Synthesis of Oxazinanones: Intramolecular Cyclization of Amino Acid-Derived Diazoketones via Silica-Supported HClO4 Catalysis

Abstract

A Brønsted acid catalyzed intramolecular cyclization of N-Cbz-protected diazoketones, derived from α-amino acids, is described. The reaction proceeds under metal-free conditions and is promoted by ecofriendly silica-supported HClO4 as the catalyst and methanol as the solvent. This transformation enables the short synthesis of various 1,3-oxazinane-2,5-diones under mild reaction conditions and in good yields (up to 90%). The set-up is very simple; by just mixing all reagents together with no work-up necessary before purification, this protocol takes a greener approach.

Practical Synthetic Method for Amino Acid-Derived Diazoketones Shelf-Stable Reagents for Organic Synthesis

“…1 H NMR (400 MHz, chloroform-d): δ 5.38 (s, 1H), 5.30 (d, J = 9.4 Hz, 1H), 3.94 (d, J = 9.4 Hz, 1H), 1.44 (s, 9H), 1.01 (s, 9H). 13 (16); 96 (20); 70 (23); 59 (10); 57 (75); 56 (24); 55 (12); 44 (11); 43 (10); 41 (57); 39 (22) (S)-tert-Butyl (4-Diazo-3-oxo-1-phenylbutan-2-yl)carbamate (2d). Yellow crystalline powder, yield = 85% (184 g).…”

“…int. ): 313 (1); 211 (4); 210 (4); 209 (5); 208 (4); 194 (5); 192 (5); 186 (3); 168 (3); 166 (9); 164 (4); 151 (3); 150 (4); 149 (2); 148 (4); 130 (38); 123 (14); 121 (11); 116 (11); 98 (33); 95 (16); 93 (19); 86 (18); 70 (12); 59 (38); 57 (90); 56 (63); 55 (53); 53 (10); 51 (14); 50 (18); 44 (43); 43 (18); 42 (32); 41 (98); 39 (100); 38 (18) (22); 130 (5); 123 (8); 100 (13); 88 (17); 70 (14); 69 (10); 59 (32); 58 (20); 57 (100); 56 (16) tert-Butyl (3-Bromo-2-oxopropyl)(methyl)carbamate (3g), Orange Oil. Yield = 89% (181 g).…”

“…Therefore, these reagents could be considered as part of a chiral pool. , Recently, several preparative methods for synthesizing MedChem-relevant compounds based on AADDK reagents have been developed . In particular, preparations of chiral β-amino acids, azetidin-3-ones, , lactams, , oxazinones, dihydropyridones, N -protected α-aminoglyoxals, and hetarylaminomethyl derivatives are worth mentioning (Figure A). Despite the existing alternative approaches to the preparation of AADDKs that emerged in the literature, ,, interaction of activated derivatives of N -protected amino acids with diazomethane still remains the most efficient method .…”

Practical synthetic method for amino acids derived diazo-ketones – shelf-stable reagents for organic synthesis.

“…3,4 Recently, a number of preparative methods for the synthesis of Med-Chem-relevant compounds based on AADDK reagents have been developed. 5 In particular, preparations of chiral βamino acids, 6 azetidin-3-ones, 7,8 lactams, 9,10 oxazinones, 11 dihydropyridones, 12 N-protected α-aminoglyoxals and hetarylaminomethyl derivatives 13 are worth mentioning (Figure 1, A). Despite the existing alternative approaches to preparation of AADDKs emerged in the literature, 1,2,13 interaction of activated derivatives of N-protected amino acids with diazomethane still remains the most efficient method.…”