkynes without strong electronic and steric biases. 2-(Diisopropylphosphino)-N,N-diisopropylbenzamide (Aphos^ip-H) is newly synthesized and used as the ligand in the copper-catalyzed hydroboration of internal alkynes using bis(pinocolato)diboron (B₂pin₂) with a broad substrate scope. The alkenyl boronate products are efficiently obtained with good regio- and stereoselectivity and high yields (up to 38 examples). The origin of the regioselectivity could be rationalized by a balanced steric interaction between the Aphos^ip-H-ligated copper catalyst and the alkyne substrates.

Conjugated polyene molecules are prone to isomerization upon exposure to light, high temperatures, and basic/acidic conditions. It poses a challenge in organic synthesis. Chapter 3 deals with a one-pot synthesis of 1,3-dienes and polyenes by combination of the above described copper-catalyzed hydroboration of internal alkynes with the palladium-catalyzed Suzuki–Miyaura cross-coupling using Aphos^ip-H as the common ligand. The alkenyl boronates, without purification, undergo coupling reactions with alkenyl halides at 35 °C in the presence of a weak base (K₃PO₄·3H₂O) to furnish 1,3-dienes and conjugated polyenes.

The palladium-catalyzed Suzuki–Miyaura cross-coupling of secondary alkyl boronates and related boron species is less common due to side reactions such as β-hydride elimination, protodeboration, and configuration erosion. Described in Chapter 4 are the results on the Pd–PhPCy₂-catalyzed Suzuki–Miyaura cross-coupling of aryl chlorides with racemic secondary potassium alkyltrifluoroboronates possessing a β-Weinreb-type amido moiety. The products are formed at 95 °C in CPME–H₂O mixed solvent system in moderate yields and can be transformed into aldehydes and ketones via conventional reactions.

Finally, the results on synthesis of the C19–C30 fragment of iriomoteolide-13a are compiled and discussed in Chapter 5. The macrolide is isolated from a benthic dinoflagellate Amphidinium sp. (strain KCA09053) and possesses the most complex molecular architecture among iriomoteolides with undefined absolute configuration. A stepwise double intramolecular S_N2 reaction strategy has been explored for the construction of the C19–C30 bis-THF fragment. In particular, the substrate compatibility for Sharpless asymmetric dihydroxylation (AD) of the densely functionalized C21–C22 double bond and the gold(I)-catalyzed Meyer–Schuster rearrangement of the C26–C28 propargylic alcohols has been examined. These results should have a good reference value for total synthesis of iriomoteolide-13a.

The main experimental procedures, the characterization data of major compounds, and the cited references are found at the end of the thesis. Copies of original ¹H and ¹³C NMR spectra of the key compounds are given in Appendix.