Just ask silicon: An experimentally straightforward yet effective Walden‐type analysis showcases the usefulness of silanes with a stereogenic silicon center as stereochemical probes. The B(C6F5)3‐catalyzed hydrosilylation and likely the related hydrogenation proceed through linear B‐H‐Si‐O transition states, as verified by flawless inversion of the absolute configuration at silicon (see scheme).

alcohols · asymmetric catalysis · kinetic resolution · organocatalysis · siliconThe importance of the silicon-oxygen linkage to temporarily protect a hydroxy group is reflected in its extensive use in the synthesis of complex molecules.[1] A relatively simple adjustment of the steric and electronic environment at the silicon atom accounts for literally dozens of common silicon-based proctective groups that are orthogonal in both the protection and deprotection steps. In the classic protocol for the formation of a silicon-oxygen bond, [2] a chlorosilane B is treated with an alcohol A in the presence of a nucleophilic catalyst and a stoichiometric amount of a base, often a pyridine derivative or tertiary amine (A + B!D, Scheme 1).Alternatively, but less-well established, the hydroxy group can be efficiently silylated by transition-metal-catalyzed dehydrogenative coupling of a hydrosilane C with A (A + C!D, Scheme 1); in this approach dihydrogen is generated as the sole by-product. [3] Despite the ubiquity of the silicon-oxygen bond in synthetic intermediates, the stereoselective silylation of alcohols-as opposed to the related asymmetric acylation of alcohols [4] -is largely underdeveloped. This elusive methodology might be utilized in the desymmetrization of meso diols [5] as well as in the kinetic resolution [6] of racemic mixtures of alcohols.[7] A pivotal observation reported in the seminal paper by Corey and Venkateswarlu might even guide the design of nucleophilic catalysts for an asymmetric siliconoxygen bond-forming process: imidazole was found to substantially enhance the reaction rates.[2] This reaction was believed to proceed with a silylated imidazole as the actual silylating reagent instead of the less-reactive corresponding chlorosilane. [8] However, prior to the recent development of an imidazole-containing catalyst (see below), Ishikawa and co-workers employed enantiopure guanidine bases as chlorosilane activators in the, at that time unprecedented, enantioselective silylation reaction.[9] These authors reasoned that a combination of a chiral guanidine base and a chlorosilane would kinetically resolve racemic unfunctionalized alcohols (Scheme 2). Indeed, an equimolar mixture of activator 3 and iPr 3 SiCl was capable of discriminating between the enantiomers of 1-indanol (rac-1) and 1-tetralol (rac-2). The levels of enantioselection for ethers (R)-4 (58 % ee) and (R)-5 (70 % ee) remained modest and conversion was poor despite the use of a stochiometric amount of the chiral reagent.To render this process catalytic in nucleophilic 3, Ishikawa and co-workers also examined the activation of the chlorosilane by 3 in the presence of the achiral tertiary amine Et 3 N, but no asymmetric induction at improved conversion was observed.[9] We also note that, based on an analysis of the acidities of the conjugate acids involved, catalytic turnover of the chiral activator might be difficult to achieve, since this

The first organocatalytic enantioselective radical polycyclization has been accomplished using singly occupied molecular orbital (SOMO) catalysis. The presented strategy relies on a selective single-electron oxidation of chiral enamines formed by condensation of polyenals with an imidazolidinone catalyst employing a suitable copper(II) oxidant. The reaction proceeds under mildly acidic conditions at room temperature and shows compatibility with an array of electron-poor as well as electron-rich functional groups. Upon termination by radical arylation, followed by subsequent oxidation and rearomatization, a range of polycyclic aldehydes has been accessed (12 examples, 54-77% yield, 85-93% ee). The enantioselective formation of up to six new carbocycles in a single catalyst-controlled cascade is described. Evidence for a radical-based cascade mechanism is indicated by a series of experimental results.

The value of a novel chemical transformation is often underappreciated at the time of its discovery. The reasons are doubtlessly manifold, but the "chemical zeitgeist" subtly determines how the new reaction will be received by the chemical community. The enantioselective reduction of carbonyls by copper-catalyzed hydrosilylation was certainly outshone by other asymmetric hydrogenation techniques. A seminal report at an early stage indicated the considerable potential of this catalytic process, yet it was disregarded for more than a decade. A refined mechanistic picture in connection with a plethora of new chiral ligands then led to copper-catalyzed 1,2- as well as 1,4-reductions of carbonyl compounds with excellent levels of enantioselection at high substrate-to-catalyst ratios and even more remarkable substrate-to-ligand ratios. The tide is turning for inexpensive copper catalysts in asymmetric hydride transfer reactions!

Abstract:The cyclic silicon-stereogenic silane (SiR)-5 decorated with three different substituents of distinct steric demand is an exceptionally useful chiral reagent in asymmetric organosilicon chemistry. Several approaches for its large-scale preparation in optically pure form have been investigated. These hinge upon the resolution of racemic silane rac-5 which, in turn, is accessible in multi-gram quantities by a straightforward one-pot two-step reaction sequence. For this, a classical as well as a novel kinetic resolution via its diastereomeric silyl ethers derived from enantiopure secondary alcohols as resolving agents has been elaborated: (1) the use of (À)-menthol [(À)-7] allowed for a quantitative separation of silyl ethers (SiS)-10 and (SiR)-10 by practical fractional crystallization and (2) a diastereoselective copper-catalyzed dehydrogenative silicon-oxygen coupling using pyridyl alcohols (S)-16 or (R)-16 capable of two-point binding has been devised and assessed as a novel kinetic resolution strategy for the synthesis of a silane with silicon-centered chirality. Subsequent stereospecific reductive cleavage of the silicon-oxygen bond enabled the preparation of (SiR)-5 and (SiS)-5 in excellent enantiomeric excesses of up to 99 % ee.