TW552265B - Novel asymmetric catalyst - Google Patents

Abstract

The present invention provides a new La-bonded BINOL complex for asymmetric Michael addition, which is stable during storage and reusable. The powdered La-bonded BINOL complex, prepared by reacting La (0-i-Pr)3 and 1.0 equivalent of oxygen-containing bonded BINOL in THF followed by removing solvent under reduced pressure, is stable in air and shown to be stably stored for a long time. After being stored for 4 weeks, the La-bonded BINOL complex does not show a change in catalytic activity based on the observation of chemical recovery and ee value (95% recovery, > 99% ee). The La-bonded BINOL complex according to the present application is widely applied to various substrates for asymmetric Michael reaction in comparison with conventional catalysts. The asymmetric Michael reaction of an enone (such as a cyclic enone (having a 5- to 9-membered ring) and an acyclic enone) and a beta-dicarbonyl compound in the presence of the present complex yield Michael adducts with good to excellent ee values. The homogeneous asymmetric complex, which is not supported on a polymer, can be recovered from the reaction mixture and reused in catalytic Michael reaction. After being recovered for 4 times, the recovered complex can still catalyze Michael reaction and yield Michael adducts with a high ee value (98% ee).

Description

552265 A7 B7 Wisdom of the Ministry of Economic Affairs / iMrg (Printed by Industrial and Consumer Cooperatives V. Description of Invention (1) [Technical Field] The present invention relates to a catalyst composition for asymmetric Michael addition reaction. More specifically, The present invention relates to a method for producing a stone-dicarbonyl compound and a cyclic or acyclic ketene additive, which is characterized by the asymmetrical Michael addition reaction formed by the stable combination of metal and BINOL complex Catalyst composition and its use-its catalyst composition. [Past Technology] Until now, there have been many reports about asymmetric reaction catalysts, but it has been an unresolved issue to promote the recovery and reuse of asymmetric catalysts. For this problem, soluble and non-soluble polymers have been developed to support asymmetric catalysts 1. Among these polymers, asymmetric catalysts are supported, except for exceptions, which are mirror-isomeric compared to non-polymer-supported catalysts. Bioselectivity or efficiency will decrease 2 '3. On the other hand, because it is difficult to recycle in use, the only reusable one is a non-polymer supported asymmetric catalyst 4. And, there is almost no reusable Asymmetric Lewis acid catalyst 2 b — d '4 4. When used as a catalyst, it has both utility and high reactivity to moisture. Therefore, for this technical field, it has been developed to be highly recyclable and reusable. Stable and asymmetric Lewis acid catalysts have become important targets. In recent years, the inventors have reported that under reaction conditions, the exchange of nucleophilic reagents and ligands makes G a-L i-complexes efficient Diazepam is oxygenated to Binol 56. However, from the standpoint of its catalyst stability, the X m group metal complexes such as A 1 and G a complexes are sufficient. The inventors expect ene Earth metal as the way to connect BINOL complexes ---------- (Please read the precautions on the back before filling this page) Order __. Μ-- This paper size applies to China National Standard (CNS) A4 specification (210X297mm) -4- 552265 A7 B7 V. Description of the invention (2) The metal of the isonic acid is useful. It is not only stable to moisture, but also has a long ionic radius. Because of its contrast with G a-L i -linked BINO complex, the oxygen It is located in the ene earth metal, so it is a more stable complex 7. [Disclosure of the Invention]-It is expected to develop a catalyst that can be used as a catalyst with high efficiency and high asymmetry in the Michael addition reaction, and can be recovered and Re-use, asymmetric Michael addition reaction catalyst that can be stored for a long time under high stability. The inventor developed a formula containing the following formula ----------- (Please read the precautions on the back before filling in this page)

Ordered by the Ministry of Economic Affairs, Intellectual Property and Employee Consumer Cooperatives [wherein, M is a hydrogen atom or a metal with one electron valence] Asymmetric Michael addition catalyst catalyst composition. Particularly preferred is as follows

The La-linked BINO complex (complex 4) shown is a homogeneous catalyst that can be reused and stored with high stability for asymmetric Michael addition reactions, and can be confirmed experimentally. This reaction not only has high selectivity for isomerization and interconversion, but also its usefulness in the synthesis of its products.8 The use of the catalyst is also applicable to the Chinese standard (CNS) A4 specification (210X297 mm) on this paper scale. A7 B7 V. Description of the invention (3) The advantage of easy. In recent years, the catalytic asymmetric Michaelisson reaction promoted by palm metal has been recognized as a method for efficiently forming a heterogeneous, tautoselective carbon-carbon combination. Although the efficient catalytic asymmetric Michael addition reaction has been achieved by the present inventors 8 b '9 and others 1 Q -12, there are more improvements in the generality and stability of the catalyst. Large demand, for example, only applies to ALB8b as a cyclic ketene. For attempts to modulate the efficiency of BINOL complexes, lanthanide was selected as the Lewis acid center. Asymmetric Michael addition reaction of 2 -cyclohexene-1 -one (1) with diphenylmethyl (2) malonate to use a metal (La only) and dissimilar metals (La — Li, La— Na, La-K) complex for investigation. Refer to the following reactions.

— Printed by Yan 0 Ministry of Economic Affairs Intellectual Property 笱 Employee Consumer Cooperatives These results are summarized in Table 1 -6- -------, — ^^ 衣-(Please read the precautions on the back before filling out this page ) __ This paper size applies Chinese National Standard (CNS) A4 specification (210X297 public director) 552265 Printed by the Intellectual Property Workers Consumer Cooperative of the Ministry of Economic Affairs A7 B7 V. Description of the invention (4) Table 1: via (R, R) -La -M-Contact asymmetrical Michael addition reaction promoted by BINOL complexes Temperature (° C) Time (hours) Yield (%) aee (%) b 1 Li 0 24 21 35 2 Na '0 24 41 43c 3 K -20 24 16 54c 4 Η (4) 0 45 53 85 a single ion yield. Determined by b HPLC analysis. Formation of e-image isomers. Best; results are obtained using an alkali metal that does not contain La-linkage: BINOL complex (complex 4), this complex uses lanthanum metal as the Lewis acid, and the lanthanum naphthalene oxide moiety It must be used as a Brunsted test basis to promote the reaction. After the reaction conditions were optimized, the present inventor finally found that using DME as a solvent and even a room temperature of compound 3 (94% yield and> 99% asymmetric yield (ee)) Table 2, 0 weeks). (Please read the precautions on the back before filling out this page) The paper size applies to Chinese National Standard (CNS) A4 specification (210 × 297 mm) -7- 552265 A7 B7 V. Description of the invention (5) Table 2. Via storage (R , R) -La-linked BINO complex 4 promotes contact asymmetric Michael addition reaction-(R, R) -La · linked BINO complex 4 (10% by weight) Compound 1 + Compound 2 ... .............—— Product 3 DME, rt, 72 time storage time (weeks) a 0 1 2 3 4 Yield (%) b 94 93 94 94 95 ee (%) c > 99 > 99 > 99 > 99 > 99 a (R, R) -La linked BINO complex 4 was stored in the air. b single-off yield. Determined by eHPLC analysis. As shown in Table 2, this novel La-linked BINO complex (complex 4) is very stable even in the air and may be stored for a long time. This complex 4 was easily prepared from (〇 一 i-Pr) 313 and 1 · 〇 equivalents of linked BIONOL 5 'These complexes were mixed in THF and the solvent was removed under reduced pressure to obtain a pale yellow powder complex 4 --------- ^^ 衣-(Please read the precautions on the back before filling this page) Order the intellectual property of the Ministry of Economic Affairs ^ 7 The paper size printed by the employee consumer cooperative applies Chinese national standards (CNS ) A4 specifications (210 ×: 297 mm) 552265 A7 B7 V. Description of the invention (6)

(Rf?)-Linked-BINOL 5 La (0-APr) 3

THF

This air stable complex 4 does not require any treatment and can be stored at ambient temperature for at least 4 weeks. As shown in Table 2, no catalyst activity was observed for both chemical yield and asymmetric yield (e e) under the storage catalyst. After 4 weeks of storage, a yield of 95% and an asymmetric yield (e e) of> 99% were obtained. Although the structure of the complex 4 is not fully elucidated, it is considered that the complex 4 is the monomer 14 based on the previous structural investigations of Ga — L i -linked BINO. The development of novel and stable catalysts that can be preserved seems to have succeeded in investigating the scope and boundaries of dissimilar matrices. As shown in Table 3, the complex 4 promotes the Michael addition reaction with a variety of cyclic ketene (η = 0-4) and a variety of malonates, and produces a Michael additive with good to excellent ee. 15. (Please read the notes on the back before filling out this page) • ^^ 衣 ·

、 1T Printed by the Consumer Cooperative of Intellectual Property Bureau of the Ministry of Economic Affairs This paper size applies to Chinese National Standard (CNS) A4 specification (210X297 mm) -9- 4 ^ 6 2 2 5 A7 B7 V. Description of the invention (〇

η ； 02R1 、 co2r1 4 (10 mol%)

DME 0

6 R1 = Bn, R2, Η: 2 1 R1 = Me, R2 = H: 10 I R1 = Bnf R2 = Me: 11 〇 9 2 4 (10 mo!%) + Or —'- i- Ph ^ ^ Me 1〇DME 20 η 2 0 η = η = 2 π = 3 π = 4 / 'Yan R1 n R2 ^ 〇2R1 3,12-19 〇 Me 23 -f

, C02Et ρΛ ^ 0 # 21f22 002R1 4 (10 md%) toluene

Please read the notes on the back first, and then this page) The paper printed by the Employees' Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs is compliant with China National Standard (CNS) A4 (210 X 297 mm) • 10-5 ^ 2265 A7 B7 5 Description of the invention (8) Table 3: Contact asymmetric Michael addition reaction promoted by (R, R) -La-linked BINO 4 Experimental number of ketene β dedicarbonylation ... Compound temperature (° C) Time ( H) Product yield a (%) eeh (%) 1 6 2 4 85 12 85 > 99 2 6 10 4 85 13 96 > 99 3 1 2 rt 72 3 94 > 99 4 1 2 4 85 3 98 > 99 5 1 10 rt 72 14 95 > 99 6: 1 11 rt 84 15 84 98 7 7 2 4 85 16 96 > 99 8 7 10 4 85 17 97 > 99 9C 8 10 rt 96 18 82 99 10 9 2 4 120 19 61 82 11 20 2 -40 56 21 97 78 12 20 10 -40 56 22 95 74 13d 23 24 -30 36 25 97 75 3 Single ion yield. Determined by Bhplc analysis. ° Reaction It is performed in DMF / THF (9: 1). D24 is added dropwise over 24 hours. Complex 4 such as 20 acyclic ketene 2 (97%, 78% ee) and 10 (95%, 74% ee) The reaction to the Michael addition has this paper standard applicable to Chinese national standards CNS) A4 specification (210X297 mm) -------. 丨-Please read the notes on the back before filling out this page) Order printed by the Intellectual Property Bureau Staff Consumer Cooperative of the Ministry of Economic Affairs -11-552265 A7 B7 5 、 Explanation of invention (9) (Please read the precautions on the back before filling out this page} Effect 15. Moreover, through the Michael addition reaction of 2 3 and 2 4 2 5 can obtain a yield of 97% and 75% Ee, of which the newly formed palm center will be induced by the supply of Michael. The inventors only know that the efficient catalytic Michael addition reaction of 8- and 9-membered cycloketene and propylene glycol has not been It is reported that this is an example of the first general Michael addition reaction in which the catalyst showed such a wide range.… Finally, based on the large difference between the solubility of complex 4 and product 3, complex 4 was recovered. It is confirmed that it can be reused. Successful implementation of this method is shown in Table 4. After the reaction is completed, pentane is added to precipitate the complex 4 at 0 t. The solution containing the product and traces of complex 4 was purified and separated by intubation. The remaining precipitate was dried under reduced pressure to obtain powdery complex 4 1 6 again. The recovered complex 4 was reused several times. Although a slight loss of activity was observed, the expected addition product 3 of the complex addition 4 of the recovered complex 4 was promoted to achieve a very high asymmetric yield (e e) even after 4 uses. Table 4. Catalytic asymmetric Michael addition reaction cycle of catalyst after reuse 1 2 3 4 Yield (%) a 82 94 68 50 ee (%) b > 99 > 99 99 98 Ministry of Economic Affairs Single-liquid yields printed by the Property Bureau's M-Industrial Cooperative. Determined by BHPLC analysis. Compared with the so-called catalysts reported so far, it has a broader general. The paper size is applicable to China National Standard (CNS) A4 specification (210X297 mm) -12- 552265 A7 B7

V. Description of the invention (1P (please read the notes on the back before filling this page). Successfully developed the asymmetric Michael addition reaction which can be stored under stable conditions and can be used in the La-connection binol. After being stored for 4 weeks (> 99% ee), this powder complex 4 is very effective for the catalytic asymmetric Michael addition reaction. Moreover, recovery and reuse of complex 4 can be achieved. The recovered complex 4 can be confirmed to produce very high e ... e products even after 4 cycles. The present invention will be described in more detail in the following examples. [Examples] [Experimental Methods and Experimental Conditions] General experiment: Intellectual property of the Ministry of Economic Affairs ^ 7 The infrared spectrum (IR) printed by Xiaogong Consumer Cooperative was recorded under a JASC〇FT / IR 4 1 0 Boryet transform infrared spectrophotometer. The NMR spectrum was JE〇L JNM— LA500 spectrometer is operated and recorded at 500 MHz for 1 Η NMR and 125 · 65 MHz for 13 C NMR. For 1 H NMR, the chemical shift in CDC 13 is recorded at the low magnetic field edge of TMS (= 〇), or Record the number of CHC 13 (7 · 26ppm) 値For 13C NMR, record the number 値 for CHC 1 3 (77. OOppm for 1 3 C NMR) as the internal reference for chemical shift. The optical rotation was measured by JASC 〇 P — 10 0 10 polarimeter. EL plastomers The spectrum was measured with JEOL JMS — DX303 or JMS — BU20 GC mate. Column chromatography was performed with Merck 60 (2 3 0 — 4 0 0 sieve AST). Excess image isomers (asymmetric paper) Standards apply to Chinese National Standards (CNS) Α4 specifications (210X297 mm) -13- 552265 A 7 B7

V. Description of the invention (V: ee) Determined by HPLC analysis. HPLC was performed with the following JASCO HPLC system: pump, 880 — PU or PU — 980; detector, 875 — UV or UV — 970, measurement at 25 4 nm; column, DAICEL CHIRALPAK AS, AD, DAICELCHIRALCELOD or 〇J; mobile phase, hexane 2-propanol; flow rate, 0. 30 to 1.0 m 1 / min. The reaction is carried out in a dry solvent under an argon atmosphere unless otherwise stated. Tetrahydrofuran (THF) and dimethoxyethane (DME) were distilled from sodium phenylbenzophenone ethylate. Toluene and pentane were distilled from sodium. La (〇 一 i— Pr) 3 is Kojundo Chemical Laboratory Co., LTD., 5-1-28, Chiyoda, Sakado-shi, Saitama 350-02 14, Japan (fax, + + (8 1) -492- 84-1351). Other reagents were prepared by general methods. [Example 1] (R, R)-La-Preparation of Binol-linked complexes-78t: (R, R)-La in THF (10mL)-Binol 5 (containing 1.01g, 7 · To a stirred solution of 4 w / w% of solvent (diethyl ether and hexane), 1.5 mm ο 1 e), La (〇 一 i-Pr) 3 (7.5mL, 1.5 mmo 1 e, THF 2M, La (〇i-Pr) 3 powder and dried THF (reconstituted) solution. After the solution was stirred at room temperature for 5 hours, the solvent was evaporated under reduced pressure. The resulting residue was dried under reduced pressure (approximately 4 mm H g) for 2 hours to obtain a light yellow powder (R, R)-L a-linked to BIN0L complex 4 (this paper size applies to Chinese national standards ( CNS) Α4 specification (210X297 mm) .I-(Please read the precautions on the back before filling this page)

1. 1T Intellectual Property of the Ministry of Economic Affairs ^ Printed by Employee Consumption Cooperative -14- 552265 A7 B7 5. Description of the invention (7 1.13g, 1.5mmole). The powdered catalyst can be maintained at room temperature and air for at least 4 weeks. (Please read the precautions on the back before filling this page) [Example 2] Asymmetric Michael Addition Reaction (Promote contact with asymmetric Michael addition reaction by (R, R) — La-linked BINO complex (General operating sequence) -78 ° C, (R, R) — La — Binol complex (45.1 mg, 0.06 mmole) in the test tube [prepared according to the above operation method] was added with D M E (1.5 m L), and the mixture was stirred at the same temperature for 5 minutes. After that, 2-cyclohexene-1-one (1) (58 # L, 0.60mmole) and diphenylmethyl malonate (2) (150 / zL, 0.60mmole) were added. Printed by the 8th Industrial Cooperative of the Property Bureau. The mixture was stirred at -78 ° C for 5 minutes, and then removed with dry ice and acetone. The reaction mixture was stirred at 4 ° C. When the mixture was diluted for 8 to 5 hours, it was diluted with ethyl acetate. After washing with saturated NΗ4C1, brine, and drying with MgS04. The solvent was evaporated under reduced pressure, and the residue was purified by flash chromatography (Si02, hexane / acetone 10/1) to obtain > 99% ee of 3 (223.8mg, 0.588mmole, yield 9 8 %). (Synthesis of Michael Product 3, 12-19, 21, 22, and 25) Michael Product 3, 1 2, 1 3, 16, 6, 7 and 19 are synthesized in the normal operation sequence. The Michael addition reaction system is compound 1. 4. The paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm). -15- 552265 A7 B7. 5. Description of the invention (1 Yin, 15 and 18 at room temperature) For 2 1 and 22, it is -40 ° C, (Please read the notes on the back before filling this page), and for 2 5 is performed at -30 ° C. 1 5 and 18 use D Μ E / THF = 9/1 co-solvent system. For the synthesis of 25, 2 4 is added dropwise over 24 hours. For the absolute configuration of 3, 1 2-1 7 and 25, please refer to Reference 9 and its reference. References cited. The absolute configuration of 1 8 ~, 19, 2_1, and 2 2 was determined based on previous results. [Example 2-1] (R)-3-[bis (benzyloxycarbonyl) Methyl] cyclohexanone (3): mp 43 t:; IR (KBr) v 1740, 1261 cm'1; 1 Η NMR (CDC 1 3) 5 1.46 (dddd, J = 3.0, 11.5, 11.5, 11.5 Hz , 1H), 1.62 (ddddd, J = 2_2, 4.4, 12.3, 12.3, 12.3Hz, 1H), 1.84 — 2.08 (m, 2H), Intellectual Property of the Ministry of Economics ¾ Printed by employee consumer cooperatives 2.12-2.64 (m, 5H ), 3.41 (d, J = 7.6Hz, lH), 5.14 (s, 2H), 5.16 (s, 2H), 7.25- 7.36 (m, 10H); 1 3 CNMR (CDC 1 3) (5 24.4, 28.6, 38.0, 40. 9, 45.0, paper size Applicable to China National Standard (CNS) A4 specification (210X297 mm) -16- 552265 A7 B7 V. Description of the invention (56.6, 67.2, 128.2, 128.4, 128.5, 135.0, 167.4, 167.5, (Please read the precautions on the back before (Fill in this page) 2 0 9.3; MS m / z 2 8 9 [M +-Β η]; [α] 〇2 4 + 1. 25 (c 2.21, CHCls (> 9 9% ee)-); Η PLC (DAICEL CHIRALPAK AS, 2-propanol / hexane 10/90, flow rate 0 · 9mL / min, detection at 210nm) tr 37 points (main) and 50 points (secondary); analysis by C23H24〇5 calculates 値: C, 7 2 · 6 1; Η, 6 · 3 6 Measured 値; C, 72.40; Η, 6.13. [Example 2-2] (R)-3-[Bis (benzyloxycarbonyl) methyl] cyclopentanone (12): colorless oil; IR (pure product) 1 7 4 0, 1 2 1 1 cm 1 1 »1 Η NMR (CDC 1 3) ά 1.51 — 1.72 (m, lH), printed by Intellectual Property of the Ministry of Economic Affairs, Employee Consumer Cooperatives 1.99 (dd, J = 11.2, 18.5Hz, lH), 2.06 — 2.38 (m , 3H), 2.45 (dd, J = 7.9, 18.5 Hz, lH), 2.78- 2.97 (m, lH), 3.45 (d, J = 9.6 Hz, lH), 5.14 (s, 2H), 5.16 (s, 2H), this paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) -17-552265 A7 B7 V. Description of the invention (silicon 7. 2 5 — 7 ;; 7 (m, 1 〇Η); 2 CNMR (CDC 1 a) 57. 4, 3 6 · 3, 3 8 · 1 7.3, 67.3, 128.2 28.6, 135.0, 135 4 2 · 7, 5 6 12 8.5, 1, 1 6 7 · 7 4 7 8 , 2 1 MS m / z 275 [M + — Bn] a) 〇 2 4 + 3 7. 8 9 9% ee)); c 3 3 CHC 1 > HRMS [M + — Bn] C15H15〇5 Calculation 値: 2 7 5.0 9 1 9; Measured radon: 2 7 5. 0 9 31. The optical purity of 1 2 was converted to an acetonone derivative as shown below, and analyzed by palm Η PLC (DAICEL CHIRALCEL OD, 2-propanol / hexane 3/97, flow rate 0.43 mL / min, measured at 210 nm , T R 5 5 points (primary) and 5 8 points (secondary)). (Please read the notes on the back before filling out this page) Order Printed by the Industrial and Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs h

TsOH ^ JOOOBn ΧΟΟΒπ Ο ΧΟΟΒη DUCOOBn 12 [Examples 2-3 (R)-3 [Bis (methoxycarbonyl) methyl] cyclopentanone (3 cm: colorless oil; IR (pure product) v 2 9 5 7 7 3 5 -1. This paper size applies to Chinese National Standard (CNS) A4 (210X297 mm) -18- 552265 A7 B7 V. Description of the invention (1 Η NMR (CDC 1, 9 9 (ddd, J 8.7 H z, 1 H) • 4 2.14 — 2.26 (m, 2H), 2 · 2 9-2, 3 6 (m, 1 H), 2.41 (dd, J = 2.6, 18.7Hz

H • 80 — 2.89 (m, 1H) .36 (d, J = 9.5Hz, • 73 (s, 3H), 3.75 CNMR (CDC 1 3) 5 1 H), (s, 3 H); --- ----, — clothing-- (Please read the precautions on the back before filling this page) 7 6 a 3 6. 4, 3 丨 1 6 8. 4, 1 6 + 98 · 8 2

.2, 4 2 · 8, 8 · 5, 2 1 6 · 8; c 0.54 C H C Ordered by the Consumers ’Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs > 9 9% e e)). The optical purity of 13 was converted to an acetone ketone derivative as shown below, and analyzed by palm Η PLC (DAICEL CHIRALCEL OD, 2-propanol / hexane 3/97, flow rate 0.50 mL / min, 210 Detected at nm, tR is 25 points (main) and 28 points (secondary). 0 XOOCH3 13 d ΓΛ

TsOH ry xo〇ch3 This paper size is applicable to China National Standard (CNS) A4 specification (210X297 mm) -19- 552265 Μ B7 V. Description of the invention (7 [Examples 2-4] (R)-3 — [Double (Methoxycarbonyl) methyl] cyclohexanone (14): IR (pure product) υ 1 7 3 2, 1 2 5 9 cm-1; (Please read the precautions on the back before filling out this page) 1 Η NMR (CDC 1 3) 5 1.46 (dddd, J = 2.6, 12.2, 12.2,: L 2. 2 H z-, 1 H), 1.62 (ddddd, J = 2.6, 4.2, 12.2, 12.2, 12.2 Hz, 1H ), 1.86 — 1.97 (m, lH), 1.98 — 2.11 (m, lH), 2.15 — 2.31 (m, 2H), 2.31 — 2.59 (m, 3H), 3.32 (d, J = 7.9Hz, lH), 3.71 (s, 3H), 3.72 (s, 3H); 1 3 CNMR (CDC 1 a) 5 24.4, 28. 7, 37.9, 38.0, 40. 9, 45.0, 52. 5, 56.5, 168.1, 168.2 , 209.4; Printed by the Intellectual Property of the Ministry of Economic Affairs

MS m / z 228 [M +]; [a] D24 + 3.99 (c 2-10 CHCls (> 99% ee)); Η PLC (DAICEL CHIRALPAK AS, 2-propanol / hexane 10/90, flow rate 0 · 5mL / min, detected at 210nm) tR 57 points C main) and 72 points (secondary); analysis of C!! H 6 0 5 calculates 値: C, 5 7 · 8 8; Η, 7 · 0 7 Measured 値: C, -20- This paper size is in accordance with Chinese National Standard (CNS) A4 (210X297 mm) 552265 A7 B7 V. Description of the invention (1 Yin 57.70; H, 7.01 ° [Actual rotation example 2 — 5] (R) — 3-[bis (benzyloxycarbonyl) ethyl] cyclohexanone (15): colorless oil; IR (pure product) v 1 7 3 2, 1 2 3 1 cm: 1;… 1 Η NMR (CDC 1 a) 5 1.18-1. 38 (m, lH), 1. 4 4 (s, 3 Η), 1.50 — 1.62 (m, lH), 1.74 — 1.84 (m, lH), 1.95 -2 · 08 (ιη, 1Η), 2.08 — 2.25 (m, 2H), 2.30 — 2.43 (m, 2H), 2.48 — 2.62 (m, lH), 5.08 — 5.13 (m, 4H), 7.20 — 7.35Cm , L〇H); (Please read the notes on the back before filling out this page) Printed by the Intellectual Property Bureau of the Ministry of Economic Affairs, Consumer Cooperatives 1 3 CN MR (CDC 1 3) δ 16 8, 2 4 .6, 2 6.6, 4 1 .0, _ 4 2.6, 4 3. 2, 6 0 • 1, 6 7.1, 6 7 • 2,, 1 2 8.1, 128.4, 128.5, 135.3, 170.5 , 170.6, 210.0; MS m / z 303 〔M +-Bn〕; ia) 〇 2 4 + 〇 3 6 (c 3.93 CHC 1 3 (> 9 8) This paper size applies the Chinese National Standard (CNS) A4 specification ( 210X297mm) -21-552265 A7 B7 V. Description of the invention (1%% ee)); Η PLC (DAICEL CHIRALPAK AS, 2-C (Please read the precautions on the back before filling this page) Alcohol / hexane 10 / 90, flow rate 1 · OmL / min, detected at 210 η πΓ) t R 2 1 minute (main) and 47 points (secondary); HRMS [M + — Bn] Calculation of ChHhOs 値: 303. 1233; actual measurement 値: 303. 1232. [Examples 2-6] (R)-3-[Bis (benzyloxycarbonyl) methyl] cycloheptanone (16): colorless oil; IR (pure product) v 3 0 2 0, 2 9 3 5 , 1732, 1700, 1216 11152cm · 1; 1 Η NMR (CDC 1 3) 5 1.41 — 1.56 (m, 3H), 1. 81-1.91 (m, 3H), 2.46- 2.57 (ml 5H), 3.42 (d , J = 6.9 Hz, lH), 5. 1 5 (s, 4 H), 7.26 — 7. 36 (m, 10H); 1 3 CNMR (CDC 1 3) δ Employee Consumer Cooperatives, Intellectual Property Bureau, Ministry of Economic Affairs Printed 24.3, 28.6, 34.0, 35.7, 43.5, 47.2, 57.4, 67.2, 128.3, 128.4, 128.5, 135.1, 167.8, 2 12.3; MS m / z 395 [M +]; [a 〕 D24 + 27.4 (c 0.70 CHCl3 (> 99% ee)) This paper size is applicable to Chinese National Standard (CNS) A4 specification (210X297 mm) -22- 5§2265 A7 B7 V. Description of the invention (2? ( Please read the notes on the back before filling in this page) 1 6 The optical purity, as shown below, after conversion to acetophenone derivatives, palm Η PLC analysis (DAICEL CHIRALCEL〇D, 2 Hexane 3/9 7, flow rate 0.81111 ^ / min, detected at 210 nm, tr 26 points (main) and 28 points (secondary make decision.

1 € [Examples 2-7] (R)-3 — [Bis (methoxycarbonyl) methyl] cycloheptanone (1 7): colorless oil; IR (pure product) v 2 9 3 4,1 7 3 1 ， 1 6 8 7 cm "1; 1 Η NMR (CDC 1 3) 5 1 · 35- 1.60 (m, 3H), 1.83 — 1.94 (m, 3H), 2.46- 2.57 (m, 5H), 3.33 (d, J = 7.0 Hz, 1H), 3.74 (s, 3H), 3.75 (s, 3H); Printed by the Intellectual Property of the Ministry of Economic Affairs, Industrial and Consumer Cooperatives 1 3 CNMR (CDC 1 3) 5 24. 4 , 28.7, 34.1, 35.7, 43. 6, 47 · 2, 52 · 5, 57 · 1, 168.5, 168.6, 212.4; MS m / z 242 [M +]; [α) 〇21 · 2 + 49. 7 ( c 1.76 CHC 1 a (This paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) -23- 5 prepared 2265 A7 B7 V. Description of the invention (> 99% ee))); HRM s calculated 値: 242 · II54 1? @ I P @ ^ The following analysis was converted to acetophenone derivatives by 'palm Η PLC analysis (DAICEL CHIRALCEL 〇D, 2-propanol / Alcohol 3/97' flow rate 0.811111 ^ / Min, detection at 21〇11, tR 26 (primary) and 28 points (secondary) are determined. M ό., Jcooch3 ^ COOCH3

TsOH

.s < C00CH3

OBn NaOBn CCXiCHa THF

(Please read the notes on the back before filling in:: Write this page) 17 Printed by Intellectual Property of the Ministry of Economic Affairs, Employee Consumer Cooperative [Examples 2-8] (R)-3-[Bis (methoxycarbonyl) methyl 〕 Cyclooctanone (1 8): colorless oil; pure IRC) 2; 2 9 5 2, 1 7 3 3, 1 6 9 6 cm'1; 1 Η NMR (CDC 1 3) 5 1.29- 1.51 ( m, 4H), 1.58- 1.73 (m, 2H), 1.80- 1.91 (m, 2H), 2.32 (ddd, J = 3.5, 5.5, 13, 1 H), 4 H z 2 7

d d d, J • 2 3. 7 H z

H 2 · 4 9 (dd .7 7 H z, 1 H) This paper size is applicable to China National Standard (CNS) A4 specification (210X297 mm) -24- 552265 A7 B7 V. Description of the invention (2 ?, 2.57 (ddd , J = 4.8, 11.0, 1 3 · 4 H z, 1 Η), (Please read the precautions on the back before filling this page) 2.-7 9- 2.87 (m, lH), 3.36 (d, J = 7.4Hz, 1H, 3.736 (s, 3H), 3.740 (s, 3H); 1 3 C-NMR (-CDC13) 5 23.6, 25. 8, 26.9, 31.3, 36.3, 4 2-1, 45.0, 52- 5, 56.9, 168.7, 168.8, 215.3; MS m / z 256 [M]; [a] D24-28.1 (c 0.698 CHCls (99% ee)); Η PLC (DAICEL CHIRALPAK AS, 2-propanol / hexane 10/90, flow rate 1.0 mL / min, detected at 210 nm) tR 29 points (main) and 35 points (secondary). [Examples 2-9] (R)-3-[bis (benzyloxycarbonyl) ) Methyl] cyclooctanone (19): colorless oil; IR (pure product) v 2927, 1732, printed by M Industrial Consumer Cooperative, Intellectual Property Bureau, Ministry of Economic Affairs, 1700 cm'1; 1 Η NMR (CDC 1 3) 5 1.25 — 1.47 (m, 5H), 1.50 — 1.60 (m, 3H), 1.72 — 1.86 (m, 2H), 2.31-2.39 (m, 2H), this paper size applies National Standard (CNS) A4 Specification (210X297 mm) -25- 552265 A7 B7 V. Description of the Invention (2.47- 2.55 (m, 2H), 2.87 — 2.94 (m, lH), (Please read the precautions on the back first) Fill out this page again) 3.4 5 (d, J = 7.4 Hz, lH), 5.14 (d, J = 12.1 Hz, lH + lH overlap), 5.16 (d, J = 12.1 Hz, lH), 5 · 1 7 ( d, -J = 12.1Ηζ, 1Η), 7.28 — 7.35 (m, 10H); 1 3 CNMR (CDC 1 3) 5 23.0, 24.5, 26.01, 26.04, 31.2, 35.3, 43.1, 47.1, 57.7, 67.1, 67.2, 128.29, 128.33, 128.4, 128.6, 135.2, 168.0, 168.1, 215.6; MS m / z 422 [M +]; [a] D23 · 9- 10. 8 (c 0.8 5 5 CHCl3 ( 82% ee)); Η PLC (DAICEL CHIRALPAK AS, 2-propanol / hexane 10/90, flow rate 0 · 6mL / min, detected at 210nm) tr 3 2 points (sub) and 41 1 points (main) . Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs [Example 2 — 10] (R) —Phenyl 2- (benzyloxycarbonyl) -3-methyl-5—oxy-5—phenylpentanoic acid Ester (2 1): IR (pure product) ^ 2964 ^ 1731 ^ 1682cm · 1; 1 Η NMR (CDC 1 3) 5 This paper size applies to China National Standard (CNS) A4 (210X297 mm) -26- 552265 Printed by the Intellectual Property of the Ministry of Economic Affairs and Employee Cooperatives Λ-::, A7 B7 V. Description of the invention (1.05 (d, J = 6.7Hz, 3H), 2.85 (dd, J = 8.6, 16.8Hz, 1H) ), 2_9 5- 3.04 (m, lH), 3.17 (dd, J4.6, 16.8Hz, 1H), 3.59 (d, J = 6.4Hz, lH), 5. 1 1 (d, -J = 1 2 2 H z, 1 H), 5.13 (d, J = 100 Hz, 1 H), 5.14 (d, J = 100 Hz, 1 H), 5.16 (d, J = 12.2 Hz, 1 H) , 7.25- 7.32 (m, 10H), 7.40 (dd, J = 7.3, 8.5Hz, 2H), 7.53 (tt, J = 1.2, 7.3Hz, 1H), 7.85 (dd, J = 1.2, 8.5Hz, 2H ); 1 3 CNMR (CDC 1 a) 5 17.8, 29.5, 42.5, 56.4, 67.0, 67.1, 128.1, 128.27, 128.34, 1 2 8. 5 9 1 2 8 • 6 y 1 3 3 • 0, 1 3 5 • 3 j 1 3 6. 8 5 1 6 8 • 3 1 1 6 8 • 4, 1 9 8 • 5 y Μ S m / Z 4 3 0 CM +] [a] 〇 2 3 — 2 • 1 2 (C 1. 0 4 C Η C 1 3 (7 8% ee)) HPLC (DAICEL CHIRALPAK AD J 2 — propanol / hexane 4/9 6 j flow rate 0 • 5 m L / min, detectable at 240 nm) t R 5 8 points (Main) and 6 3 points (deputy). This paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) (Please read the precautions on the back before filling this page) Order -27- 552265 A7 B7 V. Description of the Invention (2 Yin [Example 2 — 1 1] (Please read the precautions on the back before filling out this page) (R) —Methyl 2 —Cmethoxymethoxy — 3 —Methyl 5 —oxy Base ... a 5-phenylvalerate (22): Palmarity 22 has been reported. References Martens, J.J .; Hegedus, L.S .; Tamariz, J.J.rg. Chem. 1991, 56, 5666. All spectra and analytical data are the same as known compounds. … [A] D22- 4.9〇 (c 1.47, CHC13 (74% e e));

Η P L C (DAICEL CHIRALPAK AS, 2-propanol / hexane 4/96, flow rate 0 · 3mL / min, detected at 240nm) tR 4 4 points (sub) and 48 points (main). [Example 2 — 1 2] (S) -Ethyl 2-oxy-1 1- (3-oxybutyl) -cyclohexanecarboxylate (2 5) · • Colorless oil; IR (pure product) > 1718, 1244cm-1; 1 Η NMR (CDC 1 3) 5 1.26 (t, J = 7.1Hz, 3H), printed by the Consumer Cooperative of Intellectual Property Bureau of the Ministry of Economic Affairs 1.40 — 1.51 (m, 1H), 1.58 — 1. 89 (m, 4H), 1.95 — 2.14 (m, 2H), 2 · 1 2 (s, 3 H), 2.28 — 2.64 (m, 5H), 4.16 — 4.25 (ιπ'2Η),- 28-This paper size applies Chinese National Standard (CNS) A4 specification (210X297 mm) 552265 A7 B7 V. Description of invention (邛 1 3 CNMR (CDC 1 3) 14.1, 22.5, 27 3 6 · 6, 3 8 · 8 , 4 1 172.0, 207.7 ,: MS m / z 2 4 0 C Μ + [〇i 3 5 7 7 2 D--6 5 · 2 (3 Η 〇n 5.5, 0 0 7 2 8 5 9 4 9 2 9 c • 3

C C 7 5% e e)); C 6 4. 9 8; H, 8 H, 8 · 17. The optical purity of 2 5 was converted to an acetone derivative as shown below, and then analyzed by PLC analysis (DAICEL CHIRALCEL OJ, alcohol / hexane 10/90, flow rate 0 · 4mL / min, detected at 22 nm, tR 18 points (deputy) and 22 points (main).

〇4 analysis to calculate 値: C 9 Measured 値: C, 6 4 · 6 9; 2-Prop 0) (Please read the precautions on the back before filling this page)

TsOH [Example 3] Catalytic asymmetry of catalyst reuse for accompanying catalysts Reprinted by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs (La, R) — La — Linked to BIN0L Complex 4 (2 2 5

mg, 0.3 mmole, 10 mole%) was added to DME (7.5 ml) at -78 t, and then warmed gently until the mixture completely dissolved complex 4. The DME solution of this complex 4 was -78. (: Add 2-cyclohexene-1 monoketone (1) (0-29mL This paper size applies to Chinese National Standard (CNS) A4 specifications (210X297 mm) -29-552265 A7 B7 V. Description of the invention (27 ( Please read the notes on the back before filling in this page), 3.0 mmole) and diphenylmethyl malonate (2) (0.75 mg, 3.0 mmole). This mixture is kept at the same temperature at 4 ° C. Stir at temperature for 110 hours. After the reaction is complete, add pentane (3 OmL) to the reaction mixture at 0 ° C, and leave it at the same temperature for 1 hour. Separate the supernatant with a cannula, and the remaining precipitate Wash with pentane C 1 0 m LX 2) ... and add 1 NHC 1 aqueous solution to the reaction mixture to stop the reaction. Extract with Et20, dry with Na2S04, filter and concentrate. The resulting residue is subjected to flash column chromatography (Silica gel, 20% acetone in hexane) to obtain 3 (9.40 · 3 mg, 82%) as a colorless oil. The precipitate was dried under reduced pressure for 30 minutes to obtain a light yellow powder (R, R) —La—Binol complex 4 was linked, and this was treated with THF (6.0 m L) for 4 hours at 0 t before reuse. T was removed under reduced pressure for 1 hour. After HF, the complex 4 was recovered and reused. [Example 4] Calculation of the optimum (R, R) — Ga — La — Bingo 6 complex 5 was used as the structure, and the model compound ((R, R) -La-Linked diphenol complex) is optimized for calculations. First, it replaces (R, R) printed by the Consumer Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs — G a — L a — Central metal connected to BINO (from G a to L a) and the cations of phenolic oxygen (from Li to Η) to obtain (R, R)-L a —the initial structure of BINOL. Using ramdom conformational search, Hu Jin refers to the Monte Carlo method (stage 1 0, 0 0 0), followed by the minimization of molecular mechanics (

UNIVERSAL in Cerius2 (Molecular Simulations Inc.) The paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) -30- 552265 A7 B7 V. Description of the invention (2 Yinchang 1 7 (v · 1 · 0 2) Calculate to obtain (R, R) — L a-the lowest energy stereo coordination of BINOL. Secondly, because of the simplification (R, R)-丄 a-the optimized structure of BINOL, (R, R)-L a —The initial structure of the connection of diphenol. Calculated using ab initio (

Caussian 9819 (Gaussian Inc.) used H F / L a η 2 D Z level) to perform the minimum geometric optimization of (R_, R)-L a-linked diphenol. Although this optimization could not reach the (R, R) -L 3 -linked diphenol's resting point with a large degree of freedom, after calculating the distance between the lanthanum and oxygen of the linker for 9 stages, it has changed to 2.62 to 2 69A range (please read the precautions on the back before filling this page)

from X-ray structure from MM calculation. from ab initio calculation G Old-O ·: 4.62 Λ LaO ·: 3 · 02 Λ La-〇 ·: 2.62-2.69 A Printed by the Consumer Cooperative of Intellectual Property Bureau of the Ministry of Economic Affairs [Industry Usability] The present invention provides a La-linked BINO complex complex that has novel stability and can be stored for a long period of time as a catalyst for asymmetric Michael addition reaction. This catalyst is very stable in the air and confirmed to be able to be stored for a long time. Compared to the catalysts reported to date, this catalyst shows a broader matrix universality for asymmetric Michael addition reactions. The asymmetric Michael addition reaction of various ketene with / 3-dicarbonyl compounds has an effect, and it is possible to obtain good or even excellent yields and asymmetrical Michael additions. This paper size applies the Chinese National Standard (CNS) A4 specification (210X297 mm) -31-5-52265 A7 B7 Printed by the staff of the Bureau of Intellectual Property 4 of the Ministry of Economic Affairs and printed by the cooperative. V. Description of the invention (Also, it is determined that this polymer does not support Homogeneous asymmetric complexes can be recovered and reused from the reaction mixture. [References] (1) For a recent .review, see: Comprehensive Asymmetric Catalysi s; Jacobsen, EN, Pialtz, A .. Yamamoto, H .. Eds. ; Springer: New Yor,. K; 1999; Chapter 38. (2) For examples of recycling of the polymer-supported asymmetric catalysts itself, see: (a) Nozaki, K.; Itoi, Y.; Shibahara, F.; Shira kawa, E .; Ohta, T .; Takaya. H .; Hiyama, TJ Am. Chem. Soc. 1998, 120. 4051. (b) Ann is, DA; Jacobsen, ENJ Am. Chem. Soc. 1999. 121. 4147. (c) Sellner, H .; Seebach, D. Angew. Chem., Int. Ed. Engl. 1999, 38, 1918. (d) Heckel. A .; Seebach. D. angew. Chem., Int. Ed. Engl. 200 0, 39, 163 · (e) VachaL P .; Jacobsen. EN Org. Lett. 2000, 2, 867. (3) For a example of recycling of the polymer-suppor ted metal and the chiral ligand independently, see: Kobayashi, S .; Endo. M .; Nagaya nia, SJ Am. Chem. Soc. 1999, 121, 1 1229. (4) (a) Martinez / LE; Leighton. JL ; Carsten, DH; Jacobse nt ENJ Am. Chem. Soc. 1995, 1 17, 5897. (b) Tokunaga, M.; Larrow, JF; Kakiuchi, F.; Jacobsen, EN Science 1997, 277, 936. (5 ) For a recent review, see: Lewis Acid Reagents. A Practical (Please read the notes on the back before filling this page) This paper size is applicable to China National Standard (CNS) 8-4 specifications (2ΐ〇χ297mm) -32- 552265 A7 B7 V. Description of the invention (30)

Approach; Yamamoto, H., Ed .; Oxford University Press: New York; 1999. (6) Matsunaga, S .; Das, J .; Roels, J .; Vogh EM; Yamainoto. N .; lida. T .; Yamaguchi, K .; Shibasaki, MJ Am. Chem. Soc. 2000, 122, 225 2. (7) The X-ray data of LiCl free Ga-Li-1inked-BINOL complex show ed that there was no coordination between oxygen in the linker and gall ium. See Rei. (6). (8) _ (a) Magnus ,. P.; Sear, NL .; Kirn, CS; Vicker, NJ Org. Ch em · 1992, 57, 70 · ( b) Shimizu, S .; Ohori, K .; Arai, T .; Sasai, H .; Shi basaki, MJ Org. Chem. 1998. 63, 7547. (c) Ohori. K .; Shimizu. S .; 0 hshima, T.; Shibasaki. M.'Chirality 2000, ^ 12, 401. (9) For a review, see: Shibasaki, M.; Sasai, H.; Arai. T. Angew.

Chem ·, Int · Ed · Engl. 1997, 36, 1236 · (10) For recent fevies, see: (a) Comprehensive Asymmetric Catalys is; Jacobsen ,. EN, Pfaltz, A., Yamamoto, H. t Eds .; Springer: New Yor k; 1999; Chapter 31. (b) Tye, HJ Chem. Soc., Perkin Trans. I, 2000, 275. (11) For a representative example of the catalytic asymmetric Mich ael reactions oi enones with malonates, see: Yamaguchi, M.; Shiraishi, T.; Hirama, MJ Org. Chem. 1996. 61, 3520. (12) For representative examples of other catalytic asymmetric Mic hael reactions, see: (a) Feringa, BL; Pineschi, M .; Arnold, LA; lmbos, R .; de Vries, A. Η. M. Angew. Chem .. Int. Ed. Engl. 1997. 36t 26 20. (b) Takaya, Y .; Ogasawara, M. ; Hayashi. T.; Sakai. M.; Miyaura. NJ Aid. Chem. Soc. 1998, 120, 5579. (c) Corey. EJ; Noe. MC; Xu, F · Tetrahedron Lett · 1998, 39, 5347 · (d) Evans, DA; Rovis, T .; Kozl owski. MC; Tedrow, JSJ Am. Chem. Soc. 1999. 121. 1994. (e) Ji, J .: Barnes, D.M .: Zhang, J .; King, S. A .; Wittenberger · S · J.: Morton · Η. EJ Am. Chem. Soc. 1999, 121, 10215 and references cited therein. (13) La (Oi-Pr)., Can be purchased from Kojundo Chemical Laboratory Zhang scale is applicable to China National Standard (CNS) A4 specification (210 X 297 mm) Please read the notes of Sj first

Employees' Cooperatives of the Intellectual Property Bureau of the Ministry of Economic Affairs, India 5 Farmers -33- 552265 A / B7 V. Description of Invention (31)

Co., Ltd., 5-1-28, Chiyoda, Sakado-shi, Saitama 350-0214, Japan (fax: + (81M92-84-i351) · (14) Computational optimization oi a model compound (La-1inked- bip henol complex) using molecular mechanics calculation followed by ab ini tio calculation indicated that the distance between lanthanum and oxyge n id the linker should be 2.62-2.69 A, which is nearly equal to that be tween lanthanum and phenolic oxygen (2.58-2.65 A ). It seems reasonable to consider that the oxygen atom in the linker would also function as coordinative moiety and so 1inked-OBINOL would function as pentadentate, · ligand toward la, thus making the La-1inked-BINOL complex 4 unusually stable. See Supporting Information for details and references to the c alculation. (15) The absolute configurations oi 18, 19, 21 and 22 were tentati vely determined on the basis of the previous results. See Ref. (9). (16) The recovered powdered complex 4 contained ca. 10-15¾ oi 3. (17) (a) Rappe, AK; Casewit, CJ; Colwell, K. A .; Goddard III, WA; Skiff, WM; J. Am. Chem. Soc. 1992f 114, 10024. (b) Casewit. C. J .; Colwell, KS; Rappe. AKJ Am Chem. Soc. 1992, 1 14, 10035.

(c) Casewit, CJ; Colwell, KS; Rappe, AKJ Am. Chem. Soc. 1992, 114, 10046. (d) Rappe, AK; Colwell. KS; Casewit, CJ Inorg. C hem .. 1993. 32. 3438. '

(18) Gaussian 98, Revision A. 7, MJ Frisch, GW Trucks, Η. BS chlegel, GE Scuseria, MA Robb, JR Cheeseman, VG Zakrzewski, JA Montgomery. Jr., RE Stratmann, JC Burant, S. Dapprich. JM Mi Ham. AD Daniels, KN Kukdin, MC Strain, 0. Farkas, J. Tom asi, V. Barone. M. Cossi, R. Cammi, B. Mennucci, C. Pomelli, C. Adamo, S. Clifford, J. Ochterski. GA Petersson, PY Ayala. Q. Cui, K. Mor okuma, DK Malick, AD Rabuck. K. Raghavachari, JB Foresman, J.

Cioslowski, J. V. Ortiz, AG Baboul, BB Steianov, G. Liu, A. Liash This paper size is applicable to China National Standard (CNS) A4 (210 x 297 mm) (Please read the precautions on the back 3 (Write this page) n ϋ I i_i * 1 I 一 aJ_ I I MB MM I ΜΜ II _ Printed by the Consumers ’Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs? Clothing -34 · 552265 A7 __B7 V. Description of the invention (32) enko · P · Piskorz, I. Komaromi. R · Gomperts · R. L · Martin · D · J · Fox ’τ ·

Keith M. A. A. Laham, CY Peng, A. Nanayakkara, C. Gonzalez, M. Cha llaconbe, P. M. W. Gill, B. Johnson, W. Chem, M. W. Wong.] · L. Andres, C. Gonzalez, M. Head-Gordon. ES Replogle, and JA Pople. Gaussian, Inc .. Pittsburgh PA, 1998. (19) (a) DunDing Jr .. TH, Hay, PJ In Modern Theoretical Chem istry; Schaefer 111 HF. Ed .; Plenum: New York, 1976; vol. 3, 1. (b) Hay, P. J .; Watit, W · R · J · Chen. Phys · 1985, 81, 170 (C) Wadt. W · R .; Hay, PJJ Chem. Phys. 1985, 82. 284. (d) Hay, PJ; Wadt, WRJ Chem. Phys. 1985, 82. 299.

------------- V 仏 ---- I I--Order -------- line (please read the notes on the back first and write this page) I Ministry of Economy Wisdom The paper size printed by the employee's consumer cooperative of the Property Bureau applies the Chinese National Standard (CNS) A4 regulations (210 X 297 public love) -35-

Claims (1)

552265 Printed by the Consumer Cooperative of the Intellectual Property Bureau of the Ministry of Economic Affairs A8 B8 C8 D8 N 丨 1 · A compound characterized by the compound represented by Formula 1 [In the formula, M is a hydrogen atom or a one-electron valent metal]. 2. The compound according to item 1 of the scope of patent application, wherein M is a hydrogen atom. 3. The compound according to item 1 or 2 of the patent application scope, wherein the compound can catalyze an asymmetric Michael addition reaction. 4. The compound according to item 3 of the patent application range, wherein the asymmetric Michael addition reaction is a reaction of a / 5-dicarbonyl compound with a cyclic or acyclic enone. 5 ·· Species / 3-dicarbonyl compound and cyclic or acyclic ketene production method, characterized in that yS -dicarbonyl compound and cyclic or acyclic ketene The reactant in the presence of the compound of item 1. 6. The manufacturing method according to item 5 of the patent application, wherein the compound is the compound according to item 2 of the patent application. ------- · _Aw% .— (Please read the notes on the back before filling out this page) * 11 This paper size is applicable to China National Standard (CNS) A4 (210X297 mm) _ 36