An Unexpected and Easy Way of Freezing the Configuration of a Triaryl Phosphane Oxide

Abstract

Configurationally stable triaryl phosphane oxides are important for reactions with transfer of chiral information. Apart from introducing bulky substituents to suppress fast inversion of helicity at room temperature, the use of a second chiral element which induces chirality in the triaryl phosphane oxide, so that it adopts only one configuration, is suitable. With regard to chirality transfer, C(2)-symmetric imidazole cyclopeptides were tested for obtaining a configurationally stable phosphane oxide. Density functional calculations showed almost equal energies of the three possible triaryl phosphane oxides (MMM)-1, (PPP)-1, and (MP)-1. Surprisingly, after synthesis only the MMM conformer is present in solution, and its configurational stability was proved by variable-temperature and 2D NMR experiments as well as CD measurements. In view of the results of the DFT calculations, formation of stable (MMM)-1 cannot be explained thermodynamically but by kinetic reaction control. This concept of freezing the conformation of a triaryl phosphane oxide can in future be used to easily prepare configurationally stable stereoisomeric propellerlike compounds.

Copper-Catalyzed Addition of H–P(O) Bonds to Arynes

“…High-resolution mass spectra (HRMS) were recorded on ESI-TOF. The known compounds 3aa , 3ab , 3ad , 3ae , 3af , 3ah , 3aj , 3ak , 3ba , 3bd , 3bf , 3ca , 3cd , 3cf , 3ea , 3fa , 3fe , and 3ga showed characterization data in full agreement with previously reported data.…”

“…White amorphous solid (60 mg, 98%): 1 H NMR (400 MHz, CDCl 3 ) δ 7.71–7.62 (m, 2H), 7.56 (d, J = 12.4 Hz, 2H), 7.54–7.52 (m, 1H), 7.48–7.42 (m, 2H), 7.39–7.37 (m, 1H), 7.34–7.31 (m, 5H), 2.36 (s, 6H); 13 C NMR (100 MHz, CDCl 3 ) δ 138.4 (d, J = 12.0 Hz), 133.2 (d, J = 104 Hz), 132.8 (d, J = 103 Hz), 132.7 (d, J = 2.8 Hz), 132.5 (d, J = 9.5 Hz), 132.1 (d, J = 9.9 Hz), 131.8 (d, J = 2.7 Hz), 129.2 (d, J = 10.3 Hz), 128.3 (d, J = 4.7 Hz), 128.5 (d, J = 29.1 Hz), 21.4; 31 P NMR (162 MHz, CDCl 3 ) δ 29.6.…”

The Anancomeric Character of the Pharmacophore 1,3,4-Thiadiazoline Framework in Chiral Spiro-Cyclohexyl Derivatives: Effects on Stereochemistry and Spiro-Junction Lability. Thermodynamic Aspects

“…Due to the tetrahedral nature of the spiro atom, the two rings are not coplanar but twisted almost perpendicularly to each other. These particular arrangements, which are carriers of strong steric constraints, make the construction of all-carbon quaternary centers a formidable challenge for synthetic organic chemists and may markedly characterize the biological activity of synthetic and natural substances that include them in their structure. − …”

Elucidation of the mechanisms governing the thermal diastereomerization of bioactive chiral 1,3,4-thiadiazoline spiro-cyclohexyl derivatives towards their anancomeric stereoisomers

“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] In addition to the electronic effects exerted by groups substituting the heterocyclic moiety, the manifested biological activity can also derive from the particular stereochemistry 21 and structural rigidity characterizing the pharmacophoric portion that interacts with the target active site, [22][23][24][25] as observed, for example, for some classes of spiro-heterocycles. [26][27][28][29][30][31][32] Spiro-1,3,4-thiadiazoline derivatives, endowed with anti-inammatory, analgesic, antifungal and/or antimicrobial activities, [33][34][35][36] represent signicant examples of biologically active heterocyclic compounds in which the 1,3,4-thiadiazoline ring and the connected rigid spiro-structure act as a single 'hybrid pharmacophore' framework. We have recently reported 36 a quite in depth thermodynamic study focused to clarify the thermodynamic and stereochemical properties possessed by the chiral 1,3,4-thiadiazoline-spiro-cyclohexyl derivatives 1-3, reported in Fig.…”