Synthesis of Chiral 1,1′-Iminodicarboxylic Acid Derivatives from α-Amino Acids, Aldehydes, Isocyanides, and Alcohols by the Diastereoselective Five-Center–Four-Component Reaction

✍ Scribed by Dr. Anton Demharter; Dipl.-Chem. Werner Hörl; Dr. Eberhardt Herdtweck; Prof. Dr. Ivar Ugi

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 827 KB
• Volume: 35
• Category: Article
• ISSN: 0044-8249
• DOI: 10.1002/anie.199601731

✦ Synopsis

An important ~o r k i n g hypothesis of polyoxometalate chemistry is that. in general. nietal atoins hearing three or more terminal oxygen atoms in MO, octahedra d o 1101 occur. For this "Lipscomb rule" see W. N. Lipscomb. Inorg. Climi 1965.4. 132 161 Crystal data of 1' space group P5, u =1432.8(2). ( ' =1829 8(3)pm, V = 3253(1) x 10hpmi, Z = 2. pialLd = 2 78 gem--', T = 188 K. R = 0.083 for 4533 independent reflections (F>4.Ou(F)) Crystal data of 2-space group Pi. u =1282.0(4). h =1380.3(4), c =1531.5(5)pm. T = 83.46(2), /j =77.37(2). ; = 68.92(2) , V = 2466(1) x 10' pm3. 2 = 1. pca,cd = 3.32 g ~m -~, T = 294 K. R = 0.067 for 6614 independent reflections (Fz4.Ou(F)). Further details of the crystal structure investigation may be obtained from the Fachinformationszentrum Karlsruhe. D-76344 Eggenstein-Leopoldshafen (Germany) on quoting the depository number CSD-59227. The cluster anion 2a was also obtained as Further investigations[*] have shown that the diastereomeric excess can be controlled by temperature and metal catalysts. Apart from alcohols, other classes of compounds such as amines and thiols can react as nucleophiles in U-5C-4CR. Like other Ftg. 1. Crystallographic structure of 9 (SCHAKAL) Selected bond lengths [pm] and angles ["I for molecule A [B]: N1 -C3 147.0(2) [145.6(2)], C2-C3 149.0(3) [154.1(2)], C4-C3 157 8(3) [153.1(3)], Nl-C7 144.6(2) [145.0(2)], C7-C8 155.0(2) 102.8(2) [103.4(2), C2-C3-C4 110.0(2) [109.8(2)1. Nl-C7-C8 111.6(1)[111.6(1)], NI-C7-Cl1 112.5(1) [111.5(2)], C8-C7-Cll 112.2(1) [ l l l 1(1)].

[154.2(2)], C7-Cll 153.5(2) [153.2(2)]; Nl-C3-C2 114.4(2) [112.1(2)], Nl-C3-C4 multicomponent reactions, the U-5C-4CR is extremely suitable for generating combinatorial chemical libraries.['] These findings confirm the authors' opinion that multicomponent reactions in general, and especially the U 4 C R , will play a prominent part in research, development, and applications.

Experimental Procedure

The ?-amino acid (10 mmol) in methanol (100 mL) was cooled to -30°C. Then aldehyde and isocyanide (each 10 mmol dissolved in 5 mL methanol) were added. After 3 h the mixture was allowed to warm to room temperature When the reaction was complete (clear solution, between three hours and two days), the solvent was removed in vacuo. The crude product was virtually free of by-products and often needed no further purification Small amounts of starting materials could be removed by washing a solution in ether with water. The mixtures of diastereomers were viscous oils or sticky solids. The diastereomers were separated by flash chromatography.