Thiophene-based macrocycles via the Suzuki–Miyaura cross coupling reaction

Tetrahedron 70 (2014) 6803e6809

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Thiophene-based macrocycles via the SuzukieMiyaura cross coupling reaction Anca Petran a, b, Anamaria Terec a, Elena Bogdan a, Albert Soran a, Eszter Lakatos a, Ion Grosu a, * a Babes-Bolyai University, Supramolecular Organic and Organometallic Chemistry Center (SOOMCC), Cluj-Napoca, 11 Arany Janos Str., 400028 Cluj-Napoca, Romania b National Institute of Research and Development for Isotopic and Molecular Technologies (INCDTIM), Cluj-Napoca, 65-103 Donath Str., Cluj-Napoca, Romania

a r t i c l e i n f o

a b s t r a c t

Article history: Received 7 May 2014 Received in revised form 3 July 2014 Accepted 15 July 2014 Available online 19 July 2014

SuzukieMiyaura cross coupling reaction was used for access to new macrocycles exhibiting oligoethyleneoxide bridges and embedding bithiophene, terthiophene or 3,7-bis(thiophen-2-yl)-N-ethyl-10Hphenothiazine units. The synthesis was performed under various reaction conditions and different coupling types in order to establish the correlation between yields and employed solvents and bases. The structure of the compounds was supported by single crystal X-ray diffractometry, NMR, and MS experiments. Ó 2014 Elsevier Ltd. All rights reserved.

Keywords: SuzukieMiyaura cross coupling Macrocycles Bithiophenes Terthiophenes Phenothiazines

1. Introduction The arylearyl cross coupling reactions has a spectacular development in recent decades, becoming arguably the most important and easiest way to access new CeC bonds.1 Despite the increasing interest in the classic Suzuki reaction and its improvements,2 and the continuously larger number of macrocyclic compounds,3 there are relatively few works dedicated to the synthesis of macrocycles using the Suzuki-type (cross-)coupling procedure. € ter,4 T. J. J. Mu € ller,5 R. Jasti,6 and To date, the groups of D. A. Schlu 7 Z. Bo have reported many successful Suzuki cross coupling procedures for access to macrocyclic compounds, all of them with rigid structures. In other cases, procedures inspired by the Suzuki reaction were used for intramolecular macrocyclizations, but access to the appropriate substrates (for the coupling reactions) was quite difficult requesting several synthetic steps.8 Palladium (Pd0) mediated synthesis of some cyclophanes was also reported.9 The reaction of alkylidene diboronic esters with dihalogenoaromatic derivatives in order to give [n]cyclophanes (1þ1 reaction) led also to the corresponding [n.n]cyclophanes (2þ2 reaction), however in

* Corresponding author. Tel.: þ40 264593833; fax: þ40 264590818; e-mail address: [email protected] (I. Grosu). http://dx.doi.org/10.1016/j.tet.2014.07.061 0040-4020/Ó 2014 Elsevier Ltd. All rights reserved.

both cases, the reported yields were low.9a The cyclophane with two porphyrin units connected by two phenothiazine bridges obtained in the reaction of a bis(bromoaryl)porphyrin with the 3,7diboronic-dipinacolate of N-methylphenothiazine revealed a high ability for the formation of host guest complexes with C60.9d On the other hand, thiophene derivatives have emerged as important targets for materials science, as they can easily electropolymerize to give conducting polymers. Macrocyclic thiophenes or polythiophenes were developed in order to take advantage of the specific binding ability of macrocycles towards different cations and to examine the possibility of the development of new electrochemical sensors. The main investigated structures reported in the literature are compounds bearing macrocycles attached through a chain to the thiophene units,10 thiophenomacrocycles,11 or macrocyclic compounds embedding bithiophene,12 terthiophene,13 quaterthiophene or sexithiophene entities.14 The dibrominated derivatives of thiophene itself,15 of bi- and terthiophene16 as well as of 10-ethyl-3,7-dithienyl-10H-phenothiazine (see Supplementary data) are easily accessible and thus, considered as attractive candidates for macrocyclization reactions by Suzuki cross-coupling procedures. In this context, we considered it to be of interest to investigate different strategies for the synthesis of macrocycles I, II, and III (Chart 1) using SuzukieMiyaura cross coupling reaction and to

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obtain new host molecules through direct connection of different aromatic building blocks.

(strategy A), generated by the modification of the employed solvents and bases (Table 1), were studied for the target macrocycles 6, 7, and 11. The investigated mixtures of solvents were diglyme/water and DMF/water and the considered bases (playing also the template role) were Cs2CO3 and K2CO3 (both recommended in the literature).5a,17 Analysis of data of Table 1 reveals better results for all investigated substrates when diglyme/water and Cs2CO3 were used. These reaction conditions were further used for all syntheses, following either A or B strategies. Table 1 Yields of macrocycles 6, 7, and 11, obtained under different reaction conditions using strategy A No.

1 2 3

Chart 1.

2. Results and discussion Two approaches for the rapid access to thiophene-based macrocycles IeIII were considered (A and B; Scheme 1). One of the strategies (A) envisaged the preparation of the corresponding diboronic diester of thiophene derivatives V, followed by their reaction with the dibrominated compounds bearing oligo(ethyleneoxide) units IV. The other approach (B), which appears to be more tempting, was based on the cross-coupling reaction of diboronic diesters containing oligo(ethylene oxide) bridges VI with dibrominated thiophenes VII (Scheme 1). In both cases high-dilution was employed and the concentrations of the reagents were of 5 mM. The MS investigations of the row products did not reveal the formation of oligomers (dimers, trimers).

Reaction conditions

Yields (%)

Solvent

Base

6

7

11

Diglyme/H2O (5/1) Diglyme/H2O (5/1) DMF/H2O (5/1)

K2CO3 Cs2CO3 Cs2CO3

13 27 19

22 33 26

17 34 20

The cross-coupling reaction of thiophene diboronic diester 1 with dibrominated derivatives 4 or 5 failed and no macrocyclic coupling product could be isolated (Scheme 2). The reaction of bithiophene diboronic diester 2 with the larger podand 5 successfully led to macrocycle 6, while its reaction with the shorter podand 4 failed to form the macrocyclic compound. Contrarily, the larger diboronic diester 3 gave the target macrocycles 7 and 8 in its coupling reaction with both podands 4 and 5, respectively. The different results recorded for macrocyclization of bithiophene and terthiophene diboronic diesters 2 and 3 with podands 4 and 5 can be correlated with the geometry of the diphenyl-polythiophene entities and the better fitting between the size of the thiophene substrates and the length of the chains in podands 4 or 5. This assumption was further confirmed by the synthesis of macrocycles 11 and 12 (Scheme 3), which were obtained from 3,7dithiophenyl-N-ethyl-10H-phenothiazine diboronic diester 10 with both considered dibrominated podands 4 and 5, higher yields being recorded for macrocycle 11 having the smaller cavity. The 4,40 -bithiophene diboronic diester 13 reacted with podands 4 and 5 in a manner similar to that observed for its isomer 2. No formation of macrocycle was recorded for the shorter podand 4, while the reaction with 5 gave macrocycle 14 in 18% yield.

Scheme 1. Strategies for access to macrocycles IeIII.

The macrocyclization reactions using approach A are shown in Schemes 2e4. In order to determine the most favorable conditions for the arylearyl cross-coupling reactions of these substrates, different experimental conditions for the SuzukieMiyaura reaction

In addition to the investigations of the reaction conditions (Table 1), the ‘one pot’ reaction (strategy A) was tested starting from dibrominated compound 9 (see Supplementary data). During this procedure, the diboronic diester 10 was not isolated, while THF was

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Scheme 2.

Scheme 3.

Scheme 4.

used as solvent and tBuOK as base and template. The yields were considerably lower (15% for 11 and 10% for 12) than those obtained in the procedure involving the separation and purification of the diboronic dipinacolate 10. Compared to A, the synthesis strategy B (Scheme 1) reverses the functionalities of the two cross-coupling reaction partners, the dibrominated thiophene-based derivatives 9 and 15e18 being reacted with diboronic diesters 19 and 20 (prepared from the corresponding dibrominated podands 4 and 5, Scheme 5), in order to give macrocycles 6e8, 11, 12, and 14 (Scheme 6). The yields for the macrocycles 6, 8, 12, and 14 are somewhat better when employing the B strategy (Table 2), nevertheless the purification step is considerably easier for all macrocycles. Thus, considering the overall effort to get access to the target macrocycles, method B seems to be favored. Strategy B reveals itself as an efficient procedure to obtain a wide range of macrocycles embedding various aromatic moieties using a reduced number of boronic esters podands and devotes Suzuki cross-coupling reaction as one versatile macrocyclization procedure. The structure of the macrocycles was determined in solution based on NMR and MS spectra, while macrocycles 6 and 11 afforded suitable crystals for the solid state molecular structure determination by single crystal X-ray diffractometry.

Scheme 5.

The molecular structure of 6 (Fig. 1a) reveals a slightly twisted arrangement of the aromatic rings. Cycles C9C10C11C12C13C14 and S2C5C6C7C8 are coplanar, but the dihedral angle between the two thiophene units (S2C5C6C7C8) and (S1C1C2C3C4) is 22.66 , while the dihedral angle with the plane of the other benzene ring (C23C24C25C26C27C28) is larger, being of 51.64 . The oligoethyleneoxide chain lies almost linearly defining a narrow cavity for the macrocycle. In the lattice, no intermolecular associations through H/O or H/S bonds within the sum of the corresponding van der Waals radia were observed. Crystal packing showed only several weak H/p interactions [d(H18B0 /centroid(C5C6C7C8S2))]¼2.99  A and [d(H15B0 /centroid(C1C2C3C4S1))]¼2.84  A (Fig. 1b and c). These interactions determined a linear polymer-like arrangement of the molecules (Fig. 1b and c). Compound 11 crystallized as a solvate with one CH2Cl2 molecule per asymmetric unit (Fig. 2a and b). The solvent molecule is held within the macrocycle through the cooperative effect of weak interactions, at the limit of the sum of van der Waals radia (CeH41A/O2; d¼2.634  A; S1/Cl1; d¼3.558  A; S2/Cl2; d¼3.496  A).

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Scheme 6.

Table 2 Comparative data of the synthetic strategies of macrocycles 6e8, 11, 12, and 14 Macrocycle

Strategies and yields (%) A

B

‘One pot’

6 7 8 11 12 14

27 33 17 34 17 18

28 27 19 28 25 22

d d d 15 10 d

As expected, the phenothiazine moiety adopts the ‘butterfly’ structure (as 9,10-dihydroanthracene)18 with a flattened boat conformation of the central heterocycle and displaying a pseudoequatorial orientation of the ethyl group located at position 10 (N atom). The benzene rings of the phenothiazine unit exhibit a dihedral angle of 129.90 , defining a concavity that brings closer the extremities of the aromatic system that are relied by the oligoethyleneoxide bridge. Formation of molecules’ columns was observed in the lattice of 11 (Fig. 2c). The molecules of the same column show similar orientations of the concavities of phenothiazine moieties, while the molecules of neighboring columns exhibit antiparallel orientations of these concavities. In one column, 0 the molecules display double CeH/p [d(C26 eHB/centroid 15 16 17 18 2 2600 150 160 170 180 20 (C C C C S ))¼d(C eHB/centroid (C C C C S ))¼ 0 2.93  A; shown in pink] and CeH/O contacts [d(C36eH/O4 )¼ 360 4  d(C eH/O )¼2.71 A; shown in yellow]. The supramolecular assembly is further ensured by a number of aromatic-

aromatic (p/p) contacts [d(centroid(C31C32C33C34C35C36)/cen0 0 0 0 0 0 troid(C31 C32 C33 C34 C35 C36 ))¼3.62  A; the benzene rings are parallel; the distance between their planes is 3.45  A and the lateral shift is 1.08  A; shown in blue] and CeH/Cl contacts, involving the captured solvent molecules and H atoms of the oligoethylene chains of neighboring macrocycles [d(C27eHA/Cl2)¼2.97  A; d(C28eHA/Cl1)¼3.20  A; shown in green] (Fig. 2c). In addition, between two columns, double CeH (aromatic)/p contacts are established involving one of the benzene rings of the phenothiazine moiety as H donor and a thiophene ring (of a neighboring macrocycle) as H acceptor [d 0 0 0 0 (C11 eH/centroid(C37C38C39C40S3))¼d(C11eH/centroid(C37 C38 C39 400 30  C S ))¼3.500 A; shown in red]. 3. Conclusions The SuzukieMiyaura cross-coupling reaction was successfully used for the obtaining of crown ether type macrocycles based on bithiophene, terthiophene or 3,7-dithiophenyl-phenothiazine aromatic units and oligoethyleneoxide chains. Synthesis of macrocycles via cross coupling reaction was conveniently performed through both considered strategies, when the two podands played one by one, the role of dibrominated and diboronic reaction partners, respectively. However, the approach involving the dibrominated heteroaromatic substrates and the diboronic dipinacolate derivatives of bis(aryl)oligo(ethyleneoxide) chains, proved to be the most profitable method for the access to various heteroaromatic macrocycles. The molecular structure of two macrocycles (one with bithiophene and one with phenothiazine units) obtained by single

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Fig. 1. Solid state molecular structure of 6 (view of the asymmetric unit with 40% probability ellipsoids), views of supramolecular associations through weak H/p interactions (b; only hydrogen atoms involved in interactions are shown) and view of the lattice along the c axis of unit cell (c). Symmetry equivalent atoms are given by ‘prime’ [0.5þx, 0.5y, 0.5þz].

crystal X-ray diffractometry revealed peculiar conformations of the aromatic parts, while for phenothiazine macrocycle the formation of a solvate with dichloromethane was observed. 4. Experimental part 4.1. General experimental data 1

H NMR (300 or 500 MHz) and 13C NMR (75 or 125 MHz) spectra, COSY, HSQC, and HMBC were recorded in C6D6, DMSO-d6 or acetone-d6 at room temperature using the solvent line as reference. Thin layer chromatography (TLC) was conducted on silica gel 60 F254 TLC plates and preparative column chromatography was performed using 40e63 mm silica gel. Solvents were dried and distilled under argon using standard procedures. Chemicals of commercial grade were used without further purification. MSs were recorded using an ion-trap MS equipped with a standard ESI/ APCI source.

Crystallographic data were collected at room temperature and the crystals were mounted on a cryoloop with Paraton oil. The structures were solved by direct methods (SHELXS-97)19 and refined by full matrix least-squares procedures based on F2 with all measured reflections (SHELXL-97).19 All non-hydrogen atoms were refined anisotropically. The drawings were created with Diamond program.20 Further details on data collection and refinement methods can be found in Supplementary data. These data can be also obtained free of charge from the (Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: (þ44) 1223-336-033; or e-mail: [email protected]). The deposition numbers are: CCDC-856167 (6) and CCDC-856168 (11). 4.2. General procedure for the SuzukieMiyaura macrocyclization (approaches A or B) Equimolecular amounts (1 mmol) of diboronic dipinacolate and dibrominated compound and 4 equiv of Cs2CO3 (4 mmol) were solved

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Fig. 2. Views of the asymmetric unit of 11 (a: ORTEP representation with 40% probability ellipsoids; b: representation with van der Waals radia) and view of the lattice along the a axis revealing the supramolecular associations in crystalline 11 (c).

in a mixture of diglyme/H2O¼5:1 (V¼200 mL). The reaction mixture was degassed to remove oxygen and then Pd(PPh3)4 was added (0.05 mmol). The reaction mixture was refluxed overnight under Ar. Then, the solvent was removed under vacuum and water was added to the crude product (70 mL) and then the water phase was extracted with DCM (370 mL). The organic phase was dried with MgSO4, the solvent was evaporated at reduced pressure, and the residue was purified on chromatographic column (pentane/ethyl acetate). Diboronic dipinacolates 1,21 2,22 3,23 and 1324 were already reported by other groups, while diboronic diesters 10, 19, and 20 were first obtained for this work using usual procedures (see Supplementary data). Dibrominated thiophene compounds 15e18 were already reported.15,16 Compounds 4, 5, and 9 were obtained by different methods accordingly with their structure (see Supplementary data). 4.2.1. 2,5,8,11,14-Pentaoxa-33,34-dithia-pentacyclo[26.3.1.1.15,19 1. 20,23 1. 24,27 ]pentatriconta-1(35),15,17,19(32),20,22,24,26,28,30decaene 6. Yields 27% A (19 mg) and 28% B (20 mg); yellow solid, mp¼118e120  C; Rf¼0.52 (pentane/ethyl acetate¼7:3). Calculated for C28H28O5S2: C, 66.12; H, 5.55; S, 12.61. Found: C, 66.19; H, 5.38; S, 12.77. 1H NMR (500 MHz, C6D6): d (ppm)¼3.37e3.43 (overlapped peaks, 8H, 6-H, 7-H, 9-H, 10-H), 3.48e3.52 (overlapped peaks, 6H, 3-H, 4-H, 12-H, 13-H), 3.77 (t, 2H, J¼7.4 Hz, 3-H, 13-H), 6.58e6.71 (overlapped peaks, 6H, 16-H, 21-H, 22-H, 25-H, 26-H, 31-H), 6.92e6.95 (m, 2H, 18-H, 29-H), 7.01e7.03 (m, 2H, 17-H, 30-H), 7.24 (t, 2H, 3J¼1.8 Hz, 32-H, 35-H). 13C NMR (75 MHz, C6D6): d (ppm)¼ 67.5 (CH2), 69.5 (CH2), 69.8 (CH2), 70.9 (CH2), 114.0 (CH), 117.7 (CH),

122.9 (C), 123.80 (CH), 124.2 (CH), 130.1 (CH), 130.6 (CH), 135.5 (C), 143.2 (C), 159.7 (C). ESI-MS: m/z¼509.1 [MþH]þ. 4.2.2. 2,5,8,11-Tetraoxa-34,35,36-trithia-hexacyclo[26.3.1.1.12,16 1. 17 , 2 0 1. 21, 241. 2 5, 2 8 ]heptatriconta-1(37),12,14,16(33),17,19,21, 23,25,27,29,31-dodecaene 7. Yields 33% A (25 mg) and 27% B (21 mg); yellow solid, mp¼219e220  C; Rf¼0.54 (pentane/ethyl acetate¼5:1). Calculated for C30H26O4S3: C, 65.91; H, 4.79; S, 17.59. Found: C, 66.09; H, 4.67; S, 17.71. 1H NMR (300 MHz, C6D6): d (ppm)¼3.46 (s, 4H, 6-H, 7-H), 3.52 (t, 4H, J¼4.8 Hz, 4-H, 9-H), 3.76 (t, 4H, J¼4.8 Hz, 3-H, 10-H), 6.69e6.81 (overlapped peaks, 6H, 13-H, 19-H, 22-H, 23-H, 26-H, 32-H), 7.02 (t, 2H, J¼8.1 Hz, 14-H, 31-H), 7.08 (d, 2H, J¼4.5 Hz, 18-H, 27-H), 7.16e7.18 (m, 2H, 15-H, 30-H), 7.28 (t, 2H, J¼2.4 Hz, 33-H, 37-H). 13C NMR (75 MHz, C6D6): d (ppm)¼67.4 (CH2), 69.8 (CH2), 70.9 (CH2), 112.5 (CH), 113.8 (CH), 118.8 (CH), 123.4 (CH), 120.4 (C), 124.8 (CH), 127.9 (CH), 130.1 (CH), 136.0 (C), 141.5 (C), 144.5 (C), 159.8 (C). ESI-MS: m/z¼547.2 [MþH]þ. 4.2.3. 2,5,8,11,14-Pentaoxa-37,38,39-trithia-hexacyclo[30.3.1. 1.15 ,19 1. 20 ,231. 24, 27 1. 2 8, 31 ]tetraconta-1(40),15,17,19(36),20,22, 24,26,28,30,32,34-dodecaene 8. Yields 17% A (14 mg) and 19% B (16 mg); yellow solid, mp¼158e160  C; Rf¼0.46 (pentane/ethyl acetate¼7:3). Calculated for C32H30O5S3: C, 65.06; H, 5.12; S, 16.28. Found: C, 65.22; H, 4.97; S, 16.11. 1H NMR (300 MHz, C3D6O): d (ppm)¼3.75e3.87 (overlapped peaks, 8H, 6-H, 7-H, 9-H, 10-H), 4.21e4.23 (m, 4H, 4-H, 12-H), 4.33e4.36 (m, 4H, 3-H, 13-H), 6.85e6.87 (m, 2H, 16-H, 35-H), 7.32 (t, 2H, J¼8.2 Hz, 17-H, 34-H), 7.42e7.50 (overlapped peaks, 10H, 18-H, 21-H, 22-H, 25-H, 26-H,

A. Petran et al. / Tetrahedron 70 (2014) 6803e6809

29-H, 30-H, 33-H, 36-H, 40-H). 13C NMR (75 MHz, C3D6O): d¼67.4 (CH2), 69.9 (CH2), 70.4 (CH2), 70.7 (CH2), 111.1 (CH), 116.7 (CH), 117.0 (CH), 124.4 (CH), 128.8 (CH), 130.0 (CH), 131.2 (CH), 134.8 (C), 135.8 (C), 138.0 (C), 143.0 (C), 159.8 (C). ESI-MS: m/z¼591.2 [MþH]þ.

Supplementary data

4.2.4. 34-Ethyl-11,14,17,20-tetraoxa-38,41,44-trithia-34-aza-octacyclo[28.7.5.1. 2 , 51. 6 ,10 1. 21, 2 51. 2 6 , 29 0. 33 , 4 3 0. 3 4 , 45 ]hexatetraconta2,4,6,8,10(39),21,23,25(40),26,28,30,32,35,37,42,45-hexadecaene 11. Yields 34% A (33 mg) and 28% B (27 mg); yellow solid, mp¼226e228  C; Rf¼0.26 (pentane/ethyl acetate¼5:1). Calculated for C40H35NO4S3: C, 69.64; H, 5.11; N, 2.03; S, 13.94. Found: C, 69.47; H, 4.97; N, 2.16; S, 13.70. 1H NMR (500 MHz, C6D6): d (ppm) 1.15 (t, 3H, J¼7.0 Hz, NeCeCH3), 3.35 (s, 4H, 15-H, 16-H), 3.41 (q, 2H, J¼7.0 Hz, NeCH2e), 3.58 (t, 4H, J¼6.7 Hz, 13-H, 18-H), 3.90 (t, 4H, J¼6.7 Hz, 12-H, 19-H), 6.60 (d, 2H, J¼8.4 Hz, 32-H, 36-H), 6.86 (ddd, 2H, J¼8.4 Hz, J0 ¼2.3 Hz, J00 ¼1.2 Hz, 7-H, 24-H), 6.99 and 7.12 (d, 2H, J¼3.7 Hz and d, 2H, J¼3.7 Hz; 3-H, 4-H, 26-H, 27-H), 7.06 (t, 2H, J¼J0 ¼8.2 Hz, 8-H, 23-H), 7.15e7.18 (m, 2H, 31-H, 37-H), 7.23 (dd, 2H, J¼8.6 Hz, J0 ¼2.5 Hz, 9-H, 22-H), 7.28e7.31 (m, 2H, 42-H, 46-H), 7.75 (d, 2H, J¼1.2 Hz, 39-H, 40-H). 13C NMR (125 MHz, C6D6): d (ppm)¼ 14.3 (CH3), 29.7 (CH2), 66.0 (CH2), 69.5 (CH2), 70.7 (CH2), 110.5 (CH), 115.7 (CH), 115.9 (CH), 116.8 (CH), 122.3 (CH), 123.7 (CH), 124.7 (CH), 126.2 (C), 127.0 (CH), 130.0 (CH), 130.8(C), 135.8 (C), 143.3 (C), 144.3 (C), 146.4 (C), 159.6 (C). ESI-MS: m/z¼690.2 [MþH]þ.

References and notes

4.2.5. 37-Ethyl-11,14,17,20-tetraoxa-41,44,47-trithia-37-aza-octacyclo[31.7.5.1. 2, 51. 6 ,10 1. 24 ,2 8 1. 2 9, 32 0. 36 , 46 0. 38, 4 8 ]nonatetraconta2,4,6,8,10(42),24,26,28(43),29,31,33,35,38,40,45,48-hexadecaene 12. Yields 17% A (18 mg) and 25% B (26 mg); yellow solid, mp¼203e204  C; Rf¼0.23 (pentane/ethyl acetate¼7:3). Calculated for C42H39NO5S3: C, 68.73; H, 5.36; N, 1.91; S, 13.11. Found: C, 68.88; H, 5.15; N, 2.07; S, 13.17. 1H NMR (500 MHz, DMSO-d6): d (ppm)¼ 1.39 (t, 3H, J¼7.1 Hz, NeCeCH3), 3.60e3.67 (overlapped peaks, 8H, 15-H, 16-H, 18-H, 19-H), 3.80 (t, 4H, J¼6.3 Hz, 13-H, 41-H), 4.04 (q, 2H, J¼7.1 Hz, NeCH2e), 4.16 (t, 4H, J¼6.3 Hz, 22-H, 19-H), 6.86 (dd, 2H, J¼8.4 Hz, J0 ¼2.2 Hz, 7-H, 27-H), 7.11 (t, 2H, J¼2.2 Hz, 42-H, 43H), 7.20 (d, 2H, J¼8.4 Hz, 35-H, 39-H), 7.34 (t, 2H, J¼J0 ¼7.9 Hz, 8-H, 26-H), 7.41 and 7.52 (d, 2H, J¼4.1 Hz and d, 2H, J¼4.1 Hz; 3-H, 4-H, 30-H, 31-H), 7.41e7.43 (m, 2H, 34-H, 40-H), 7.50 (d, 2H, J¼2.0 Hz, 45-H, 49-H), 7.65 (dd, 2H, J¼7.9 Hz, J0 ¼2.3 Hz, 9-H, 25-H). 13C NMR (125 MHz, DMSO-d6): d (ppm)¼13.5 (CH3), 29.4 (CH2), 67.3 (CH2), 69.3 (CH2), 70.1 (CH2), 70.3 (CH2), 111.2 (CH), 114.9 (CH), 116.8 (CH), 117.3 (CH), 123.8 (CH), 124.1 (C), 124.8 (CH), 125.3 (CH), 126.2 (CH), 129.5 (C), 130.7 (CH), 135.2 (C), 142.3 (C), 142.6 (C), 145.3 (C), 159.4 (C). ESI-MS: m/z¼734.3 [MþH]þ. 4.2.6. 2,5,8,11,14-Pentaoxa-22,25-dithia-pentacyclo[26.3.1. 1.15,191.20,231.24,27] pentatriconta-1(35),15,17,19(32),20,23(33),24(34), 26,28,30-decaene 14. Yields 18% A (25 mg) and 22% B (31 mg); yellow solid; mp¼94e96  C; Rf¼0.16 (pentane/ethyl acetate¼7:3). Calculated for C28H28O5S2: C, 66.12; H, 5.55; S, 12.61. Found: C, 66.25; H, 5.71; S, 12.47. 1H NMR (500 MHz, C3D6O): d (ppm)¼ 3.66e3.69 and 3.75e3.78 (m, 4H and m, 4H; 6-H, 7-H, 9-H, 10-H), 3.82 (t, 4H, J¼6.3 Hz, 4-H, 12-H), 4.17 (t, 4H, J¼6.3 Hz, 3-H, 13-H), 6.87e6.89 (m, 2H, 16-H, 31-H), 7.34 (t, 2H, J¼8.2 Hz, 17-H, 30-H), 7.40e7.42 (overlapped peaks, 4H, 18-H, 29-H, 32-H, 35-H), 7.71 (d, 2H, J¼1.5 Hz, 33-H, 34-H), 8.36 (d, 2H, J¼1.5 Hz, 21-H, 26-H). 13C NMR (125 MHz, C3D6O): d (ppm)¼66.7 (CH2), 69.2 (CH2), 70.8 (CH2), 71.1 (CH2), 112.3 (CH), 113.4 (CH), 117.9 (CH), 118.8 (CH), 123.9 (CH), 129.9 (CH), 136.5 (C), 137.4 (C), 142.3 (C), 159.4 (C). ESI-MS: m/ z¼509.1 [MþH]þ. Acknowledgements We are grateful for the financial support of this work by CNCSUEFISCDI (Project PN-II-ID-PCCE-2011-2-0027).

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Supplementary data related to this article can be found at http:// dx.doi.org/10.1016/j.tet.2014.07.061.

1. (a) Diederich, F.; Stang, P. J. Metal-catalysed Cross-coupling Reactions; WileyVCH: New York, NY, 1999; (b) Lessene, G.; Feldman, K. S. In Modern Arene Chemistry; Astruc, D., Ed.; Wiley-VCH, GmbH. KGaA: Weinheim, Germany, € rti, L.; Czako  , B. Strategic Applications of Named Reactions in Organic 2004; (c) Ku Synthesis; Elsevier Academic: San Diego, USA, 2005; (d) Modern Arylation Methods; Ackermann, L., Ed.; Wiley-VCH, GmbH. KGaA: Weinheim, Germany, 2009; (e) Wu, X.-F.; Anbarasan, P.; Neumann, H.; Beller, M. Angew. Chem., Int. Ed. 2010, 49, 9047e9050. 2. (a) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457e2483; (b) Yin, L.; Liebscher, J. Chem. Rev. 2007, 107, 133e173; (c) Slagt, V. F.; de Vries, A. H.; de Vries, M. J. G.; Kellogg, R. M. Org. Process Res. Dev. 2010, 14, 30e47. 3. (a) Pedersen, C. J. J. Am. Chem. Soc. 1967, 89, 7017e7036; (b) Lindoy, L. F. The Chemistry of Macrocyclic Ligand Complexes; Cambridge University Press: UK, 1989; (c) Steed, J. W.; Atwood, J. L. Supramolecular Chemistry; Wiley & Sons: New York, NY, 2009; (d) Davis, F.; Higson, S. Macrocycles: Construction, Chemistry and Nanotechnology Applications; Wiley & Sons: New York, NY, 2011. € ter, A. D. Chem.dEur. J. 1999, 5, 421e429; (b) Sakamoto, J.; 4. (a) Hensel, V.; Schlu € ter, A. D. Macromol. Rapid Commun. 2009, 30, Rehahn, M.; Wegner, G.; Schlu € ter, A. 653e687; (c) Jakob, S.; Moreno, A.; Zhang, X.; Bertschi, L.; Smith, P.; Schlu D.; Sakamoto, J. Macromolecules 2010, 43, 7916e7918. € ller, T. J. J. Synthesis 2008, 1121e1125; (b) Memminger, K.; 5. (a) Franz, A. W.; Mu € ller, T. J. J. Org. Lett. 2008, 10, 2797e2800. Oeser, T.; Mu 6. (a) Xia, J.; Jasti, R. Angew. Chem., Int. Ed. 2012, 51, 2474e2476; (b) Hirst, E. S.; Jasti, R. J. Org. Chem. 2012, 77, 10473e10478; (c) Xia, J.; Golder, M. R.; Foster, M. E.; Wong, B. M.; Jasti, R. J. Am. Chem. Soc. 2012, 134, 19709e19715; (d) Darzi, E. R.; Sisto, T. J.; Jasti, R. J. Org. Chem. 2012, 77, 6624e6628; (e) Sisto, T. J.; Golder, M. R.; Hirst, E. S.; Jasti, R. J. Am. Chem. Soc. 2011, 133, 15800e15802. 7. Huang, W.; Wang, M.; Du, C.; Chen, Y.; Qin, R.; Su, L.; Zhang, C.; Liu, Z.; Li, C.; Bo, Z. Chem.dEur. J. 2011, 17, 440e444. 8. (a) Zhu, J. Org. Lett. 2000, 2, 3477e3480; (b) Bodwell, G. J.; Li, J. Angew. Chem., Int. Ed. 2002, 41, 3261e3262; (c) Carbonnelle, A.-C.; Wang, Q.; Zhu, J. Chimia 2011, 65, 168e174. 9. (a) Bodwell, G. J.; Li, J. Org. Lett. 2002, 4, 127e130; (b) Smith, B. B.; Hill, D. E.; Cropp, T. A.; Walsh, R. D.; Cartrette, D.; Hipps, S.; Shachter, A. M.; Pennington, T. W.; Kwochka, W. R. J. Org. Chem. 2002, 67, 5333e5337; (c) Kotha, S.; Chavan, A. S.; Shaikh, M. J. Org. Chem. 2012, 77, 482e489; (d) Sakaguchi, K.; Kamimura, T.; Uno, H.; Mori, S.; Ozako, S.; Nobukuni, H.; Ishida, M.; Tani, F. J. Org. Chem. 2014, 79, 2980e2992. €uerle, P. J. Mater. Chem. 1999, 9, 2139e2150; (b) Le vesque, I.; 10. (a) Scheib, S.; Ba Leclerc, M. J. Chem. Soc., Chem. Commun. 1995, 2293e2294; (c) Boldea, A.; vesque, I.; Leclerc, M. J. Mater. Chem. 1999, 9, 2133e2138. Le €uerle, P.; Scheib, S. Acta Polym. 1995, 46, 124e129; (b) Ba €uerle, P.; Go €tz, G.; 11. (a) Ba Hiller, M.; Scheib, S.; Fischer, T.; Segelbacher, U.; Bennati, M.; Grupp, A.; Mehring, M.; Stoldt, M.; Seidel, C.; Geiger, F.; Schweizer, H.; Umbach, E.; Schmelzer, M.; Roth, S.; Egelhaaf, H. J.; Oelkrug, D.; Emele, P.; Port, H. Synth. Met. 1993, 61, 71e79; (c) Berlin, A.; Zotti, G.; Zecchin, S.; Schiavon, G. Synth. Met. 2002, 131, 149e160. 12. (a) Marsella, M. J.; Swager, T. M. J. Am. Chem. Soc. 1993, 115, 12214e12215; (b) Demeter, D.; Blanchard, P.; Grosu, I.; Roncali, J. Electrochem. Commun. 2007, 9, 1587e1591; (c) Demeter, D.; Lar, C.; Grosu, I.; Roncali, J. Tetrahedron Lett. 2013, 54, 1460e1462. 13. Demeter, D.; Blanchard, P.; Allain, M.; Grosu, I.; Roncali, J. J. Org. Chem. 2007, 72, 5285e5291. 14. Jousselme, B.; Blanchard, P.; Levillain, E.; Delaunay, J.; Allain, M.; Richomme, P.; Rondeau, D.; Gallego-Planas, N.; Roncali, J. J. Am. Chem. Soc. 2003, 125, 1363e1370. 15. Keegstra, M. A.; Brandsma, L. Synthesis 1988, 890e891. 16. (a) Dahlmann, U.; Neidlein, R. Helv. Chim. Acta 1996, 79, 755e766; (b) Wang, N.€rthner, F.; Goetz, X. Synth. Commun. 2003, 33, 2119e2124; (c) Beauerle, P.; Wu G.; Effenberger, F. Synthesis 1993, 1099e1103. € llen, K. Chem.dEur. J. 17. (a) Nolde, F.; Qu, J.; Kohl, C.; Pschirer, N. G.; Reuther, E.; Mu 2005, 11, 3959e3967; (b) Sakamoto, T.; Pac, C. J. Org. Chem. 2001, 66, 94e98; (c) Han, X.; Chen, X.; Vamvounis, G.; Holdcroft, S. Macromolecules 2005, 38, 1114e1122; (d) Shang, R.; Xu, Q.; Jiang, Y.-Y.; Wang, Y.; Liu, L. Org. Lett. 2010, 12, 1000e1003. 18. Eliel, E. L.; Wilen, S. H. Stereochemistry of Organic Compounds; Wiley: New York, NY, 1994; p 783. 19. Sheldrick, G. M. Acta Crystallogr. 2008, A64, 112e122. 20. Brandenburg, K. DIAMOND; Crystal Impact GbR: Bonn, Germany, 2006. 21. Capan, A.; Ozturk, T.; Veisi, H.; Goren, A. C.; Ozturk, T. Macromolecules 2012, 45, 8228e8236. 22. Li, Y.; Li, Z.; Wang, C.; Li, H.; Lu, H.; Xu, B.; Tian, W. J. Polym. Sci., Part A: Polym. Chem. 2010, 48, 2765e2776. 23. Hassan Omar, O.; Babudri, F.; Farinola, G. M.; Naso, F.; Operamolla, A.; Pedone, A. Tetrahedron 2011, 67, 486e494. 24. Lumpi, D.; Schoepf, M.; Horkel, E.; Froehlich, J.; Wagner, C.; Ramer, G.; Lendl, B. Chem. Commun. 2012, 2451e2453.