An Atropisomerically Enforced Phosphoric Acid for Organocatalytic Asymmetric Reactions

Abstract

Three BINOL-derived phosphoric acids exhibiting atropisomerism in the 3,3′-positions were obtained by Suzuki coupling reaction. The diastereomeric mixture was resolved by HPLC. Structural assignment was achieved by NOE-NMR analysis and by TD-DFT simulation of the electronic circular dichroism (ECD) spectra. The three atropisomeric catalysts were tested in three enantioselective reactions, comparing their ability to induce enantioselectivity with related, well-known, phosphoric

Noncovalent Interactions between Stacked Arenes in 1,8‐Bis‐(1‐naphthyl)‐naphthalenes

“…On the contrary, the ECD spectra of the syn isomers (Figure 8, bottom) do not clearly show any exciton coupling because of the opposite sign of the two α angles. This causes the two exciton couplings due to the two different rings to partially compensate because of the opposite sign of the dihedral angles with the 1,8‐naphthyl ring, [36] and only the residual difference is present in the experimental spectrum. The weakness of the spectra for the syn isomers with respect to the anti , and the occurrence of the maximum value of the CD signal of the syn isomers in correspondence with the null point of the exciton coupling of the anti isomers confirm this hypothesis (see Figure S13 of ESI for a comparison of ECD spectra with the corresponding UV).…”

Catalytic Enantioselective Povarov Reactions of Ferrocenecarbaldehyde‐Derived Imines – Brønsted Acid Catalysis at Parts‐Per‐Million Level Loading

“…Products 4 a – e derived from para ‐substituted/unsubstituted anilines were produced as single cis ‐diastereoisomers and in nearly enantiopure form in all cases, demonstrating the outstanding efficiency of catalyst 3 c in imparting enantioselectivity to this reaction (entries 1–5). The absolute and relative configuration of cycloadduct 4 b was determined as S , S by single crystal X‐ray diffraction (Figure ), and is fully consistent with previous chiral phosphoric acid catalysed Povarov reactions ,–,. The configuration of all products 4 (and 5 – 8 , vide infra) was assigned by analogy.…”

“…We then verified the applicability of imine 1 a in other asymmetric Povarov reactions, by reacting it with four different dienophiles 2 b – e , known to be competent in chiral phosphoric acid catalysed Povarov reactions ,,,. As shown in Scheme , product 5 derived from benzyl ( E )‐prop‐1‐en‐1‐ylcarbamate 2 b was obtained with good results, using conditions similar to the ones employed for 2 a .…”

“…A higher catalyst loading (1 mol% instead of 0.1 mol%) and longer reaction times were necessary, presumably due to the higher steric hindrance of enecarbamate 2 b compared to unsubstituted 2 a . As expected, dienophile 2 c (a dienecarbamate reacting at the vinylogous double bond), required instead a different catalyst ( 3 e ) to afford the cycloadduct 6 with good enantioselectivity. Moving to heteroarene activated dienophiles, 2‐vinylindole 2 d reacted very well under conditions related to the ones used for 2 a and 2 b , using just 1 mol% of catalyst 3 c at 40 °C.…”

Catalytic Asymmetric Aza‐Diels‐Alder Reaction: Pivotal Milestones and Recent Applications to Synthesis of Nitrogen‐Containing Heterocycles

“…Under the optimized anhydrous conditions, which included using Brønsted acid catalyst ( S )‐ VIIIb and 3 Å molecular sieves (MS), indole‐containing cycloadducts 227 or 228 were produced in very good yield mainly as syn diastereoisomer with good to perfect enantioselectivity (Scheme 84). Antipode compound ent ‐ 227 a (R=Ph) could be prepared from corresponding anil 210 and 2‐vinylindole under catalysis with the ( R )‐ VIIIb analog bearing atropoisomeric 2‐methylnaphthyl rather than the TRIP group at 3,3′‐positions [237] . The reaction with highly nucleophilic 3‐vinylindole proceeded via successive Mannich/Friedel–Crafts steps rather than by a concerted mechanism.…”