Highly selective single and multiple deuteration of unactivated C(sp3)-H bonds

Abstract

Selective deuteration of unactivated C(sp3)-H bonds is a highly attractive but challenging subject of research in pharmaceutical chemistry, material science and synthetic chemistry. Reported herein is a practical, highly selective and economical efficient hydrogen/deuterium (H/D) exchange of unactivated C(sp3)-H bonds by synergistic photocatalysis and hydrogen atom transfer (HAT) catalysis. With the easily prepared PMP-substituted amides as nitrogen-centered radical precursors, a wide range of structurally diverse amides can undergo predictable radical H/D exchange smoothly with inexpensive D2O as the sole deuterium source, giving rise to the distal tertiary, secondary and primary C(sp3)-H bonds selectively deuterated products in yields of up to 99% and excellent D-incorporations. In addition to precise monodeuteration, this strategy can also achieve multideuteration of the substrates contain more than one remote C(sp3)-H bond, which opens a method to address multi-functionalization of distal unactivated C(sp3)–H bonds.

Functionalized nanoparticles: Tailoring properties through surface energetics and coordination chemistry for advanced biomedical applications

“…The nitrogen-centered radical precursor PMP-substituted amides, which can be easily prepared, can be used to generate a wide range of structurally diverse amides that can undergo predictable radical H/D exchange smoothly by utilizing inexpensive D 2 O as the deuterium source. 219 This results in up to 99% yields of selected deuteration of primary, secondary, and tertiary C(sp 3 )-H bonds with excellent D incorporation. As well as precision monodeuteration, this strategy also achieves multideuteration of substrates containing multiple remote C(sp 3 )-H bonds, creating a method for multifunctionalization of unactivated distal C(sp 3 )-H bonds.…”

“…As well as precision monodeuteration, this strategy also achieves multideuteration of substrates containing multiple remote C(sp 3 )–H bonds, creating a method for multifunctionalization of unactivated distal C(sp 3 )–H bonds. 219…”

Assignment of the absolute configuration of molecules that are chiral by virtue of deuterium substitution using chiral tag molecular rotational resonance spectroscopy

“…Data are reported as s = singlet, d = doublet, t = triplet, q = quartet, p = pentet, m = multiplet, br = broad; coupling constant(s) in Hz; integration. 13 C NMR spectra were recorded on a Varian 76 MHz or 101 MHz spectrometer and are reported in ppm using deuterated solvent as an internal standard (CDCl 3 at 77.16 ppm). 2 H NMR spectra were recorded on a Varian 61-MHz spectrometer.…”

“…The absolute configuration assignment by chiral tag MRR measurements agreed with the expectation from the reaction mechanism. Second, the carbon framework geometry of the ethylbenzene-d1 complex with TFIP was determined using 13 C isotopomer spectra in natural abundance to confirm the cluster geometry used to assign the absolute configuration.…”

“…9 Recently, precision deuteration of small molecules has emerged at the forefront of new reaction discovery. [10][11][12][13][14][15][16][17][18][19][20][21][22] Precision deuteration techniques are used to control the exact placement and quantity of deuterium being installed into an organic molecule. This is challenging from both a synthetic and analytical perspective.…”