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Synthesis of enamines, enamides and related compounds
A general atom economic method for the isomerization of a broad range of N-allyl amides enables the synthesis of Z-di-, tri-, and tetrasubstituted enamides with exceptional geometric selectivity. Applications of these geometrically defined enamides toward the synthesis of cis vicinal amino alcohols and tetrasubstituted α-borylamido complexes are discussed.
B. M. Trost, J. J. Cregg, N. Quach, J. Am. Chem. Soc., 2017, 139, 5133-5139.
A facile and practical method for the synthesis of N-acetyl α-arylenamides from the corresponding ketoximes with ferrous acetate as the reducing reagent offers mild reaction conditions, simple purification procedures, and high yields for a variety of N-acetyl enamides.
W. Tang, A. Capacci, M. Sarvestani, X. Wei, N. K. Yee, C. H. Senanayake, J. Org. Chem., 2009, 74, 9528-9530.
A new synthesis of enamides from ketones involves a phosphine-mediated reductive acylation of oximes. The resulting enamides are isolated in good yields and excellent purity.
H. Zhao, C. P. Vandenbossche, S. G. Koenig, S. P. Singh, R. P. Bakale, Org. Lett., 2008, 10, 505-507.
A transition-metal-free catalytic hydrosilylation based on t-BuOK (5 mol %) and (MeO)3SiH or (EtO)3SiH allows the reduction of tertiary amides to their corresponding enamines with high selectivity in very good yields.
A. Volkov, F. Tinnis, H. Adolfsson, Org. Lett., 2014, 16, 680-683.
Among the reported examples of new reactivity of the hypervalent iodine reagent DMP (Dess-Martin periodinane) are the one-step oxidation of secondary amides to imides and N-acyl vinylogous carbamates or ureas and the direct oxidation of benzylic and related primary amines to the corresponding nitriles.
K. C. Nicolaou, C. J. N. Mathison, Angew. Chem. Int. Ed., 2005, 44, 5992-5997.
Slow addition of 3 - 5 eq. of α-bromo esters to aliphatic or aromatic nitriles in the presence of activated zinc in refluxing tetrahydrofuran yielded the corresponding enamino esters or, after acid hydrolysis, β-keto esters. Slow addition and use of tetrahydrofuran as solvent substantially improved the yield of the Blaise reaction and also enabled the conversion of bromoacetates to give α-unsubtituted products.
S. M. Hannick, Y. Kishi, J. Org. Chem., 1983, 48, 3833-3835.
β-Amino-α,β-unsaturated esters are produced by a sonochemical Blaise reaction of nitriles, zinc powder, zinc oxide and ethyl bromoacetate in THF in a commercial ultrasonic cleaning bath.
A. S.-Y. Lee, R.-Y. Cheng, Tetrahedron Lett., 1997, 38, 443-446.
Reaction of aryl nitriles with potassium ethyl malonate in the presence of zinc chloride and a catalytic amount of Hünig's base provided β-amino acrylates in moderate to good yield. Compared to the classical Blaise reaction, this reaction is safer, devoid of lachrymatory reagent, and is possible with less zinc chloride.
J. H. Lee, B. S. Choi, J. H. Chang, H. B. Lee, J.-Y. Yoon, J. Lee, H. Shin, J. Org. Chem., 2007, 72, 10261-10263.
A BF3ˇOEt2-catalyzed cyclization of 1-iodoalkyne and α-keto acid followed by an amine-mediated ring-opening enable a metal-free direct synthesis of β-ketoenamines in one pot. The reaction tolerates transition metal-sensitive functional groups.
X. Zeng, C. Liu, W. Yang, Y. Weng, X. Wang, Y. Hu, J. Org. Chem., 2019, 84, 3656-3661.
The in situ generated Blaise reaction intermediate, a zinc bromide complex of β-enaminoester, reacts with various alkynes under mild conditions to afford α-vinylated β-enaminoesters in good to excellent yields.
Y. S. Chun, Y. O. Ko, H. Shin, S.-g. Lee, Org. Lett., 2009, 11, 3414-3417.
α,β-Dehydroamino acid derivatives were synthesized in good yields from α-bromoketones or α-bromoesters and hydroxamates via a sequential procedure involving displacement of bromide by hydroxamate anion, followed by a base-induced elimination-isomerization reaction.
Y. Sun, X. Wang, X. Zheng, K. Zhao, Synlett, 2008, 861-866.
A NaOH catalyzed rearrangement of propargylic hydroxylamines allows a highly stereoselective access to Cbz-protected β-enaminones. A subsequent synthesis of pyrimidines shows the synthetic potential of these β-enaminones.
E. Gayon, M. Szymczyk, H. Gérard, E. Vrancken, J.-M. Campagne, J. Org. Chem., 2012, 77, 9205-9220.
An iodine-mediated oxidative dehydrogenation of β-acylamino ketones gives β-ketoenamides in moderate yields. Only Z-isomers are produced due to the intramolecular H-bonding interaction in the HI-elimination step.
H.-H. Chang, F. Hu, W.-C. Gao, T. Liu, X. Li, W.-L. Wei, Y. Qiao, Synlett, 2016, 27, 1592-1596.