Kinetische Racematspaltung von chiralen sekundären Alkoholen durch dehydrierende Kupplung mit zurückgewinnbaren, siliciumstereogenen Silanen

Abstract

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.

Preparation of a Privileged Silicon‐Stereogenic Silane: Classical versus Kinetic Resolution

“…As in the classical resolution, reductive cleavage of the silicon-oxygen linkage in epi-G should then eject the optical antipode ent-A along with the resolving reagent D. This novel two-step procedure [20] complements our recent kinetic resolution of racemic alcohols with enantiomerically enriched silanes A. [7] As indicated above, the reductive cleavage of the silyl ethers G with aluminum hydrides such as DIBAL-H liberates the corresponding silanes A with complete preservation of stereochemical information at silicon (Scheme 3). The observed retention of the configuration is rationalized by an S N i-Si mechanism [2] and was recently secured for silane (SiS)-3 (R = i-Pr) by X-ray analysis.…”

“…However, within our previous study of the inverted scenario we became aware of tert-butyl-substituted pyridylmethanol 16 as a reasonably efficient resolving reagent. [7,26] Alcohol 16 is one of the few synthetically accessible compounds whose structural motif resembles our requirements and which is available in (both) enantiopure form(s), (S)-16 and (R)-16.…”

“…Our recently reported kinetic resolution of chiral non-racemic alcohols using silicon-stereogenic silanes as resolving agents revealed three requirements for the alcohol: [7] (1) the alcohol must incorporate a pending donor, which provides a temporary residence site for the copper catalyst; (2) such an alcohol must be readily available in enantiomerically pure form; and (3) the formed diastereomeric silyl ethers should be separable by chromatography or fractional crystallization to enable further enrichment of stereoisomers.…”

“…Gratifyingly, the structural features of (SiR)-5 allowed for stereoselective transformations that had failed for its congeners before. [5,7] An additional challenging obstacle is the restricted number of procedures for the preparation of enantiomerically enriched silanes A (Figure 2). [13] In principle, silicon-element double bond-containing molecules B are attractive prochiral precursors for reagent-as well as catalyst-controlled asymmetric construction of A by enantiofacial discrimination.…”

“…Moreover, we devised a novel concept for the non-enzymatic kinetic resolution of chiral secondary alcohols employing asymmetrically substituted silanes as recyclable resolving agents. [7] A rationale for the notorious track record of failure [4] is probably provided by the structure of standard silane (SiR)-1 [8] (Figure 1), which illustrates the pivotal features intrinsically connected with asymmet- FULL PAPERS rically substituted silanes: [4] (1) relatively long carbon-silicon bonds thwarting compact stereochemistry-determining transition states and (2) insufficient stereochemical differentiation at silicon. In order to create more conformational rigidity as a measure against the detrimental carbon-silicon bond length, the silicon center might be embedded into a cyclic framework [(SiS)-2 [9] and (SiR)-3/A C H T U N G T R E N N U N G (SiS)-3,…”