Heck Reactions of 6‐ and 2‐Halopurines

Abstract

Under the conditions of the Heck reaction, 9-benzyl-6-iodopurine affords mainly the corresponding 6,6Ј-dimer, the Heck product being formed only in low yield (Յ12 %). With 7-benzyl-6-iodopurine the dimerization is suppressed and the Heck product is obtained in 32-91 % yield. 9-Substituted 6-chloro-2-iodopurines react smoothly, giving 2-alkenyl-6- IntroductionAmong a vast number of biologically active purine derivatives, alkenylpurines play an important role.[1] 6-Alkenylpurines, for example, are associated with antimycobacterial, [2] cytotoxic [3] and cytokinin [4] activity and with inhibition of 15-lipoxygenase.[5] Some 6-alkenylpurines have been designed as covalent analogues of DNA base pairs [6] or novel cross-linking agents, [7] and have also been used for the synthesis of fluorescent nucleoside analogues.[8] Moreover, 2-alkenyladenosine derivatives have been reported to function as inhibitors of adenosine receptors. [9] Several methodologies have been used for the preparation of alkenylpurines. 6-Styrylpurine was first prepared by condensation of 6-methylpurine with benzaldehyde in the presence of HCl.[10] Another, more general, synthetic approach to 6-alkenylpurines, is based on Wittig reactions between 9-protected (purin-6-yl)methylene-triphenyl-λ 5 -phosphanes (Wittig reagents) and aldehydes or ketones.[11]Cyclic 6-alkenyloxypurines have been prepared by intramolecular cyclization of 6-(hydroxyalkyn-1-yl)purines, [12] while 6-enaminopurines are accessible by addition of amines to 6-alkynylpurines.[13] Partial hydrogenation of 2-alkynyl- [14] and 8-alkynylpurines [15] to give the corresponding alkenes has also been reported. Hydrogenation of 6-alkynylpurines to 6-alkenylpurines was reported to proceed satisfactorily only with 9-unprotected bases, with overhydrogenation taking place otherwise.[4a] However, the most versatile methodology for the preparation of alkenylpurines -nowadays used almost without exception -is based on transitionmetal-catalyzed cross-coupling reactions.[16] Alkenylpurines [a]

Aqueous Heck Cross-Coupling Preparation of Acrylate-Modified Nucleotides and Nucleoside Triphosphates for Polymerase Synthesis of Acrylate-Labeled DNA

“…In nucleoside chemistry it has been often used for modifications of pyrimidines 19 but is difficult for modifications of purines. 20 Only very recently, Shaughnessy reported 21 the first aqueousphase Heck reactions for modification of 5-iodo-2′-deoxyuridine. Here we report on the development of the aqueus Heck coupling for modifications of pyridimine and 7-deazapurine nucleoside mono-and triphosphates and the use of acrylatemodified dNTPs for enzymatic synthesis of modified DNA.…”

“…The Heck reaction is another very useful type of cross-coupling extensively applied in attachment of alkenyl groups . In nucleoside chemistry it has been often used for modifications of pyrimidines but is difficult for modifications of purines . Only very recently, Shaughnessy reported the first aqueous-phase Heck reactions for modification of 5-iodo-2′-deoxyuridine.…”

Vinyl Esters and Vinyl Sulfonates as Green Alternatives to Vinyl Bromide for the Synthesis of Monosubstituted Alkenes via Transition-Metal-Catalyzed Reactions

“…Surprisingly, styrene provided substituted diene in a low isolated yield. This was an unexpected finding because styrene r well under Heck reaction conditions with heteroaryl [115], aryl [116], and vin Significantly better tolerance of the functional groups is achieved during the crosscoupling reaction of vinyl nonaflate with the organocopper reagent when catalyzed by an iron complex (Scheme 8) [110]. For the preparation of functionalized Grignard reagents, it is necessary to use the approach developed by Professor Knochel [111][112][113][114].…”

Pd-catalyzed allylic substitution of purin-8-yl(allyl) acetate: Route to (E)-alkenylpurines

“…The solvents were dried and degassed by standard procedures, silica gel (Merck, Silica Gel 60, 40-63 µm) was used for column chromatography. 9-Isopropyl-6-methoxy-9H-purine 32 (1a), 9-isopropyl-6-chloro-9H-purine 33 (1b), 6-chloro-9-isopropyl-2-(2-phenylethenyl)-9H-purine 30 (6) and butyl 3-(6-chloro-9-isopropylpurine-2-yl)acrylate 30 (8) were prepared by the reported procedures, other compounds were purchased.…”