Synthesis of Cyclic Acylated Enamino Esters from Enol Lactones, 4-Keto amides, and 5-Hydroxy Lactams

Abstract

Enol lactones react with an amine to give either a keto amide or a hydroxy lactam under mild conditions. Subsequent dehydration with p-toluenesulfonic acid P"SA) gives a cyclic acylated enamino ester in good yield (Tables 1 and 2, Schemes 2 and 4). The key prostaglandin analog precursor 18 and the gly-gly dipeptide analogs 26a and 26b were prepared using the reported conditions. Acetylation of the chloro hydroxy lactam 31, prepared from the chloro enol lactones 29, followed by elimination of acetic acid gave the chloro acylated enamino esters 28.

Stereoselective Chlorination and Bromination of Enamides and Enamines via an Electrostatic Attraction Effect Using (1,1-Diacetoxyiodo)benzene and a Halide Source

“…further optimized by varying the amounts of PIDA between 0.5-1.3 equiv and NiCl 2 ·6H 2 O between 1.0-2.5 equiv (Table 1, entries [14][15][16][17][18][19][20]. The optimized reaction conditions were 1.0 equiv of enamine, 1.2 equiv of PIDA and 2.0 equiv of NiCl 2 ·6H 2 O in acetonitrile which produce a yield of 64% (Table 1, entry 19).…”

“…16 (11) To a solution of 5m (0.5 mmol, 142 mg) in HOAc (2 mL) was added NaBH 4 (1.5 mmol, 57 mg) portion wisely at 15 o C. Then the mixture was stirred at room temperature for 2 h (monitored by TLC). After completion, the reaction mixture was quenched with ice water (5 mL), neutralized with saturated NaHCO 3 (aq) and extracted with DCM (2×5 mL 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60…”

Comparison of amine-induced cyclization of 6-chloro-1-hexynylphosphonate and isobutyl 7-chlorohept-2-ynoate

“…[3][4][5][6][7][8] Various methods are known for preparing cyclic b-enamino esters, such as from unsaturated esters possessing a pendent cyano moiety and B-Ar-9-BBNs in the presence of a rhodium(I) catalyst, 9 by iodine-promoted cyclization of enamino esters, 10 from enol lactones, 4-keto amides, and 5-hydroxy lactams, 11 Knovenagel reactions on lactam-derived acetals, 12,13 imino ethers, 14,15 iminium chloride, 16 or (alkylthio) alkylidenium salts followed by decarboxylation. 17,18 Other routes include Eschenmoser's sulfide-contraction procedure via thiolactams 19 and Wittig reaction of N-sulfonyl lactams, 20 application of the intramolecular aza-Wittig reaction, 21 from the formal ring transformation reaction of lactones, 22,23 by reaction of Meldrum's acid with chloroimidates, 24 from thiolactams with subsequent conversion to pyrroles, 25 from u-azido-b-keto esters, 26 from N-alkyl lactams.…”

Synthesis of Lactam-Based Peptidomimetics from β-Keto Esters and β-Keto Amides

“…The cis peptide bond mimetics were conveniently prepared from readily available amino acids−aspartic acid for the side chain to side chain cyclic mimetics (see 10a and Scheme 1) and, in the case of α-H to side chain cyclization, by employing Seebach oxazolidinone chemistry (see 10b and Scheme 3). Some related synthetic studies have been published by us and others . Initial work on derivatizing these peptidomimetics (see Scheme 4) is also presented.…”