Chiral Crown Conformation of Rh₂(S-PTTL)₄: Enantioselective Cyclopropanation with α-Alkyl-α-diazoesters

Abstract

Herein, we provide crystallographic and computational evidence that Hashimoto’s Rh2(S-PTTL)4 catalyst adopts a “chiral crown” conformation with a reactive chiral face and an unreactive achiral face. In Rh2(S-PTTL)4, all four t-butyl groups are aligned on the same face of the catalyst, and each C-(t-Bu) bond is roughly parallel to the central Rh-Rh bond. This orients the four phthalimido groups on the opposite face of the catalyst. Also described is an enantioselective and diastereoselective protocol for intermolecular Rh2(S-PTTL)4 catalyzed cyclopropanation using α-alkyl-α-diazoesters. Intermolecular cyclopropanation is selective over two competing intramolecular pathways: C–H insertion and β–hydride elimination. Based on DFT calculations and the Davies-Singleton model for cyclopropanation, a model for asymmetric induction is proposed.

Chiral Dirhodium(II) Carboxylates: New Insights into the Effect of Ligand Stereo-Purity on Catalyst Structure and Enantioselectivity

“…From the current structure and in light of the recent advances in the field, it is evident that the previously reported flattened rectangular shape structure of the crown cavity [47,48] is subject to substantial variations which appear to be influenced by the identity of the axial bound ligand and, at least in the solid state, by the intermolecular interactions including crystal packing forces. Whilst of irregular shape, the crown cavity of the current structure(s) (Figure 3a,b) can be described as being quite square shaped of ca.…”

“…Although the complex molecules are still retaining the chiral crown cavity of approximate C 4 symmetry similar to the regular cavity structure of [Rh 2 (S-PTTL) 4 . (EtOAc)] [47,48], the inherent weakness of the cavity walls is apparent in the obtained aquated Rh 2 (S-PTTL) 4 structure(s) (Figure 3a,b). This is owing to the obvious absence of strong interactions between adjacent N-phthaloyl units.…”

“…13-14 Å width if compared to the rectangular shaped cavity reported for [Rh 2 (S-PTTL) 4 . (EtOAc)] (12.8 x 14.1 Å) [47,48].…”

“…Another report claimed that racemization free N-protection of amino acids was possible in refluxing acetic acid [56]. These later reports did not, however, support their claims by any 4 and associated catalysts; (b) Schematic presentation of the daisy chain manner by which the Rh 2 (S-PTTL) 4 binding pocket is constructed (c) Space filling of mono-EtOAc adduct of Rh 2 (S-PTTL) 4 (top and side views) [35,47,48]. (Adapted from Adly, F.G.; Gardiner, M.G.…”

“…In the case of published X-ray crystal structures of various solvated adducts of Rh 2 (S-PTTL) 4 [47,48], Rh 2 (S-tert PTTL) 4 [35], Rh 2 (S-NTTL) 4 [49], Rh 2 (S-PTAD) 4 [35] and others [35,50,51], the incorporation of a ligand stereogenic center begets a "chiral cavity" or a "chiral pocket". Figure 2 [47,48] depicts the two most important features that are responsible for the establishment of the chiral binding pocket in Rh 2 (S-PTTL) 4 and related complexes; C-C bond torsion (bond connecting carboxylate carbon to α-carbon) that is positioned so as to guide the C-N single bond leading to a clockwise twist of the chiral cavity walls (Figure 2a), and C-N bond torsion (bond units (featuring alternating O ... H-C closest contacts, Figure 2c). The overall visual result is that the eight oxygen atoms of the ligands' N-phthaloyl units are placed at alternate high and low positions around the periphery of the carbene binding pocket (Figure 2b) [35].…”