Enantioselective Allylation of Carbonyl Compounds with Titanium-Carbohydrate Complexes.код для вставкиСкачать
Enantioselective Allylation of Carbonyl Compounds with Titanium-Carbohydrate Complexes ** By Martin Riediker* and Rudolf 0. Duthaler Among the stereoselective reactions reported so far the allylation of carbonyl compounds is unique in that several stereogenic centers can be generated in one step and the products exhibit versatile functionality.['] High enantioselectivity and double stereocontrol are achieved with allylnietal compounds containing chiral ligands, especially good results being obtained with allylboron compounds,['] allylstann a n e ~ [ and ~ ] allyI~ilanes.[~~ Largely due to the pioneering work of Seebach et aI.['"] and Reefz,[sblallyltitanium compounds and other organotitanates have been established as inexpensive, easily accessible and ecologically unobjectionable reagents. The chiral titanium complexes investigated so far, which have mainly been developed for asymmetric alkylation, were, however, not suited for the enantioselective transfer of ally1 groups.r6. The high diastereocontrol which can be achieved with such allyltitanium reagents [ 5 . would, nevertheless, lead one to expect that good enantioselectivity should also be realizable under suitable conditions. One of the first successes in this context was the high induction which was achieved in the transfer of chiral allyl groups to aldehydes.['] By reaction of cyclopentadienyltitanium(w) trichloride 1 with commercially available 1,2: 5,6-di-O-isopropylidene-a-D-glucofuranose ("diacetone-glucose")/triethylamine we obtained the stable dialkoxy(chloro)cyclopentadienyl titanate 2, which, in the absence of moisture, can be stored either as stock solution in ether (0.05-0.1 M) or toluene (0.1 0.2 M) o r as crystalline solid after precipitation with hexane . . 1 3 + (CpTiOH.0)" R*OH 5 Scheme 1. a) 1,2: 5.6-Di-O-isopropylidene-~-~-glucofuranosejEt~N~Et~O, room temperature (RT); b) Et,O, 0 T ; c) 1. -78 C. 2. H,O/THF. - 3 0 . C to RT. (Scheme 1). Highly stereoselective reagents can be prepared from this novel complex by exchange of the remaining chloro ligand for transferable groups." 'I Thus, reaction of 2 with allylmagnesium chloride affords the allyltitanium complex 3, which is brought to reaction in [*I ['I [**I Dr. M. Riediker [ '1, Dr. R. 0. Duthaler Zentrale Forschungslaboratorien. Ciba-Geigy AG Postfach, CH-4002 Basel (Switzerland) Present address: Research Laboratories, Plastics Division, Ciba-Geigy Corporation Ardsley, NY 10502 (USA) Enantioselective Syntheses with Titanium-Carbohydrate Complexes. Part 1. situ at -74°C with aldehydes; addition at the re-side leads, with numerous substrates, to homoallyl alcohols 4 in good yields and with high enantiomeric purity (Scheme 1, Table 1). The temperature dependence of this reaction is asTable 1. Enantioselective allylation of aldehydes with the reagent 3 (cf. Scheme 1). R Prod. Yield "1 Phenyl p-Nitrophenyl 2.3-Dihydro-1.4Benzodioxin-6-yl I-Naphthyl 9-Anthryl 9-Phenanthryl Vinyl x-Styryl Ethyl n-Propyl n-Nonyl lsobutyl lsopropyl Cyclohenyl [gl /err-Butyl Config. ce ["/.I la1 Ref. IbI [cl [& II 4a 4b 4c 85 82 78 R R R [el 90 91 90 pa]  4d 4e 4f 4g 4h 4i R R[e] R[e] R S S R R R 88 94 92 86 90 93 93 92 85 90 92 131 4m 4n 83 80 60 61 51 67 78 88 55 67 78 [2a] -11 7 [2e] -10.4 -22.4 [2a] 1.2  + 8.2 40 58 R 88 [2a] 4j 4k 41 R S (c) [dl +43.7 +23.6 +23.5 +76.2 + 19.9 +53.9 [2a] [2a] pa] -132 - 13.5 - 38 + +10.3 [a] The yields are. in general. not optimized. [b] Determination of the enantiomeric excess by capillary G C (Chirasil-L-Val" 1121) after derivatization with isopropyl isocyanate (4a, b,d, h, i, k-m, 0 ) or (R)-( +)-3.3,3-trifluoro-2methoxy-2-phenylpropionyl chloride 1131 (4g,j,n) o r by HPLC on a "Bakerbond Chiral Ionic DNBPG Column" (4c, or on cellulose triacetate  (4e). [c] The signs of the rotations in benzene correspond to the configurational assignments in the cited works. [d] Concentration in benzene. [el New compound: the configuration was assigned on the basis ofanalogies. [f'J I n Et,O. [g] In EtOH. n tonishingly small; thus, reaction with benzaldehyde at 0 "C furnishes the product 4 a with 80 % ee. By controlled hydrolysis the filterable titanate 5 can be precipitated and by treatment with HCI (g) reconverted into CpTiC1, l.[l6]In the process the chiral auxiliary diisopropylideneglucose can either be recovered or, after hydrolysis with 0.1 N HCI, be separated by aqueous extraction. As exemplified in Scheme 2 with the reactions of 6a, b, titanates such as 7a-c with substituted allyl groups are also highly enantioselective allylating reagents. These compounds are prepared from the corresponding lithium or Grignard reagents. As in the case of achiral allyltitanates['. 81 the diastereomeric purity of the products 8b,c is near the limit of detection ( 2 99%).['21 Reaction of racemic hydratopaldehyde 9 with 0.5 equivalents of allyl titanate 3 leads to formation of the stereoisomeric homoallyl alcohols 10-13 (80% based on 3) in the ratio 70.8:0.9:24.2:4.1, whereby loll1 are the products from (R)-9 and 12/13 those from ( 3 - 9 (Scheme 2). The moderate differentiation of enantiomers (2.5: 1) as well as the higher diastereoselectivity in the case of the more reactive enantiomer (R)-9 (97% de, matched case) would indicate a certain Cram selectivity of the reagent 3, which, however, is outweighed by the enantiofacial differentiation (71 % de in the case of (59-9, mismatched case). The titanium reagent 3 exhibits the usual chemoselectivity:''] at -74°C it does not react with ketones. At O'C, however, aryl ketones are transferred smoothly into tertiary homoallyl alcohols, but the asymmetric induction is, as expected, small (ca. 50% ee; 80% ec, however, in the case of acetophenone). In contrast to the allyl compounds, analogous alkyl- and aryltitanates d o not react with aldehydes, even at elevated temperatures. CpTi(OR*), 0 R I A H + 6 a , R ' = lsobutyl 6a, 6b, R'= lsobutyl R'= lsopropyl R 2 9" ___c d -78% R l T ?a, R Z - V i n y l 8 a , 6 8 %(90% 7b, 7c, 8b, 8c, R Z = C,H, R 2 = CH, EH, ee) 5 9 % ( 8 8 %ee j 46%(83%ee) CH, 10 (56.6%) 11 (0.7%) 12 13 (3.3%) (19.4%) Scheme 2. With the chiral reagents 3 and 7a-c the enantioselective allylation of aldehydes has been achieved for the first time with organotitanium compounds. Boron reagentsI2' exhibit a similar stereoselectivity, but the advantage of titanium must not be overlooked, e.g. simple preparation, chemoselectivity, inexpensive auxiliaries, as well as the possibility of recovering diisopropylideneglucose and CpTiCI, 1. Still a drawback of this method is, however, that the high price of L-glucose impedes an equally good access to the other enantiomers of the homoally1 alcohols 4. Concerted efforts are therefore currently directed a t solving this problem with other ligands. E.uperirnen tnl Stock solution of 2 in ether: A solution/suspension of 1 (11.0g. 50mmol. i n Et,O (400 mL. distilled over Naihenzophenone) was freshly treated with 26.0 g (0.1 mol) of 1.2: 5,6-di-O-isopropylidene-a-o-glucofuranose (R*OH, crystallized from cyclohexane) under argon in the absence of moisture. After 2 min at room temperature (RT) a solution of 15.2mL ( l l 0 m m o l ) of Et,N in 125 m L of Et,O was added dropwise to the stirred mixture within 1 h. The resulting suspension was stirred for ca. 15 h ; the E t , N . HCI was then filtered off under argon and washed three times with ca. 50 mL of Et,O (14 2 g o f E t , N . HCIvacuumdried).ThecontentofZin theyellowfiltrate(0.09 calculated from the volume of the solution assuming a quantitative conversion. was (R)-l-Phenyl-3-huten-l-ol(4a): 7.2 mL of a 1.25 M solution of allylmagnesium chloride in T H F (Aldrich, 9 mmol) was added dropwise within 10 min at O'C under argon to 110 mL of a ca. 0.09 M solution of 2 in Et,O (9.9 mmol). After stirring for 1 h at 0 C the orange suspension was cooled to - 74 C and treated within 5 niin with 0.8 m L (8 mmol) of henzaldehyde. The mixture was stirred for 2 h at - 74 C . warmed to ca. - 3 0 ' C and hydrolyzed by addition of 16 m L of a ca. 5 M solution of H,O in T H F (1 h, RT). Filtration, washing with Et,O and drying (high vacuum) yielded 4.2 g of 5 (yellowish solid). The filtrate was evaporated and the solid residue stirred with 100 m L of hexane. Subsequent filtration furnished 4.4 g of R*OH. Chromatography (80 g silica gel, hexane: AcOEt 3.1) finally afforded 1.01 g (85%) of 4 a (90% w, determined as described in (121). Received: December 21. 1Y88 [Z 3095 IE] German version: Angeir. Chern. 101 (1989) 488 [ I ] a ) R. W. Hoffmann, Angew. Cltenr. Y4 (1982) 569; Angeir. Cliern. Inr. Ed. Gig /. 21 (1982) 555: b) Y. Yamamoto. A c r . C/rc,m. Rrs. 20 (1987) 243.  a ) R W Hoffmann. T. Herold. Chrm. Ber. 114(1981) 375; b) R . W. Hoffmann. Pure Appl. Chem. 60 (1988) 123; c ) H. C. Brown. P. K.Jadhav. 1 Am. C h m . SJC.. 105 (1983) 2092; d ) H. C. Brown. P. K.Jadhav. K. S. Bhat. hid. /10(1988) 1535;e) W. R. Roush. A. E. Walts, L. K. Hoong, ;bid 107 (1985) 8186; 0 W. R. Roush, L. Banfi, ihM. 110 (1988) 3979: g) W. R. Roush. K.Ando. D. B. Powers, R. L. Halterman. A. D. Palkowitz. Ewuhedron Let!. 29 (1988) 5579: h) M. T. Reetz, T. Zierke, Chon. Ind. (London) 1988. 663 (31 a ) N.Minowa. T. Mukaiyama, BUN. Chem. S o c . J p . (50 (1987) 3697; h) G. P. Boldrini, L. Lodi. E.Tagliavini, C. Tarasco. C Trombini. A. UmaniRonchi. J. Org. Chem. 51 (1987) 5441. 141 a) T. Hayashi, Y. Matsumoto. T. Kiyoi, Y. Ito, S. Kohra. Y. Tominaga. A. Hosomi. Tc.fru/fedronLerr. 29 (1988) 5667; b) R. lmwinkelried. D. Seehach. Angew. Cliem. 97 (1985) 781 :A n g e ~ Chern. . In/. Ed. Engl. 24 (1985) 765; c) A. Hosomi, Arc. Clwm. Res. 11 (1988) 200.  a) D. Seebach, B. Weidmann, L. Widler in R. Scheffold (Ed.): Motlwn STnrhrrir Merhods, Vo/. 3, Salle. Frankfurt am Main, Sauerlinder. Aarau 1983. p. 217; b) M. T. Reetz: Orgnno/itunium Rwgenr.\ in Orguwk Ssnr/leSLY, Springer, Berlin 1986.  D. Seebach, A. K. Beck, R. Imwinkelried, S. Roggo, A. Wonnacott, H c h . Chrm. Arru 70 (1987) 954. (71 a) M. T. Reetz. S.-H. Kyung, J. Westermann, Orgonofnefu/lic\3 (1984) 1716: b) H . Takahashi. A. Kawabata, K. Higashiyama. Chm?. Phunn. BUN.35 ( 1987) 1604.  a) F. Sato, K. Iida. S. Iijima. H. Moriya. M. Sato, 1 C/?em.So<..Cilrm. Commim. I Y N I , 1140: h) M. T. Reetz. M. Sauerwald. J. Org. Chon. 4Y (1984) 2292: c) S. Collins, W P. Dean, D. G. Ward. Orgunonrr/u//ir.~ 7 (1988) 2289: d ) D. Seebach, L. Widler, Hrlv. Chin?.Arro 65 (1982) 1972; e) M. T. Reetz. R. Steinbach, J. Westermann, R. Peter, B. Wenderoth, C h ~ mBer. . I18 (1985) 1441.  a) H. Roder. G Helmchen, E. M. Peters, K. Peters, H.-G. von Schnering. Angcw. Clirm. 96 (1984) 895; Angew. Cltem. In,. Ed. Engl 23 (1984) 898: b) T. Krimer, D. Hoppe. l?/roheilron Lerr. 28 (1987) 5149. [lo] R . D. Gorsich, 1 An?. Chon. S o l . 82 (1960) 421 1. [I11 M. Riediker, R. W. Lang, R. Duthaler. P. Herold, K. Oertle. G. Bold, Eur. Pat.-Anm. 0254685 (27. Jan. 1988). Ciba-Geigy AG.  H. Frank, G. J. Nicholson, E. Bayer, Angeti. Chern. 90 (1978) 396: Angriv. Ch(,m. I n f . Ed. Engl. 1 7 (1978) 363. [I31 J. A. Dale, H. S. Mosher. J. Am. Chetn. Sor. Y5 (1973) 512.  H. Koller, K:H. Rimhock, A. Mannschreck.1 Chromutogr. 282(1983) 89.  B. Cazes, C.Verniere, J. Gore, SJ,n/h.Cotnmun. 13 (1983) 73.  With one equivalent of conc. HCI a crystalline tetramer is formed; A. C. Skapski. P. G . H. Troughton, Arru Cry.s/u//ngr.S ~ r r8. 2 6 (1970) 716. Enantioselective Aldol Reaction of tevt-Butyl Acetate using Titanium-Carbohydrate Complexes ** By Rudolf 0. Duthaler,* Peter Herold, Willy Lottmhuch, Konrad Oertle, and Murtin Riediker The Aldol reaction is one of the most important methods for the stereoselective construction of complex acyclic molecules.~']Covalently bound chiral auxiliaries readily induce high stereoselectivity in the case of propionate enolates. whereas in the case of acetate enolates this could hitherto only be achieved via a circuitous route involving auxiliary substituents.l2] More recently, methods have been developed which enable the stereoselective addition of a-unsubstituted enolate~.[~ AI particularly efficient approach makes use of metal complexes with chiral l i g a n d ~ . [It~should, ] however, be mentioned, that many j3-hydroxy esters (such as 4) are accessible by enantioselective reduction of the corresponding j3-0x0 esters as ~ e I 1 . [ ~ ] The successful asymmetric allylation of carbonyl compounds with novel cyclopentadienyltitanium-carbohydrate motivated us to apply this principle also to the acetate-Aldol rea~tion!'~ We have found that, in this way, a variety of j3-hydroxycarboxylic acids are accessible in 9095 o/o optical purity (Scheme 1 , Table 1). [*I [ '1 [**I Dr. R. 0. Duthaler. Dr. P. Herold, Dr. W. Lottenbach. Dr. K. Oertle. Dr. M. Riediker [ + ] Zentrale Forschungslaboratorien. Ciba-Geigy AG Postfach. CH-4002 Bascl (Switzerland) Present address: Research Laboratories, Plastics Division. Ciba-Geigy Corporation Ardsley. NY 10502 (USA) Enantioselective Syntheses with Titanium-Carbohydrate Complexes. Part 2.--Part 1 : 161.