**2. Results**

4-Aryl-substituted homophthalic acids **10** required for the preparation of anhydrides **8** were synthesized from indanones **11**. These, in turn, were prepared either by triflic acid-promoted arylation of cinnamic acids **12** [16] or by intramolecular Heck reaction of bromochalcone **13** [17]. The Heck reaction approach was used for the methoxy-substituted substrate because the respective TfOH-promoted arylation, when attempted, led to extensive tar formation. Indanones **11** were condensed with diethyl oxalate using either

potassium or lithium *tert*-butoxide as the base, and the resulting condensation products **14** were oxidized with hydrogen peroxide in basic medium (as described previously [18]) to furnish novel homophthalic acids **10a**–**f** in modest to excellent yields over two steps from indanones **11** (Scheme 1).

**Scheme 1.** Synthesis of substituted homophthalic acids **10**.

For the prospective employment of homophthalic acids in the CCR, anhydrides **8** were prepared immediately before the reaction using acetic anhydride as the cyclodehydrating agent and were used in the condensation with imines without further purification. For the preparation of anhydrides from homophthalic acids **10a**–**d,** the cyclodehydration was performed at room temperature in dichloromethane. For substrates **10e**–**f**, due to limited solubility in the latter conditions, the same reaction was performed in toluene at 80 °C.

Although the CCR of HPA can be conducted in a range of different solvents [19], after brief optimization, we found the reaction of anhydride derived from unsubstituted diacid **10b** to furnish an optimum 72% yield of THIQ cycloadduct **9a** as a single diastereomer after refluxing the reaction partners in acetonitrile over 18 h. The same reaction conducted in refluxing toluene gave lower (66%) yield. Interestingly, the reaction in acetonitrile also proceeded to completion at room temperature but with lower yield (55%) and lower diastereoselectivity (*dr* 5:1, *trans*-/*cis*-). Thus, the conditions involving refluxing acetonitrile were extended to anhydrides **8** of this and other homophthalic acids **10** in combination with various imines prepared from aromatic aldehydes (Scheme 2).

The yields of 4-aryl-substituted THIQ acids **9a**–**u** were generally good after simple evaporation of acetonitrile and trituration of the crude material with hexane and ether, with no need for chromatographic purification. The reactions were completely diastereoselective throughout except for those yielding products **9q**–**t**. The stereochemical identity of products **9a**–**u** was unequivocally confirmed as being *trans* with respect to the vicinal aryl groups by single-crystal *X*-ray analysis of compound **9a** (Figure 4, see ESI for details). The substituents in the homophthalic portion did not apparently influence the reaction outcome. The scope of the reaction was also quite broad with respect to the aromatic, aldehyde-derived group tolerating heterocyclic motifs as well as phenyl group with a nitro group. Likewise, the scope of amines, aromatic and aliphatic alike, was also fairly broad.

**Scheme 2.** The CCR of cyclic anhydrides **8** with imines.

**Figure 4.** Crystallographic structure of compound **9a** (ORTEP plot, 50% probability level).

Despite our initial expectations of potentially lower reactivity of anhydrides **8** in the CCR due to increased steric bulk compared to HPA, the reactivity of these anhydrides was similar to that of HPA (considering the fact that the reaction also proceeded at room temperature, vide supra). This is in line with the observations by others for methyl- and benzyl-substituted versions of HPA [15].

In addition to dicarboxylic acids **10a**–**f**, we prepared 1,2,3-triazol-1-yl-substituted dicarboxylic acid **15** by copper-catalyzed [3 + 2] azide-alkyne cycloaddition of the known [20] azido-substituted homophthalic diethyl ester **16** and phenylacetylene followed by hydrolysis. Due to solubility issues, the cyclodehydration procedure to anhydride **17** was modified, and the reaction was performed in DMF using dicyclohexylcarbodiimide (DCC) as the cyclodehydrating agent. Anhydride **17** proved to be a competent substrate for the CCR; however, due to low solubility of **17** in acetonitrile, the reaction was conducted in DMF at room temperature. *Trans*-configured cycloadduct **18** was obtained as a single diastereomer in 50% yield, also with no need for chromatographic purification (Scheme 3).

**Scheme 3.** Preparation and use of 1,2,3-triazol-1-yl-substituted cyclic anhydride **17** in the CCR.
