Vol. 8, No. 2 Asymmetric Catalysis Privileged Ligands and Complexes Features include: BINAP/SEGPHOS® Ligands and Complexes Solvias® Ligand Portfolio BINAP, a powerful ligand for for Enantioselective asymmetric catalysis Hydrogenation DuPhos and BPE Phospholane Ligands and Complexes CFVol8No2FINAL.indd 1 5/15/2008 10:45:06 AM Introduction Vol. 8 No. 2 The quest for novel, efficient chiral transition metal catalysts has been an ongoing endeavor for the past 40 years. Leading this quest is the need from Aldrich Chemical Co., Inc. the pharmaceutical, flavors and fragrances, and agrochemical industries for Sigma-Aldrich Corporation enantiopure molecules. Nearly 85% of new drugs in the market are chiral. 6000 N. Teutonia Ave. This need has led to developments in asymmetric synthesis of chiral ligands Milwaukee, WI 53209, USA and metal complexes. In 2001, the Nobel Prize rewarded the pioneering work of Knowles, Noyori, and Sharpless in the development of catalytic asymmetric synthesis, highlighting the importance of chiral synthesis in chemistry. The pioneering work of Noyori in the 1980s with BINAP ligands began an era To Place Orders where catalysts and ligands became more effective and selective. Telephone 800-325-3010 (USA) Highly effective asymmetric catalytic systems give access to arrays of chiral William Sommer FAX 800-325-5052 (USA) Introduction building blocks used in the synthesis of natural products and drugs. Among Product Manager the plethora of chiral ligands, a few stand out because of their versatility. The Customer & Technical Services common feature of these “privileged” ligands is their C2 symmetry, reducing the number of possible isomeric metal complexes and the number of different Customer Inquiries 800-325-3010 substrates. Among the most recognized family of chiral ligands, BINAP, salens, Technical Service 800-231-8327 bisoxazolines, tartrate ligands, and cinchona alkaloids represent the original SAFC™ 800-244-1173 “privileged ligands” classes that affect a wide variety of transformations under outstanding enantiocontrol and with high yield. A second wave of privileged Custom Synthesis 800-244-1173 ligands has surfaced with the DuPhos phospholanes, DSM phosphoramidites, Flavors & Fragrances 800-227-4563 Solvias Josiphos families, the Reetz and Trost ligands, and ChiralQuest International 414-438-3850 phosphines. These outstanding ligand families have proven their success 24-Hour Emergency 414-438-3850 in industrially useful reactions such as hydrogenations, aldol reactions, and Web Site sigma-aldrich.com asymmetric allylic alkylations, and gained much attention from the synthetic Daniel Weibel Email [email protected] community due to the ready accessibility and modular nature of their design. Product Manager For each of the privileged ligands, representative examples are presented. ® At Sigma-Aldrich , we are committed to providing unprecedented accessibility to chiral, Subscriptions state-of-the-art “privileged ligands” used in a wide variety of C–H, C–C, C–N, and C–O bond-forming transformations. For a complete listing of products related to privileged ligands, please visit To request your FREE subscription to ChemFiles, sigma-aldrich.com/privileged. If you cannot find a product for your research efforts in organic please contact us by: synthesis or drug discovery, we welcome your input. “Please Bother Us.” with your suggestions at Phone: 800-325-3010 (USA) [email protected] or [email protected], or contact your local Sigma-Aldrich office. Mail: Attn: Marketing Communications Table of Contents Aldrich Chemical Co., Inc. Sigma-Aldrich Corporation BINAP/SEGPHOS® Ligands and Complexes ................................................................................ 3 P.O. Box 355 ® Solvias Ligand Portfolio for Enantioselective Hydrogenation .................................................. 14 Milwaukee, WI 53201-9358 DuPhos and BPE Phospholane Ligands and Complexes ........................................................... 34 Email: [email protected] catASium®—Essential Elements for Asymmetric Hydrogenations ............................................. 40 P-Phos, PhanePhos and BoPhoz™ Ligands ............................................................................... 44 ChiralQuest Phosphine Ligands and Complexes ...................................................................... 47 International customers, please contact your local Sigma-Aldrich offi ce. For worldwide contact DSM MonoPhos™ Family ......................................................................................................... 51 information, please see back cover. Reetz Ligands ......................................................................................................................... 54 BINOL and Derivatives ............................................................................................................. 56 ChemFiles are also available in PDF format on the Internet at sigma-aldrich.com/chemfi les. TADDOL .................................................................................................................................. 62 BOX ........................................................................................................................................ 64 Aldrich brand products are sold through Sigma- PYBOX .................................................................................................................................... 67 Aldrich, Inc. Sigma-Aldrich, Inc. warrants that its PHOX ...................................................................................................................................... 69 products conform to the information contained Salen Ligands .......................................................................................................................... 71 in this and other Sigma-Aldrich publications. Cinchona Alkaloids ................................................................................................................. 74 Purchaser must determine the suitability of the QuinoxP* Ligands ................................................................................................................... 79 product for its particular use. See reverse side of invoice or packing slip for additional terms and DIPAMP .................................................................................................................................. 81 conditions of sale. DIOP ....................................................................................................................................... 81 Trost Ligands ........................................................................................................................... 82 All prices are subject to change without notice. Landis Ligands ........................................................................................................................ 84 ChemFiles (ISSN 1933–9658) is a publication of Aminophosphine Ligands ........................................................................................................ 87 Aldrich Chemical Co., Inc. Aldrich is a member of the Trademarks ............................................................................................................................. 88 Sigma-Aldrich Group. © 2008 Sigma-Aldrich Co. Risk & Safety ........................................................................................................................... 90 About Our Cover The cover graphic represents the three-dimensional structure of BINAP. The phosphorus atoms are represented in blue. This chiral ligand proved to be one of the most popular, for a variety of asymmetric transformations. 2 CFVol8No2FINAL.indd 2 5/15/2008 10:45:10 AM CF8.2 Extract 4 ed XML 032508 PGD UNP ed0423 BINAP/SEGPHOS® Ligands and Complexes Since the development of BINAP by Noyori 20 years ago, extensive Ruthenium-Catalyzed Asymmetric Hydrogenation research has been accomplished using this chiral ligand. BINAP proved to be one of the most versatile ligands, catalyzing a wide range of reactions, of Amino Ketones and Complexes BINAP/SEGPHOS from hydrogenations to Heck cyclizations.1 Ohkuma et al. reported a practical asymmetric hydrogenation reaction using mild hydrogen pressure with a wide scope.5 The access to chiral The research team at Takasago International Corporation developed a alcohols from amino ketones is important for the synthesis of series of ligands and complexes for a plethora of catalyzed asymmetric reactions. Based on a biphenyl architecture, several phosphine ligands physiologically active compounds. In this new process, a diphosphine/ diamine Ru catalyst is utilized. This complex is based on DM-BINAP and have been synthesized. Two large families of ligands can be 1,1‑di-4‑anisyl-2‑isopropyl-1,2‑ethylenediamine (DAIPEN) and a distinguished, BINAP and SEGPHOS (Figure 1). BINAP is based on a ruthenium complex. Using a loading as low as 0.01 mol% of catalyst, the bisnaphthalene backbone with different phosphine derivatives. hydrogenation of various amino ketones was conducted with up to SEGPHOS is based on a bis(1,3‑benzodioxole) backbone with different 99% yield and up to 99.8% ee ( ). To illustrate the relevance of phosphine substituents. BINAP and SEGPHOS are highly reactive and Scheme 4 this new catalyst, Okuma et al. synthesized a series of known molecules selective in a variety of asymmetric hydrogenations. In conjunction with ® used in drug synthesis. ruthenium, rhodium, palladium and