Graduate Thesis Or Dissertation
 

Development of Methods for Stereoselective Carbon-Carbon Bond Formation

Public Deposited

Downloadable Content

Download PDF
https://ir.library.oregonstate.edu/concern/graduate_thesis_or_dissertations/7s75dg45j

Descriptions

Attribute NameValues
Creator
Abstract
  • Three distinct methods to achieve the stereoselective synthesis of carbon-carbon bonds were investigated, encompassing: (i) the formation of axially chiral biaryl molecules by enantioselective Suzuki cross-coupling, (ii) the synthesis of α-phenylalkylboronic esters by enantioselective chain extension, and (iii) the stereospecific synthesis of alkenes by eliminative cross-coupling of enantioenriched sp³-hybridized carbenoids. In the first part, 7,7’-dihydroxy-8,8’-biquinolyl was converted to 7’-butoxy-7-(diphenylphosphino)- 8,8’-biquinoyl in four-steps via Mitsunobu monoetherification, trifylation, phosphination, and phosphine-oxide reduction (63% overall yield). Enantiomerically pure phosphine obtained by preparative chiral stationary phase HPLC was combined with Pd₂dba₃ and investigated for the synthesis of axially chiral biaryl compounds (Ar-Ar’) from aryl bromides (ArBr) and aryl boronic acids [Ar’B(OH)₂] in the presence of K₃PO₄ in PhMe solvent (6 examples, 4-97% yield, 4-74% ee). The analogous carbocyclic ligand 2-(diphenylphosphino)-2’-methoxy-1,1’-binaphthyl (MOP) was studied for comparative purposes and found to be effective for the synthesis of hindered 2,2’-disubstituted 1,1’-binaphthyls (78-83% yield, 20-38% ee). In the second part, chain extension of boronic esters by the action of configurationally labile racemic lithium carbenoids in the presence of scalemic bisoxazoline ligands was explored for the enantioselective synthesis of α-phenylalkylboronic esters via the newly introduced principle of stereoinductive reagent-controlled homologation. Enantioenriched 2° carbinols generated by oxidative work-up (NaOOH) of initial α-phenylalkylboronate products were obtained in 35-73% yield and 70-96% ee by reaction of B-alkyl and B-aryl neopentyl glycol boronates with a combination of O-(α-lithiobenzyl)-N,N-diisopropylcarbamate and ligand 3,3-bis[(4S)-4,5-dihydro-4-isopropyloxazol-2-yl)pentane in toluene solvent (–78 °C to rt) with MgBr₂•OEt₂ additive. In the third part, enantioenriched lithiated carbamates [CArR²Li(O₂CNiPr₂)] were combined with enantioenriched α-carbamoyloxyboronates [CHR³[B(OR)₂](O₂CNiPr₂)] to achieve alkene synthesis by a cross-coupling process involving a sequence of three stereospecific fundamental steps: (i) electrophilic substitution, (ii) 1,2-metallate rearrangement, and (iii) β-elimination. By this sequence, stereochemical information encoded within the two carbenoid building blocks is translated into any desired configuration of the targeted alkene [(E)- or (Z)-isomer] as determined by choice of carbenoid stereochemical pairing, either like [i.e., (R) + (R) or (S) + (S)] or unlike [i.e., (R) + (S)], and elimination mechanism type (syn or anti). Herein, the eliminative cross-coupling concept was established for the synthesis of (E)- and (Z)-isomers of a variety of 1-aryl-1,2-dialkylethenes [10 examples of (E)-isomers, 11-70% yield, E:Z 90:10 to >98:2; 10 examples of (Z)-isomers, 19-70% yield, Z:E 67:33 to >98:2]. For example, a like combination of (S)-α-[(diisopropylamino)carbonyloxy]-1-lithio-1-phenylethane (97% ee) and N,N-diisopropyl O-[(S)-3-phenyl-1-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)]prop-1-yl carbamate (97% ee) in diethyl ether-toluene at –78 °C led to (Z)-2,5-diphenylpent-2-ene in 70% yield and E:Z = 5:95 after warming to 80 °C. By contrast, the analogous unlike eliminative cross-coupling reaction (i.e., (R)-lithiated carbamate with (S)-boryl carbamate) gave (E)-2,5-diphenylpent-2-ene in 70% yield and E:Z > 98:2.
License
Resource Type
Date Available
Date Issued
Degree Level
Degree Name
Degree Field
Degree Grantor
Commencement Year
Advisor
Committee Member
Academic Affiliation
Non-Academic Affiliation
Subject
Rights Statement
Publisher
Peer Reviewed
Language
Replaces

Relationships

Parents:

This work has no parents.

In Collection:

Items

Thumbnail Title Date Uploaded Visibility Actions
file details WuZhenhua2016.pdf 2017-08-16 Public Download