Modular and stereoselective synthesis of tetrasubstituted vinyl sulfides leading to a library of AIEgens

Tetraarylethylenes exhibit intriguing photophysical properties and sulfur atom frequently play a vital role in organic photoelectric materials and biologically active compounds. Tetrasubstituted vinyl sulfides, which include both sulfur atom and tetrasubstituted alkenes motifs, might be a suitable skeleton for the discovery of the new material molecules and drug with unique functions and properties. However, how to modular synthesis these kinds of compounds is still challenging. Herein, a chemo- and stereo-selective Rh(II)-catalyzed [1,4]-acyl rearrangements of α-diazo carbonyl compounds and thioesters has been developed, providing a modular strategy to a library of 63 tetrasubstituted vinyl sulfides. In this transformation, the yield is up to 95% and the turnover number is up to 3650. The mechanism of this reaction is investigated by combining experiments and density functional theory calculation. Moreover, the “aggregation-induced emission” effect of tetrasubstituted vinyl sulfides were also investigated, which might useful in functional material, biological imaging and chemicalnsing via structural modification.

In this work, based on our continuous interest in transitionmetal catalyzed carbene transfer reaction of α-diazo carbonyl compounds 57-59 , we describe herein that structurally diverse tetrasubstituted vinyl sulfides (TVSs) are modularly assembled for the first time by a rhodium-catalyzed ylide formation/ [1,4]acyl transfer reaction of S-acyl thiol and diazo compounds (Fig. 1c).

Results
Substrate scope of [1,4]-acyl transfer reaction. Initially, the reaction of acetyl phenthiol 1a and phenyl diazo ketone 2a was chosen as the model reaction. After screening the condition, Rh 2 (OAc) 4 was proven the best catalyst for this transformation (see Supplementary Table 1). We then tested the substrate scope of this [1,4]-acyl transfer reaction. As shown, a diverse range of Saryl ethanethioate, with different substitutes on para-, meta-, and ortho-positions of phenyl ring, were suitable substrates for [1,4]acetyl transfer reaction, affording the corresponding tetrasubstituted Z-olefins 3aa-3ka in good to excellent yields with excellent chemo-and stereo-selectivity (Fig. 2). To our delight, the alkyl groups, including benzyl, cyclohexyl, ester-containing alkyl, on the sulfur atom were tolerated (Fig. 2, 3ma-3pa). It was noteworthy that the well-known Stevens rearrangement had not been observed in this transformation. When aryl thiol with various acyl groups with steric hindrance and carbamoyl group on sulfur atom were tested in this transformation, the same [1,4]acyl and carbamoyl transfer took place, affording the corresponding Z-olefins in good efficiency (Fig. 2, 3qa-3wa). Interestingly, attempts using the ethanethioate with allyl and propargyl on S atom exclusively delivered the acyl transfer products without any [2,3]-rearrangement products being detected (Fig. 2, 3xg-3yg). Next, we began to study the substrate scope of various diazo carbonyl compounds 2. Diazo ketones 2b-2o containing various substituents, including aryl, alkyl, alkynyl, and hydrogen were compatible, delivering the expected products 3ab-3ao in good yields. Notably, diazoesters were compatible and delivered the alkene products in good yields with single Z-selectivity (Fig. 2,  3ap-3aw). Furthermore, this protocol was also applicable to     [1,4]-acyl migration products 4-9 in moderate to good yields. The structures of 3aa and 3aw were further confirmed by single-crystal X-ray crystallography analysis. Then, we envisaged that the analogous [1,4]-acyl migration reaction should be applicable to the cyclic thioester substrate, which would undergo the ring expanding reaction by three atoms and afford medium-sized lactones containing an alkenyl sulfide moiety. When the spiro four-membered ring thiolactone 10a reacted with diazoketones 2a under the standard condition, the seven-membered lactone 11a was generated in 73% isolated yield via the sequential ylide formation/ [1,4]-acyl migration as we expected. Thus, various thiolactones 10 equipped with the rings from four-member to seven-member were tested (Fig. 3). All the reactions of 10 with diazoketone 2 were carried out smoothly, affording the corresponding lactone 11b-11i with sevenmembered to ten-membered rings in moderate to good yields. It was noteworthy that the reaction of thiolactone with amide group gave the ring expansion product 11c without the N-H insertion product. This result indicates this tandem ylide formation/acyl migration reaction exhibited excellent chemoselectivity, which occurred preferentially over the N-H insertion reaction. The structures of 11c and 11e were further confirmed by single-crystal X-ray crystallography analysis (Fig. 3).
Gram-scale reaction and the transformations of products. As shown in Fig. 4, this [1,4]-acyl migration reaction of thioester and diazoketones was easy to scale-up. The 5 mmol scale reaction of 2a and 1a was carried out under 0.1 mol% Rh 2 (OAc) 4 , furnishing 1.44 g of the desired product 3aa in 83% yield. Gratifyingly, the catalyst loading could be further decreased to 0.02 mol% without effect on the yield, and the TON was up to 3650. The 22.5 mmol scale reaction of 2a and 1d could give 6.988 g of the corresponding product 3da in 73% yield. It should be noted that 3da could be obtained after simple recrystallization instead of column chromatography (see Supplementary Fig. 1 for details), demonstrating the promising synthetic practicality of this reaction. To examine the synthetic value of this protocol further, several transformations of 3aa and 3da were also performed (Fig. 4).  When the 3aa was treated with m-CPBA, vinyl sulfoxide (12) and vinyl sulfone (13) could be obtained in 81% and 65% yields, respectively (Fig. 4a, b). Meanwhile, the cross-coupling of 3da with terminal alkyne and aryl boronic acid afforded the corresponding products 14-16 in moderate to excellent yields (Fig. 4c, d).
Crossover experiment. In order to understand the reaction mechanism, a crossover experiment was conducted (Fig. 5). As a result, the expected non-crossover products 3za and 3ca were obtained in excellent yields and no crossover products (3ha or 3ca′) was observed in the crude 1 H NMR. This results proved this [1,4]-migration was a concerted rearrangement pathway.   The rhodium carbene intermediate to coordinate with the carbonyl oxygen of the thioester Int-2′ was located, while the relative free energy is 3.3 kcal/mol higher than that with sulfur. Furthermore, we also located a more stable rhodium-stabilized acylsulfur ylide Int-3′ by −6.5 kcal/mol, compared to Int-2 (see Supplementary Fig. 2 for more details). While the corresponding 1,4-acyl migration process is less favored than the free ylide, the free energy difference between two TSs (TS-3 and TS-3′) is up to 6 kcal/mol. So the free ylide should be the intermediate in this reaction. This barrier was lower than that of [2,3]-rearrangement of allyl and propargyl, which could explain the excellent chemoselectivity of this reaction (see Supplementary Figs. 3 and 4 for more details). Furthermore, this calculation demonstrated that this [1,4]-acyl migration presumably proceeds via a free ylide intermediate, which was consistent with the known [1,4]-acyl migration from O to C 64 .
Photophysical properties of TVSs. Having established this protocol to conveniently construct the library of tetrasubstituted vinyl sulfides (TVSs), we then tested the photophysical properties of these molecules. Classic AIE was observed by dissolving 3ca in the mixture solution of 1,4-dixoane and water with different fractions of water. Compound 3ca showed almost no fluorescence in 1,4-dixoane. With the gradual addition of water into the solution of 3ca in 1,4-dixoane, the emission intensity increased slightly when water fraction was less than 70%. However, when water fraction exceeded 70%, the emission intensity of 3ca increased significantly since the restriction of intramolecular rotation (Fig. 7a, b, d). All the TVSs with cis-1,2-diaryl substituents exhibit this phenomenon, and the fluorescence emission spectra of representative vinyl sulfides were also measured and the emission maxima of all the AIE-gens altered from 418 to 442 nm (Fig. 7c, and see Supplementary Information for details). The results indicated the substituents on diazo compounds 2 were vital for the AIE-activity of the producing vinyl sulfides. The TVSs with two aryls or one aryl and one alkynyl exhibited AIE-activity, while the olefins containing H, alkyl, and alkoxyl did not have AIE effect. Moreover, some AIEgens, such as 3aa, 3ca, 3da, 3sa, 3dn, and 15, exhibted interesting luminescence in solid state (Fig. 7c, and see Supplementary Table 7 for more details). Thus, these compounds might be useful for OLEDs and living animal imaging via structural modification.

Discussion
In summary, we have developed a rhodium-catalyzed rearrangement reaction of thioesters and diazoketones via sulfur ylide, which provides a modular strategy to construct a library of tetrasubstituted vinyl sulfides (TVSs) in good to excellent yields. This protocol features broad substrate scope (63 examples), mild condition, low catalytic loading, convenient operation, and easy scale-up. The TON of this reaction is up to 3650 and the product can be isolated without column, indicating that this reaction might be promising tools in industry. The mechanistic studies combining experiments and DFT calculation exhibit this [1,4]acyl shift from S to O is intramolecular pathway and has lower energy bar than known [2,3]-rearrangement via a free ylide intermediate. Furthermore, the spectroscopic properties of these molecules were studied in solution as well as solid state, and TVS is proved to be a new type of AIEgens. Some of them might be useful for OLEDs and living animal imaging via structural modification. This work would inspire the development of new sulfur-containing AIEgens and broaden the application of catalytic reactions in synthesis of materials.

Methods
General procedure for TVSs. Thioester 1 or 10 (0.5 mmol, 1.0 equiv), and Rh 2 (OAc) 4 (0.01 mmol, 2.0 mol%) were introduced into a dried glass tube under N 2 protection, and add 1 mL dry DCM as solvent, then the diazoketone 2 (0.75 mmol, 1.5 equiv) was dissolved in 1 ml of DCM and add dropwise in 5 min at room temperature. After the addition, continue to react for 1 min consumed diazo completely determined by TLC analysis. The mixture was purified by column chromatography on silica gel using PE/EtOAc as the eluent and concentrated to obtain the product 3 or 11. All new compounds were fully characterized (see the Supplementary Information).