David W. C. MacMillan (1968-)

 List 用Proline Catalyzed Asymmetric Intramolecular a-Alkylation of Aldehydes 第一次报道醛的a位直接的催化量的不对称烷基化，很漂亮！但是缺点也是也显著的，那就是，这个方法，仅仅能关三元环和五元环而已，并没有太大的用处。对于这样的问题，MacMillan 会考虑什么样的途径去解决呢？ 

    认识到the difficult and slow ionic alkylation step (a two-electron process)的不可克服的麻烦性，MacMillan 很聪明地利用the rapid steps based on less stable open-shell molecules involving one-electron pathways ，把低活性的RX 转化成高活性的R自由基，便成功排除了各种各样的副反应。可是，我们知道，自由基是一种活性非常高的活性中间体，催化量的不对称的选择性通常认为是不可获得的，凡是可以取得催化量的不对称自由基反应，通常都是SN。不过这个问题，对于MacMillan来说，这就不是什么问题了，因为他的前一篇Science:Enantioselective Organocatalysis Using SOMO Activation 已经成功解决了这个问题。他们组自己开发的imidazolidinone catalyst 可以有效地提供手性诱导的环境。 

    到这里，对于MacMillan来说，已经是万事俱备了，只欠个有效的可以把RX还原成R自由基的单电子还原剂而已。MacMillan have investigated ruthenium bipyridine complexes, which are well-established photoredox catalysts. Ru(bpy)3+  has been shown to be a potent reductant [–1.33 V versus saturated calomel electrode (SCE) in CH3CN]，可以很高效的还原RX (E1/2 for phenacyl bromide = –0.49 V versus SCE in CH3CN, where E1/2 is the half reduction potential)，从而转化成Ru(bpy)3 2+。而在光照下，tris(bipyridine)ruthenium(II), Ru(bpy)3 2+ , forms a more reactive species, *Ru(bpy))3 2+ ，an excited state in which an electron on the metal transfers to the bpy ligand, where it has enhanced oxidative and reducing power relative to the ground state。(T. D. Beeson, A. Mastracchio, J.-B. Hong, K. Ashton, D. W. C. MacMillan, Science 316, 582 (2007)) 

     “Nicewicz and MacMillan elegantly combined this photoredox process with organo-SOMO catalysis so that the desired transformation can occur in the correct sequence to generate enolate radicals by a reductive process, and, after coupling with the chiral enamine, oxidize the reaction product.”在这个精美的双活化体系中，the organocatalytic cycle 大家都很熟悉了，醛和手性二级胺缩合然后形成富电的Enamine 8；而Ru(bpy)3+把RX 4 还原生成缺电子的Radical 5, 同时转化成Ru(bpy)3 2+，在光照下，进而转化成*Ru(bpy))3 2+ ；This coupling event would concomitantly produce an electron-rich a-amino radical 9, a single-electron species that has a low barrier to oxidation (–0.92 to–1.12 V versus SCE in CH3CN)，其被*Ru(bpy))3 2+ 氧化，失去一个电子转化成Inminium 10 然后水解从而完成了the organocatalytic cycle ；同时*Ru(bpy))3 2+得到一个电子被还原成Ru(bpy)3+，也完成了the photoredox cycle。真是美妙绝伦！ 

    之前的《Enantioselective Organocatalysis Using SOMO Activation 》是两个富电子enamine 和 双键 的coupling, 首先需要一当量的单电子氧化剂如CAN 把enamine氧化成缺电子的Radical 然后和双键反应，生成Inminium而被水解完成有机催化循环，而同时双键部分生成新的Radical中心，必须有另一个当量的单电子氧化剂使其脱去一个阳离子而得到新的双键，从而最终完成coupling。由于这个过程中需要两当量的单电子氧化剂，使其大scale的反应变得困难，是其最大的缺点。 而本篇文章里面，由于是富电子的醛（enamine）和缺电子的RX进行反应，一正一反，正好般配，利用 Ru(bpy)3+/   *Ru(bpy))3 2+ 的photoredox, 所以并不需要额外的单电子氧化剂或者还原剂。值得一提的是，该反应的设计图虽然极为精巧，但实验操作却是极为简单，甚至在家用15-W fluorescent light 的活化下，无需任何加热或者冷却的操作，室温下加入20% 手性胺催化剂和0.5% photoredox catalyst，便可取得高产率和高选择性，底物适用性广泛。 


David W.C. MacMillan 
is the A. Barton Hepburn Professor of Organic Chemistry in the Department of Chemistry at Princeton University. 

Biography 
Professor MacMillan was born in Bellshill, Scotland in 1968. He received his undergraduate degree in chemistry at the University of Glasgow, where he worked with Dr. Ernie Colvin. 

     In 1990, he left the UK to begin his doctoral studies under the direction of Professor Larry Overman at the University of California, Irvine. During this time, he focused on the development of new reaction methodology directed toward the stereocontrolled formation of bicyclic tetrahydrofurans. Dave's graduate studies culminated in the total synthesis of 7-(-)-deacetoxyalcyonin acetate, a eunicellin deterpenoid isolated from soft coral Eunicella Stricta. 


    David moved to a postdoctoral position with Professor David Evans at Harvard University in 1996, where his studies centered on enantioselective catalysis, in particular, the design and development of Sn(II)-derived bisoxazoline complexes (Sn(II)box). These Sn(II)box complexes have found extensive utility in a broad range of asymmetric transformations including the first enantioselective catalytic anti-aldol process. 

    David began his independent research career as a member of the chemistry faculty at the University of California, Berkeley in July 1998. He joined the department of chemistry at Caltech in June 2000, where his group's research interests centered around new approaches to design, enantioselective catalysis and natural product synthesis. In 2004, he was appointed as the Earle C. Anthony Professor of Chemistry. Most recently, he accepted a position at Princeton University and joined the faculty in September 2006 as the A. Barton Hepburn Professor of Organic Chemistry. 

Notable contributions 
     Professor MacMillan's Research Group has made significant developments in the field of asymmetric, organocatalysis in addition to focusing on the quick and efficient development of complex molecular structures. 


Magnus.Rueping@rwth-aachen.de 

   Magnus Rueping studied at the Technical University of Berlin, Trinity College Dublin and ETH Zürich, where he completed his diploma thesis under the direction of Professor Dieter Seebach. He stayed in the Seebach group and obtained his Ph.D. from the ETH in 2002 working on the synthesis, the structural and the biological aspects of oligo(hydroxybutanoates) and of β- and γ-peptides. Magnus then moved to Harvard University to work with Professor David Evans on enantioselective transition-metal catalysis. 

   In August 2004, he was appointed the Degussa Endowed Assistant Professor of Organic Chemistry at Johann wolfgang Goethe University of Frankfurt. His group's current research interests include enantioselective organocatalysis and metal catalysis, new reaction methodology, natural product synthesis, chiral metal-coordination polymers, as well as peptide and protein chemistry.