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In order to increase the feasibility of the new protocol we aimed for the best possible recovery of the diamines (R,R)-1 and (S,S)-1 from the inclusion complexes. After trying various acids for the liberation of BINOL we found that the tartaric acids were the most suitable for our purposes. Thus after dissolution of complex (R)-2-(R,R)-1-toluene in methanol/water (10:1) and addition 1.1 equiv. of tartaric acid the corresponding (R,R)-1 tartrate salt precipitated almost quantitatively and could be separated by filtration. (R)-BINOL pre- cipitated from the filtrate during the removal of methanol from the solution and was filtered and after With both enantiomers of trans-cyclohexane-l,2- diamine easily available, we attempted to find an improved and more reliable method for the resolution of BINOL 2. Kawashima and Hirata described in their method? that, in toluene, the more soluble inclusion complex, (S)-2:(R,R)-1, can be obtained from the mother liquor in 96% ee (measured by HPLC of the liberated BINOL) after separation of the less soluble (R)-2:(R,R)-1-toluene complex. We also made this observation. However, in contrast to the described pro- cedure, after removal of volatiles, we were not able to increase further the ee by simply washing the residue with toluene. Recrystallisation of the liberated (S)- BINOL also did not give an improved ee. Also the reported procedure does not give details for the recov- ery of the precious, enantiopure diamine, which also is a valid factor for economic feasibility. There are actu- ally two points in the procedure at which the relevant

Figure 3 In order to increase the feasibility of the new protocol we aimed for the best possible recovery of the diamines (R,R)-1 and (S,S)-1 from the inclusion complexes. After trying various acids for the liberation of BINOL we found that the tartaric acids were the most suitable for our purposes. Thus after dissolution of complex (R)-2-(R,R)-1-toluene in methanol/water (10:1) and addition 1.1 equiv. of tartaric acid the corresponding (R,R)-1 tartrate salt precipitated almost quantitatively and could be separated by filtration. (R)-BINOL pre- cipitated from the filtrate during the removal of methanol from the solution and was filtered and after With both enantiomers of trans-cyclohexane-l,2- diamine easily available, we attempted to find an improved and more reliable method for the resolution of BINOL 2. Kawashima and Hirata described in their method? that, in toluene, the more soluble inclusion complex, (S)-2:(R,R)-1, can be obtained from the mother liquor in 96% ee (measured by HPLC of the liberated BINOL) after separation of the less soluble (R)-2:(R,R)-1-toluene complex. We also made this observation. However, in contrast to the described pro- cedure, after removal of volatiles, we were not able to increase further the ee by simply washing the residue with toluene. Recrystallisation of the liberated (S)- BINOL also did not give an improved ee. Also the reported procedure does not give details for the recov- ery of the precious, enantiopure diamine, which also is a valid factor for economic feasibility. There are actu- ally two points in the procedure at which the relevant

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* Corresponding author. E-mail: declan. gilheany@ucd.ie trans-Cyclohexane-1,2-diamine 1 forms the backbone of many useful chiral ligands in asymmetric catalysis! and can also be used for the resolution? of (+)-2,2’-dihy- droxy-1,1’-binaphthyl (racemic BINOL) 2 _ itself arguably an even more important backbone (vide infra). 0957-4166/$ - see front matter © 2003 Elsevier Ltd. All rights reserved. doi:10.1016/S0957-4166(03)00586-X
* Corresponding author. E-mail: declan. gilheany@ucd.ie trans-Cyclohexane-1,2-diamine 1 forms the backbone of many useful chiral ligands in asymmetric catalysis! and can also be used for the resolution? of (+)-2,2’-dihy- droxy-1,1’-binaphthyl (racemic BINOL) 2 _ itself arguably an even more important backbone (vide infra). 0957-4166/$ - see front matter © 2003 Elsevier Ltd. All rights reserved. doi:10.1016/S0957-4166(03)00586-X
Herein we report an improved method for the resolu- tion of trans-cyclohexane-1,2-diamine (rac-1). Both enantiomers could be isolated in good to excellent yields and were obtained in enantiopure form (>99.8% ee) as chemically inert bis-ammonium salts. Racemic BINOL rac-2 was prepared in significantly higher yields by a modified work up protocol and resolved using (R,R)- and (S,S)-cyclohexanediamine to give both iso- mers in enantiopure form (>99.8% ee) in very good yields. Moreover, the precious and _ enantiopure diamines were easily recovered as their corresponding monotartrate salts in 66% and 79% yields respectively. A setback in practicality, however, lies in the time consuming removal of water from the mother liquor after the first separation. In order to simplify the reso- lution, instead of water, we tried refluxing methanol as a polar and more easily removable solvent. Since the solubility of the (R,R)-1 tartrate salt in methanol is very low, the initial precipitate was obtained as a viscous, dirty white glue which contained significant amounts of trapped (S,S)-1 acetate which we then tried to re-dissolve by increasing the reflux time to 16 h before filtration. By then the precipitate was trans- formed into a white, microcrystalline powder. This method gave 49% yield (of a theoretical 50%) and 96% ee [HPLC] of the desired compound. Addition of conc. HCI and acetone afforded the (S,S)-1 dihydrochloride in 40% yield and 98% ee [HPLC] after filtration. A prolonged reflux time in order to extract more of the soluble (S,S)-1 acetate from the insoluble (R,R)-1 tar- trate, however, did not improve enantioselectivities.
Herein we report an improved method for the resolu- tion of trans-cyclohexane-1,2-diamine (rac-1). Both enantiomers could be isolated in good to excellent yields and were obtained in enantiopure form (>99.8% ee) as chemically inert bis-ammonium salts. Racemic BINOL rac-2 was prepared in significantly higher yields by a modified work up protocol and resolved using (R,R)- and (S,S)-cyclohexanediamine to give both iso- mers in enantiopure form (>99.8% ee) in very good yields. Moreover, the precious and _ enantiopure diamines were easily recovered as their corresponding monotartrate salts in 66% and 79% yields respectively. A setback in practicality, however, lies in the time consuming removal of water from the mother liquor after the first separation. In order to simplify the reso- lution, instead of water, we tried refluxing methanol as a polar and more easily removable solvent. Since the solubility of the (R,R)-1 tartrate salt in methanol is very low, the initial precipitate was obtained as a viscous, dirty white glue which contained significant amounts of trapped (S,S)-1 acetate which we then tried to re-dissolve by increasing the reflux time to 16 h before filtration. By then the precipitate was trans- formed into a white, microcrystalline powder. This method gave 49% yield (of a theoretical 50%) and 96% ee [HPLC] of the desired compound. Addition of conc. HCI and acetone afforded the (S,S)-1 dihydrochloride in 40% yield and 98% ee [HPLC] after filtration. A prolonged reflux time in order to extract more of the soluble (S,S)-1 acetate from the insoluble (R,R)-1 tar- trate, however, did not improve enantioselectivities.
4 comprehends all manipulations conducted during the resolution procedure for rac-BINOL. purification by dissolution in CH,Cl, and washing with aqueous Na,CO, gave a 94% yield of enantiomerically pure material, corresponding to a 42.4% yield overall. Complex (S)-2-(S,S)-1-toluene was treated in a similar fashion using 2.2 equiv. of racemic DL-tartaric acid, which is significantly less expensive than enantiopure D-(—)-tartaric acid, and the (S,S)-1-D-(—)-tartrate salt was recovered again almost quantitatively. (S)-BINOL was obtained enantiomerically pure in 95% yield (40.4% overall) after the same washing procedure with Na,CO,. The overall yield of enantiopure BINOL for the resolution is therefore 83%.
4 comprehends all manipulations conducted during the resolution procedure for rac-BINOL. purification by dissolution in CH,Cl, and washing with aqueous Na,CO, gave a 94% yield of enantiomerically pure material, corresponding to a 42.4% yield overall. Complex (S)-2-(S,S)-1-toluene was treated in a similar fashion using 2.2 equiv. of racemic DL-tartaric acid, which is significantly less expensive than enantiopure D-(—)-tartaric acid, and the (S,S)-1-D-(—)-tartrate salt was recovered again almost quantitatively. (S)-BINOL was obtained enantiomerically pure in 95% yield (40.4% overall) after the same washing procedure with Na,CO,. The overall yield of enantiopure BINOL for the resolution is therefore 83%.
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Organic ChemistryAsymmetric catalysis
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