Recent Advances of BINAP Chemistry in the Industrial Aspects

NEW TOOLS IN SYNTHESIS 1055

Recent Advances of BINAP Chemistry in the Industrial Aspects Hidenori Kumobayashi, Takashi Miura,* Noboru Sayo, Takao Saito, Xiaoyong Zhang Central Research Laboratory, Takasago International Corporation, 1-4-11 Nishi-yawata, Hiratsuka, Kanagawa 254-0073, Japan Fax (0463)25-2084; E-mail: [email protected] Received 24 April 2001

and ketones such as a-(acylamino)acrylic acids,6 enam- Abstract: New efficient synthetic methods of optically active BI- ides,7 a,b-unsaturated carboxylic acids,8 allylic and ho- NAP [BINAP = 2,2’-bis(diphenylphosphino)-1,1’-binaphthyl] and 9 10 its variants are described. Application of these BINAP variants in moallylic alcohols, alkylidene lactones, alkenyl 10 11 12 asymmetric catalytic hydrogenation of prochiral ketones and olefins ethers, b-keto esters, b-hydroxyketones, and b-ami- to various industrially important compounds is discussed. noketones.12 Key words: BINAP ligands, ruthenium and iridium catalysts, Starting with the development of l-menthol process using asymmetric hydrogenation, ketones, unsaturated carboxylic acids BINAP–Rh catalyzed asymmetric isomerization of allylamines,5a we have been investigating catalytic asymmetric synthesis mainly based on BINAP chemistry for two Introduction decades and have developed various asymmetric synthetic processes. All of these results are based on the success Enantioselective syntheses have been gaining more and of the marvelous abilities of the BINAP ligands. Recently more importance in a wide range of fields such as pharma- the targets of asymmetric synthesis have become varied ceuticals, agrochemicals, food additives, aromachemicals and complicated, while BINAP sometimes shows its lim- and functional materials because the biological activities itation. It becomes necessary to develop new ligands to of these materials are often associated with their absolute compensate for the limitations of BINAP. In this paper we configuration. described recent developments of BINAP chemistry, es- pecially about syntheses and applications of new BINAP Known methods to obtain enantiomerically pure com- ligands from the industrial point of view. pounds are classified as follows: 1) optical resolution, 2) modification of naturally occurring materials, 3) biological transformation, and 4) asymmetric catalysis using a New Synthetic Methods of BINAP and Its Variants prochiral compound as the starting material. Among these methods, asymmetric catalysis is emerging as one of the Since the practical methods for synthesis of 2,2’-bis(dia- most efficient and versatile methods for the preparation of rylphosphino)-1,1’-binaphthyls (BINAPs) were reported a wide range of chiral target molecules. In recent years, in 1986,13 a series of BINAP analogues have been pre- numerous catalytic asymmetric reaction processes that pared. However, this route requires harsh conditions for transform prochiral substrates into chiral products with 1 the conversion of binaphthol to the corresponding dibro- high enantioselectivity have been developed. Asymmet- mide and tedious optical resolution of BINAP derivatives ric hydrogenation is one of the most powerful tools for the (Scheme 1). synthesis of enantiomerically pure compounds. For this purpose, several kinds of metal–optically active phos- Recently, Cai et al. of Merck developed a new method for phine complexes have been synthesized so far. In general, direct asymmetric synthesis of BINAP by use of nickel- catalyzed coupling reaction of easily accessible chiral a chiral transition metal catalyst precursor LnM can be re- garded as composed of two key parts, the chiral ligand L 2,2’-bis((trifluoromethanesulfonyl)oxy)-1,1’-binaphthyl and the central metal M. Thus, the proper combination of (1) with diphenylphosphine in the presence of DABCO 14 well-designed chiral ligands and selected metals is the (Scheme 2). Similarly, Laneman et al. of Monsanto re- most important requirement for high catalytic efficiency. ported the nickel-catalyzed cross-coupling of 1 with chlo- 15 Over the past twenty-five years, various kinds of chiral rodiphenylphosphine in the presence of zinc. These phosphines have been developed by researchers in methods, however, have some drawbacks in industrializa- academic, pharmaceutical and fine chemical companies. tion, such as use of pyrophoric diphenylphosphine or Among them, 2,2’-bis(diphenylphosphino)-1,1’- moisture-sensitive chlorodiphenylphosphine. binaphthyl2 (BINAP) has been found to have remarkable On the other hand, we have explored two unique proce- chiral recognition ability and broad applicability in vari- dures for the synthesis of chiral BINAPs by using the met- ous transition metal-catalyzed asymmetric reactions such al-catalyzed coupling reaction of 1 with diarylphosphine as hydrogenation,3 hydrosilylation,4 1,3-hydrogen migra- oxides, which are readily prepared by the reaction of aryl- tion,5 etc. For example, BINAP–ruthenium catalysts are magnesium halide with diethyl phosphite and easy to han- well recognized to be highly efficient catalysts for asym- dle in large quantity.16 The first one is well illustrated by metric hydrogenations of various functionalized olefins coupling of (R)-1 with diphenylphosphine oxide, which

Synlett 2001, No. SI, 1055–1064 ISSN 0936-5214 © Thieme Stuttgart · New Yorkrt · New York 1056 H. Kumobayashi et al. NEW TOOLS IN SYNTHESIS

Biographical Sketches

Hidenori Kumobayashi thol with enantioselective cal Society of Japan Award was born in Niigata, Japan. isomerization of allylamines for Technical Development. In 1967 he obtained a B.S. catalyzed by BINAP—Rh(I) He is now a vice president at degree from Shinsyu Univer- complexes as the key reac- Takasago International Cor- sity and joined Takasago In- tion. This was followed by poration and the general ternational Corporation. In studies on efficient synthesis manager of Fine Chemical 1986 he earned his Ph. D. of key intermediates of car- Devision. His main research from Osaka University under bapenem antibiotics by using interests include asymmetric the direction of Prof. Sei Ot- BINAP—Ru(II)-catalyzed synthesis using transition suka where he worked on de- asymmetric hydrogenation metal catalysts. velopment of industrial of ketone compounds. In synthetic process of l-men- 1997 he received the Chemi-

Takashi Miura obtained a nonium salts with Prof. Paul Central Research Laboratory Ph.D. from Tokyo Metropol- G. Gassman at University of of Takasago International itan University in 1979 under Minnesota from 1979 to Corporation. Like his collab- the guidance of Prof. Michio 1981. In 1982 he joined orator, he is convinced that Kobayashi. He pursued post- Takasago International Cor- asymmetric catalysis offers doctoral research on the 2,3- poration and is now general many attractive options for sigmatropic rearrangement manager at Fine & Aroma organic chemist and indus- of sulfonium salts and sele- Chemical Laboratory in try.

Noboru Sayo, born in join the Professor Nakai’s re- Central Research Laboratory Hyogo, Japan, in 1954, stud- search group and worked in of Takasago International ied applied chemistry at the field of carbanion chem- Corporation. His main re- Shinsyu University, and ob- istry. After obtaining his search interests have been tained his M. S. degree in ap- Ph.D. in 1984, he entered associated with the develop- plied chemistry from Takasago International Cor- ment of catalytic asymmetric Okayama University in poration. Now he is assistant synthesis. 1979. He moved to Tokyo director at Fine & Aroma Institute of Technology to Chemical Laboratory in

Takao Saito was born in his Ph. D. from Osaka Uni- of Takasago International Ibaraki (Japan) in 1960. He versity under supervision of Corporation. His current obtained his M.S. degree Prof. Shun-ichi Murahashi in area of research includes the from Meiji College of Phar- 1996 and is now research as- development of new molecu- macy in 1985 and then sociate at Fine & Aroma lar catalysts. joined Takasago Internation- Chemical Laboratory in al Corporation. He received Central Research Laboratory

Xiaoyong Zhang was born University under supervision tory in Central Research in Zhejiang, China and re- of the late Prof. Hidemasa Laboratory. He is pursuing ceived his M.S. degree in or- Takaya in 1994 and then exploration of new efficient ganic chemistry at Institute joined Takasago Internation- synthetic methods of chiral of Chemistry, Chinese Acad- al Corporation where he is ligands and their application emy of Sciences in 1987. He now a senior chemist at Fine to asymmetric catalysis. earned his Ph.D. from Kyoto & Aroma Chemical Labora-

Synlett 2001, No. SI, 1055–1064 ISSN 0936-5214 © Thieme Stuttgart · New York NEW TOOLS IN SYNTHESIS Recent Advances of BINAP Chemistry in the Industrial Aspects 1057

OH i)Br ii)MgBr iii) OH Br MgBr

rac-Binaphthol rac-Dibromide

iv—vi) vii) P(O)Ph2 P(O)Ph2 PPh2

P(O)Ph2 P(O)Ph2 PPh2

rac-BINAPO (R)-(+)-BINAPO (R)-(+)-BINAP

- Scheme 1 i) Br2, PPh3, 230 °C; ii) Mg; iii) Ph2P(O)Cl; iv) (2R,3R)-( )-di-O-benzoyltartaric acid; v) fractional crystallization; vi) NaOH; vii) Cl3SiH, PhNMe2.

toluene, giving (R)-BINAP in 96% yield. This procedure has been successfully applied to the synthesis of a series of known or new chiral BINAP ligands in reasonable to OTf a or b PPh 2 good yields. It is noteworthy that most of these new BI- OTf PPh 2 NAPs had been difficult to obtain through the optical resolution route shown in Scheme 1. However, when (R)-2,2’-bis((trifluoromethanesulfo- (R)- or (S)-1 (R)- or (S)-BINAP nyl)oxy)-5,5’,6,6’,7,7’,8,8’-octahydro-1,1’-binaphtyl

Scheme 2 a) Ph2PH, NiCl2(dppe) / 75% yield (Merck); b) Ph2PCl, [(R)-2] was subjected to the phosphinylation with diphe- NiCl2(dppe), Zn / 52% yield (Monsanto). nylphoshine oxide in the presence of nickel catalyst, no coupling reaction occured. Hayashi et al. reported that monophosphinylation of (S)-1 with diphenylphosphine oxide in the presence of catalytic amount of palladium di- proceeded smoothly in the presence of 1,2-bis(diphe- acetate and 1,2-bis(diphenylphosphino)butane (dppb) in nylphosphino)ethane (dppe) and nickel (II) chloride to DMSO at 100 °C gave 2-(diphenylphosphino)-2’-((triflu- give a mixture of (R)-BINAP, (R)-BINAP(O) and (R)-BI- oromethanesulfonyl)oxy)-1,1’-binaphthyl.17 As presented NAPO in a ratio of 35.4: 60.8: 3.7 in 87% combined yield in Scheme 4, monophosphinylation of (R)-2 with diphe- (Scheme 3). This mixture was then reduced by a mixture nylphosphine oxide under Hayashi’s conditions proceed- of trichlorosilane and N,N-dimethylaniline in refluxing ed smoothly to afford (R)-2-(diphenylphosphinyl)-2-

i) OH PAr2 PAr2 P(O)Ar2 + + OH PAr2 P(O)Ar2 P(O)Ar2

(R)-1 Ar = C6H5 : Ar = C6H5 : Ar = C6H5 : (R)-(+)-BINAP (R)-(+)-BINAP(O) (R)-(+)-BINAPO

Yield (%) Ar Product from (R)-1

C6H5 (R)-BINAP 84 4-CH C H (R)-Tol-BINAP ii) PAr2 3 6 4 65 3,5-(CH3)2C6H3 (R)-DM-BINAP 61 PAr 2 4-MeO-3,5-(CH3)2C6H2 (R)-DMM-BINAP 71 4-t-BuO-3,5-(CH3)2C6H2 (R)-DMB-BINAP 57 2-Naphtyl (R)-2-Nap-BINAP 61

Scheme 3 i) Ar2P(O)H, NiCl2(dppe); ii) Cl3SiH, PhNMe2.

Synlett 2001, No. SI, 1055–1064 ISSN 0936-5214 © Thieme Stuttgart · New York 1058 H. Kumobayashi et al. NEW TOOLS IN SYNTHESIS

i) ii) OTf P(O)Ph2 PPh2 OTf (90%) OTf (93%) OTf

(R)-2 (R)-3 (R)-4

iii) ii) PPh2 PPh2 (R)-H8-BINAP + P(O)Ph (R)-5 (79%) PPh2 2 (95%)

(R)-H8-BINAP (R)-H8-BINAP(O) (R)-5 (R)-6 - Scheme 4 i) Ph2P(O)H, Pd(OAc)2 dppp, i-Pr2NEt/DMSO; ii) Cl3SiH, PhNMe2; iii) Ph2P(O)H, NiCl2(dppe), DABCO.

[(trifluoromethanesulfonyl)oxy]-5,5’,6,6’,7,7’,8,8’-octa- responding secondary alcohol in high enantioselectivity,19 hydro-1,1’-binaphthyl [R-3] in 90% yield. As (R)-3 did simple ketones that lack heteroatoms anchoring the Ru not react with diphenylphosphine oxide in the presence atom have not been hydrogenated with BINAP–Ru(II) of nickel catalyst, it was reduced with trichlorosilane- catalysts. Recently, Noyori and co-workers reported that N,N-dimethylaniline to 2-(diphenylphosphino)-2-[(triflu- a BINAP–Ru–chiral diamine–inorganic base combined oromethanesulfonyl)oxy]-5,5’,6,6’,7,7’,8,8’-octahydro- catalyst system acts as a very efficient catalyst for asym- 1,1’-binaphthyl [(R)-4] in 93% yield. Subsequent nickel- metric hydrogenation of unfunctionalized simple ketones catalyzed coupling reaction of (R)-4 with diphenylphos- such as acetophenones, benzophenones, hetero-aromatic phine oxide gave a mixture of 2,2’-bis(diphenylphosphi- ketones, and alkenyl and cyclopropyl ketones.20 In asym- no)-5,5’,6,6’,7,7’,8,8’-octahydro-1,1’-binaphthyl [(R)- metric hydrogenation of unfunctionalized ketones cata- 18 H8-BINAP, (R)-5] and its monooxide H8-BINAP(O) lyzed by this BINAP–Ru(II)–chiral diamine–inorganic [(R)-6] in 79% yield. Reduction of (R)-6 with trichlorosi- base system, the use of DM-BINAP as a chiral phosphine lane–N,N-dimethylaniline afforded (R)-5 in 95% yield not only increases the enantioselectivity but also expands (Scheme 4). the scope of the substrates hydrogenated with high Among the above easily prepared BINAP variants, enantioselectivity. For instance, the hydrogenation of 2,2'-bis(di(3,5-dimethylphenyl)phosphino)-1,1'-binaph- acetophenone in 2-propanol containing trans-RuCl2[(S)- thyl (DM-BINAP) acts as a very efficient ligand for enan- tol-binap][(S,S)-dpen] (DPEN = 1,2-diphenylethylenedi- amine) and t-BuOK with S/C = 2,400,000 afforded tio- and diastereoselective hydrogenation of 2-substituted 20d cyclic ketones and enantioselective hydrogenation of un- (R)-1-phenylethanol in 80% ee and in 100% yield. functionalized ketones with BINAP–Ru(II)–chiral di- In contrast, hydrogenation of acetophenone in 2-propanol containing trans-RuCl2[(S)-dm-binap][(S,S)-dpen] amine–base catalytic system. On the other hand, H8- BINAP shows excellent enantioselectivities in Ru(II)-cat- with S/C = 2000 or trans-RuCl2[(S)-dm-binap][(S)- alyzed asymmetric hydrogenation of olefinic compounds daipen] (DAIPEN = 1,1-di(4-anisyl)-2-isopropyl-1,2-eth- a,b ylene-diamine) with S/C = 100,000 gave (R)-1-phenyle- such as -unsaturated carboxylic acids and allyl alco- 18e hols. thanol in 99% ee and almost quantitative yield. The acetate of (R)-1-phenylethanol thus obtained is now pro- duced as a fragrance material which has clean floral, fresh DM-BINAP green note like Gardenia. On the other hand, the acetate of (S)-1-phenylethanol has metallic green note and is not fa- Enantioselective hydrogenation of functionalized ketones vorable as a fragrance material. Hydrogenation of ben- with BINAP–Ru(II) complex catalysts into optically ac- zophenones using the BINAP–Ru(II)–chiral diamine– tive secondary alcohols have been extensively studied and inorganic base system also proceeds smoothly to afford industrial processes for the synthesis of key intermediates the corresponding chiral benzhydrols with high enantiose- of antibiotic carbapenems and antibacterial Levofloxacin lectivities. In this case, it was found that the enantioselec- have been established. On the other hand, though it has tivity is markedly influenced by the structure of chiral been reported that asymmetric hydrogenation of 2-chloro- phosphine ligands. For instance, hydrogenation of 2- acetophenone with BINAP–Ru(II) catalysts gives the cor- methoxybenzophenone (7) using Ru2Cl4[(S)-bi- · · nap]2 NEt3–(S,S)-DPEN or Ru2Cl4[(S)-tol-binap]2 NEt3–

Synlett 2001, No. SI, 1055–1064 ISSN 0936-5214 © Thieme Stuttgart · New York NEW TOOLS IN SYNTHESIS Recent Advances of BINAP Chemistry in the Industrial Aspects 1059

O OH TBSO

CO2Me CO2Me OAc

NH NHCOPh NHCOPh O

(±)-9 syn-(2S,3R)-10 11 Scheme 5

(S,S)-DPEN in 2-propanol/THF (3/1) containing t-BuOK tive asymmetric hydrogenation of methyl (±)-2-(benzami- afforded (S)-2-methoxybenzhydrol [(S)-8] in 23.7% ee domethyl)-3-oxobutanoate [(±)-9], giving syn-(2S,3R)-10 and 25.7% ee, respectively. By contrast, the use of in 91% de (98% ee) and 84% de (97% ee), respectively.22 · Ru2Cl4[(S)-dm-binap]2 NEt3 resulted in (S)-8 in 72.8% This procedure has been successfully applied to the indus- ee, and even higher ee (89%) was achieved by use of the trial production of a carbapenem key intermediate 11 {RuI(p-cymene)[(S)-dm-binap]}I–(S,S)-DPEN system (Scheme 5) on a scale of 100 tons per year. (Table 1). In the year 2000, Noyori and co-workers report- However, diastereo- and enantioselective hydrogenation ed selective hydrogenation of benzophenones to benzhy- of simple ketones such as 2-substituted cyclohexanones - drols using a BINAP–Ru(II) chiral diamine complex. In has remained difficult. In 1996, Noyori and co-workers their report, 2-methoxybenzophenone was successfully reported that a BINAP–Ru–chiral diamine system acts as hydrogenated with trans-RuCl2[(S)-dm-binap][(S)- very efficient catalyst for diastereo- and enantioselective daipen] in the presence of KOC(CH3)3 to give (S)-8 in 20f hydrogenation of cyclic ketones. Hydrogenation of (±)-2- 99% ee and quantitative yield. Asymmetric hydrogena- isopropylcyclo-hexanone using RuCl [(S)-binap](dmf) – tion of a variety of benzophenone derivatives, hetero- 2 n 20g 20e (R,R)-DPEN–KOH ternary system in 2-propanol afforded aromatic and alkenyl ketones with a DM-BINAP– (1R,2R)-2-isopropylcyclohexanol in 99.6% de and 93% Ru(II)–chiral diamine complex proceeds smoothly with a ee.20c The effectiveness of a DM-BINAP–Ru(II) complex - substrate to catalyst ratio of 1,000 40,000 to chiral alco- as a catalyst in diastereo- and enantioselective hydrogena- hols with high ee and high yield. tion of 2-substituted cyclohexanone is well demonstrated in hydrogenation of (±)-2-methoxycyclohexanone [(±)- 12] to (1R,2S)-2-methoxycyclohexanol [(1R,2S)-13] (Ta- BINAP—Ru 23 diamine ble 2). t-BuOK

BINAP—Ru O OMe OH OMe diamine t-BuOK 7 (S)-8 OMe OMe O OH

Table 1 Asymmetric Hydrogenation of 2-Methoxybenzophenone (±)-12 (1R,2S)-13 (7)a

Table 2 Asymmetric Hydrogenation of Racemic 2-Methoxycyclo- hexanone [(±)-12]a

a Hydrogenation was carried out under an hydrogen pressure of 50 atm at 50 °C (substrate/catalyst = 500 mol/mol). Ru/(S,S)-DPEN/t- BuOK = 1/4/35. b Ref. 20f. a Ru-cat (0.1 mol%), (S,S)-DPEN (0.2 mol%), and KOH (3.0%) were Diastereo- and enantioselective hydrogenation of ketones used. Unless otherwise stated, reactions were carried out at 50 atm of H and 50 °C. b Reaction temperature was 5 °C. to secondary alcohols is very powerful tool for the synthe- 2 sis of chiral alcohols having contiguous stereogenic cen- ters. Diastereo- and enantioselective hydrogenation of 2- As shown in Table 2, asymmetric hydrogenation of (±)-12 · substituted 3-oxo carboxylic esters was reported in using Ru2Cl4[(S)-dm-binap]2 NEt3– (S,S)-DPEN–KOH 1989.21 In the course of our research on asymmetric hy- ternary system at 50 °C provided (1R,2S)-13 in 96% de drogenation of various functionalized ketones, we found and 96% ee, while the use of RuCl2[(S)-binap](dmf)n or · that DM-BINAP is superior to BINAP in diastereoselec- Ru2Cl4[(S)-binap]2 NEt3 afforded (1R,2S)-13 in 93% de

Synlett 2001, No. SI, 1055–1064 ISSN 0936-5214 © Thieme Stuttgart · New York 1060 H. Kumobayashi et al. NEW TOOLS IN SYNTHESIS

(87% ee) and 97% de (92% ee), respectively. In addition, Recently Takaya et al. reported that the chiral H8-BINAP– hydrogenation of (±)-12 with Ru2Cl4[(S)-dm-bi- Ru(II) complexes, Ru(H8-binap)(OCOCH3)2 (16) and · nap]2 NEt3–(S,S)-DPEN–KOH at lower reaction temper- [RuI(H8-binap)(p-cymene)]I (17), serve as even more ef- ature (5 °C) gave (1R,2S)-13 in 99% de and 99% ee, fective catalysts for the asymmetric hydrogenation of a,b- which is an important chiral building block for the synthe- and b,g-unsaturated carboxylic acids than the BINAP– sis of a tricyclic b-lactam antibiotic, sanfetrinem.24 Ru(II) ones.26 As shown in Table 3, in the presence of 0.5 mol% of (S)-16 or (R)-17 hydrogenation of tiglic acid (18a) proceeded smoothly under mild conditions, afford- H8-BINAP ing (S)- or (R)-2-methylbutanoic acid [(S)- or (R)-19a] in as high as 97% ee (entries 1–3). (S)-2-Methylbutanoic As one of the most prominent asymmetric catalytic reac- acid and its esters are very important in creating fruit fla- tions, hydrogenation of unsaturated carboxylic acids pro- vors (e.g. apple, strawberry, grape). Similarly high ee’s vides a convenient way to obtain optically active (93–96%) have been achieved in hydrogenation of other carboxylic acids, which are very important building (E)-2-alkyl-2-alkenoic acids 18b–d catalyzed by (S)-16 blocks for the synthesis of new materials such as non-ste- (entries 5, 7, and 9). On the other hand, use of the BINAP riodal anti-inflammatory (NSAI)24 agents and ferroelec- complex (R)-14 as catalyst for 18a–d caused decreases tric liquid crystals (FLCs).25 BINAP–Ru(II) complexes, both in ee’s by 5–14% and in catalytic activities (entries such as the chiral dicarboxylate complex Ru(bi- 4, 6, 8, and 10). 8a The difference between the Ru(II) com- nap)(OCOCH3)2 (14) and halide complex [RuI(binap)(p- plexes of H8-BINAP and those of BINAP in catalytic ef- cymene)]I (15), have been found to catalyze the enanti- ficiency becomes dramatic in the case of a b-aryl-(E)- oselective hydrogenation of various a,b-unsaturated car- acrylic acid, 2-methylcinnamic acid (18e), which was hy- boxylic acids in very high ee’s.8a,22 drogenated to (S)-19e by use of (S)-16 in 95% conversion at 48 h and in 89% ee (entry 11), significantly surpassing those (merely 30% conversion and 30% ee) achieved by R2 R1 R2 R1 (R)-14 (entry 12). H2, catalyst * COOH COOH The superiority of H8-BINAP over BINAP in enantiose- 18 19 lectivity was also observed in hydrogenation of other types of unsaturated carboxylic acids, including b-disub- R1 R2 stituted acrylic acids 20a (93% ee vs 75% ee, Table 4, en- a: CH3 CH3 tries 1 and 2) and 20b (70% ee vs 27% ee, entries 3 and 4), b: CH3 C2H5 c: CH3 n-C3H7 trisubstituted acrylic acid 22 (entries 5 and 6), as well as d: C2H5 n-C3H7 b,g-unsaturated substrate 24 (entries 7 and 8). e: CH3 C6H5

R1 R1 Table 3 Asymmetric Catalytic Hydrogenation of a,b-Disubstituted * 2 2 (E)-Acrylic Acidsa,26 R COOH R COOH 20 21 R1 R2

a: CF3 CH3 b: C6H5 CH3

* COOH COOH 22 23

* Ph COOH Ph COOH 24 25 a Hydrogenation was carried out in an autoclave at 10–30 °C in methanol (substrate/catalyst = 197–220 mol/mol, solvent/substrate = 5– The synthetic significance of this asymmetric catalysis is 50 mL/g) unless otherwise stated, and the chemoselectivity was 100% well demonstrated in the hydrogenation of 2-(4-isobu- 1 b as given by H NMR analysis. At 50 °C in MeOH–H2O (10:1). Sub- tylphenyl)propenoic acid (26) catalyzed by (S)-16, which strate/catalyst = 1016–1074 mol/mol. provided directly and quantitatively the important antiinflammatory agent (S)-ibuprofen [(S)-27] in 97% ee (Table 5, entry 1) as compared to 96% ee obtained with (R)-14

Synlett 2001, No. SI, 1055–1064 ISSN 0936-5214 © Thieme Stuttgart · New York NEW TOOLS IN SYNTHESIS Recent Advances of BINAP Chemistry in the Industrial Aspects 1061

Table 4 Asymmetric Catalytic Hydrogenation of a,b- and b,g- Unsaturated Carboxylic Acidsa,26 COOH COOH

26 (S)-27

COOH COOH

MeO MeO a Hydrogenation was carried out in an autoclave under an hydrogen 28 (S)-29 pressure of 100 atm at 10–25 °C in methanol (substrate/ catalyst = 200 mol/mol, solvent/substrate = 10–33 mL/g) unless otherwise stated, and the chemoselectivity was 100% as given by 1H b c NMR analysis. In THF. Substrate/catalyst = 600 mol/mol. Hydro- In addition to the above asymmetric catalytic reactions by gen pressure was 1.5 atm. use of ruthenium complexes, H8-BINAP also showed good chiral induction ability in Ir(I)-catalyzed asymmetric hydrogenation of certain prochiral ketones. Although (entry 2). Similarly, hydrogenation of 2-(6-methoxy-2- achiral iridium complexes were known to act as homoge- naphthyl)propenoic acid (28) using (S)-15 as the catalyst neous catalysts in a wide variety of reactions,27 there have gave another useful antiinflammatory agent (S)-naproxen been very limited applications of chiral iridium complex- [(S)-29] in 96% ee (entry 3).22 In this case, a large excess es to asymmetric catalysis, mainly to hydrogenation28 and of solvent methanol was used to dissolve 28. Further in- transfer hydrogenation29 of functionalized ketones as well vestigation from the industrial viewpoint showed that ad- as hydrogenation of imines and enamides.29b,30 In 1993, dition of diethylamine (3 equivalences to 28) greatly Takaya et al. reported that the new catalytic systems con- 31 increased both the solubility of 28 and the catalytic activ- sisting of [Ir(binap)(cod)]BF4 (31) or [Ir(H8-bi- 31 ity of (S)-15 (entry 4). Again, use of the analogous H8-BI- nap)(cod)]BF4 (32) and bis(o-dimethylamino- NAP-containing complex (S)-17 led to an increase in ee phenyl)phenylphosphine (33) showed outstanding enanti- by 2% (entry 5). Even higher enantioselectivity (92% ee) oselectivities in the asymmetric hydrogenation of a series and substrate to catalyst ratio (5000 mol/mol) have been of relatively simple prochiral ketones such as 1,2-benzo- b 32 realized by use of Ru[(S)-H8-binap](OCOCF3)2 (30) (en- cycloalkanones and -thiacycloalkanones, which had try 6), illustrating the industrial applicability of this catal- remained unsuccessful with conventional chiral phos- ysis. phine—metal catalysts. Again, matching between the catalyst and substrate is important. The catalytic system 31– As was observed with DM-BINAP (vide supra), H8-BI- NAP also showed excellent chiral induction ability in the 33 showed higher conversions and ee’s for hydrogenation diastereo- and enantioselective hydrogenation of methyl of 1,2-benzocycloalkanones. On the other hand, the sys- b (±)-2-(benzamidomethyl)-3-oxobutanoate [(±)-9] in tem 32–33 was more suitable for that of -thiacycloal- b CH Cl –MeOH (7: 1) with (S)-17 as the catalyst, yielding kanones 34, giving– -thiacyclopentanol (R)-35a, an 2 2 b syn-(2R,3S)-10 in 92% de and 99% ee18b as compared to important building block in the synthesis of -lactam an- 33 b those (84% de and 99% ee) obtained with (R)-1522 tibacterials, and -thiacyclohexanol (R)-35b in 75–82% (Scheme 5). and 70% ee, respectively, as compared to those obtained with the 31–33 system (60 and 40% ee, respectively).34

Table 5 Asymmetric Catalytic Hydrogenation of a-Substituted Acrylic Acidsa,26

a Hydrogenation was carried out in an autoclave in methanol. The chemoselectivity was 100% as given by 1H NMR analysis. b Substrate/catalyst ratio (mol/mol). c Solvent/substrate ratio (mL/g). d Diethylamine (3 equivalences to the substrate) was added.

Synlett 2001, No. SI, 1055–1064 ISSN 0936-5214 © Thieme Stuttgart · New York 1062 H. Kumobayashi et al. NEW TOOLS IN SYNTHESIS

The dihedral angle of the binaphthyl system is expected to NMe2 OHO PhP exert influence on the effect of the steric bulk of the diphe-

(CH2)n (CH2)n nylphosphino groups. The narrower dihedral angles S S should increase the steric repulsion between the substrate 2 34 (R)-35 and the phenyl group on phosphine. The following exper- 33 a: n = 1 imental results support our working hypothesis. The enan- b: n = 2 tioselectivities in the hydrogenation of 2-oxo-1-propanol (36) to (2R)-1,2-propanediol (37) are influenced remark- Although the mechanism of the above catalyses are not ably by the ligand choice, and increase in the following yet clear, the differences in the sense and efficiency of order: BINAP (89.0% ee), BIPHEMP (38) (92.5% ee),38 39 chiral induction between BINAP and H8-BINAP seem to and MeO-BIPHEP (39) (96.0% ee). As dihedral angles be ascribable to their structural difference. X-ray crystal- become narrower from BINAP (73.49°) to BIPHEMP lographic studies of the Ir(I) complex (S)-32 and its Rh(I) (72.02°) and MeO-BIPHEP (68.56°), higher% ee’s are analog, {Rh[(S)-H8-binap](cod)}ClO4, revealed that they obtained. In the previous X-ray crystallographic studies, it both show a significantly large dihedral angle (q) is reported that the dihedral angle between the two phenyl 18b,34 [80.0(0)° and 80.3(4)°, respectively,] between the rings in {Rh[(S)-biphemp](nbd)}ClO4 is narrower than two phenyl rings of the bitetralin moiety as compared to that between the two naphthalene rings in {Rh[(R)-bi- 35 that [74.4(2)°] between the two naphthalene rings in nap](nbd)}ClO4. In order to introduce the narrower di- 35 {Rh[(R)-binap](nbd)}ClO4. This is considered to be a hedral angle into the biaryl backbone, we could employ reflection of the larger steric hindrance of the hydrogen at- the 4,4’-bi-1,3-benzodioxole system, which is thought to oms attached to the sp3 carbon atoms in the bitetralin have the least rotational barrier among the atropisomeric 2 moiety of H8-BINAP than the hydrogen atoms on the sp biaryl systems. The dihedral angle of the bi-1,3-benzo- carbon atoms in the naphthalene rings of BINAP and is dioxole system in the ruthenium complex was estimated believed to exert influence on the arrangements of four to be 65° by using CAChe MM2 calculations. Compared phenyls on the phosphorous atoms, making the equatorial with naphthyl, Me or MeO group, its steric hindrance at coordination sites of the H8-BINAP–metal complex more these position is decreased by fixing to the cyclic system. crowded and the apical ones wider than those of the BI- Thus, we have synthesized the novel chiral diphosphine NAP analogs. Consequently, the H8-BINAP–metal com- ligand, (4,4’-bi-1,3-benzodioxole)-5,5’-diylbis(diphenyl- plexes shows different enantioselectivity on the phosphine), which is called SEGPHOS (40). coordination of substrate to metal because of the crowded equatorial sites and different hydrogenolysis rate of the metal–C bond by H2 due to a wider apical one as com- 2 pared to those in the BINAP–metal complexes.26b H2 (30 kg/cm ) O (R)-40—Ru cat. OH OH OH MeOH, 65 °C SEGPHOS 36 36 37 (98.5% ee)

Atropisomeric biaryl systems have often been used as bridges to produce an asymmetric environment, which Application of these ligands to ruthenium-catalyzed hy- can be applied to many chiral diphosphine ligands for the drogenations has given us an exceptionally active and transition-metal complex catalyzed asymmetric reactions. highly enantioselective catalytic system. The excellent The landmark ligand is the BINAP, in which the two phe- chiral recognition ability of (R)-SEGPHOS–Ru(II) com- nyl groups of the phosphine are oriented in an axial-equa- plex catalysts can be demonstrated by the hydrogenation torial relationship by the axially chiral binaphthyl of 36 to afford (2R)-37, which is a chiral building block of backbone. Despite the insufficient information in the liter- new quinolone antibacterial agents, in 98.5% ee (cf., BI- ature concerning the mechanism of the asymmetric con- NAP, 89% ee) and with substrate-to-catalyst ratio up to trol, in the biaryl-type ligands, one of the predominant 10,000.12 factors could be the dihedral angle in the chiral backbone.37

tBu O O OMe

t Me PPh2 MeO PPh2 O PPh2 O P Bu 2 t Me PPh2 MeO PPh2 O PPh2 O P Bu

O O OMe 2 tBu BIPHEMP 38 MeO-BIPHEP 39 (R)-SEGPHOS 40 DTBM-SEGPHOS 41

Synlett 2001, No. SI, 1055–1064 ISSN 0936-5214 © Thieme Stuttgart · New York NEW TOOLS IN SYNTHESIS Recent Advances of BINAP Chemistry in the Industrial Aspects 1063

Also, the (R)-SEGPHOS–Ru(II) complex was shown to M.; Ohta, T.; Takaya, H.; Noyori, R. J. Org. Chem. 1994, 59, be the efficient catalyst for the hydrogenation of the car- 297. bonyl compounds. However, the diastereoselectivity in (8) (a) Ohta, T.; Takaya, H.; Kitamura, M.; Nagai, K.; Noyori, R. J. Org. Chem. 1987, 52, 3174. (b) Ohta, T.; Takaya, H.; the hydrogenation of methyl (±)-2-(benzamidomethyl)-3- Noyori, R. Tetrahedron Lett. 1990, 31, 7189. oxobutanoate [(±)-9] was disappointingly low giving syn- (9) Takaya, H.; Ohta, T.; Sayo, N.; Kumobayashi, H.; (2S,3R)-10 with 79.6% de (Scheme 5). Aiming to attain Akutagawa, S.; Inoue, S.-I.; Kasahara, I.; Noyori, R. J. Am. the highest diastereoselectivity, we investigated to incor- Chem. Soc. 1987, 109, 1596, 4129. porate the substituents on the phenyl rings of SEGPHOS. (10) Ohta, T.; Miyake, T.; Seido, N.; Kumobayashi, H.; Takaya, H. Then we found that a diastereoselectivity was dramatical- J. Org. Chem. 1995, 60, 357. ly increased in the hydrogenation of 9 along with a high (11) Noyori, R.; Ohkuma, T.; Kitamura, M.; Takaya, H.; Sayo, N.; Kumobayashi, H.; Akutagawa, S. J. Am. Chem. Soc. 1987, enantioselectivity by employing a (-)-DTBM- 40 109, 5856. SEGPHOS –Ru(II) complex catalyst. Thus, the hydroge- (12) Kitamura, M.; Ohkuma, T.; Sayo, N.; Kumobayashi, H.; nation of 9 catalyzed by a (-)-41–Ru(II) complex gave Akutagawa, S.; Ohta, T.; Takaya, H.; Noyori, R. J. Am. Chem. (2S,3R)-10 in 98.6% de and 99.4% ee (cf., BINAP, 86% Soc. 1988, 110, 629. de).21 (13) Takaya, H.; Mashima, K.; Koyano, K.; Yagi, M.; Kumobayashi, H.; Taketomi, T.; Akutagawa, S.; Noyori, R. J. The SEGPHOS ligands based on our working hypothesis Org. Chem. 1986, 51, 629. has been shown the high efficiency in the asymmetric cat- (14) Cai, D.; Payack, J. F.; Bender, D. R.; Hughes, D. L.; alytic hydrogenations of a wide variety of carbonyl com- Verhoeven, T. R.; Reider, P. J. J. Org. Chem. 1994, 59, 7180. pounds. 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