Dynamic catalytic asymmetric transformation

Toste s group made several modifications of bis(HBHC)-digold complex 40 by placing differently substituted aryl groups at the binaphthyl 3,3 -positions of the diamine synthon and examined them in catalytic dynamic kinetic asymmetric transformations of propargyl esters (Scheme 16.14) [29b]. Drastic substituent effects on enantioselectivity were observed, with j -trifluoromethylphenyl-... 

S. Lin, L. Deiana, G. Zhao, A. Cordova, J. Sun, Angew. Chem. Int. Ed 2011, 50, 7624-7630. Dynamic one-pot three-component catalytic asymmetric transformation hy comhination of hydrogen-bond-donating and amine catalysts. 

It is well-known that catalytic amounts of aldehyde can induce racemization of a-amino acids through the reversible formation of Schiff bases.61 Combination of this technology with a classic resolution leads to an elegant asymmetric transformation of L-proline to D-proline (Scheme 6.8).62 63 When L-proline is heated with one equivalent of D-tartaric acid and a catalytic amount of n-butyraldehyde in butyric acid, it first racemizes as a result of the reversible formation of the proline-butyraldehyde Schiff base. The newly generated D-proline forms an insoluble salt with D-tartaric acid and precipitates out of the solution, whereas the soluble L-proline is continuously being racemized. The net effect is the continuous transformation of the soluble L-proline to the insoluble D-proline-D-tartaric acid complex, resulting in near-complete conversion. Treatment of the D-proline-D-tartaric acid complex with concentrated ammonia in methanol liberates the D-proline (16) (99% ee, with 80-90% overall yield from L-proline). This is a typical example of a dynamic resolution where L-proline is completely converted to D-proline with simultaneous in situ racemization. As far as the process is concerned, this is an ideal case because no extra step is required for recycle and racemization of the undesired enantiomer and a 100% chemical yield is achievable. The only drawback of this process is the use of stoichiometric amount of D-tartaric acid, which is the unnatural form of tartaric acid and is relatively expensive. Fortunately, more than 90% of the D-tartaric acid is recovered at the end of the process as the diammonium salt that can be recycled after conversion to the free acid.64... 

S. Y. Tosaki, R. Tsuji, T. Ohshima, M. Shibasaki, Dynamic ligand exchange of the lanthanide complex leading to structural and functional transformation One-pot sequential catalytic asymmetric epoxidation-regioselective epoxide-opening process, J. Am. Chem. Soc. 127 (2005) 2147. 

Cordova and coworkers developed the first organo/co-catalytic system 96/97 for the dynamic one-pot asymmetric transformation between aldehydes 92, the cyanoglycine ester 93, and enals 94 (Scheme 2.25). Through this catalytic, dynamic, three-component process, cyano-, formyl-, or ester-functionalized a-quaternary proline derivatives 95 with four contiguous stereocenters could be obtained in excellent yield and stereoselectivity [40]. Mechanistic studies revealed that the iminium activation of the carbonyl components and biomimetic cooperative combination of hydrogen bonds were essential to achieve highly chemo and stereoselective cycloaddition under this kinetically controlled process. 

The Catalysis Concept of Iminium Activation In 2000, the MacMillan laboratory disclosed a new strategy for asymmetric synthesis based on the capacity of chiral amines to function as enantioselective catalysts for a range of transformations that traditionally use Lewis acids. This catalytic concept was founded on the mechanistic postulate that the reversible formation of iminium ions from a,p-unsaturated aldehydes and amines [Eq. (11.10)] might emulate the equilibrium dynamics and 7i-orbital electronics that are inherent to Lewis acid catalysis [i.e., lowest unoccupied molecular orbital (LUMO)-lowering activation] [Eq. (11.9)] ... 

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