An improved synthesis of N-aryl and N-heteroaryl substituted homopiperazines—from conventional thermal conditions to scaling-up using microwave heating

Palladium-catalyzed coupling of functionalized primary and secondary amines with aryl and heteroaryl halides: two ligands suffice in most cases

“…71 There have only been a limited number of studies of the arylation of piperazines with aryl chlorides and these have typically used relatively large amounts of catalyst (>1 mol% Pd) and have employed activated substrates as coupling partners. 72, 73 By using a RuPhos-based catalyst system, we were able to arylate Boc-protected piperazine with a range of aryl chlorides in good yields (Table 12, entries 12a , 12b and 12e – 12g ). Under the same conditions Cbz-protected piperazine gave lower yields for these reactions.…”

Dialkylbiaryl phosphines in Pd-catalyzed amination: a user's guide

“…137 Studies of Pd-catalyzed amination with dialkylbiaryl phosphine ligands in this medium or mixtures have shown it to possess certain advantages over toluene including reduced foaming in biphasic reactions 135 and better heating under microwave irradiation. 138, 139 (For more specific recommendations of the choice of solvent, see Figures 6 – 8)…”

Structure–activity studies in the development of a hydrazone based inhibitor of adipose-triglyceride lipase (ATGL)

“…The synthesis of the homopiperazine compound 3j started with a Pd(0)-catalyzed Buchwald–Hartwig-arylation of Boc-protected homopiperazine ( 4 ) with bromobenzene using Pd(OAc) 2 /X-Phos with NaO t Bu as base, 16 which after deprotection with HCl delivered the homopiperazine as its hydrochloride salt 5 in moderate 29% yield ( Scheme 4 ). Nitrosylation of 5 and reduction with LiAlH 4 14 produced hydrazine 6 in 24% yield, which could then smoothly react with 2,4-dihydroxybenzaldehyde to the desired condensation product 3j in 97% yield.…”