Reactions of 4‐Oxoalkanoic Acids, 4. Synthesis of (±)‐6‐Alkyl‐5‐oxa‐1‐azabicyclo[4.3.0]nonan‐9‐ones, (±)‐5‐Alkyl‐4‐oxa‐1‐azabicyclo[3.3.0]octan‐8‐ones, and Substituted 1,6‐Dioxa‐3,8‐diazacyclodecanes by Reaction of Ethyl 4‐Oxoalkanoates with 3‐Aminopropanol and 2‐Aminoethanol

Abstract

Ethyl 4-oxoalkanoates 1 react at ambient temperature in dry methanol in the presence of molecular sieve 3 A in almost quantitative yield with 3-aminopropanol and 2-aminoethanol to form the bicyclic lactams rac-2 and rac-3, respectively. Owing to their carbon skeleton, ethyl 4-oxoalkanoates 1 are interesting starting materials for the synthesis of 1,4-diketones and, thus, of furans2x3), pyrroles4), and 2,3-dialkylcyclopent-2-en-1-ones'). Formally, the conversion of 1 into 1,4-diketones requires the nucleophilic substitution of the alkoxy group of 1 by an alkyl group. This can be achieved by the reaction with suitably metalated alkanes provided the +ox0 group is protected and the ester group is modified in such a way that the metalated alkane adds to the ester carbonyl group only once. Several examples are known for this strategy6). The bicyclic lactams 2 and 3, which have not been investigated so far, should be available by condensation of ethyl 4-oxoalkanoates with 3-aminopropanol and 2-aminoethanol, respectively. They were expected to correspond to the above-mentioned requirements.Indeed, by standing at ambient temperature for four days, the reaction of ethyl 4-oxoalkanoates l a -e with 3-aminopropanol in dry methanol affords the expected bicyclic lactams ruc-2a-e in yields of 82-97% as colorless liquids. The structure of these compounds has been confirmed by their I3C-NMR spectra exhibiting singlets for the carbonyl group (C-9) at 6 = 173.2-173.9 and for C-6 at 6 = 89.8-92.5. The triplets at 6 = 29.0-29.2 and 30.5-33.6 can be attributed to the pyrrolidinone ring (C-7, C-8) and the triplets at 6 = 60.7 -61.0, 24.7 -24.9, and 35.2 -35.4 to the six-membered ring (C-4, C-3, and C-2, respectively). A corresponding number of additional signals is caused by the carbon atoms of the different alkyl groups.The analogous reaction of the ethyl 4-oxoalkanoates l a -e with 2-aminoethanol in dry methanol at room tem- perature gives rise to the formation of the bicyclic lactams rac3a -e in nearly quantitative yields. The structure of these compounds has been confirmed by their IR, mass, and 13C-NMR spectra. The latter showed singlets for the carbony1 group (C-8) at 6 = 178.6-179.0 and for C-5 at

Does gastric dilation predict adverse perinatal or surgical outcome in fetuses with gastroschisis?

“…The following observations are also worthy of note. It has been reported in the literature19 that the product of the reaction shown in entry 1, readily opens and reacts intermolecularly to form the centrosymmetric dimer under aqueous acidic conditions (Scheme ). We found this to be true (indeed, it also applied to other more heavily substituted products, although to a lesser extent), but we also found that this undesired dimerization could be avoided by moderating the amount of TFA employed in the cyclization step, and, in the most vulnerable cases, by neutralizing this TFA with Et 3 N prior to concentration of the sample.…”

Single and Double Diastereoselection in Azomethine Ylide Cycloaddition Reactions with Unsaturated Chiral Bicyclic Lactams

“…The filtrate was concentrated under reduced pressure, and the resulting liquid was vacuum distilled (71−73 °C, 1 mmHg) to afford 3.86 g (40%) of (±)- 1j ‘ as clear, colorless liquid. For the known , racemic saturated bicyclic lactam ((±)- 1j ‘) (7a RS )-5-oxo-7a-methyl-2,3,5,6,7,7a-hexahydropyrrolo[2,1- b ]oxazole: R f 0.14 (1:1 EtOAc/hexanes); bp 71−73 °C, 1 torr; 1 H NMR (300 MHz, CDCl 3 ) δ 3.94 (m, 3H), 3.13 (m, 1H), 2.68 (m, 1H), 2.45 (m, 1H), 2.16 (m, 2H), 1.40 (s, 3H).…”

A Versatile Synthesis of Meyers’ Bicyclic Lactams from Furans: Singlet‐Oxygen‐Initiated Reaction Cascade

“…The following observations are also worthy of note. It has been reported in the literature [19] that the product of the reaction shown in Entry 1, readily opens and reacts intermolecularly to form the centrosymmetric dimer under aqueous acidic conditions (Scheme 3). We found this to be true (indeed, it also applied to other more heavily substituted products, although to a lesser extent), but we also found that this undesired dimerisation could be avoided by moderating the amount of TFA employed in the cyclisation step, and, in the most vulnerable cases by neutralising this TFA with NEt 3 prior to concentration of the sample.…”