Asymmetric Synthesis of O-Acetylcyanohydrins with Chiral Salen Complexes, Papers of Art

Download Asymmetric Synthesis of O-Acetylcyanohydrins with Chiral Salen Complexes and more Papers Art in PDF only on Docsity! Catalytic Asymmetric Synthesis of O-Acetylcyanohydrins from Potassium Cyanide, Acetic Anhydride, and Aldehydes, Promoted by Chiral Salen Complexes of Titanium(IV) and Vanadium(V) by Yuri N. Belokon*a), Paola Cartac), Andrey V. Gutnova), Viktor Maleeva), Margarita A. Moskalenkoa), Lidia V. Yashkinaa), Nicolai S. Ikonnikova), Nikolai V. Voskoboevb), Viktor N. Khrustaleva), Michael North*c) a) A. N. Nesmeyanov Institute of Organo-Element Compound, Russian Academy of Sciences, 119991 Moscow, Vavilov 28, Russia (fax: (
7)-095-135-5085; e-mail : yubel@ineos.ac.ru) b) Higher Chemical College, Russian Academy of Sciences, 125047 Moscow, Miusskaya pl. 9, Russia c) Department of Chemistry, King×s College, Strand, London, WC2R 2LS, UK (fax:
44(0)870-131-3783; e-mail : michael.north@kcl.ac.uk) Dedicated to Professor Dieter Seebach on the occasion of his 65th birthday The utility of the chiral [Ti(
-O)(salen)]2 complexes (R)- and (S)-1 (H2salen was prepared from (R,R)- or (S,S)-cyclohexane-1,2-diamine and 3,5-di(tert-butyl)-2-hydroxybenzaldehyde) as catalysts for the asymmetric addition of KCN and Ac2O to aldehydes to produce O-acetylcyanohydrins was investigated. It was shown that the complexes were active at a substrate/catalyst ratio of 100 :1 and produced the O-protected cyanohydrins with ee in the range of 60 ± 92% at  40
. Other complexes, [Ti2(AcO)2(
-O)(salen)2] ((R)-4) and [Ti(CF3COO)2(salen)] ((R)-5), were prepared from (R)-1 by treatment with different amounts of Ac2O and (CF3CO)2O, and their catalytic activities were tested under the same conditions. The efficiency of (R)-4 was found to be even greater than that of (R)-1, whereas (R)-5was inactive. The synthesis of the corresponding salen complexes of VIVand VV, [V(O)(salen)] ((R)-2) and [V(O)(salen)(H2O)] [S(O)3OEt] ((R)-3), was elaborated, and their X-ray crystal structures were determined. The efficiency of (R)-3 was sufficient to produce O-acetyl derivatives of aromatic cyanohydrins with ee in the range of 80 ± 91% at  40
. Introduction. ± As enantiomerically pure cyanohydrins are versatile intermediates in organic synthesis, many synthetic approaches to their syntheses are being vigorously pursued [1]. The catalytic ways of making this class of compounds rely upon the asymmetric addition of a cyanide source to the carbonyl group of aldehydes, as catalyzed by enzymes [2] or purely chemical chiral catalysts [3]. Enantiomerically enrichedO-protected cyanohydrins are customarily made by the reaction of aldehydes with Me3SiCN usually catalyzed by chiral Lewis acids [1]. We recently reported an efficient catalysis of this reaction by the chiral binuclear [TiIV(salen)] complex 1 (Fig. 1), active at a ratio of substrate/catalyst as high as 1000 :1 and promoting the addition at room temperature with ee in the range of 80 ± 92% [4]. Very efficient catalysts based on bifunctional complexes of AlIII and TiIV have also been developed by Shibasaki and co-workers, givingO-(trimethylsilyl) derivatives of cyanohydrins with ee as high as 90 ± 99% at  42
[5]. Unfortunately, Me3SiCN is an expensive material, and HCN is extremely toxic. Evidently, there is a need to find cheaper and safer initial materials for the synthesis of enantiomerically pure O-protected cyanohydrins. This paper reports the asymmetric synthesis of O-acetylcyanohydrins by the reaction of KCN, acetic anhydride (Ac2O),
    ± Vol. 85 (2002) 3301 and aldehydes catalyzed by complexes 1 (Scheme 1) and the analogously built VIV and VV complexes (R)-2 and (R)-3, respectively. A preliminary report of some of these results was published earlier [6]. Results and Discussion. ± Initial experiments revealed that the combination of KCN, benzaldehyde, and Ac2O (added as the last ingredient) in the presence of 1 mol- % of catalysts (R)- or (S)-1 produced enantiomerically enrichedO-acetylcyanohydrins of (S)- or (R)-configuration, respectively. The transformation showed good reprodu- cibility and the absence of any side reactions. The reaction was strongly dependent on the nature of the cyanide counterion. The best results of the model reaction, according to Scheme 1 (dihydrocinnamaldehyde, alkali-metal cyanide, Ac2O, CH2Cl2,  42
, 8 h under vigorous stirring in the presence of (S)-1), were obtained with KCN, and the range of enantiomer purity of the resulting (R)-O-acetylcyanohydrin was as follows: KCN (82% ee)
RbCN (76% ee)
NaCN (56% ee)
CsCN (54% ee)
LiCN (4% ee). The addition of 1 equiv. of Bu4NBr to the mixture resulted in the formation of completely racemic product. The reaction of benzaldehyde and KCN catalyzed by (R)-1, according to Scheme 1, was also solvent-dependent and gave, at  20
after 8 h of stirring, (S)-O-acetylman- delonitrile (-(acetyloxy)benzeneacetonitrile) with the following ee: 1,2-dichloro- Scheme 1. Synthesis of Chiral O-Acetylcyanohydrins Promoted by Salen-Type Chiral Complexes
    ± Vol. 85 (2002)3302 Fig. 1. Chiral dinuclear [TiIV(salen)] catalysts 1 also catalyze the synthesis of enantiomerically enriched O-acetylcyanohydrins. In addition, it was of interest to learn if similarly constructed complexes of VV could be involved in the catalytic cycle. Therefore, the VIV and VV complexes (R)-2 and (R)-3, respectively, were prepared from the same initial material (Scheme 2), the only difference being the use of an inert-gas atmosphere in case of (R)-2 and the necessary presence of an oxidizing agent, O2, in case of (R)-3 (the enantiomeric complexes can be obtained in the same manner). The solid-state structures of (R)-2 and (R)-3 were determined by X-ray analysis (Figs. 2 and 3). Both complexes are monomeric with a central VO moiety and the distorted planar chiral salen ligand occupying the four coordination sites of the central metal. The remaining positive charge of the central VV atom of (R)-3 is neutralized by an ethyl sulfonate anion (presumably formed in situ from the vanadyl sulfate and EtOH) that is not coordinated to the metal. Instead, a H2Omolecule occupies the remaining vacant coordination position at the metal in (R)- 3, whereas in (R)-2, the position is taken by one toluene solvent molecule sandwiched between two molecules of the VIV complex. Under the experimental conditions of the addition of KCN and Ac2O to benzaldehyde catalyzed by (R)-1 (without any additives), the corresponding VIV and VV complexes showed different catalytic behavior. In spite of its efficiency in promotion of the addition of Me3SiCN to aldehydes, (R)-2 was not a very efficient catalyst compared to the TiIV complex in the addition of KCN to aldehydes. On the other hand, VV-derived (R)-3 proved to be catalytically active, converting aldehydes into the correspondingO-acetylcyanohydrins in the presence of KCN and Ac2O at low temperatures. As expected, (R)-3 converted aldehydes into (S)-cyanohydrins, and its
    ± Vol. 85 (2002) 3305 Scheme 2. Synthesis of Salen Complexes of VIV and VV
    ± Vol. 85 (2002)3306 Fig. 3. Molecular structure of (R)-2 with 30% probability ellipsoids of anisotropic displacements. The two independent molecules and three solvate toluene molecules are shown. Fig. 4. Crystal structure of salt (R)-3 (one of the two independent structures are illustrated) with 50% probability ellipsoids of anisotropic displacements. The solvate toluene molecule is not shown. enantiomer furnished (R)-cyanohydrins. Table 3 summarizes the results of syntheses catalyzed by (R)-3. Although we have no experimental data related to the mechanism of VV catalysis, some similarity with the TiIV catalyst can be assumed, as the sense of chirality and the magnitude of asymmetric induction were almost the same in both (R)-1 and (R)-3 cases. The key step of the formation of the CCN bond is most likely similar for both Me3SiCN addition and KCN/Ac2O addition catalyzed by (R)-1 and (S)-1, as the almost identical ee and sense of chirality testify (cf. data of [4a,b] and the data of Table 2). The key feature of the mechanism, suggested by us earlier [4b], is the formation of an intermediate chiral Ti-cyanide-metalloacetal complex where the cyanide ion attacks the aldehyde carbonyl C-atom intramolecularly with the formation of a Ti-coordinated cyanohydrin. According to this mechanism, the O-atom or O-atoms, bridging two TiIV ions of the salen complexes, play the most important role in the scheme. The controlled interaction of 1 equiv. of Ac2O with (R)-1 gave the corresponding mono-bridged dinuclear [Ti2(AcO)2(salen)2(
-O)] ((R)-4 ; Scheme 3), the solid-state structure of which was established by X-ray-analysis (see Fig. 5). Any attempts to obtain diacetato complex [Ti(AcO)2(salen)] by the interaction of (R)-4 with another equiv. of Ac2O resulted in failure, and even further, after heating (R)-4 in Ac2O, only the initial mono-bridged complex and some decomposition products were detected. In accordance with the mechanism, complex (R)-4 was an even more efficient catalyst than (R)-1, catalyzing the formation of (S)-O-acetylmandelonitrile with an ee of 70% and kobs 0.021 s1 at room temperature, as compared to an ee of 74% and kobs 0.01 s1 obtained under identical conditions without any additives in the case of (R)-1. The [Ti(CF3COO)2(salen)] complex (R)-5 could also be easily prepared by treatment of (R)-1 with (CF3CO)2O and was found to be catalytically inactive in the Me3SiCN addition and only marginally active in the KCN/Ac2O addition. Furthermore, addition of benzaldehyde to (R)-4 before addition of KCN was necessary for the catalysis to be observed. If KCN was added first to (R)-4, no catalytic reaction was detected. Thus, the presented data serve to support the suggestion that the O-bridged dinuclear complexes and metalloacetal formation serve to generate the real catalyst of the cyanation reaction. The underlying reason for the failure to apply (CF3CO)2O or AcCl in the reaction could be traced to the complete breaking of the O-bridges in the catalysts by the too active acylating agents. The breaking of the Ti-O bond of the coordinated cyanohydrin by interaction with Ac2O or ROH may be the rate-limiting stage. The latter feature of the mechanism can Table 3. Addition of KCN/Ac2O to RCHO in the Presence of VV Catalyst (R)-3a) Aldehyde ee of (S)-O-Acetylcyanohydrinb) Yield [%] PhCHO 90.3c) 87.2c) 3-MeOC6H4CHO 84.88 97 (NMR) 2-ClC6H4CHO 77.62 99 (NMR) a) Conditions: concentration of aldehydes 0.4 ± 1.2 (mol ratio aldehyde/KCN/Ac2O 1 : 4 : 4), promoted by 1 mol-% of (R)-3 in CH2Cl2/tBuOH/H2O 2500 : 10 : 1), 10 h, stirring at  42
. b) Determined by chiral GLC. c) On a 4 ± 6 g scale experiment.
    ± Vol. 85 (2002) 3307 fresh portion of the phosphate buffer (200 ml) was then added to the org. layer. The mixture was vigorously stirred for 30 min until the soln. turned yellow. The org. layer was then washed with H2O, dried (Na2SO4), and evaporated and the resulting yellow residue dried at 1 Torr: (R)- or (S)-1 (1.3 g, 71%). (R)-1: M.p. 315
(dec.).  25D 267 (c 0.01, CHCl3). IR (CH2Cl2): 2962s, 2865m, 1625s, 1555m, 687w. 1H-NMR (400 MHz, CDCl3): 1.04 (s, 9 H); 1.22 (s, 9 H); 1.31 (s, 9 H); 1.40 (s, 9 H); 2.5 ± 2.6 (m, 4 H); 4.0 ± 4.1 (m, 2 H); 6.95 (s, 1 H); 7.05 (s, 1 H); 7.23 (s, 1 H); 7.42 (s, 1 H); 7.75 (s, 1 H); 8.15 (s, 1 H). 13C-NMR (75 MHz, CDCl3): 24.6; 24.9; 28.1; 29.7; 30.1; 31.5; 31.7; 34.1; 35.0; 35.7; 65.7; 69.8; 121.0; 125.8; 127.5; 128.0; 128.5; 137.6; 138.0; 139.1; 139.4; 157.1; 161.3. Anal. calc. for C72H104N4O6Ti2: C 71.04, H 8.61, N 4.60, Ti 7.87; found: C 71.03, H 8.80, N 4.46, Ti 7.91. 4. [VIV(salen)] Complex (R)-2. The solns. of (1R,2R)-N,N-bis[3,5-di(tert-butyl)salicylidene]cyclohexane- 1,2-diamine (1.0 g, 1.8 mmol) in pyridine (4 ml) and of vanadyl sulfate hydrate (0.55 g, 2.0 mmol) in hot EtOH (40 ml) were mixed under Ar and refluxed for 2 ± 3 min until a crystalline solid began to precipitate. The mixture was allowed to cool to r.t., and light-green crystals were collected by filtration after 3 h, washed thoroughly with EtOH, and dried in vacuo: 1.01 g (90.3%) of pure (R)-2.  25D 442 (c 0.01, CHCl3). IR (KBr): 1615s, 984w. Anal. calc. for C36H52N2O3V: C 70.68; H 8.57; N 4.58; V 8.33; found: C 70.65; H 8.51; N 4.57; V 8.31. Data of (S)-2 :  25D 
467 (c 0.01, CHCl3). 5. [VV(salen)] Complex (R)-3. The solns. of (1R,2R)-N,N-bis[3,5-di(tert-butyl)salicyliden]cyclohexane-1,2- diamine (1.0 g, 1.8 mmol) in THF (20 ml) and of vanadyl sulfate hydrate (0.55 g, 2.0 mmol) in hot EtOH (32 ml) were mixed and stirred under reflux for 2 h in air. Then the solvent was evaporated and the residue dissolved in CH2Cl2 and submitted to column chromatography (SiO2, CH2Cl2, then AcOEt/MeOH 2 :1): 0.6 g (53%) of (R)- 3. Dark-green crystalline solid that can be recrystallized from benzene/CH2Cl2.  25D 914 (c 0.01, CHCl3). IR (KBr): 1618s, 1250w, 965w. 1H-NMR (400 MHz, CDCl3): 0.83 (t, J 7.2, 3 H); 1.33 (s, 18 H); 1.49 (s, 18 H); 1.7 ± 2.2 (m, 8 H); 3.41 (q, J 7.2, 2 H); 3.81 (m, 1 H); 4.26 (m, 1 H); 7.49 (s, 1 H); 7.52 (s, 1 H); 7.68 (s, 1 H); 7.73 (s, 1 H); 8.53 (s, 1 H); 8.73 (s, 1 H). Anal. calc. for C38H59N2O7SV¥H2O: C 60.30, H 8.12, N 3.70, S 4.24; found: C 60.45, H 8.12, N 3.62, S 4.30. 6. [Ti2(AcO)2(
-O)(salen)2] Complex (R)-4. To a soln. of (R)-1 (0.243 g, 0.0002 mol) in hexane (10 ml), Ac2O (0.038 ml, 0.0004 mol) was added, and the mixture was stirred for 12 h. The precipitated solid was then filtered off and washed with benzene: 0.205 g (77.7%) of nearly pure (R)-4 that was further purified by recrystallization from benzene/CH2Cl2.  25D 178 (c 0.05, CHCl3). IR (KBr): 1629s, 707w. 1H-NMR (400 MHz, CDCl3): 1.07 (s, 9 H); 1.32 (s, 9 H); 1.35 (s, 9 H); 1.44 (s, 9 H); 1.25 ± 3.25 (m, 16 H); 3.45 (m, 1 H); 4.18 (m, 1 H); 7.15 (s, 1 H); 7.20 (s, 1 H); 7.42 (s, 1 H); 7.52 (s, 1 H); 7.99 (s, 1 H); 8.10 (s, 1 H). Anal. calc. for C76H110N4O9Ti2 ¥H2O: C 68.25, H 8.44, N 4.19; found: C 68.01; H 8.43 N 4.09. 7. Attempted Synthesis of [Ti(AcO)2(salen)] Complex. A soln. of (R)-1 (24.4 mg, 0.00002 mol) in Ac2O (7 ml, 0.074 mol) was stirred for 12 h. The resulting soln. was evaporated and the residue examined by 1H-NMR: spectrum identical to those of (R)-4. 8. [Ti(CF3COO)2(salen)] Complex (R)-5. To a soln. of (R)-1 (0.243 g, 0.0002 mol) in CH2Cl2 (5 ml), (CF3CO)2O (0.115 ml, 0.00081 mol) was added, and the mixture was stirred for 12 h. The resulting mixture was filtered, and the filtrate was evaporated: 0.314 g (96%) of nearly pure (R)-5.  25D 25 (c 0.05, CHCl3). IR (KBr): 1629s. 1H-NMR (400 MHz, CDCl3): 1.34 (s, 9 H); 1.49 (s, 9 H); 1.22 ± 2.05 (m, 6 H); 2.13 (m, 2 H); 2.63 (m, 2 H); 4.02 (m, 2 H); 7.35 (m, 1 arom. H); 7.62 (m, 1 arom. H); 8.38 (s, 2 CHN). Anal. calc. for C40H52F6N2O6Ti: C 58.68, H 6.40, N 3.42; found: C 58.65, H 6.75, N 3.11. Under the same conditions, but with 0.00042 mol (0.059 ml) of (CF3CO)2O, complex [Ti2(CF3COO)2(
- O)(salen)2] was obtained.  25D 124 (c 0.05, CHCl3). IR (KBr): 1629s, 707w. 1H-NMR (400 MHz, CDCl3): 1.08 (s, 18 H); 1.32 (s, 18 H); 1.36 (s, 18 H); 1.40 (s, 18 H); 1.2 ± 1.4 (m, 8 H); 1.66 (m, 4 H); 2.00 (m, 2 H); 2.40 (m, 2 H); 3.81 (m, 2 CHN); 3.41 (m, 2 CHN); 7.21 (m, 2 arom. H); 7.26 (m, 2 arom. H); 7.50 (m, 2 arom. H); 7.56 (m, 2 arom. H); 8.12 (s, 2 CHN); 8.19 (s, 2 CHN). Anal. calc. for C76H104F6N4O9Ti2 ¥ 3 CF3COOH: C 55.66, H 6.09, N 3.17; found: C 55.18, H 5.51, N 3.08. 9. Addition of KCN/Ac2O to Aldehydes Catalyzed by 1: General Procedure: The experiment with (S)-1 is described as example: A stirred mixture of KCN (12.37 g, 0.19 mol), (S)-1 (0.487 g, 4 ¥ 104 mol), tBuOH (3.7 g, 4.8 ml, 5.0 ¥ 102 mol), and 2-chlorobenzaldehyde (6.68 g, 5.35 ml, 4.75 ¥ 102 mol) in dry CH2Cl2 (120 ml) was cooled to  42
, and Ac2O (19.4 g, 17.9 ml, 0.19 mol) was then added in one portion. The mixture was stirred for 7 h at  42
. Solid salts were filtered and washed thoroughly with CH2Cl2. To remove the catalyst, the filtrate was passed through a silica-gel pad (10 mm 50 mm) eluting with CH2Cl2. The solvent was evaporated, and the resulting yellowish residue distilled in vacuo: 8.87 g (88.6%) of (R)-(2-chlorophenyl)(cyano)methyl acetate. B.p. 127 ± 130
/0.2 Torr. ee 88.3%.  25D 
27 (c 1, CHCl3). n 25D  1.5189. 1H-NMR (200 MHz, CDCl3,): 2.15 (s, 3 H); 6.66 (s, 1 H); 7.32 ± 7.70 (m, 4 H). Anal. calc. for C10H8ClNO2: C 57.30, H 3.85, Cl 16.91, N 6.68; found C 56.93, H 3.83, Cl 17.03, N 6.69.
    ± Vol. 85 (2002)3310 10. Addition of KCN/Propanoic Anhydride to Benzaldehyde Catalyzed by 1. To a stirred mixture of KCN (2.54 g, 39.21 mmol) and catalyst 1 (0.119 g, 0.098 mmol) in dry CH2Cl2 (20 ml) cooled to  90
, tBuOH (0.98 ml, 10.3 mmol), followed by H2O (0.1 ml, 4.4 mmol), benzaldehyde (0.95 ml, 9.8 mmol), and propanoic anhydride (5.08 ml, 39.2 mmol) were added. The mixture was warmed to  40
and stirred for 48 h. The mixture was filtered, the solid washed thoroughly with CH2Cl2, and the filtrate passed through a silica-gel pad (10 mm 50 mm) eluting with CH2Cl2 to remove the catalyst. The solvent was evaporated and the residue purified by flash chromatography (AcOEt/hexane 1 :5): 1.83 g (99%) of (S)-cyano(phenyl)methyl propanoate. ee 92%.  25D  5.09 (c 1.08, CHCl3). IR (neat): 2987m, 1756s. 1H-NMR (CDCl3): 1.20 (t, J 7.5, MeCH2); 2.3 ± 2.6 (m, MeCH2); 6.45 (1 s, CHCN); 7.4 ± 7.6 (m, 5 arom. H). 13C-NMR (CDCl3): 7.70; 26.70; 62.13; 115.65; 127.16; 128.59; 129.69; 131.29; 170.67. EI-MS: 189 (15, [M
H]
), 133 (30), 116 (34), 57 (100). 11. Addition of KCN/Ac2O to Benzaldehydes Promoted by Catalyst (R)-3 : General Procedure. To a stirred mixture of KCN (12.37 g, 190 mmol), tBuOH (3.7 g, 4.8 ml, 50 mmol), and benzaldehyde (5.21 g, 5 ml, 47.5 mmol) in CH2Cl2 (50 ml), H2O (0.5 ml, 31 mmol) was added. The mixture was then cooled to  42
(MeCN/CO2) and (R)-3 (0.35 g, 0.475 mmol) in CH2Cl2 (20 ml) was added, followed by Ac2O (11.41 g, 10.55 ml, 190 mmol) in one portion. The mixture was vigorously stirred for 10 h at  42
. Solid salts were then filtered and washed thoroughly with CH2Cl2. To remove the catalyst, the mixture was filtered through a silica-gel pad (10 mm 50 mm) eluting with CH2Cl2. The solvent was evaporated and the resulting light green residue fractionated in vacuo: 7.5 g (87.2%) of cyano(phenyl)methyl acetate. B.p. 95 ± 97
/0.2 Torr. ee 90.3% (S). 12. X-Ray Crystal-Structure Determination. The details of crystal-data collection and structure-refinement parameters for compounds (R)-2, (R)-3, and (R)-4 are listed in Table 4. The structures were solved by the direct methods and refined by the full-matrix least-squares technique on F 2 with anisotropic approximations for non-
    ± Vol. 85 (2002) 3311 Table 4. Crystallographic Data for Compounds (R)-2, (R)-3, and (R)-4 (R)-2 (R)-3 (R)-4 Empirical formula C36H52N2O3V¥ 1.5 C7H8 [C36H54N2O4V]
[C2H5O4S] ¥ 0.5 C7H8 C76H110N4O9Ti2 ¥H2O Mr 749.94 800.94 1337.50 Crystal size [mm] 0.2 0.1 0.05 0.5 0.3 0.2 0.3 0.2 0.1 Crystal system monoclinic triclinic monoclinic Space group P21 P1 C2 a [ä] 13.039(2) 8.826(2) 14.656(3) b [ä] 12.525(2) 16.220(3) 31.261(6) c [ä] 26.445(5) 16.494(3) 16.180(3)  [
] 90 108.43(3) 90  [
] 99.331(4) 91.55(3) 91.48(3)  [
] 90 95.10(3) 90 V [ä3] 4261.9(14) 2227.5(8) 7411(3) Z 4 2 4 dc [Mg/m3] 1.169 1.194 1.199 Diffractometer SMART CCD 1000 Siemens P3 Syntex P21 Radiation,  [ä] MoK , 0.71073 MoK , 0.71073 MoK , 0.71073
[mm1] 0.273 0.319 0.274 T [K] 120 293 163 Scan mode  and  /2 /2 max [
] 27 25 25 Absorption correction semi-empirical none none Tmin, Tmax 0.7568, 0.9281 ± ± Reflections collected 41462 9259 6970 Independent reflections 18506 8348 6744 Reflections with I
2 (I) 11325 7131 5048 Refined parameters 946 966 857 R1 0.0561 0.0497 0.0765 wR2 0.1412 0.1324 0.2070 Flack parameter 0.00(2) 0.00(2) 0.01(5) S 0.900 1.029 1.033 H-atoms. The crystals of (R)-2 and (R)-3 contain 1.5 and 0.5 solvate toluene molecules, respectively. The crystal of (R)-4 contains two solvate H2Omolecules. Both the molecules of (R)-4 and molecules of solvate H2O occupy special positions on the two-fold (C2) axis. Two of the eight tert-butyl groups of molecules of (R)-4 are disordered over two sites by turning by 60
around Calk ±Car bond with occupancies 0.7 :0.3 and 0.85 :0.15, respectively, for two independent molecules. Positions of all H-atoms of (R)-2, (R)-3, and (R)-4 were geometrically calculated and refined isotropically in the riding model with fixed displacement parameters (Uiso(H) 1.5Ueq(C) for the Me groups and Uiso(H) 1.2Ueq(C) for the other groups). The absolute configurations were objectively determined by the refined Flack parameters. All calculations were carried out by means of the SHELXTL (PCVersion 5.10) program [8]. The crystallographic information files have been deposited at the Cambridge Crystallographic Data Centre (CCDC) , No 186928, 186929, and 186930. Copies of the data can be obtained, free of charge, on application to the CCDC, 12 Union Road, Cambridge CB2 1EZ UK (fax:
44(1223)336033; e-mail : deposit@ccdc.cam.ac.uk). REFERENCES [1] M. North, Synlett 1993, 807; F. Effenberger, Angew. Chem., Int. Ed. 1994, 33, 1555; M. North in −Comprehensive Organic Functional Group Transformations×, Eds. A. R. Katritzky, O. Meth-Cohn, C. W. Rees, and G. Pattenden, Pergamon Press, Oxford, 1995, Vol. 3, Chapt. 18; R. J. H. Gregory, Chem. Rev. 1999, 99, 3649. [2] H. Griengl, H. Schwab, M. Fechter, TIBTECH 2000, 18, 252; A. Schmid, J. S. Dordick, B. Hauer, A. Kiener, M. Wubbolts, B. Witholt, Nature (London) 2001, 409, 258; H. Hirohara, M. Nishizawa, Biosci. Biotechnol. Biochem. 1998, 62, 1. [3] J.-I. Oku, N. Ito, S. Inoue, Macromol. Chem. 1979, 180, 1089; A. Mori, Y. Ikeda, K. Kinoshita, S. Inoue, Chem. Lett. 1989, 2119. [4] a) Yu. N. Belokon, S. Caveda-Cepas, B. Green, N. S. Ikonnikov, V. N. Khrustalev, V. S. Larichev, M. A. Moscalenko, M. North, C. Orizu, V. I. Tararov, M. Tasinazzo, G. I. Timofeeva, L. V. Yashkina, J. Am. Chem. Soc. 1999, 121, 3968; b) Y. N. Belokon, B. Green, N. S. Ikonnikov, V. S. Larichev, B. V. Lokshin, M. A. Moscalenko, M. North, C. Orizu, A. S. Peregudov, G. I. Timofeeva, Eur. J. Org. Chem. 2000, 2655; c) Yu. N. Belokon, B. Green, N. S. Ikonnikov, M. North, T. Parsons, V. I. Tararov, Tetrahedron 2001, 57, 771. [5] Y. Hamashima, M. Kanai, M. Shibasaki, Tetrahedron Lett. 2001, 42, 691; Y. Hamashima, D. Sawada, H. Nogami, M. Kanai, M. Shibasaki, Tetrahedron 2001, 57, 805; K.Yabu, S. Masumoto, S.Yamasaki, Y. Hamashima, M. Kanai, Wu Du, D. Curran, M. Shibasaki, J. Am. Chem. Soc. 2001, 123, 9908. [6] Y. N. Belokon, A. V. Gutnov, M. A. Moskalenko, L. V. Yashkina, D. E. Lesovoy, N. S. Ikonnikov, V. S. Larichev, M. North, Chem.Commun. 2002, 244. [7] Y. N. Belokon, M. North, T. Parsons, Org. Lett. 2000, 2, 1617. [8] G. M. Sheldrick, −SHELXTL×, V5.10, Bruker AXS Inc., Madison, WI-53719, USA, 1997. Received May 29, 2002
    ± Vol. 85 (2002)3312