Z-Selective hydroamidation of terminal alkynes with secondary amides and imides catalyzed by a Ru/Yb-system

Computational study of the mechanism and selectivity of ruthenium-catalyzed hydroamidations of terminal alkynes

“…However, under experimental conditions, no Markovnikov product was observed. 33 , 34 Gratifyingly, our calculated results reveal that the formation of the Markovnikov product involves very high transition barriers for both the nucleophilic transfer 5 → 6m (Δ ‡ G SDL = 25.8 kcal mol –1 ) and subsequent reductive elimination steps from 6m via the transition state [7m–1] ‡ (Δ ‡ G SDL = 37.1 kcal mol –1 ; Fig. S13 † ).…”

“…S14 † ) requires substantially higher energy values, precluding the formation of the Z -enamide product in high yields, as substantiated by the experimental findings. 34 The calculated route for Z -enamide formation overrules any possibility of H 2 migrating to the oxygen atom of 2-pyrrolidinyl unit. Apart from the fact that they are well separated (H 2 –O = 2.641 Å in 8a ), the same H 2 is necessary to accomplish a successful reductive elimination step (Fig.…”

“…With bis(dicyclohexylphosphino)methane (dcypm), the stereoselectivity is inverted, and the Z -enamides are preferentially formed ( Scheme 2 ). 34 …”

Concise Total Synthesis of Hydrazidomycin A, a Rare Hydrazide Metabolite of Streptomyces atratus

“…However, it has been reported that the palladium-catalyzed cross-coupling of tert-butyl carbazate with vinyl halides in the presence of cesium carbonate in DMF takes place only at the more acidic NHBoc proton (Boc = tert-butoxycarbonyl). [12][13][14][15] We reasoned that a hydrazide-derived phthalimide could be used for the ruthenium-catalyzed hydroamidation of tetradec-1-yne to yield the corresponding alkenylated Z-configured product. Thus, we devised the assembly of the N-alkenylhydrazine by the Pd-catalyzed cross-coupling of tert-butyl carbazate with (Z)-tetradecenyl bromide, acylation of the NH 2 function with methoxy acetic acid, followed by deprotection and acylation with decanoic acid (Scheme 1).…”

“…[10] We reasoned that this protocol would be a suitable starting point for the total synthesis of hydrazidomycin A (1), as it would not require additional protection of the NH 2 group and further deprotection steps would be avoided. [15] First, the free NH 2 function of 6 was protected as phthalimide by heating it at reflux with phthalic anhydride in toluene for several hours. However, this route was hampered because of unwanted side reactions, and cleavage of the Boc group resulted in an unstable enehydrazine.…”