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Feng et al. Sci China Chem
the desired product 3,3-disubstituted oxindole 3a was
achieved in 95% yield with 96.5:3.5 er by employing
Pd(OAc)2 as the catalyst, (S)-MeO-BIPHEP (L1) as the ligand
and K2HPO4 as the base in mixed solvent (PhCl/acetone =
9/1) under balloon pressure of CO (entry 1). The absolute
configuration of 3a was unambiguously confirmed by X-ray
tails). (S)-2-Furyl-MeOBIPHEP (L2) afforded 3a in good
enantioselectivity with low chemo- and regioselectivity, ac-
companied with undesired 6-endo-trig cyclization product 4a
in 12% yield and esterification product 5a in 14% yield
(entry 2). Other bidentate phosphine ligands, such as (S)-
Difluorphos (L3), (S,Rp)-Josiphos (L4) and (S,S)-DM-SDP
(L5), provided 3a in moderate enantioselectivities (entries 3–
5). The Box-type ligand L6 inhibited the transformation
(entry 6). Moreover, we investigated other solvents, while no
better results were achieved (entries 7–10). KH2PO4 per-
formed the reaction in low conversion, and Cs2CO3 led to
compound 5a as the major product (entries 11 and 12).
With the optimal reaction conditions in hand, we then in-
vestigated the substrate scope for the synthesis of oxindoles
(Scheme 2). Aryl carbamoyl chlorides 1 with various groups
on the phenyl ring proceeded smoothly to give the corre-
sponding oxindoles 3b–3h in 90%–99% yields with up to
96:4 er. The heteroaromatic ring, such as pyridine, was also a
suitable substrate, providing 3i in 91% yield. This reaction
also demonstrated good compatibility of R1 group. Lots of
(hetero)aromatic ring and alkyl groups were all well com-
patible, delivering 3j–3q in 92%–98% yields. Modifying the
substituent group on N atom with isopropyl or benzyl group,
products 3r and 3s were achieved in moderate yields with
good enantioselectivities. Subsequently, various alcohols
were investigated. Primary alcohols including those with
functional groups, such as acetal and trimethylsilyl groups,
were both accommodated, affording the products 3t–3x in
85%–97% yields with up to 96.5:3.5 er. Cyclic secondary
alcohols also proved to be qualified for this reaction (3y and
3z). With p-methoxyphenol as nucleophile, 3aa could be
furnished in 73% yield with 96:4 er. However, amines pose a
significant
challenge
to
this
carbamoyl-
carbonylation reaction due to their relatively strong amido-
Inspired by these positive results, we turned our attention
to the construction of chiral γ-lactams. After optimizing the
reaction parameters such as ligands, bases, solvents and
the desired product 7a was ultimately achieved in 83% yield
and 96:4 er with Pd(OAc)2 as the catalyst, L1 as the ligand
and KHCO3 as the base in a mixed solvent (MeCN/acetone =
1/2) under balloon pressure of CO. Under the standard re-
action conditions, chiral γ-lactams 7b–7k were obtained in
good yields with up to 96:4 er (Scheme 3). The absolute
Scheme 2 Substrate scope for the synthesis of oxindoles (color online).
configuration of 7d was confirmed by X-ray crystallography
the aryl group with benzyl, no desired product was detected,
and only premature esterification side product was achieved.
This result indicated that the N-protecting group is essential