New Pyrimidylboronic Acids and Functionalized Heteroarylpyrimidines by Suzuki Cross‐Coupling Reactions

Abstract

We report the synthesis of 2-chloro-5-pyrimidylboronic acid (6) and 2-amino-5-pyrimidylboronic acid (8) by lithium-halogen exchange followed by reaction with triisopropylborate. Their reactivity with heteroaryl halides in Suzuki-Miyaura cross-coupling reactions has been evaluated. New highly functionalized 5-heteroarylpyrimidine derivatives 24-33

Scope of the Palladium-Catalyzed Aryl Borylation Utilizing Bis-Boronic Acid

“…This finding does not appear to be unique to this method. Through a thorough literature search of heteroaryl boronates synthesized from B 2 Pin 2 or H-BPin, two trends can be found: either the method reported is purely for one functionalized heteroaryl, − or only a few examples were synthesized under reaction conditions considered under a “general” methods procedure. ,,,,− Also noteworthy is that the heteroaryls examined in this search are among just a handful of heteroaryl borylated products that can be found in the literature, and there is no publication dedicated solely to the Miyaura borylation of heteroaryls using B 2 Pin 2 . Our findings, coupled with the literature results, provide evidence that a general method for the borylation of hetereoaryls remains elusive, and that each substrate or general class of substrates may need to be treated on a case-by-case basis.…”

A mechanistic proposal for the protodeboronation of neat boronic acids: boronic acid mediated reaction in the solid state

“…3(B), identifies commonly occurring supramolecular structural features. [35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54] Such compounds were prepared under similar conditions and so their yields can reasonably be compared. Hall stated that boronic acids regularly form these interactions in the solid state.…”

“…The yield of the compound leading to this crystal structure was compared to that of all other boronic acids described in the same paper. [35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54] Such compounds were prepared under similar conditions and so their yields can reasonably be compared. It was found (see ESI †) that compounds which form crystal structures that satisfy the geometric requirements highlighted in Fig.…”

Transition metal-catalyzed functionalization of pyrazines

“…The overall yield of cross-coupled product was improved by the subsequent addition of a second equivalent of boronic acid to the reaction mixture after 24 h reflux. 27 Attempting the synthesis of the dragmacidin D scaffold, another example of the Suzuki coupling of halogenated pyrazine with hetarylboronic acids has been reported. Reacting 2,5dibromo-3-methoxypyrazine with tosyl-protected indolylboronic acids solely yielded the 2-arylated product (Scheme 12).…”