Mechanistic Insights into the BINOL-Derived Phosphoric Acid-Catalyzed Asymmetric Allylboration of Aldehydes

Abstract

BINOL-derived phosphoric acids catalyze the asymmetric allylboration of aldehydes. DFT and QM/MM hybrid calculations showed that the reaction proceeds via a transition state involving both a hydrogen-bonding interaction from the catalyst hydroxyl group to the pseudoaxial oxygen of the cyclic boronate and a stabilizing interaction from the phosphoryl oxygen of the catalyst to the formyl hydrogen of the aldehyde. These interactions lower the energy of the transition structure and provide extra rigidity to the system. This mechanistic pathway is consistent with the experimentally observed enantioselectivity except in one case. We have used our model's predictions to guide our own experimental work. The conflict is resolved in favor of our calculations.

Mechanistic Insights into a BINOL-Derived Phosphoric Acid-Catalyzed Asymmetric Pictet–Spengler Reaction

“…47 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 The Gibbs free energies of the structures in the reaction catalyzed by 7 relative to 3:7…”

“…These results are consistent with the findings from our study of aldehyde allylboration and allenylboration demonstrating the generality of this reaction model. 43,47 All eight TSI diastereomers are again higher in energy than TSII (SRR) and the Boltzmann ratio for TSII (SRR) is 0.981, indicating that it is the major pathway.…”

Origins of Stereoselectivities in Chiral Phosphoric Acid Catalyzed Allylborations and Propargylations of Aldehydes

“…At almost the same time, Grayson, Pellegrinet, and Goodman published a computational study of allylboration reactions. 9 In the Goodman et al work, it was proposed that the hydroxyl group of BINOL phosphoric acid H-bonds to the pseudo-axial oxygen of the boronate, and the phosphoryl oxygen interacts with the aldehyde formyl hydrogen through electrostatic interactions (Figure 2). Due to the large size of the real catalyst, Goodman used ONIOM calculations on the full catalyst PA1 .…”

Asymmetric Synthesis of β‐Substituted α‐Methylenebutyro‐ lactones via TRIP‐Catalyzed Allylation: Mechanistic Studies and Application to the Synthesis of (S)‐(−)‐Hydroxymatairesinol

“…Experiments using the preformed phosphoric acid salt (TRIP − NH 4 + ) showed reduced conversions and stereoselectivities. Alternatively, the Zn 2+ -TRIP species (acting as a catalytically active Lewis acid) would lead to a transition state intermediate via single coordination with a long distance beween the chirality-inducing ( i- Pr) 3 C 6 H 2 ligands and the lactone moiety, which could not explain the high (dia)stereoinduction experimentally observed20a (see Figures S01 and S02 in the Supporting Information).…”

“…The stereochemical outcome of the asymmetric synthesis of 1 was opposite to that of the allylboration with the same catalyst14 owing to the different mechanism of the latter reaction, which requires acidic activation of the boronic ester 20. Based on the experimental results ( anti -configured products) and the considerations on the catalyst’s nature (protonated phosphoric acid coordinated to zinc) DFT calculations yielded only model structure 15 as energetically and mechanistically reasonable intermediate (Figure 1), when stationary points were investigated using the M06 functional with a triple-ζ basis set (6-311G**) 21.…”