The creation of quaternary stereogenic centers with high enantioselectivity is challenging, in part, because of the high steric repulsion between the substituents on the carbon center that is generated during construction. Nevertheless, significant progress has been made towards this goal in recent years, even in conformationally flexible acyclic systems.[1] However, whilst in many cases high e.r. values have been achieved, the selectivities are invariably substrate-dependent.We have approached this problem from a different perspective and considered the possibility of employing stereospecific homologations of tertiary boronic esters 1. Such boronic esters can be easily prepared from the corresponding secondary alcohols with very high e.r. values by using the methodology developed by our group, [2] or alternatively, by borylation of allylic carbonates/Michael acceptors reported by Hoveyda and co-workers (Scheme 1).[3] However, whilst the homologation reaction may seemingly appear to be a straight forward extension of the literature it should be noted that hindered tertiary boranes (e.g., thexyl) have often been employed as nonmigrating groups in homologations of boranes, [4] and examples of related transformations of tertiary boronic esters are rare. [5,6] Furthermore, extending methodology from secondary to tertiary substrates is rarely straightforward as the extra steric demand often results in lower selectivity or alternative reaction pathways being followed.[7] Herein we describe our success in creating quaternary stereogenic centers with very high e.r. values and with a range of versatile functional groups; the subsequent application of the methodology in synthesis is also presented.We began our studies using the tertiary boronic ester 2 a which was subjected to standard Matteson homologation conditions [6] using chloromethyl lithium [6b] at low temperature. However, whilst the homologated alcohol product was obtained after oxidation in reasonable yield, almost 20 % of the oxidation product 4, seemingly derived from the starting material 2 a, was also isolated even when a large excess (4.0 equiv) of LiCH 2 Cl was employed (Scheme 2).Analysis of the reaction by 11 B NMR spectroscopy prior to oxidation revealed that in addition to the signal of desired boronic ester 5 at d = 32 ppm, a new peak at d = 49 ppm was observed, which is indicative of the presence of borinic ester 6.[8] This ester must have formed from the unexpected migration of the oxygen substituent [9] instead of the normally favored carbon migration, presumably as a consequence of the very hindered nature of the boronic ester. We reasoned that using a bulkier and less polar leaving group (smaller dipole moment) would favor the conformation required for C migration and therefore explored LiCH 2 Br as an alternative reagent.[10] Making this simple modification resulted in an improved yield of the desired homologated product (83 % yield) with only about 5 % of the product derived from O migration (Scheme 2).This reagent was applied to a series of ...

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.

Due to the high versatility of chiral cyanohydrins, the catalytic asymmetric cyanation reaction of carbonyl compounds has attracted widespread interest. However, efficient protocols that function at a preparative scale with low catalyst loading are still rare. Here, asymmetric counteranion-directed Lewis acid organocatalysis proves to be remarkably successful in addressing this problem and enabled a molar-scale cyanosilylation in quantitative yield and with excellent enantioselectivity. Also, the catalyst loading could be lowered to a part-per-million level (50 ppm: 0.005 mol%). A readily accessible chiral disulfonimide was used, which in combination with trimethylsilyl cyanide, turned into the active silylium Lewis acid organocatalyst. The nature of a peculiar phenomenon referred to as a “dormant period”, which is mainly induced by water, was systematically investigated by means of in situ Fourier transform infrared analysis.

A new catalyst is designed, synthesized, and evaluated for the asymmetric Michael addition of nitroalkanes to nitroalkenes. The obdurate nature of this reaction has made this a formidable challenge to subdue by asymmetric catalysis. The catalyst design includes a thiourea function to activate the nitroalkene by a double H-bond and a 4-dimethylaminopyridine unit to deprotonate the nitroalkane and to bind the resulting nitronate anion also by a double H-bond. The chiral scaffold for the catalyst is 2,2'-diamino-1,1'-binaphthalene (BINAM), and a bis-conjugate is prepared by the attachment of the thiourea unit and the dimethylaminopyridine moiety (DMAP) via the two amino groups. The resulting catalyst will effect the reaction of nitroalkanes to a variety of nitrostyrenes and gives excellent asymmetric inductions (91-95% ee) over a range of 10 substrates. Remarkably, the asymmetric induction increases with decreasing catalyst loading with the optimal compromise between rate and induction at a loading of 2 mol %.