5.7 Predicting Product Distribution
Toste and Sigman have recently published a mechanistic investigation into
Pd-catalysed enantioselective diarylation of benzyl acrylates with chiral anion
phase transfer catalyst (CAPT) (Fig. 18) [108]. The products of this reaction contain
a stereogenic centre at the β-carbon. Accompanying this reaction is an unwanted
Heck reaction, leading to the formation of a by-product. A QSSR was used to
Y
R 2 R 3
R 4
X
X = Br, I
Y = NMe, NBn, N-allyl, O
n = 0, 1
R i = H, alkyl, alcoxy, alkylthiol, alkylamine, alkylamide, F, TMS
n
Y
R 3
R 4
n
R 1
R 1
R 2
RLi, Chiral ligand
N
H
N
(+)-sparteine surrogate
Chiral ligand
Fig. 17 Enantioselective intramolecular carbolithiations
O
Ar
O
PhN 2 BF 4
Ar’B(OH) 2
Pd 2 (dba) 3 CHCl 3
Phosphate cat. (PA)
NaHCO 3 , Et 2 O, 20 º C, 20 h
Ar’
O
Ar
Ph O
Ph
O
Ar
O
Prod
Heck
Byprod
Fig. 18 QSSR for Pd-catalysed enantioselective diarylation of benzyl acrylates. Reprinted with
permission from Yamamoto E, Hilton MJ, Orlandi M, Saini V, Toste FD, Sigman MS. (2016) J Am
Chem Soc 138:15877–15880. Copyright 2017 American Chemical Society
Ligand Design for Asymmetric Catalysis: Combining Mechanistic and. . .
185