A Convenient Approach to 16‐, 19‐, and 22‐Membered 2,2′‐Bipyridine Thiacrown Ethers and Their Conformation Preferences

Abstract

A convenient, three‐step synthesis of 1:1 thiacrown ether macrocycles 5a–c containing a fused cyclopenteno[c]2,2′‐bipyridine subunit has been accomplished through first homocoupling of 1,2,4‐triazine bisulfides 3a–c tethered to poly(ethylene glycol) chains with potassium cyanide and secondDiels–Alder/retro‐Diels–Alder reaction of such obtained thiamacrocycles 4a–c with 1‐pyrrolidino‐1‐cyclopentene. Macrocycles 5a–c were oxidized to nonracemic monosulfoxides 6a–c by using Davis' oxaziridine and tested in the asymmetric addition of the diethylzinc to benzaldehyde. The crystal structure determinations of 5a–c and 6b and theoretical calculations at the DFT/B3LYP/6‐311G** level were used to establish their cis or trans conformations in the solid state and the gas phase.

A facile approach to 2,2′-bipyridine based thiacrown ethers and their sulfoxides by DA-rDA reaction of 5,5′-bi-1,2,4-triazine thiamacrocycles. The conformation studies

“…The calculated conformations of 2,2′-bipyridine systems in 5a-c are very similar to those obtained from X-ray analysis of structurally related annulated 2,2′-bipyridine thiamacrocycles. 7 In the case of 5a the cis conformation is forced by the strain effect in the twelve-membered thiaethereal chain during the cyclization process. The elongation of the thiaethereal chain in 5b and 5c can give the possibility to change the mutual orientation of pyridine rings.…”

“…Syntheses of 1,8-bis(1,2,4-triazin-3-ylsulfanyl)-3,6-dioxaoctane 3a, 1,11-bis(1,2,4-triazin-3-ylsulfanyl)-3,6,9-trioxaundecane 3b, 1,14-bis(1,2,4-triazin-3-ylsulfanyl)-3,6,9,12-tetraoxatetradecane 3c, 4,7-dioxa-1,10-dithia [10]3,3′-5,5′-bis(1,2,4-triazin-3-ylsulfanyl)cyclophane 4a, 4,7,10-trioxa-1,13-dithia [13]3,3′-5,5′-bis(1,2,4-triazin-3-ylsulfanyl)cyclophane 4b, 4,7,10,13-tetraoxa-1,16-dithia [16]3,3′-5,5′-bis(1,2,4-triazin-3-ylsulfanyl)cyclophane 4c were performed according to our published procedures. 6,7 General procedure for the preparation of thiacrown ethers (5a-c) and (6a-b) Method A. A solution of 2,5-norbornadiene (1.8 ml) in p-cymene (4 ml) containing compounds 4a-b (0.59 mmol) was heated for 20-24 h (see Table 1) at 140 °C.…”

New synthetic strategy to create intricate thiaoxacyclophanes via ring‐closing metathesis

“…To synthesize sulfur, oxygen, and nitrogen-containing hetera-and heterocyclophanes, commonly used methods are macrocyclization at high dilution, [11] Wurtz coupling, [12] ring-closing metathesis (RCM), [13] transition metalcatalyzed cross-coupling between the aromatic unit and aliphatic chain, [14] and ring contraction techniques such as Steven's rearrangement, [15] Wittig rearrangement, [16] and sulphone pyrolysis. [17] Some examples of selected natural [18] and unnatural oxa-and thiacyclophanes synthesized via RCM (Rykowski et al, [19] Kotha et al, [20] Tamm et al [21] ), high dilution technique (Yamato et al [22] ), and cross-coupling reactions (Beaudry et al [23] ) are shown in Figure 1. For building thiacyclophanes, these conventional synthetic strategies have several drawbacks, like long reaction time, and high temperature in high dilution procedures or a mixture of macromolecules or oligomers formation in the Wittig rearrangement and Wurtz coupling.…”

“…Some examples of selected natural [18] and unnatural oxa‐ and thiacyclophanes synthesized via RCM (Rykowski et al ., [19] Kotha et al ., [20] Tamm et al [21] [22] …”