Stereoselective Synthesis of Enamides by a Peterson Reaction Manifold

Abstract

Gallenkamp melting point apparatus (uncorrected). Elemental analyses: Kolbe, Mülheim/Ruhr. All commercially available compounds (Lancaster, Aldrich) were used as received.

A concise, total synthesis of the TMC-95A/B proteasome inhibitors

“…45 and references therein) that utilizes hydroxyalkyl silanes for the preparation of enamides was evaluated. The requisite strong base used in this Peterson olefination protocol was anticipated to be too harsh for the sensitive functionality present in the TMC-95 macrocyclic core.…”

Room Temperature Copper(II)-Catalyzed Oxidative Cyclization of Enamides to 2,5-Disubstituted Oxazoles via Vinylic C–H Functionalization

“…: 178-179 °C). 35 1 H NMR (400 MHz, DMSO- d 6 ) δ: 10.97 (d, J = 9.6 Hz, 1H), 8.81 (s, 1H), 8.43-8.39 (ovrlp, 2H), 7.82 (t, J = 8.0 Hz, 1H), 7.65 (dd, J = 14.4 Hz, 9.6 Hz, 1H), 7.41 (d, J = 8.0 Hz, 2H), 7.31 (t, J = 7.6 Hz, 2H), 7.18 (t, J = 7.6 Hz, 1H), 6.51 (d, J = 14.8 Hz, 1H). 13 C NMR (100 MHz, DMSO- d 6 ) δ: 161.9, 147.8, 136.3, 134.7, 134.1, 130.3, 128.8, 126.5, 126.4, 125.4 123.8, 122.3, 114.0.…”

“…: 148-150 °C). 35 1 H NMR (400 MHz, DMSO- d 6 ) δ: 10.04 (d, J = 10.4 Hz, 1H), 7.41 (dd, J = 14.8 Hz, 10.4 Hz, 1H), 7.31 (d, J = 7.2 Hz, 2H), 7.26 (t, J = 7.2 Hz, 2H), 7.12 (t, J = 7.2 Hz, 1H), 6.15 (d, J = 14.8 Hz, 1H), 2.23 (m, 1H), 1.77-1.72 (ovrlp, 4H), 1.63 (d, J = 8.8 Hz, 1H), 1.43-1.35 (m, 2H), 1.29-1.12 (ovrlp, 3H). 13 C NMR (100 MHz, DMSO- d 6 ) δ: 173.3, 136.8, 128.6, 125.9, 125.0, 123.9, 111.0, 43.9, 29.0, 25.4, 15.2.…”

E- and Z-Stereoselectivity in the preparation of enamides from glycidyl sulfonamides and carbamates

“…TS-B) between the epoxide methylene and the sulfonamide unit. 1c-e (entries [3][4][5] illustrates that formation of the Z-isomer is proportional to the steric bulk of the carbamate N-substituent. That the effect is steric, and not electronic, in origin was confirmed by comparing phenyl case 1d with that of the p-methoxy analogue 1f; exactly the same E : Z ratio was obtained in each case (entries 4 and 6).…”

“…In this regard, new methods for access to this functional unit have been introduced lately based on, inter alia, cross coupling processes; 2 hydroamination of alkynes; 3 and the Peterson reaction. 4 In relation to this and based on our ongoing drug discovery programmes, we wished to prepare a range of enamines of general structure 2, possessing different pendant nitrogen groups. We envisaged that a base-induced epoxide-allylic alcohol rearrangement 5 of the appropriately N-functionalised glycidyl amine 1 would represent an extremely concise entry into this series of compounds from simple starting materials (Scheme 1).…”