Oxidative Amination of Cuprated Pyrimidine and Purine Derivatives

Abstract

Using regioselective cuprations (via magnesiations), various primary, secondary and tertiary aminated pyrimidine and purine derivatives were prepared by the oxidative coupling of lithium amidocuprates using chloranil. DNA and RNA units such as aminated uracil or thymine, and adenine, as well as a CDK inhibitor, purvalanol A, were all obtained under mild conditions and satisfactory yields.

Deprotonative Metalation of Aromatic Compounds by Using an Amino‐Based Lithium Cuprate

“…61.9–63.2 °C); 1 H NMR (CDCl 3 , 300 MHz): δ =2.01 (s, 3 H), 3.92 (s, 3 H), 3.95 (s, 3 H), 7.94 ppm (s, 1 H); 13 C NMR (CDCl 3 , 75 MHz): δ =12.0 (CH 3 ), 53.9 (CH 3 ), 54.7 (CH 3 ), 111.2 (C), 156.9 (CH), 164.2 (C), 169.7 ppm (C). These data are consistent with those reported in the literature 43…”

“…2,4‐Dimethoxy‐5‐methylpyrimidine (13 a) : Eluent: heptane/EtOAc (80:20); white powder; m.p. 64–65 °C (lit 43. 61.9–63.2 °C); 1 H NMR (CDCl 3 , 300 MHz): δ =2.01 (s, 3 H), 3.92 (s, 3 H), 3.95 (s, 3 H), 7.94 ppm (s, 1 H); 13 C NMR (CDCl 3 , 75 MHz): δ =12.0 (CH 3 ), 53.9 (CH 3 ), 54.7 (CH 3 ), 111.2 (C), 156.9 (CH), 164.2 (C), 169.7 ppm (C).…”

Efficient Synthesis of Deazaguanosine‐Derived tRNA Nucleosides PreQ0, PreQ1, and Archaeosine Using the Turbo‐Grignard Method

“…This is significantly shorter and higher yielding than previous routes. [22,23] For the synthesis of C7-substituted deazaguanosine derivatives such as PreQ 0 and archaeosine, we expanded the scope of the novel and versatile reagent iPrMgCl·LiCl (Turbo-Grignard) [24] from uracil [25,26] and adenosines [26,27] to a further class of nucleosides: the deazaguanosines (Scheme 2). Using the Turbo-Grignard enables mild conditions at low temperature compared to a reaction using CuCN.…”

Functionalization of heterocyclic compounds using polyfunctional magnesium and zinc reagents

“…In the presence of chloranil amidocuprate 87 undergoes an oxidative coupling providing the adenine derivative 88 in 71% yield. A treatment with D-valinol ( 89 ) affords the desired CDK inhibitor, purvalanol A ( 84 ) in 65% yield (Scheme 15) [44]. …”