A combined NMR, DFT, and X-ray investigation of some cinchona alkaloid O-ethers.
Structures and conformational behavior of several cinchona alkaloid O-ethers in the solid state (X-ray), in solution (NMR and DFT), and in the gas phase (DFT) were investigated. In the crystal, O-phenylcinchonidine adopts the Open(3) conformation similar to cinchonidine, whereas the O-methyl ether derivatives of both cinchonidine and cinchonine are packed in the Closed(1) conformation. Dynamic equilibria in solutions of the alkaloids were revealed by combined experimental-theoretical spin simulation/iteration techniques for the first time. In the (1)H NMR spectra in CDCl3 and toluene-d8 at room temperature, Closed(1) conformation was observed for the O-silyl ethers as a separate set of signals. For O-methyl ether derivatives Closed(1) could be separated only at -30 degrees C in CDCl3 or toluene-d8 and for O-phenylcinchonidine at -70 degrees C in CDCl3/CD2Cl2. The ratio between the Closed(2) and Open(3) conformers was estimated by analyzing the vicinal coupling constant (3)J(H9,H8) at ambient and low temperatures. The observed conformational equilibria of O-(tert-butyldimethylsilyl)cinchonidine in CDCl 3 and toluene-d8 are in good agreement with the theoretically estimated equilibrium populations of the conformations according to Boltzmann statistics. The conformational equilibria of four cinchona alkaloid O-ether solutes in CDCl3 and toluene-d8 are discussed in the light of their relevance to the mechanism of 1-phenyl-1,2-propanedione (PPD) hydrogenation over cinchona alkaloid modified heterogeneous platinum catalysts. It was demonstrated that the conformation found to be abundant in the liquid phase has no direct correlation with the enantioselectivity of the PPD hydrogenation reaction.
Busygin
Igor
I
Laboratory of Organic Chemistry, Abo Akademi University, FI-20500 Turku, Finland.
Nieminen
Ville
V
Taskinen
Antti
A
Sinkkonen
Jari
J
Toukoniitty
Esa
E
Sillanpää
Reijo
R
Murzin
Dmitry Yu
DY
Leino
Reko
R
D000465:Algorithms; D002384:Catalysis; D047188:Chalcones / Q000737:chemistry; D002930:Cinchona Alkaloids / Q000737:chemistry*; D018360:Crystallography, X-Ray / Q000379:methods*; D004987:Ethers / Q000737:chemistry*; D005740:Gases; D006865:Hydrogenation; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008956:Models, Chemical; D008968:Molecular Conformation; D010984:Platinum / Q000737:chemistry; D012997:Solvents / Q000737:chemistry; D013237:Stereoisomerism; D013696:Temperature
D047188:Chalcones; D002930:Cinchona Alkaloids; D004987:Ethers; D005740:Gases; D012997:Solvents; D010984:Platinum; C100349:1-phenyl-1,2-propanedione