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.

Ligand-stabilized copper(I)-hydride catalyzes the dehydrogenative Si-O coupling of alcohols and silanes-a process that was found to proceed without racemization at the silicon atom if asymmetrically substituted. The present investigation starts from this pivotal observation since silicon-stereogenic silanes are thereby suitable for the reagent-controlled kinetic resolution of racemic alcohols, in which asymmetry at the silicon atom enables discrimination of enantiomeric alcohols. In this full account, we summarize our efforts to systematically examine this unusual strategy of diastereoselective alcohol silylation. Ligand (sufficient reactivity with moderately electron-rich monophosphines), silane (reasonable diastereocontrol with cyclic silanes having a distinct substitution pattern) as well as substrate identification (chelating donor as a requirement) are introductorily described. With these basic data at hand, the substrate scope was defined employing enantiomerically enriched tert-butyl-substituted 1-silatetraline and highly reactive 1-silaindane. The synthetic part is complemented by the determination of the stereochemical course at the silicon atom in the Si-O coupling step followed by its quantum-chemical analysis thus providing a solid mechanistic picture of this remarkable transformation.

An investigation of the stereochemical course of the reductive metallation of silyl chlorides with silicon-centred chirality has revealed two major events which are detrimental to stereoselection during silyl anion formation: (1) chloride-induced racemisation of silyl chlorides and (2) nonstereoselective formal dimerisation during metallation providing the corresponding disilane. In control experiments, the stereochemical course of these processes has been independently verified for the reductive metallation of the enantioenriched cyclic silyl chloride (SiS)-7a (R = H, er Ն 88:12). A screening of several related derivatives of (SiS)-7a led to the sterically encumbered silyl chloride (SiR)-7c (R = iPr, er Ն 94:6) which displays some unique features. This structural modification pre-

Non-enzymatic kinetic resolution [1] of racemic mixtures is a competitive strategy in asymmetric synthesis for the preparation of chiral building blocks. [2,3] The general approach relies on either a chiral reagent to undergo or a chiral catalyst to promote a stereoselective reaction of one enantiomer over the other. Within the theme of the former scenario, we devised a novel concept based on an unprecedented diastereoselective transition-metal-catalyzed dehydrogenative silicon-oxygen coupling of silicon-stereogenic silanes A and racemic alcohols rac-B (Scheme 1). [4] We envisioned that if a preferential reaction of A with (S)-B to produce diastereoenriched C were viable, the optical antipode (R)-B would remain in enantioenriched form. Moreover, stereospecific reductive cleavage of the siliconoxygen bond in C would allow complete recovery of the resolving reagent A. Importantly, both silicon-oxygen bond formation and cleavage would have to proceed without any erosion of stereochemical information at the silicon atom. Herein, we describe this novel concept of utilizing siliconstereogenic silanes A in a kinetic resolution reaction.We initially sought suitable reaction conditions for silane alcoholysis with a particular emphasis on the stereochemical course at the silicon atom. Several heterogeneous and homogeneous catalysts are available, [5,6] and we selected the copper(i)-catalyzed dehydrogenative coupling introduced by Lorenz and Schubert. [7] Oxygen-sensitive [{(Ph 3 P)CuH} 6 ] [8] is effectively replaced by a robust precatalyst (CuCl, Ph 3 P, NaOtBu) reported by Buchwald and co-workers [9] which also enables simple variation of the phosphine ligand.We then screened this catalyst in the methanolysis of several asymmetrically substituted silanes [10]

Enantiomere an der Angel: Eine neuartige kinetische Racematspaltung von zur Zweipunktanbindung befähigten Alkoholen gelang unter Verwendung von Silanen mit siliciumzentrierter Chiralität. Diese Strategie beruht auf einer diastereoselektiven dehydrierenden Si‐O‐Kupplung unter Kupferkatalyse (siehe Schema). Das zur Racematspaltung eingesetzte Silan kann ohne Verlust an stereochemischer Information am Si‐Atom vollständig zurückgewonnen werden.