Lewis Acid-Promoted Diastereoselective Cross-Coupling of Boronic Acids and Aryl-Substituted 1,2-Diols
- 주제(키워드) diol , boronic acid , lewis acid , cross coupling , 9-norneolignan
- 주제(DDC) 615.1
- 발행기관 아주대학교
- 지도교수 이동주
- 발행년도 2021
- 학위수여년월 2021. 8
- 학위명 박사
- 학과 및 전공 일반대학원 약학과
- 실제URI http://www.dcollection.net/handler/ajou/000000031249
- 본문언어 영어
- 저작권 아주대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
A Lewis acid-promoted highly diastereoselective C(sp3)–C(sp2) cross-coupling reaction of aryl-substituted 1,2-diols and a variety of styryl, aryl, heteroaryl and polyaryl boronic acids as nucleophiles has been developed in a one-pot process under mild reaction conditions. The regioselective opening of aryl-substituted cyclic boronic esters promoted by a Brønsted or Lewis acid and subsequent intramolecular 1,4-transfer of the carbon ligand from boron atom to the same face of the resulting resonance-stabilized planar benzylic carbenium ion in a stereospecific fashion led to highly diastereoselective C–C bond formation at the benzylic carbon center. The synthetic value of this method has been demonstrated by a unified enantioselective total synthesis of 9-norneolignan natural products (–)-agatharesinol, (–)-agatharesinol acetonide, (–)-sugiresinol and (+)-hinokiresinol in 6 to 8 steps from the commercially available methyl 3-(4-hydroxyphenyl)acrylate.
more목차
Chapter 1 : Diastereoselective Carbon–Carbon Bond Formation at the -Chiral Benzylic Carbon Center 1
1.1. Introduction and Background 2
1.2. Literature Precedents for Diastereoselective Carbon–Carbon Bond Formation at the -Chiral Benzylic Carbon Center 3
1.2.1. Diastereoselective Friedel-Crafts Arylation of -Chiral Benzylic Carbenium Ions Promoted by Lewis or Protic Acid 3
1.2.2. Stereoselective and Regioselective Reaction of Cyclic Ortho Esters with Phenols 5
1.2.3. Metal-Free Opening of Epoxides with RBF3K Promoted by TFAA 5
1.2.4. Transition Metal-Free Stereocomplementary Cross-Coupling Reaction of Arl-Substituted 1,2-Diols with Trifluoroborates and Boronic Acids 6
1.3. Referemces 8
Chapter 2 : Lewis Acid-Promoted Diastereoselective Cross-Coupling of Boronic Acids and Aryl-Substituted 1,2-Diols 9
2.1. Substituted Phenethyl Alcohols from Aryl-Substituted Cyclic Boronic Esters Promoted by an Acid 10
2.2. Nucleophilic substitution reaction in aromatic substituted secondary alcohol using boronic acid 11
2.2.1. Optimization of the Reaction Conditions 11
2.2.2 Confirmation of the Configuration at the Newly Generated Benzylic Stereocenter 13
2.2.3 One-Pot and Gram-Scale Approach 15
2.2.4 Scope and Limitations of Substrates 16
2.2.5 Stereoconvergent Reaction of Diastereomeric 1,2-Diols and Proposed Reaction Mechanism 19
2.3 Nucleophilic substitution reaction in aromatic substituted tertiary alcohol using boronic acid 22
2.3.1 Optimization of the Reaction Conditions 22
2.3.2 Scope and Limitations of Substrates 23
2.3.3 Stereoconvergent Reaction of Diastereomeric 1,2-Diols and Proposed Reaction Mechanism 29
2.3.4 Confirmation of Diastereoselectivity through NOE 2D NMR 32
2.4. Experimental section 34
2.5 Reference 102
Appendix 103
Chapter 3 : Enantioselective Total Synthesis of 9-Norneolignan Natural Products (–)-Agatharesinol, (–)-Agatharesionol Acetonide, (–)-Sugiresinol and (+)-Hinokiresinol 190
3.1. Introduction and Background 191
3.2. Retrosynthetic Analysis for a Unified Enantioselective Total Synthesis of 9-Norneolignan Natural Products 194
3.3. Preparation of the Common Synthetic Precursor 196
3.4. Enantioselective First Total Syntheses of (–)-Agatharesinol, (–)-Agatharesinol Acetonide and (–)-Sugiresinol 196
3.5. Enantioselective Total Syntheses of ent-(+)-Hinokiresinol 199
3.6. Experimental Section 200
3.7. References 214
Appendix 216
