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2006 VOLUME 6 NUMBER 10 Asymmetric Synthesis QUINOXP* LIGANDS CARREIRA DOLEFIN LIGANDS VAULTED BIARYL LIGANDS AND BINOL DERIVATIVES OXAZOLIDINETHIONE AND THIAZOLIDINETHIONE AUXILIARIES GLEASON CHIRAL AUXILIARY SHI EPOXIDATION DIKETAL CATALYST SHVO’S CATALYST (7R,10S)-(+)-1-Aza-10-isopropyl-8-oxa-4-thiabicyclo(5,3,0)-2-decanone chiral lactam auxiliary capable of forming chiral quaternary centers sigma-aldrich.com Introduction Vol. 6 No. 10 Asymmetric synthesis remains a challenge to synthetic chemists as the demand for enantiomerically pure compounds continues to increase. Many scientists working in Aldrich Chemical Co., Inc. chemical synthesis and drug discovery are striving to find new methods for asymmetric Sigma-Aldrich Corporation synthesis that would lead to the development of new and exciting chiral auxiliaries. In 6000 N. Teutonia Ave. addition, asymmetric catalysis is exploding, as new methods for obtaining enantiomerically Milwaukee, WI 53209, USA pure compounds has fueled a rapidly growing field in chemical synthesis. This edition of ChemFiles describes the applications of new chiral ligands and auxiliaries for use in asymmetric synthesis. Sigma-Aldrich is proud to carry over 5,000 chiral products To Place Orders for the successful construction of complex asymmetric architectures. In most cases, the Telephone 800-325-3010 (USA) cutting-edge methodologies illustrated herein exhibit exceptional levels of stereoselectivity. FAX 800-325-5052 (USA) Introduction For a complete listing of products related to asymmetric synthesis, please visit us at sigma-aldrich.com/asymmetric. Customer & Technical Services At Sigma-Aldrich™, we are committed to being your preferred supplier for all of your research needs. If you are unable to find a product for your research in asymmetric Customer Inquiries 800-325-3010 synthesis, we welcome your input. “Please Bother Us” with your suggestions and contact Technical Service 800-231-8327 your local Sigma-Aldrich office. SAFC™ 800-244-1173 Custom Synthesis 800-244-1173 Flavors & Fragrances 800-227-4563 International 414-438-3850 Coming Soon! 24-Hour Emergency 414-438-3850 Web Site sigma-aldrich.com The NEW 2007–2008 Email [email protected] Aldrich Handbook of Fine Chemicals ...featuring over 35,000 listings including 2,000 new products. Subscriptions To request your FREE subscription to ChemFiles, please contact us by: Phone: 800-325-3010 (USA) Order your FREE copy today! Mail: Attn: Marketing Communications (Shipping January 2007) Aldrich Chemical Co., Inc. Sigma-Aldrich Corporation 35,000 Chemical Listings P.O. Box 355 Milwaukee, WI 53201-9358 10,000 Structures Email: [email protected] 2,000 NEW Products 6,100 Citations International customers, please contact your 3,000 Application Notes local Sigma-Aldrich office. For worldwide contact Enhanced Application information, please see back cover. Index ChemFiles are also available in PDF format on the Advanced Product Tables Internet at sigma-aldrich.com/chemfiles. Aldrich brand products are sold through Sigma- Aldrich, Inc. Sigma-Aldrich, Inc. warrants that its products conform to the information contained in this and other Sigma-Aldrich publications. Purchaser must determine the suitability of the Call 1-800-325-3010 (USA) to reserve your copy or visit product for its particular use. See reverse side of sigma-aldrich.com/handbook16 today! invoice or packing slip for additional terms and conditions of sale. All prices are subject to change without notice. About Our Cover ChemFiles is a publication of Aldrich Chemical The cover graphic depicts the structure of the Gleason Chiral Auxiliary, (7R,10S)-(+)-1-aza- Co., Inc. Aldrich is a member of the Sigma-Aldrich 10-isopropyl-8-oxa-4-thiabicyclo[5.3.0]-2-decanone. This chiral lactam auxiliary has been Group. © 2006 Sigma-Aldrich Co. successfully employed in the stereocontrolled synthesis of all carbon quaternary centers. The unique methodology developed by Gleason allows for the creation of either antipode of the product using a single isomer of the auxiliary. sigma-aldrich.com 3 QuinoxP* Ligands t-Bu Me Various optically active phosphine ligands incorporating a chiral N P center at phosphorus display exceptional enantiosectivities in QuinoxP* 1 metal-catalyzed asymmetric synthesis. For instance, known N P classes of P-chiral phosphine ligands offer good to excellent NHAc NHAc 2 Me t-Bu 2 2 1 R * R enantiocontrol in Ru- and Rh-catalyzed hydrogenation reactions. R R1 [Rh(nbd)2]BF4 (1 mol %) The one limitation associated with these ligands is their sensitivity R3 R3 H2 (3 atm), MeOH, 6 h to air, which has impeded widespread applicability in bench-top chemistry. Imamoto and co-workers have addressed this deficiency Scheme 1 QuinoxP* Ligands through the development of QuinoxP*, which is based on an 3 electron-withdrawing quinoxaline architecture. Entry R1 R2 R3 ee (%) (config) Sigma-Aldrich is pleased to offer both enantiomers of QuinoxP* a 1 CO2Me Ph H 99.9 (R) for the research market.† The reactivity profile of these innovative, chiral ligands is covered below and highlights the impressive 2 CO2Me 4-AcO-3-MeOC6H3 H 99.6 (R) breadth of valuable transformations mediated by QuinoxP*. These 3 Me H CO2Me 99.7 (R) powerfully efficient ligands exhibit high levels of enantiocontrol 4 Me CO Me H 99.2 (R) in synthetic transformations ranging from metal-catalyzed 2 asymmetric 1,4-additions of arylboronic acids to enantioselective 5 Ph H H 99.9 (R) 3 alkylative ring opening to asymmetric hydrogenations. It is 6 1-adamantyl H H 96.3 (S) worth noting that QuinoxP* is not oxidized at the stereogenic a The reaction was completed within 1 h. phosphorus center on standing at ambient temperature in air for more than 9 months. Table 1 Imamoto has also gone to great lengths to develop t-Bu Me enantiomerically pure P-chiral ligands for industrially useful N P transformations such as asymmetric hydrogenation. Impressively, 3 mol % a diverse array of prochiral amino acid and amine substrates were N P hydrogenated with great efficiency to yield highly enantiopure Me t-Bu amine derivatives (Scheme 1). These experiments were carried [RhCl(C2H4)2]2 (3 mol %) O Ph O out at room temperature in methanol under low pressures of PhB(OH)2, KOH, dioxane/H2O, 1 h hydrogen (3 atm). All hydrogenation reactions were complete 97%, 99% ee in 6 hours and with enantiomeric excesses ranging from 96 to 99.9%. Dramatic stereochemical reversal, consistent with the Scheme 2 results observed with the related (S,S)-tert-Bu-BisP* ligands,4,5 was obtained when 1-acetylamino-1-adamantylethene was t-Bu Me hydrogenated to afford the S-configuration amine with >96% N P enantioselectivity (Table 1). 5 mol % O Imamoto and co-workers have also exploited the high activity N P OH rder: 1.800.325.3010 R1 1 2 Me t-Bu R R of the QuinoxP* ligand in rhodium-catalyzed enantioselective O 2 1 PdCl (cod) (5 mol %), R Zn, CH Cl , rt 1,4-additions of arylboronic acids to a,b-unsaturated carbonyl R 2 2 2 2 R1 substrates.3 High yields of the addition products were obtained by running the reactions between 40 and 50 ºC (Scheme ). The exceptional enantiocontrol exerted by this Rh(I)-catalyzed system is Scheme 3 evident in the robust performance when compared to the use of BINAP as the chiral ligand.6 Entry R1 R2 Time (h) Yield (%)a ee (%) (config) Additionally, Imamoto and co-workers have succeeded in developing a Pd-catalyzed C–C bond-forming reaction, which 1 H Me 2 90 95.6 (1S,2S) displays high enantioselectivities with both dimethyl- and 2 H Et 15 88 97.6 (1S,2S) diethylzinc (Scheme 3, Table ). This alkylative ring-opening 3 F Me 2 90 93.8 (1S,2S) methodology benefits from simply premixing PdCl2(cod) and QuinoxP* for 2 hours at room temperature, leading to a highly a Isolated yield. T e c h n i c a l active catalyst. This catalyst system affords excellent yields of Table 2 the ring-opened products and selectivities that rival the highest reported for this transformation. These results, when combined with the outstanding methodologies presented above, indicate that QuinoxP* is broadly useful for a variety of asymmetric 3 metal-catalyzed transformations. S ervice: 1.800.231.8327 (R,R)-,3-Bis(tert-butylmethylphosphino)quinoxaline 8 (S,S)-,3-Bis(tert-butylmethylphosphino)quinoxaline 8 C18H28N2P2 C18H28N2P2 t-Bu t-Bu FW: 334.38 Me FW: 334.38 Me N P N P N P N P Me t-Bu t-Bu Me 676403-100MG 100 mg 676411-100MG 100 mg 676403-500MG 500 mg 676411-500MG 500 mg Ready to scale up? For competitive quotes on larger quantities or custom synthesis, contact SAFC™ at 1-800-44-1173 (USA), or visit www.safcglobal.com. 4 m-Dichlorotetraethylene dirhodium(I) 8 Dichloro(1,5-cyclooctadiene)palladium(II) C8H16Cl2Rh2 C8H12Cl2Pd CH2 H2C Cl Cl FW: 388.93 H2C CH2 FW: 285.51 Rh Rh Pd [12081-16-2] H2C Cl CH2 [12107-56-1] Cl CH2 H2C 275891-250MG 250 mg 656763-100MG 100 mg 275891-1G 1 g 656763-1G 1 g Carreira DOLEFIN Ligands H CO For the past years, the Carreira group has been employing 3 CH3 chiral [2.2.2]bicyclooctadienes derived from (R)- or (S)-carvone in Ir(I)-catalyzed kinetic resolution of allylic carbonates7 and Rh(I)-catalyzed conjugate addition reactions of boronic acids.8 H3C More recently, Carreira has developed the ligand 1 (Figure 1), 1 which exhibited substantially improved enantioselectivity in the Figure 1 1,4-addition of arylboronic acids to a,b-unsaturated carbonyls.9 This new ligand facilitates selective preparations of diarylmethine stereogenic centers, even when there is little differentiation 2 1.5 mol % X between the two aryl groups. Heretofore, the stereoselective [Rh(C2H4)2Cl2]2 O 3.3 mol % 1 synthesis of this motif had been a challenge, with rather limited B(OH) 2 0.5 eq KOH O methods for its preparation.10 Ot-Bu + 2 MeOH/H O (10:1) Ot-Bu X1 X 2 50 °C In one report, tert-butyl cinnamate was converted to (S)-tert-butyl X1 3-(4-methoxyphenyl)-3-phenylpropanoate in the presence of the X1 = H, X2 = OMe 85%, 93% ee Carreira Carreira DOLEFIN Ligands Rh(I)-1 complex in excellent yield and selectivity.
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  • Organic Zeolite Analogues Based on Multi-Component Liquid Crystals: Recognition and Transformation of Molecules Within Constrained Environments

    Organic Zeolite Analogues Based on Multi-Component Liquid Crystals: Recognition and Transformation of Molecules Within Constrained Environments

    Materials 2011, 4, 183-205; doi:10.3390/ma4010183 OPEN ACCESS materials ISSN 1996-1944 www.mdpi.com/journal/materials Review Organic Zeolite Analogues Based on Multi-Component Liquid Crystals: Recognition and Transformation of Molecules within Constrained Environments Yasuhiro Ishida 1,2,3,* 1 RIKEN, Advanced Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan 2 PRESTO, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan 3 Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-8656, Japan * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel.: +81-48-462-1111 (ext. 6351); Fax: +81-48-467-8214. Received: 29 November 2010; in revised form: 4 January 2010 / Accepted: 5 January 2010 / Published: 11 January 2011 Abstract: In liquid crystals (LCs), molecules are confined in peculiar environments, where ordered alignment and certain mobility are realized at the same time. Considering these characteristics, the idea of “controlling molecular events within LC media” seems reasonable. As a suitable system for investigating this challenge, we have recently developed a new class of ionic LCs; the salts of amphiphilic carboxylic acids with 2-amino alcohols, or those of carboxylic acids with amphiphilic 2-amino alcohols, have a strong tendency to exhibit thermotropic LC phases. Because of the noncovalent nature of the interaction between molecules, one of the two components can easily be exchanged with, or transformed into, another molecule, without distorting the original LC architecture. In addition, both components are common organic molecules, and a variety of compounds are easily available.