DEDICATED TO DR. ALFRED BADER ON THE OCCASION OF HIS 85TH BIRTHDAY VOL. 42, NO. 1 • 2009 The Super Silyl Group in Diastereoselective Aldol and Cascade Reactions Iterative Cross-Coupling with MIDA Boronates: towards a General Strategy for Small-Molecule Synthesis Editorial “Please Call Me Alfred” On April 28 of this year, Dr. Alfred Bader, undeniably the world’s Centre of Queen’s University best-known Chemist Collector, celebrated his 85th birthday. Alfred’s in Kingston, Ontario (Canada). amazing life story has been covered extensively in books, magazines, This gift is one of several and lectures, by Alfred himself and by others, and need not be sizeable ones that he has repeated here. Furthermore, most of our readers are undoubtedly made to Queen’s in gratitude aware of Alfred’s strong connections, past and present, not only for the education he received to Sigma-Aldrich, but also to the Aldrichimica Acta, which he has there in the 1940s. showered with his attention for many years. Many of Alfred’s Lesser known, but not paintings have graced the covers of the Acta, including this issue, less important to Alfred, is his which is featuring one of Alfred’s favorite paintings. Bible scholarship, particularly We honor and thank Alfred for his outstanding contributions of Old Testament themes, to Sigma-Aldrich and to the worlds of chemistry, business, and art. which he has studied all his To what he calls the “ABC” (Art, Bible, Chemistry) of his life, one life and taught for a good Photo Courtesy of Alfred Bader should add a “D” for Donating. Alfred’s philanthropic activities are many years. Another lesser Dr. Alfred Bader in 2005 considerable and ongoing, and cover a wide range of causes that known trait of Alfred is his are near and dear to Alfred’s heart. modesty and unassuming The magnitude of Alfred’s philanthropic efforts was made lifestyle, which used to lead many a new employee of Aldrich, possible by the considerable financial rewards that he has reaped in the days when Alfred was company president, to think, when from two of his lifelong passions. The first is a spectacularly successful running into him for the first time, that he was just another chemical business (Aldrich and Sigma-Aldrich) that he helped found employee. After meeting Alfred for the first time and calling and successfully managed for years. The second is his passion for him Dr. Bader, the editor of this publication was gently chided collecting art works, particularly of Dutch and Flemish Masters, for calling him Dr. Bader, rather than Alfred, which is what he as well as rare stamps. His collection of about two hundred such insists on being called even by people who don’t know him paintings has been donated by Alfred to the Agnes Etherington Art that well. On behalf of all Sigma-Aldrich employees, past and present, we wish Alfred a very happy 85th birthday and many more in years to come. SAFC® Launches New Vendor Audit Services On March 19, 2009, SAFC® announced details of its new Vendor Standard audits available include: Audit Services, designed to extend audit reach for customers that • ISO 9001:2008 (previously ISO 9001:2000) need to secure global supply chain integrity through enhanced • ISO 13485:2003 traceability and quality confirmation for critical raw materials and • 21 CFR 211 key intermediates. SAFC’s Vendor Audit Services are an extension • 21 CFR 820 of in-house auditing programs, and provide pharmaceutical and • ICH Q7A biotechnology firms with a team of highly trained auditors that • GAMP 5 have extensive regulatory compliance expertise and are on the • GLP ground in local regions, including China. • 21CFR58 SAFC can also perform audits to customer specifications upon request. SAFC’s Typical Audit Services Timeline 1–6 weeks depending 1–5 Days 1 Week 3–4 Weeks on vendor availability Contact SAFC On-site audit Preliminary report Final Report for vendor audit performed submitted to customer delivered to customer Please contact us at safcglobal.com/auditservices for more information. 1 “PLEASE BOTHER US.” VOL. 42, NO. 1 • 2009 Joe Porwoll, President Aldrich Chemical Co., Inc. Aldrich Chemical Co., Inc. Sigma-Aldrich Corporation 6000 N. Teutonia Ave. Milwaukee, WI 53209, USA Professor Stephen Buchwald of the Massachusetts Institute of Technology kindly suggested that we make the single-component palladacycle precatalysts of SPhos and XPhos. These complexes simplify the use of these Buchwald ligands in a pre-defined metal-to-ligand ratio. To Place Orders The precatalysts are air- and moisture-stable, and can achieve high yields in C–N cross-coupling reactions using catalyst loadings as low as 0.1 mol % and 10-minute reaction times. Telephone 800-325-3010 (USA) FAX 800-325-5052 (USA) NH2 or 414-438-2199 Pd NH2 Cl Mail P.O. Box 2060 Pd O Cl PCy2 t-Bu CH3 O i-Pr i-Pr Milwaukee, WI 53201, USA PCy2 t-Bu CH3 MeO OMe Customer & Technical Services i-Pr Customer Inquiries 800-325-3010 704946 704954 Technical Service 800-231-8327 Biscoe, M. R. et al. J. Am. Chem. Soc. 2008, 130, 6686. SAFC® 800-244-1173 704946 SPhos-palladium(II)phenethylamine chloride (1:1 MTBE solvate) Custom Synthesis 800-244-1173 250 mg Flavors & Fragrances 800-227-4563 1 g International 414-438-3850 704954 XPhos-palladium(II)phenethylamine chloride (1:1 MTBE solvate) 24-Hour Emergency 414-438-3850 250 mg Web Site sigma-aldrich.com 1 g Email [email protected] Naturally, we made these useful catalyst precursors. It was no bother at all, just a pleasure to be able to help. General Correspondence Editor: Sharbil J. Firsan, Ph.D. Do you have a compound that you wish Aldrich could list, and that would help you in your P.O. Box 355, Milwaukee, WI 53201, USA research by saving you time and money? If so, please send us your suggestion; we will be delighted to give it careful consideration. You can contact us in any one of the ways shown on Subscriptions this page and on the back cover. To request your FREE subscription to the Aldrichimica Acta, please contact us by: TABLE OF CONTENTS Phone: 800-325-3010 (USA) The Super Silyl Group in Diastereoselective Aldol and Cascade Reactions ................................................3 Matthew B. Boxer, Brian J. Albert, and Hisashi Yamamoto,* University of Chicago Mail: Attn: Mailroom Aldrich Chemical Co., Inc. Iterative Cross-Coupling with MIDA Boronates: towards a General Strategy for Sigma-Aldrich Corporation Small-Molecule Synthesis ...................................................................................................................................................................................................17 Eric P. Gillis and Martin D. Burke,* University of Illinois at Urbana-Champaign P.O. Box 2988 Milwaukee, WI 53201-2988 ABOUT OUR COVER Email: [email protected] Two Squirrels (oil on panel, International customers, please contact your local 33.0 3 40.6 cm) was painted around Sigma-Aldrich office. For worldwide contact infor- 1616 and is attributed to the Flemish mation, please see the back cover. painter Jan Brueghel (or Bruegel) the Elder (1568–1625), also known The Aldrichimica Acta is also available on the as ˝Velvet” Brueghel and ˝Flower” Internet at sigma-aldrich.com/acta. Brueghel. He was the second son of Pieter Brueghel the Elder and trained Aldrich brand products are sold through Sigma- with his older brother, Pieter Brueghel Aldrich, Inc. Sigma-Aldrich, Inc., warrants that its the Younger, in the family workshop in products conform to the information contained in Antwerp. this and other Sigma-Aldrich publications. Purchaser The painting, which reflects the must determine the suitability of the product for its painter’s focus later on in life on painting particular use. See reverse side of invoice or packing flowers and animals, depicts two Detail from Two Squirrels. Photograph © Alfred Bader slip for additional terms and conditions of sale. sprightly squirrels clutching a gnarly, twisting branch set against an empty sky. This simple, engaging, and humorous depiction of a pair of lively small animals parallels the practice, at that time, of hanging portraits of husband and wife. Its high level of finish suggests that it probably was executed on commission or for sale in the market. The luminous effect created by the thin pigment Aldrichimica Acta (ISSN 0002–5100) is a publication layers and the fine detail are reminiscent of the style of the Brueghel family. of Aldrich. Aldrich is a member of the Sigma-Aldrich Group. © 2009 Sigma-Aldrich Co. This painting is part of the Bader Collection of Dutch and Flemish Paintings at the Agnes Etherington Art Centre of Queen’s University, Kingston, ON, Canada. VOL. 42, NO. 1 • 2009 New Products from Aldrich R&D Aldrich is Pleased to Offer Cutting-Edge Tools for Organic Synthesis Double-Allylation Reagents Copper(I) Fluoride Complex for Aldol Reaction Reagents bearing multifunctional handles are of interest for the preparation Chiral tertiary alcohols are important building blocks for the synthesis of of complex molecules. Professor Hall and coworkers developed a new more complex molecules such as biologically active compounds or potential multifunctional reagent that provides high diastereo- and enantiocontrol in drugs. Shibasaki and coworkers developed a new copper fluoride catalyzed a number of reactions, such as in the nucleophilic addition to aldehydes. aldol reaction of ketones using ketene silyl acetals. Various aromatic ketones were screened and led to the desired aldol products in good yields and high selectivity. O 1) LiCHCl2, THF, -100 °C B O H 2) TMSCH2MgBr, PPh3 -100 to -78 °C F Cu PPh 691615 3 PPh3 706000 RCHO OH O 1. (2.5 mol%) B R SiMe Taniaphos® (4 mol%) O H BF3 –OEt2 (1 equiv) 3 (EtO)3SiF (200 mol%) CH2Cl2, -78 °C O OTMS OH O PhBF3K (10 mol%), DME (4M) SiMe3 63 - 85% yield 1 * 1 2 + R * OCH 79 - 98% ee R R OCH3 R2 3 2.