Protecting‐Group‐Free Synthesis of 3‐Amino‐3‐α‐prenyl‐oxindoles through the Direct Prenylation of Isatin‐Derived Imines

Abstract

A zinc‐mediated α‐selective prenylation of isatin‐derived imine using prenyl bromide as the prenyl source in a sealed tube has been developed. The protocol enables an efficient access to various 3‐amino‐3‐α‐prenyl‐oxindoles from cheap and readily available chemicals in good to excellent yields. The obtained prenylated adduct can be further manipulated to other more complicated derivatives through cyclization or oxidation, which demonstrated the synthetic usefulness of this methodology. Additionally, we demonstrated that this zinc‐mediated methodology is also applicable to cinnamylation and geranylation.

Mannich‐Type Reactions of Alkylzinc Reagents

“…Apart from the use of the highly active allylzinc halides [4][5][6][7][8] and Reformatsky reagents, [9,10] Mannich-type reactions using organozinc halides have been achieved using highly electrophilic C=N containing substrates. [11] To this extent, the most common reaction partners are N-acyliminium, [12,13] but other examples using immonium, [14] N-acylpyridinium, [15,16] trifluoropyruvate, [17][18][19][20] iminoester, [21][22][23] or isatin [24] derivatives have been reported. The use of less electrophilic imines bearing a 2-pyridylsulfonyl electron-withdrawing group on the nitrogen atom has also been described, but the use of an additional copper catalyst is essential to increase the electrophilicity of the carbon atom.…”

One-Pot Synthesis of Aza-Morita-Baylis-Hillman Adducts via Zinc-Mediated Allylation of 4-Bromocrotonates and Imines

“…4-Bromocrotonates are commercially available and highly functionalized compounds containing important structural moieties including allylic bromides and α,β-unsaturated esters, and they are frequently used as building blocks for the synthesis of a great variety of chemical products, especially in the Reformatsky reactions. In view of our previous works on and continuous interest in allylation reaction, we envisioned that if bromocrotonates could be used as a reaction component in the allylation of imines, then, the double bond of the initially formed allylated product could be isomerized to form α,β-unsaturated compounds. If successful, this process might directly lead to the synthesis of β-substituted MBH-type products in a one-pot operation, and as a result, the two issues above mentioned could be solved efficiently.…”