國科會化學中心－綠色/永續化學網路資源共享網
http://gc.chem.sinica.edu.tw/		 Synthesis
 
引言  

在合成化學(chemical synthesis)中，碳-碳鍵的形成反應一直是有機合成化學最重要的課題。20世紀是有機化學蓬勃發展的黃金歲月，許多新反應的開發不但造就了無數精彩絕倫的天然物全合成，同時也對製藥工業的發展有莫大的貢獻。隨著taxol, brevetoxins, epothilones, eleutherobin等等複雜天然物全合成的完成，在20世紀結束前，有機化學家們已經可以自信的說:只要有充足的人力、經費和時間，似乎已經沒有任何已知結構之天然物是人類所無法合成征服的。因此，在新世紀開始之際，合成化學的重要課題除了需要尋找更有效率、更有選擇性的化學反應之外，還要知道如何運用更環保的方式來合成這些化合物。這些項目包括如何減少反應的時間和所需的能源(例如微波催化和光化學反應等)，如何減少溶劑的使用(例如離子液體和supercritical media等)，如何減少反應物和試劑的浪費(例如atom economy的觀念)，如何更有效率並且能多樣性的合成化合物以避免在製備過程的資源浪費(例如combinatiorial synthesis)，以及如何使用更有效率和環保的催化劑 (例如biocatalysis 和organocatalysis)。其中所謂的biocatalysis除了單一步驟的enzymatic reaction之外，也著眼在如何利用基因工程的技術，修飾之後再利用在multi-step合成天然物或類似物的工程上。即利用導向演化（directed evolution）原理和生物技術來產生更多樣化的化合物。換言之，學習自然界天然物生物合成與演化的方式，利用人為的遺傳基因與蛋白質工程來加速其生合成途徑（biosynthetic pathways）的進行，創造出更多樣性的天然與非天然有機分子的類似物。這類型的「組合式生物合成（combinatorial biosynthesis）」也是新型藥物開發另一種嶄新的途徑。此外，organocatalysis (biomimetic catalyst)雖然是一個很早就發現的課題，但是之後因為許多無機和金屬試劑的快速發展，這個領域在過去數十年來一直未能受到有機化學家的重視。不過，近年來這個情況已迴然不同。因為organocatalysis除了可以進行一些無機試劑所無法完成的反應之外，另外一個重要因素就是綠色化學。例如Grubbs catalyst 雖然可以進行很有效率的metathesis反應，但是許多製藥公司就曾經三令五申要求所屬開發部門在開發製程時避免使用該試劑。因為後續去除產物所含之微量Ru的工作相當繁雜。很難降低後續產物中Ru的含量至符合FDA的要求，或者需要更高的純化和廢棄物處理成本。Organocatalyst是有機化合物，許多甚至是無害並且degradable的天然物，因此幾乎沒有污染的問題。上述這些項目都是有機合成化學目前和未來幾年所重視的課題。

 
 
實例

M. Mauksch, S. B. Tsogoeva, I. M. Martynova, S.-W. Wei. Evidence of Asymmetric Autocatalysis in Organocatalytic  Reactions. — Angew. Chem. Int. Ed. 2007, 46, 393; Angew. Chem. 2007, 119, 397

For the New Plant-cell Fermentation Method in the Synthesis of Paclitaxel by Bristol-Myers Squibb, see: Chemical and Chemical Engineering News, Volume 82, Number 28, July 12, 2004 pp. 25-30

Two-step Synthesis of Carbohydrates by Selective Aldol Reactions —  Alan B. Northrup and David W. C. MacMillan, SCIENCE, 17 SEPTEMBER 2004 VOL 305, 1752-1755.
   
書籍

RSC Green Chemistry Series —Series Editors: Clark, James, Kraus, George. Organic Synthesis using Green Chemistry Methods New(2008.08.18)
Methods and Reagents for Green Chemistry: An Introduction — Wiley 出版社2007年最新出版書刊
Enantioselective Organocatalysis: Reactions and Experimental Procedures (Hardcover) —
by Peter I. Dalko (Editor), Publisher: Wiley-VCH (23 Feb 2007), ISBN-10: 3527315225, ISBN-13: 978-3527315222
Solvent-free Organic Synthesis (Green Chemistry) by Koichi Tanaka —  This book offers graphical summaries and detail reaction procedures of 537 examples of solvent-free organic reactions and is important book for either research or teaching green organic synthesis.
Green Reaction Media in Organic Synthesis Edited by: Koichi Mikami — This book provides an overview on the organic reaction using three most commonly used green reaction media, ionic liquids, fluorous solvents, and supercritical CO2.
Greener Approaches to Undergraduate Chemistry Experiments —  Fourteen greener experiments are designed for undergraduate laboratory.The experiments covers general organic syntheses, catalyses, microwave assisted syntheses as well as a construction of solar cell devices.

Asymmetric Organocatalysis: From Biomimetic Concepts to Applications in Asymmetric Synthesis —  Albrecht Berkessel, Harald Groger, ISBN: 3-527-30517-3, 454 pages , March 2005

Green Organic Chemistry - Strategies, Tools, and Laboratory Experiments —  by Kenneth Doxsee - James Hutchison

Microwaves in Organic Synthesis — by Andre Loupy (Editor) Hardcover, November 2002

Solvent-free Organic Synthesis — by Koichi Tanaka Hardcover, March 2003

Organic Synthesis Engineering (Hardcover) — by L. K. Doraiswamy

New Trends in Green Chemistry (Hardcover) — by V.K. Ahluwalia, M. Kidwai
   
Review Articles
Organocatalysis Lost: Modern Chemistry, Ancient Chemistry, and an Unseen Biosynthetic Apparatus — Barbas, C. F. III, Angew. Chem. Int. Ed. 2008, 47, 42. New(2008.08.18)

Asymmetric Organocatalysis: From Infancy to Adolescence — Alessandro Dondoni, A.; Alessandro Massi, A. Angew. Chem. Int. Ed. 2008, 47, 4638. New(2008.08.18)
Chemical Reviews - Organocatalysis Benjamin List, Ggest Editor — List, B. Ed. thematic issues (12), Chem. Rev. 2007, 107, 5413-5884. New(2008.08.18)
Organocatalytic Synthesis of Bioactive Natural Products — de Figueiredo, R. M.; Christmann, M. Eur. J. Org. Chem. 2007, 2575. New(2008.08.18)
Catalytic Asymmetric Carbon-Carbon Bond Formations: Their Evolution from Biocatalysis to Organocatalysis over the Millennium — Ikunaka, M. Org. Pro. Res. Develop. 2007, 11, 495. New(2008.08.18)
Asymmetric Organocatalytic Domino Reactions — Enders, D.; Grondal, C.; Httl, M. R. M. Angew. Chem. Int. Ed. 2007, 46, 1570. New(2008.08.18)
Tandem and Domino Catalytic Strategies for Enantioselective Synthesis — Chapman, C. J.; Frost,C. G. Synthesis 2007, 1. New(2008.08.18)
The Crystallization Behavior of Proline and Its Role in Asymmetric Organocatalysis — Christmann, M.; Braese, S. Ed. Asymmetric Synthesis: The Essentials; Wiley-VCH; Weinheim, Germany, 2007. (i) Kellogg, R. M. Angew. Chem. Int. Ed. 2007, 46, 494. New(2008.08.18)

Enantioselective organocatalysis — Matthew J. Gaunt, Carin C.C. Johansson, Andy McNally and Ngoc T. Vo Drug Discovery Today _ Volume 12, Numbers 1/2 _ January 2007, 8-27.

Green Electrochemistry. Examples and Challenges —  This is a short assay published in Pure and Applied Chemistry. In this article the green electrochemical method has been used for the synthesis of organic compounds.This is an example to demonstrate that electrochemical is another green method for the synthesis of organic compounds.
Publications with a Green Chemistry Theme —  A list of 1999-2004 papers with green chemistry theme update(2008.9.8)
Green Solvents for Sustainable Organic Synthesis: State of the Art —  A critical article published in Green Chemistry
Solventless Syntheses of Mesotetraphenylporphyrin: New Experiments for a Greener Organic Chemistry Laboratory Curriculum — A rare green porphyrin synthesis article which might be important if the scale can be larger and the column chromatography can be omitted
The Evolution of a Green Chemistry Laboratory Experiment: Greener Brominations of Stilbene —  Two new greener alkene bromination reactions that offer enhanced laboratory safety and convey important green chemistry concepts are described
Green Solvents for Sustainable Organic Synthesis: State of the Art — Sheldon, R. A. Pure Appl. Chem.2000, 72, 1233–1246. Atom efficiency and catalysis in organic synthesis
Special Issues: Asymmetric Organocatalysis, Accounts of Chemical Research — June 2004 Volume 37, Issue 8Guest Editors: K. N. Houk; Benjamin List

Special Issues: Bioorganic Chemistry and Organocatalysis —  Synfacts, Issue 05/2006
Asymmetric Organocatalysis —  Jayasree Seayad and Benjamin List, Org. Biomol. Chem., 2005, 3, (5), 719-724.
Enamine-Based Organocatalysis with Proline and Diamines: The Development of Direct Catalytic Asymmetric Aldol, Mannich, Michael, and Diels-Alder Reactions — Notz, Wolfgang; Tanaka, Fujie; Barbas, Carlos F., III, Accounts of Chemical Research (2004), 37(8), 580-591.
   
Hot Articles
Enantioselective Organocatalytic Direct Aldol Reactions of alpha-Oxyaldehydes: Step One in a Two-step Synthesis of Carbohydrates — Alan B. Northrup, Ian K. Mangion, Frank Hettche, and David W. C. MacMillan, Angew. Chem. Int. Ed. 2004, 43, 2152 –2154 update(2008.9.8)
Two-Step Synthesis of Carbohydrates by Selective Aldol Reactions —  Alan B. Northrup and David W. C. MacMillan, SCIENCE, 17 SEPTEMBER 2004 VOL 305, 1752-1755. update(2008.9.8)
Enantioselective Organocatalytic Cyclopropanations. The Identification of a New Class of Iminium Catalyst Based upon Directed Electrostatic Activation —  Roxanne K. Kunz and David W. C. MacMillan, J. AM. CHEM. SOC. 2005, 127, 3240-3241
A Dash of Proline Makes Things Sweet —  Science 17 September 2004:Vol. 305. no. 5691, pp. 1725 – 1726.
In the Golden Age of Organocatalysis —  Dalko, PI;Moisan, L, ANGEW CHEM INT ED, 2004, 43, 5138-5175
   
演講之powerpoint檔案/Summer School之資料

Green Chemistry & Catalysis for Sustainable Organic Synthesis — Roger A. Sheldon. DelftUniversity of Technology. RASheldon Lecture given at University Pierre et Marie Curie,. Paris, May 12, 2004

New Proline Derivatives as Catalysts for Asymmetric Organic Synthesis —  Deborah A. Longbottom. Steven V. Ley. University of Cambridge
Top Green Chemistry Challenges for the Pharmaceutical Industry — ACS Green Chemistry Institute之下，GCI Pharmaceutical Roundtable
討論出之合成上之綠色挑戰，值得推薦。
   
Awards
Announcement: OBC Lecture Award Winner 2007 in Organocatalysis

2005 Alternative Synthetic Pathways Award

   
Conferences
Gordon Research Conference on Green Chemistry — Aug 3-8, 2008 New(2008.08.18)
“International Symposium on Catalysis and Fine Chemicals 2007” at Nanyang Technological University from 17 to 21 December 2007.
New Horizons in Catalysis: The Art of Catalysis in Process Chemistry — 12 - 13 April 2007, Barcelona, Spain
  more...
 
Scholarship/Summer School

Young Chemists' Workshop On Organocatalysis — 2006 Sweden