Analysis of Stereochemical Convergence in Asymmetric Pd-Catalysed Allylic Alkylation Reactions Complicated by Halide and Memory Effects

Catalytic Asymmetric Synthesis of Allylic Alcohols and Derivatives and their Applications in Organic Synthesis

“…[61] In 2003, Gais and co-workers elegantly used the Trost complex 9-[Pd 2 (dba) 3 ] for the deracemization of symmetric cyclic and acyclic allylic carbonates in the presence of water, thereby affording enantioenriched allylic alcohols directly, in high yield and mostly excellent enantiomeric excess without an external nucleophile (Scheme 24). [64] The conditions developed for 53, namely the presence of KHCO 3 , were then applied to the deracemization of nonsymmetric acyclic allylic carbonates to afford the corresponding allylic alcohols in moderate to excellent enantiomeric excess and perfect regioselectivity (the absence of KHCO 3 for the deracemization of 54 resulted in a significantly reduced ee value; Scheme 26). Substitution and decarboxylation generates the allylic alcohol product.…”

“…Despite this, the first examples of asymmetric addition of organozinc reagents to ketones were only reported in 1998 by the research groups of Fu [73] and Yus, [74] who used 58 and 60 ( Figure 3). A large number of reviews [71,75] and books [76] have been published on this area, so only recent catalytic systems illustrating the different ligands employed are summarized in Table 2 and Figure 3 (61)(62)(63)(64)(65)(66)(67)(68)(69). A large number of reviews [71,75] and books [76] have been published on this area, so only recent catalytic systems illustrating the different ligands employed are summarized in Table 2 and Figure 3 (61)(62)(63)(64)(65)(66)(67)(68)(69).…”

“…[63] These results have been ascribed by the authors to a strong memory effect of 46 a in the Pd-catalyzed allylic substitution. [64] The conditions developed for 53, namely the presence of KHCO 3 , were then applied to the deracemization of nonsymmetric acyclic allylic carbonates to afford the corresponding allylic alcohols in moderate to excellent enantiomeric excess and perfect regioselectivity (the absence of KHCO 3 for the deracemization of 54 resulted in a significantly reduced ee value; Scheme 26). [63] In 2004, Faller and Wilt used 12 ( Figure 2) for the resolution of nonsymmetric allylic carbonates by using sodium carboxylates as nucleophiles.…”

Reactivity control in palladium-catalyzed reactions: a personal account

“…Accordingly, the carbon trans to phosphorus has more p-character, as indicated by the respective chemical shifts in the 13 C-NMR spectra (Scheme 20) [56,60]. These parameters predict the preferential attack by the nucleophile at the terminus trans to the phosphorus [54,56,61]. Furthermore, a strong memory effect has been found to operate in the allylic substitution reactions [54,56,61].…”

2H-quadrupolar coupling-based analysis of stereochemical and regiochemical memory in the Pd-catalysed allylic alkylation of iso-cinnamyl type substrates employing the chiral monophosphine ligands ‘MOP’ and ‘MAP’

“…These include intimate ionpairing [6a], ionic strength [10], P ,O -chelation [6e], PdÁ/ allyl-oligomerisation [6i] and conformational loss of chelated ligand C 2 -symmetry [10]. However, the origins of the memory effect with MOP and MAP are less complex [6g] and we have introduced a simple stereochemical convergence ('sc') term by which the effects are readily quantified through the deployment of a 2 H label at the stereogenic centre of the substrate [11].…”