No abstract

The catalytic hydrogenation of alkenes, ketones, and imines is arguably one of the most important transformations in chemistry. Powerful asymmetric versions have been realized that require metal catalysts or the use of a stoichiometric amount of metal hydrides [Eq. (1)]. [1] Although effective and industrially relevant catalytic asymmetric hydrogenations and transfer hydrogenations of olefins and ketones have been developed, the corresponding imine reductions, although potentially highly useful for the synthesis of enantiomerically pure amines, are less advanced.[2] Living organisms employ organic dihydropyridine cofactors such as nicotinamide adenine dinucleotide (NADH) in combination with enzyme catalysts for the reduction of imines.[3] Chemical transition metal catalyzed asymmetric imine reductions have also been developed, [4] and are used, in at least one case, on an industrial scale. [5] However, with the exception of interesting Lewis base catalyzed asymmetric imine hydrosilylations, [6] organocatalytic and metal-free variants were not known. Recently, we and MacMillan and co-workers developed an asymmetric transfer hydrogenation of a,b-unsaturated aldehydes catalyzed by a chiral ammonium salt by using Hantzsch esters as a biomimetic hydrogen source. [7] Rueping et al. [8] very recently reported the development of a novel and elegant approach using Hantzsch esters as the reducing reagent for the catalytic asymmetric reduction of imines using a chiral Brønsted acid catalyst previously developed by Akiyama et al.

In Xenopus oocytes, the spindle assembly checkpoint (SAC) kinase Bub1 is required for cytostatic factor (CSF)-induced metaphase arrest in meiosis II. To investigate whether matured mouse oocytes are kept in metaphase by a SAC-mediated inhibition of the anaphase-promoting complex/cyclosome (APC/C) complex, we injected a dominant-negative Bub1 mutant (Bub1dn) into mouse oocytes undergoing meiosis in vitro. Passage through meiosis I was accelerated, but even though the SAC was disrupted, injected oocytes still arrested at metaphase II. Bub1dn-injected oocytes released from CSF and treated with nocodazole to disrupt the second meiotic spindle proceeded into interphase, whereas noninjected control oocytes remained arrested at metaphase. Similar results were obtained using dominant-negative forms of Mad2 and BubR1, as well as checkpoint resistant dominant APC/C activating forms of Cdc20. Thus, SAC proteins are required for checkpoint functions in meiosis I and II, but, in contrast to frog eggs, the SAC is not required for establishing or maintaining the CSF arrest in mouse oocytes.

A novel organocatalytic asymmetric reductive amination of aldehydes has been developed. Treating racemic alpha-branched aldehydes with p-anisidine and a Hantzsch ester in the presence of our previously developed phosphoric acid catalyst, TRIP, gave beta-branched secondary amines in excellent yields and enantioselectivities via an efficient dynamic kinetic resolution. The process is applicable to several different aromatic aldehydes and amines but gives slightly reduced enantiomeric ratios with aliphatic aldehydes.