A catalytic asymmetric heteroatom Diels-Alder reaction of unactivated imines with Danishefsky's diene is described which gives high asymmetric induction for N-benzhydryl imines derived from a variety of aldehydes. The catalyst is derived from B(OPh) 3 and the VAPOL ligand and gives good induction but the reaction stalls and does not give high conversion (~50%). It was found that in the presence of the both the chiral catalyst and excess amounts of B(OPh) 3 the reaction proceeds to completion and gives high yields of the dihydropiperidinone product. Despite the presence of large quantities of the non-chiral Lewis acid B(OPh) 3 the asymmetric induction of the product remains constant (90% ee) as the amount of B(OPh) 3 is steadily increased and does not drop off until the ratio of B(OPh) 3 to VAPOL is 100:1 (82% ee). These observations are interpreted as involving highly separated and different activities for the chiral and non-chiral Lewis acids present in the reaction. Specifically, the excess B(OPh) 3 serves to bind to the product and release the chiral catalyst to turnover more starting material. The B(OPh) 3 does not compete in turning over of the starting material and a series of binding studies reveals that this likely due to a combination of two factors. The binding studies reveals that the chiral catalyst binds to the starting imine seven times more strongly than does B(OPh) 3 . However, in order to explain the constant asymmetric induction observed despite the addition of increasing amounts of B(OPh) 3 the rate of the reaction of the imine complexed with the chiral catalyst must be at least 10 times faster than the reaction of the imine complexed with B (OPh) 3 . Finally, a catalyst generated from BINOL and B(OPh) 3 does not show this phenomenon.Attempts to develop chiral catalysts for asymmetric reactions of imines must confront the problem that the product is more basic than the starting imine thus leading to difficulty in turnover. 1 A scenario in which both turnover and asymmetric induction could be realized would involve two catalysts, one chiral and one non-chiral (eq. 1). If the non-chiral catalyst was in excess then it could free up the chiral catalyst to turn over the reaction. Asymmetric induction could be achieved if the chiral catalyst has a larger binding constant than the nonchiral catalyst for imine 1, or if the chiral catalyst promotes the reaction at a sufficiently greater rate that it can overcome its molar disadvantage, or if both were to pertain. We report here the discovery of such a two catalyst system where at least 20 turnovers can be achieved in a heteroatom Diels-Alder reaction with no loss of induction. This type of dual-Lewis acid catalyst system with orthogonal functions is to our knowledge unprecedented. 2,3 E-mail: wulff@chemistry.msu.edu. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptThe first report of a heteroatom Diels-Alder reaction of an imine catalyzed by a chiral Lewis acid involved a catalyst prepared from (R)-BI...
Nucleobase radicals are the major family of reactive intermediates formed when nucleic acids are exposed to hydroxyl radical, which is produced by gamma-radiolysis and Fe.EDTA. Significant advances have been made in understanding the role of nucleobase radicals in oxidative DNA damage by independently generating these species from photochemical precursors. However, this approach has been used much less frequently to study RNA molecules. Norrish type I photocleavage of the tert-butyl ketone (2b) enabled studying the reactivity of 5'-benzoyl-5,6-dihydrouridin-6-yl (1b). High mass balances were observed under aerobic or anaerobic conditions, and O(2) did not affect the photochemical conversion of the ketone (2b) to 1b. Competition studies with O(2) indicate that the radical abstracts hydrogen atoms from beta-mercaptoethanol with a bimolecular rate constant = 2.6 +/- 0.5 x 10(6) M(-1)s(-1). The major product formed in the presence of O(2) was 5'-benzoyl-6-hydroxy-5,6-dihydrouridine (6). In contrast, 5-benzoyl-ribonolactone (7), a hypothetical product resulting from C1'-hydrogen atom abstraction by the peroxyl radical, could not be detected. Overall, tert-butyl ketone 2b is a clean source of 5'-benzoyl-5,6-dihydrouridin-6-yl (1b) and should prove useful for studying the reactivity of the respective radical in RNA.
Under the aegis of boron Lewis acids, prepared from either the vanol or vapol ligand, vinyl aziridinyl ketones can be obtained with a high degree of asymmetric induction from the catalytic asymmetric aziridination reaction (AZ) of imines
Reaction. -The reactions of Danishefsky's diene with benzhydryl imines derived from aromatic aldehydes proceed with high enantioselectivities by use of a catalyst which is prepared prior the reaction from one equivalent of B(OPh)3 relating to the imine and 5-10 mol% of (S)-VAPOL. Imines derived from aliphatic aldehydes give markedly differing enantioselectivities under these conditions. High e.e. values are observed for imines derived from α-branched aliphatic aldehydes. Imines derived from unbranched, α,β-unsaturated, or α,α-disubstituted aldehydes are unreactive or provide racemic products. -(NEWMAN, C. A.; ANTILLA, J. C.; CHEN, P.; PREDEUS, A. V.; FIELDING, L.; WULFF*, W. D.; J. Am. Chem. Soc. 129 (2007) 23, 7216-7217; Dep. Chem., Mich. State Univ., East Lansing, MI 48824, USA; Eng.) -Klein 42-134
A high degree of asymmetric induction is obtained for the boron Lewis acid catalyzed reaction of vinyl diazomethyl ketones with imines. The catalyst is prepared prior the aziridination reaction by heating of (S)-VAPOL with 3 equiv. of B(OPh)3. The aziridinyl vinyl ketone (IIIa) is stereoselectively reduced to either alcohols (IV) or (V). The alcohols are transformed into five-carbon amine units. -(DENG, Y.; LEE, Y. R.; NEWMAN, C. A.; WULFF*, W. D.; Eur.
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