University of Illinois Urbana-Champaign

New frontiers in allylic C––H amination via palladium/sulfoxideoxazoline catalysis

Ma, Rulin

Content Files
MA-DISSERTATION-2019.pdf

MA-DISSERTATION-2019.pdf

Download File Copy Link To File
Format
Portable Document Format
Media Type
application/pdf
Size
6.28 MB
API Resource
/items/112316/bitstreams/367674
Bundle
Content
Primary
YES
Downloads
69

Permalink

https://hdl.handle.net/2142/105195

Description

Title
New frontiers in allylic C––H amination via palladium/sulfoxideoxazoline catalysis
Author(s)
Ma, Rulin
Issue Date
2019-04-15
Director of Research (if dissertation) or Advisor (if thesis)
White, Maria Christina
Doctoral Committee Chair(s)
White, Maria Christina
Committee Member(s)
  • Burke, Martin D.
  • Hergenrother, Paul J.
  • Sarlah, David
Department of Study
Chemistry
Discipline
Chemistry
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Date of Ingest
2019-08-23T20:47:24Z
Keyword(s)
  • ALLYLIC C––H AMINATION
  • PALLADIUM/SULFOXIDE-OXAZOLINE CATALYSIS
  • anti-1,3 amino alcohol
  • syn- 1,3-amino alcohol
  • Vitamin D3 analogue
  • chiral diamino alcohol
  • quinone oxidant
  • (±)-MeO-SOX
  • (±)-CF3-SOX
  • 2,5-dimethylbenzoquinone
  • 1,4 benzoquinone
Abstract
Direct allylic C––H functionalization of terminal olefin represents an orthogonal approach to traditional methods to build C––O, C––N and C—C bond due to less oxidation state manipulation and synthetic overhead. In particular, site, chemo- and stereoselective methods for Pd(II)-catalyzed allylic C––H amination exists. However, all these reactions proceed via near ligandless conditions (e.g. reversibly coordinating sulfoxide ligands) and require benzoquinone oxidant to coordinate to Pd metal to promote the functionalization step (known as “serial ligand catalysis). This mechanism with sulfoxide ligands renders catalyst deactivation and the ability to tune the functionalization step limited. This work describes the development of racemic sulfoxide-oxazoline (SOX) ligands for Pd(II) catalyzed allylic C––H amination. By combining sulfoxide moiety, known for promoting heterolytic allylic C—H cleavage and oxazoline moiety, a stronger coordinating element that can keep the ligand associating with the Pd metal, we create a highly modular, oxidative stable ligand platform that is capable to support both Pd(II) and Pd(0) processes in allylic C––H amination. The first chapter of this dissertation describes the development of a general strategy for C––H to C––N coupling of sulfonamides with olefins via Pd(II)/ (±)-MeO-SOX catalysis. Due to the ubiquity of C—N bonds in natural products and pharmaceuticals, the cross-coupling of amines with hydrocarbons under fragment coupling conditions (1 equivalent) stands to significantly impacted chemical synthesis. Herein, we disclose a C(sp3)—N fragment coupling reaction between abundant terminal olefins and N-triflyl protected aliphatic and aromatic amines via Pd(II)/(±)-MeO-SOX catalyzed intermolecular allylic C––H amination. A range of (56) allylic amines are furnished in good yields (avg. 76%) and excellent regio- and stereoselectivity (avg. >20:1 linear:branched, >20:1 E:Z). For the first time, a variety of singly activated aromatic and aliphatic nitrogen nucleophiles, including ones with stereochemical elements, can be used in fragment coupling stoichiometries for intermolecular C––H amination reactions. Mechanistic studies reveal that the SOX ligand framework is effective in promoting functionalization by supporting cationic -allyl Pd intermediates. The second chapter of this dissertation describes the development of a Pd(II)/(±)-MeO-SOX/2,5-dimethylbenzoquinone condition for intramolecular C––H amination that enables unprecedented access to anti-1,3 amino alcohols in good yields (33 substrates, avg. 66%) and high selectivities (avg. 10:1 dr). Switching ligand to (±)-CF3-SOX using a less bulky quinone oxidant (BQ), the kinetic syn- 1,3 amino alcohol motif can be accessed in comparable yields and selectivities. Advantages of stereodivergent nature of this allylic C––H amination method are showcased in the synthesis of anti- and syn- 1,3-amino alcohol Vitamin D3 analogue intermediates in half the steps and higher overall yield of previous route. Moreover, all eight possible stereoisomers of a medicinally important chiral diamino alcohol core are generated from two chiral pool amino acids. Mechanistic studies revealed that the anti-oxazinanone is furnished through C—H amination that furnishes the syn-isomer followed by Pd(0)-isomerization process promoted by the electron rich (±)-MeO-SOX ligand and a bulky quinone oxidant.
Graduation Semester
2019-05
Type of Resource
text
Permalink
http://hdl.handle.net/2142/105195
Copyright and License Information
Copyright 2019 Rulin Ma

Owning Collections

Graduate Dissertations and Theses at Illinois PRIMARY
Graduate Theses and Dissertations at Illinois
Dissertations and Theses - Chemistry