Room to swing a cat: A chiral disulfonimide has been designed as a powerful new motif for asymmetric catalysis. As a first illustration, a highly efficient and enantioselective Mukaiyama aldol reaction has been developed (see scheme). The actual catalyst is proposed to be an N-silyl imide which is generated in situ

Viel Platz: Ein chirales Disulfonimid wurde als leistungsfähiges neues Motiv für die asymmetrische Katalyse entwickelt. Als erste Illustration seiner Eignung wird eine hocheffiziente enantioselektive Mukaiyama‐Aldolreaktion beschrieben (siehe Schema) und dabei ein in situ erzeugtes N‐Silylimid als tatsächlicher Katalysator angenommen.

The term vinylogy, which describes a unique property of p systems where the electron density and reactivity is amplified along conjugated bonds, was proposed 75 years ago by Fuson.[1] The principle becomes particularly relevant in the context of the aldol reaction: While metal dienolates often furnish mixtures of a-and g-addition products, [2] the corresponding dienolsilanes react with high selectivity at the remote g position.[3] Asymmetric vinylogous Mukaiyama aldol reactions furnish structural subunits commonly occurring in natural products, as illustrated by the research groups of Carreira, Denmark, Kalesse, and others.[4] Several catalytic, asymmetric versions have been developed over the last few years.[5] However, general and highly stereoselective methods that tolerate a wide range of unactivated substrates are still needed. Moreover, bisvinylogous aldol additions, potentially furnishing a,b,g,d-unsaturated esters in a single step, have to our knowledge not been successfully developed to date.[6]Herein we report asymmetric vinylogous aldol additions, catalyzed by our recently introduced pre-Lewis acidic disulfonimide catalysts 1.[7] We also describe the unprecedented extension of the Mukaiyama aldol addition towards a bisvinylogous e-selective and highly enantioselective variant.Initial computational studies revealed the expected reactivity trends of the extended ketene acetals (Scheme 1). DFT calculations for attack by an electrophile (f À (r)) provided the corresponding condensed Fukui functions (CFF), and the electrostatic potentials (ESP).[8] The data obtained for nucleophiles of type 3 were in line with those previously reported, thus suggesting the reaction occurred preferentially in the g position (a = 0.09, g = 0.14).[3f] Interestingly for nucleophiles of type 4, compounds that have been obtained previously though never studied in terms of their application in aldol additions, [9] the calculations point to nucleophilic attack from the terminal position as well (a = 0.07, g = 0.07, e = 0.11). However, the values for the different positions vary less than for nucleophiles of type 3, possibly suggesting a less distinct selectivity. Furthermore, the nature of the aldehyde should also influence the outcome of the reaction.Despite the advancements in the asymmetric catalysis of vinylogous Mukaiyama aldol reactions, organocatalytic systems proved to be more challenging to establish. Probably the best system to date was reported by Denmark and co-workers, who described the Lewis base activation of Lewis acids by utilizing chiral hexamethylphosphoramide (HMPA) derivatives in combination with SiCl 4 .[10] However, even this method has its limitations, either in scope or reactivity, and requires stoichiometric amounts of the Lewis acid.As a starting point for our experimental work we explored our chiral disulfonimide catalyst 1 in the reaction of 2-naphthaldehyde with crotonate-derived nucleophile 3 a in different solvents at different temperatures. These studies revealed that Et 2 O at À78 8C was optimal ...

This contribution describes the development and demonstration of the ambient-temperature, high-speed living polymerization of polar vinyl monomers (M) with a low silylium catalyst loading (≤ 0.05 mol % relative to M). The catalyst is generated in situ by protonation of a trialkylsilyl ketene acetal ((R)SKA) initiator (I) with a strong Brønsted acid. The living character of the polymerization system has been demonstrated by several key lines of evidence, including the observed linear growth of the chain length as a function of monomer conversion at a given [M]/[I] ratio, near-precise polymer number-average molecular weight (M(n), controlled by the [M]/[I] ratio) with narrow molecular weight distributions (MWD), absence of an induction period and chain-termination reactions (as revealed by kinetics), readily achievable chain extension, and the successful synthesis of well-defined block copolymers. Fundamental steps of activation, initiation, propagation, and catalyst "self-repair" involved in this living polymerization system have been elucidated, chiefly featuring a propagation "catalysis" cycle consisting of a rate-limiting C--C bond formation step and fast release of the silylium catalyst to the incoming monomer. Effects of acid activator, catalyst and monomer structure, and reaction temperature on polymerization characteristics have also been examined. Among the three strong acids incorporating a weakly coordinating borate or a chiral disulfonimide anion, the oxonium acid [H(Et(2)O)(2)](+)[B(C(6)F(5))(4)](-) is the most effective activator, which spontaneously delivers the most active R(3)Si(+), reaching a high catalyst turn-over frequency (TOF) of 6.0×10(3) h(-1) for methyl methacrylate polymerization by Me(3)Si(+) or an exceptionally high TOF of 2.4×10(5) h(-1) for n-butyl acrylate polymerization by iBu(3)Si(+), in addition to its high (>90 %) to quantitative efficiencies and a high degree of control over M(n) and MWD (1.07-1.12). An intriguing catalyst "self-repair" feature has also been demonstrated for the current living polymerization system.