Synthesis and catalytic applications of derivatives of 7,7'-dihydroxy-8,8'-biquinolyl (azaBINOL) Public Deposited

http://ir.library.oregonstate.edu/concern/graduate_thesis_or_dissertations/00000222f

Descriptions

Attribute NameValues
Creator
Abstract or Summary
  • The synthesis of axially chiral polyfunctional derivatives of 8,8'-biquinolyl was explored and the catalytic action of appropriate derivative types investigated in three separate processes: (1) the silylcyanation of carbonyl groups and imines, (2) alkylation of a glycine Schiff-base via phase transfer-catalysis, and (3) direct amide bond formation from simple amines and carboxylic acids. 7,7'-Dihydroxy-8,8'-biquinolyl ('azaBINOL') was prepared from 2-chloroaniline by a four-step sequence comprised of: Skraup reaction (94% yield of 8-chloroquinoline), a zinc-mediated reductive coupling (69% yield of 8,8'-biquinolyl), a substrate directed double C-H functionalization via Pd(II)-mediated acetoxylation with iodobenzene diacetate (51% yield of 7,7'-diacetoxy-8,8'-biquinolyl), and saponification (>85% yield of 7,7'-dihydroxy-8,8'-biquinolyl). This second-generation approach to azaBINOL could be executed without recourse to chromatographic purification stages and, in the key Pd(II)-mediated step, a chiral atropos biaryl system emerges from an essentially achiral tropos biaryl system. In the first catalysis study, the addition of trimethylsilylcyanide (TMSCN) to aldehydes as catalyzed by 6,6'-bis(methylaminosulfonyl)-7,7'-dihydroxy-8,8'-biquinolyl (40) was further investigated and this process was extended to the silylcyanation of ketones and imines for the first time. It was established that, in the absence of additives, all non-trivial functional groups present in bissulfonamide 40 are essential for catalytic activity with the exception of free sulfonamide NH (i.e., a biquinolyl moiety, free phenolic hydroxyl groups, and sulfonyl groups at C6 and C6' are required but tertiary sulfonamides can replace the secondary sulfonamides without detriment). Competitive silylcyanation of benzaldehyde in the presence of para-substituted benzaldehydes as catalyzed by bissulfonamide 40 was conducted and a Hammett analysis performed. The kinetic data revealed a good linear free-energy relationship (R² = 0.928) and a modestly positive reaction constant (ρ = +1.52). The catalytic action of bissulfonamide 40 is proposed to arise from hydrogen-bonding and Brønsted acid effects that are dependent on its biaryl structure and vinylogous sulfamic acid character. TMSCN addition was generally achieved in good to high yield (to aldehydes: 42-92% yield; to ketones: 22-82% yield; to N-benzyl aldimines: 14-78%) but the modest enantioselectivity previously encountered for the silylcyanation of aldehydes as catalyzed by scalemic samples of bissulfonamide 40 and using aged TMSCN could not be reproduced with new batches of pure TMSCN. For the second catalysis study, diether derivatives of azaBINOL were prepared by the classical Williamson method and these configurationally stable materials N-alkylated with either methyl iodide or benzyl bromide to afford axially chiral biquinolinium cations. The cations were evaluated as chiral phase-transfer catalysts (PTCs) for the alkylation of the Schiff-base formed from glycine tert-butyl ester and benzophenone according to O'Donnell's protocol for α-amino acid synthesis (PTC, BnBr, aq. KOH, PhMe). The enolate of the glycine Schiff-base was successfully C-benzylated under these reaction conditions; however, the biquinolinium PTCs experienced base induced decomposition during the reaction and enantioselectivity was not observed. For the final study, (7'- butoxy-8,8'-biquinol-7-yl)boronic acid (56) was prepared from azaBINOL by a four-step sequence comprised of: monoetherification under Mitsunobu conditions (80% yield), trifylation of remaining OH group with triflic anhydride (85% yield), Miyaura borylation of the triflate with bispinacolato diboron catalyzed by Pd(0) (70% yield), and boronic ester hydrolysis (53% yield). Boronic acid 56 exhibited modest catalytic activity for the dehydrative coupling of unbranched primary amines and carboxylic acids in MeCN solvent in the presence of 4Å molecular sieves (21% yield of PhCONHBn) but was not sufficiently reactive to produce amides from α-branched primary amines.
Resource Type
Date Available
Date Copyright
Date Issued
Degree Level
Degree Name
Degree Field
Degree Grantor
Commencement Year
Advisor
Committee Member
Academic Affiliation
Non-Academic Affiliation
Keyword
Subject
Rights Statement
Peer Reviewed
Language
Replaces
Additional Information
  • description.provenance : Approved for entry into archive by Julie Kurtz(julie.kurtz@oregonstate.edu) on 2013-07-01T21:19:16Z (GMT) No. of bitstreams: 1 chaowang2013.pdf: 18340587 bytes, checksum: b5b7d9eb7e4df9e005e7a9f6cc677265 (MD5)
  • description.provenance : Made available in DSpace on 2013-07-18T16:36:03Z (GMT). No. of bitstreams: 1 chaowang2013.pdf: 18340587 bytes, checksum: b5b7d9eb7e4df9e005e7a9f6cc677265 (MD5) Previous issue date: 2013-06-20
  • description.provenance : Approved for entry into archive by Laura Wilson(laura.wilson@oregonstate.edu) on 2013-07-18T16:36:03Z (GMT) No. of bitstreams: 1 chaowang2013.pdf: 18340587 bytes, checksum: b5b7d9eb7e4df9e005e7a9f6cc677265 (MD5)
  • description.provenance : Submitted by Chao Wang (wangcha@onid.orst.edu) on 2013-06-29T00:08:41Z No. of bitstreams: 1 chaowang2013.pdf: 18340587 bytes, checksum: b5b7d9eb7e4df9e005e7a9f6cc677265 (MD5)

Relationships

In Administrative Set:
Last modified: 08/04/2017

Downloadable Content

Download PDF
Citations:

EndNote | Zotero | Mendeley

Items