DOI: 10.1595/147106709X474226 Novel Chiral Chemistries Japan 2009 PGMs RETAIN THEIR PIVOTAL ROLE IN ASYMMETRIC CATALYSIS Reviewed by David J. Ager DSM, PMB 150, 9650 Strickland Road, Suite 103, Raleigh, NC 27615, U.S.A.; E-mail: [email protected] The third Novel Chiral Chemistries Japan simultaneous use of bio- and chemocatalysis to (NCCJapan) Conference and Exhibition was held enable dynamic kinetic resolutions (DKR) to be in Tokyo on 18th and 19th April 2009 (1). The sec- carried out. The initial work was performed with ond meeting had been held in 2007 (2) and the first secondary alcohols. The readily available enzyme, in 2006. All meetings in the series have followed a Candida antarctica lipase B (CALB) (Novozym® similar format, with keynote addresses and sup- 435), which is derived from a yeast, is used to acy- porting lectures, although this time there were late one enantiomer of a secondary alcohol. A some dual presentations in which two speakers ruthenium catalyst then racemises the unreacted from the same company gave complementary talks enantiomer. Initially the Shvo catalyst, 1, was used on slightly different topics within a single time slot. but the racemisation is slow and requires heating to Professor Takao Ikariya (Tokyo Institute of give acceptable reaction rates. Use of the Technology, Japan) and his team, in particular monomeric ruthenium catalyst 2 provides faster Kyoko Suzuki, must be congratulated for the reactions, even at ambient temperatures. excellent job they did to ensure that the conference ran smoothly. As in previous meetings, Professor Ph O O Ph Ikariya put together an exciting mix of speakers H from both academia and industry across the world. Ph Ph Ph Ph There were around 130 attendees, with the major- Ph H Ph ity being from Japan. Ru Ru OC During the coffee and lunch breaks there was 1 CO OC CO an exhibition by companies with products mainly associated with chiral chemistry. The exhibitors Ph Ph ranged from companies that provide biocatalysts and chemical catalysts including ligands, to chro- Ph Ph matography, chemistry services and instrument Ph Ru Cl manufacturers. OC 2 CO Keynote Presentations The opening keynote address was given by CALB provides the (R)-acetate, while a spe- Professor Yoshiji Takemoto (Kyoto University, cially treated subtilisin Carlsberg enzyme gives the Japan) on asymmetric catalysis with multifunction- (S)-product ester. With 1,3-dihydroxy com- al ureas. The reactions described included pounds, the selectivity of the enzyme ensures high asymmetric versions of the Michael and Mannich selectivity for the (R,R)-diacetoxy product. reactions, hydrazination and the aza-Henry reac- However, due to the slow racemisation rates with tion with 1,3-dicarbonyl compounds, as well as the Shvo catalyst system, significant amounts of Petasis-type additions to quinolines and conjugate meso-products were formed with 1,4- and 1,5-diols. additions to enones. Use of the faster catalyst 2 alleviates this problem. The second keynote address was given by Analogous uses of the concept have been Professor Jan-Erling Bäckvall (Stockholm Univer- employed for the DKR of chlorohydrins, amines sity, Sweden). This lecture covered his work on the and allenic alcohols. Platinum Metals Rev., 2009, 53, (4), 203–208 203 The third keynote address was given by OMe Professor Hisashi Yamamoto (University of Chicago, U.S.A.) on the uses of Brønsted acids in organic synthesis. The emphasis of the talk was on the use of triflimide, (CF3SO2)2NH, as a superacid H2N that can regenerate itself during a Mukaiyama aldol OMe reaction. The use of the tris(trimethylsilyl)silyl (TTMS) group as a ‘super silyl’ group also makes H2N the enol ether more reactive. 4 (S)-DAIPEN Asymmetric Catalysis In addition to these keynote addresses there for the reduction of α,β- and γ,δ-enoic acids for were fifteen other presentations. Topics included pharmaceutical applications, such as in the the uses of biocatalysis, transition metal catalysis preparation of an intermediate for Solvay’s and the synthesis of target molecules, among SONU 20250180. α,β-Enoic acids can also be others. In line with the emphasis of this publica- reduced by an iridium or rhodium catalyst with tion, those talks relating to the use of platinum Me-BoPhozTM, 5, as the chiral ligand or by a group metals (pgms) have been highlighted. rhodium–Xyl-PhanePhos, 6, system. Fred Hancock (Johnson Matthey Catalysis and Chiral Technologies, U.K.) gave an overview of some case histories in which Johnson Matthey had P(xyl)2 N looked for an appropriate catalyst to perform an PPh 2 PPh2 asymmetric transformation. He described the Fe P(xyl)2 advantages of chemocatalytic and enzymatic meth- ods for the reduction of carbonyl compounds for 5 (R)-Me-BoPhozTM 6 (R)-Xyl-PhanePhos a number of example systems. The reduction of aryl ketones can be achieved in high yield and with high enantioselectivity by the system RuCl2[(R)- André de Vries and David Ager (DSM, The P-Phos][(S)-DAIPEN], 3a and 4, in a manner anal- Netherlands and U.S.A., respectively) gave a joint ogous to the method developed by Noyori (3). The presentation. de Vries described the advantages of use of this system with xyl-P-Phos, 3b, was illus- performing asymmetric hydrogenations of unsatu- trated for a pharmaceutical application as part of rated carbon–carbon multiple bonds with a the synthesis of Nycomed’s imidazo[1,2-a]pyridine rhodium catalyst using the MonoPhosTM family of BYK-311319. The P-Phos family of ligands can ligands, 7 (4). The method can be automated, also be used in the catalyst system [RuCl2(P- which allows for rapid screening of products. Phos)(DMF)n] (DMF = N,N-dimethylformamide), R4 5 3 OMe 3 R R a Ar = Ph ((R)-P-Phos) N b Ar = xyl ((R)-xyl-P-Phos) O P NR1R2 MeO PAr2 O MeO PAr2 R5 R3 N R4 TM OMe 7 MonoPhos family of ligands Platinum Metals Rev., 2009, 53, (4) 204 Higher reaction rates and enantioselectivities can 1 be observed when two different monodentate lig- R SO2 X = Cl R2 ands are used at the same time. This has resulted Ph N R1 = aryl or alkyl in an economical process for the preparation of 2 Ru Ar–R = cymene, part of Novartis’ renin inhibitor, Aliskiren. The mesitylene or TM phosphoramidite MonoPhos ligands are also Ph N X hexamethylbenzene H2 useful for the reduction of carbonyl groups, 10 including β-keto esters, with ruthenium as the metal. Iridium systems with phosphoramidites can Ian Lennon (Chiral Quest, Inc, U.K.) described be used to prepare phenylalanines by asymmetric the chemistry and uses of a number of ligand sys- hydrogenation, and also provide high selectivity in tems developed by Chiral Quest. C3-TunePhos, 11, the reduction of imines. Ager discussed enzymatic provides excellent enantioselectivity for the reduc- methods to prepare cyanohydrins with high enan- tion of β-keto esters. The analogue C3*-TunePhos, tioselectivity, and the development of the 12, extends this to ketones and α-keto esters as industrial production of DSM’s PharmaPLETM, a well as retaining its selectivity with β-keto esters. recombinant pig liver esterase that can be used in TangPhos, 13, has proven to be a useful ligand in pharmaceutical applications. the rhodium-catalysed reduction of dehydroamino Professor Andreas Pfaltz (University of Basel, acids, itaconates and enamides. The latter class of Switzerland) continued the asymmetric hydro- compounds can now be accessed from oximes by genation theme with his iridium-catalysed a rhodium-on-carbon-catalysed hydrogenation in asymmetric reduction of unfunctionalised alkenes the presence of acetic anhydride. The analogue of in the presence of P,N-ligands. In addition to the TangPhos, DuanPhos, 14, provides excellent well-established system 8, which can be used with stereoselectivity for the reduction of function- a wide variety of alkene substitution patterns, the alised aryl alkyl ketones, while BINAPINE, 15, phosphinooxazolines, 9, have also proven useful, provides access to β-amino esters. particularly with trisubstituted alkenes. For this Christophe Le Ret (Umicore AG & Co KG, class of reductions, it is particularly important to Germany) described a different aspect of asym- use a non-nucleophilic counterion for the metal, metric hydrogenation: the formation of such as tetra[3,5-bis(trifluoromethyl)phenyl]borate metal–ligand complexes and the influence of the (BArF). metal precursor. For rhodium, an example ligand was MandyPhosTM, 16. For the asymmetric reduction of (Z)-acetamidocinnamic acid methyl ester, with Rh(nbd)2 (nbd = 2,5-norbornadiene) O O as the metal source, in situ formation of the cata- lyst or the use of the P,N-complex gave a slower PAr2 N PAr2 N hydrogenation rate than the P,P-complex system. 8 R 9 Ph With ruthenium, it was found that the use of 2 3 Ar = Ph or o-Tol bis(η5-2,4-dimethylpentadienyl)ruthenium(II), 17, was superior for complex formation with Kunihiko Murata (Kanto Chemical Co, Inc, MandyPhosTM and other ferrocene-based ligands. Japan) described the development of the rutheni- Wataru Kuriyama (Takasago International um-based asymmetric transfer hydrogenation Corp, Japan) described the synthesis of chiral alco- catalyst 10 for the reduction of ketones, which hols by the catalytic reduction of esters. The system removes the need for a chiral phosphine ligand. is based on a ruthenium–diamine complex, 18. For The diamine provides the asymmetry. This catalyst high enantioselectivity, the stereogenic centre has can also be used to carry out asymmetric Henry to be present in the substrate, as it is in α-alkyl, β- and Michael reactions. amino, β-alkoxy, β-hydroxy and α-hydroxy esters. Platinum Metals Rev., 2009, 53, (4) 205 12 C3*-TunePhos H H O O PPh 2 PAr2 P H P PPh 2 PAr2 t-But t-But O O Bu Bu 13 TangPhos 11 C3-TunePhos Ar = Ph, 4-MePh, t 3,5-di- BuPh, 3,5-diMePh or 4-MeO-3,5-di-tBuPh H H H H P P P P t-ButBu t-ButBu 15 BINAPINE t-ButBu tBu-Bu 14 DuanPhos NMe2 Ph Ph H2 Ph P H N Ph Fe Ru PPh2 Ru Ph PH N Ph Ph H Ph 2 PhPhBH3 Me2N PPh2 18 16 MandyPhos 17 The key to success was performing the reactions in David Chaplin (Dr Reddy’s Laboratories Ltd, the absence of base.