Amino Turbo Chirality and Its Asymmetric Control.

Abstract

A series of new targets containing 3 chiral elements of central, orientational, and turbo chirality have been designed and synthesized asymmetrically. The absolute configurations and conformations of these types of chirality were concurrently controlled by using chiral sulfonimine auxiliary and unambiguously determined by x-ray diffraction analysis. These targets include alpha unnatural amino acid derivatives, which may play an important role for drug design, discovery, and development. Three propellers of turbo framework are covalently connected to a chiral C(sp³) center via C(sp²)-C(sp³) bonding along with a C-N axis, while one of them is orientated away from the same carbon chiral center. The turbo or propeller chirality is characterized by 2 types of molecular arrangements of propellers, clockwise (PPP) and counterclockwise (MMM), respectively. The turbo stereogenicity was found to depend on the center chirality of sulfonimine auxiliary instead of the chiral C(sp³) center, i.e., (S)- and (R)-sulfinyl centers led to the asymmetric formation of PPP- and MMM-configurations, respectively. Computational studies were conducted on relative energies for rotational barriers of a turbo target along the C-N anchor and the transition pathway between 2 enantiomers meeting our experimental observations. This work is anticipated to have a broad impact on chemical, biomedical, and materials sciences in the future.