Catalytic Enantioselective Addition of Me2Zn to Isatins

Abstract

Chiral α-hydroxyamide L5 derived from (S)-(+)-mandelic acid catalyzes the enantioselective addition of dimethylzinc to isatins affording the corresponding chiral 3-hydroxy-3-methyl-2-oxindoles with good yields and er up to 90:10. Furthermore, several chemical transformations were performed with the 3-hydroxy-2-oxindoles obtained.

Dimethylzinc-mediated enantioselective addition of terminal alkynes to 1,2-diketones using perhydro-1,3-benzoxazines as ligands

“…On the other hand, when 1-(4-methoxyphenyl)-2-(4-(trifluoromethyl)phenyl)ethane-1,2-dione 5b acted as the electrophile, the product 6b was obtained as a single regioisomer, as a result of the alkynylation of the carbonyl attached to the electronically deficient aromatic ring (Table 5, entry 3). The alkynylation also proceeds with total regioselectivity if there are two electron-withdrawing chlorine substituent group (Table 5, entries [8][9][10] or two electrondonating methoxy groups in one of the aromatic rings (Table 5, entries 4-7). In all cases the enantioselectivity was good.…”

“…3 The utilization of activated ketones bearing an electronwithdrawing-group in alpha position to the carbonyl group overcome these problems of lack of reactivity, as shown in the enantioselective alkylation and alkynylation to α-ketoesters 4,5 fluorinated ketones, 6,7 and isatines. 8,9 However, this excess of reactivity along with the fact that, many times, this particular kind of electrophile may act as a chelating ligand and enhance the reactivity of the nucleophilic species, might be a problem due to the competing non-catalyzed reaction pathway, which would have a detrimental effect on the enantioselectivity. Recently, we have shown that chiral conformationally restricted perhydro-1,3-benzoxazines derived from (-)-8-aminomenthol behave as excellent ligands for the enantioselective addition of organozinc reagents to carbonyl compounds, 10 including αketoesters.…”

Catalytic Asymmetric Addition of Diorganozinc Reagents to Pyrazole‐4,5‐Diones and Indoline‐2,3‐Diones

“…Especially, there are few methods for the catalytic asymmetric synthesis of chiral 3‐hydroxy‐3‐methyl‐2‐oxindoles in previous report [16] . Shibashaki [16d] and Pedro's group [16e] reported the enantioselective addition of Me 2 Zn to isatins catalyzed by proline‐derived aminodiol and α‐hydroxyamides ligand, respectively, and only moderate ee values were obtained. We performed the reaction between N ‐substituted isatins 4 and Me 2 Zn in the presence of DCM at −40 °C.…”

“…However, when the protecting group was electron‐withdrawing group such as acetyl, the product 5 m was obtained in moderate yield, albeit with high ee . The absolute configuration of 5 was determined by comparison to reported literature [16e] …”