*2.4. Application of Stepwise Approach to An Iodoaryl Compound*

To demonstrate that our stepwise approach is useful for synthesis of 3-(1, 3-diarylallylidene)oxindoles **3**, which are not accessible by previous palladium-catalyzed methods, we synthesized **3** with an iodoaryl moiety using a Knoevenagel/allylic oxidation/Wittig strategy (Scheme 5). Due to its high reactivity toward the palladium catalyst, the iodoaryl group was not compatible with palladium-catalyzed reactions. Ti(O*<sup>i</sup>* Pr)4/pyridinemediated Knoevenagel condensation of oxindole **1** with *p*-iodoacetophenone gave 3 methyleneoxindole **5e** in 89% yield, with a preference for the *Z*-isomer (*Z*:*E*=10:1). Allylic oxidation of **5e** afforded aldehyde **7e** in 78% yield. In addition, the last Wittig reaction of **7e** produced **3ea** (80% yield), which could not be formed using previous methods. The iodoaryl group of **3ea** could be used as a functional handle for further molecular modifications. For example, Suzuki-Miyaura reaction of **3ea** introduced another phenyl group to give **9** in 84% yield.

**Scheme 5.** Synthesis of iodoaryl compound **3ea** and its Suzuki-Miyaura reaction.

In conclusion, we have developed two complementary stepwise approaches to synthesize (*E*)-3-(1,3-diarylallylidene)oxindoles **3** from oxindole **1** (Knoevenagel/allylic oxidation/Wittig and Knoevenagel/aldol/dehydration). These strategies enable the synthesis of various **3**, regardless of substituents on the aryl moiety. Especially, **3** with palladium-sensitive functional groups, such as iodoaryl groups, could be obtained by these stepwise methods, which could help to expand the applications of (*E*)-3-(1,3-diarylallylidene)oxindoles.
