Synthesis of Fluorinated and Fluoroalkylated Heterocycles Containing at Least One Sulfur Atom via Cycloaddition Reactions

Abstract

Fluorinated heterocycles constitute an important group of organic compounds with a rapidly growing number of applications in such areas as medicinal chemistry, agrochemicals production, polymer chemistry, as well as chemistry of advanced materials. In the latter case, fluorinated thiophenes are considered as a lead class of compounds with numerous spectacular applications. On the other hand, cycloaddition reactions offer a superior methodology for stereo-chemically controlled synthesis of heterocycles with a diverse ring size and a variable number of heteroatoms. A comprehensive review of methods based on cycloaddition reactions and applied for construction of fluorinated and/or fluoroalkylated S-heterocycles has not yet been published. For this reason, the main goal of the presented review was to fill the existing gap and to summarize the results published over last six decades. In this context, the [3+2]- and [4+2]-cycloadditions (Huisgen reactions, and Diels–Alder reactions, respectively) are of special importance. Some questions related to the discussed mechanisms of cycloaddition processes observed in reactions with electron deficient, fluorinated substrates (dipolarophiles and dienophiles), and electron-rich sulfur containing counter partners, are of fundamental importance for the development of interpretations of organic reaction mechanisms.

(±)-N-(1,2-Bis(3,4-dimethoxyphenyl)ethyl)-2-(2-fluoro-[1,1′-biphenyl]-4-yl)propanamide

“…The NMR spectral measurements were collected using a Bruker Avance Neo 400 spectrometer (BAS-IOCCP-Sofia, Bruker, Billerica, MA, USA). 1 H NMR and 13 C NMR spectra for compound 3 were taken in DMSO-d 6 at 400 MHz and 101 MHz, respectively. Chemical shifts are given in relative ppm and were referenced to tetramethylsilane (TMS) (δ = 0.00 ppm) as an internal standard; the coupling constants are indicated in Hz.…”

“…184-186 • C), yield 93% (0.507 g), R f = 0.54 (diethyl ether), 1 H NMR (400 MHz, DMSO-d 6 ) δ 8.45 (complex signal, 2H, 2 x NH), 7.55 (dq, J = 7.7, 1.5 Hz, 2H), 7.49 (td, J = 3.4, 2.9, 1.6 Hz, 4H), 7.45-7.36 (m, 4H), 7.36-7.31 (m, 1H), 7.19-7.14 (m, 2H), 7.06 (dd, J = 12.3, 1.8 Hz, 1H), 7.01-6.97 (m, 2H), 6.93-6.88 (m, 2H), 6.87-6.82 (m, 4H), 6.81 (s, 1H), 6.79-6.73 (m, 3H), 6.71-6.63 (m, 2H), 5.03-4.95 (complex signal, 2H, 2 x CHN), 3.77 (s, 3H), 3.74 (s, 3H), 3.73 (s, 3H), 3.71 (s, 3H), 3.71-3.69 (complex signal, 2H, 2 x CHCH 3 ), 3.69 (s, 3H), 3.62 (s, 3H), 3.59 (s, 3H), 3.58 (s, 3H), 2.99-2.76 (complex signal, 4H, 2 x CH 2 ), 1.29 (d, J = 7.1 Hz, 3H), 1.25 (d, J = 7.0 Hz, 3H). 13…”

“…In this respect, there has been a rise in the development of a number of novel fluorine-containing compounds in recent years, as well as modifications to existing ones. These chemicals are extremely interesting in terms of understanding their biological features and potential future use in pharmacy [13].…”

Trifluoromethylated 4,5-Dihydro-1,2,4-triazin-6(1H)-ones via (3+3)-Annulation of Nitrile Imines with α-Amino Esters

“…Several synthetic strategies towards F-containing heterocycles, including cycloadditions and cyclocondensation reactions, functional group interconversions, and catalytic C–H functionalizations, have been developed in recent decades and are nicely summarized elsewhere [ 15 , 16 , 17 , 18 ]. In this context, there is increasing interest in the chemistry of fluoroalkylated 1,3-dipoles, which are recognized as highly useful building blocks for Huisgen (3+2)-cycloaddition reactions [ 19 , 20 , 21 , 22 , 23 , 24 ].…”

Monofluoromethylation of N-Heterocyclic Compounds

“…General information on monofluorination reactions to form monofluoroalkyl derivatives is well presented in the works [36][37][38]. The synthesis of fluoroalkylated sulfur heterocycles was described in a recent review [39].…”