Dimethyldioxirane Oxidation of Enamines: First Spectral Evidence for Enamine Oxides by Stabilization through N‐Silylation

Abstract

Dimethyldioxirane ~~~~~The oxygen transfer to the enamines la-f by dimethyldioxcorresponding a-amino ketone 3c (hydride shift) and the amirane (DMD) in acetone solution leads to the a-amino epoxides ides 4d -f (alkyl shift). The a-[bis(trimethylsilyl)]amino epox2a-f. The stability of the a-amino epoxides 2a-f depends ides 2a, b represent the first observable enamine oxides and only on the type of substitution at the nitrogen atom. Thus, emphasize the value of stabilizing such labile epoxides while the epoxides 2a, b could be characterized spetroscopi-through disilylation of the enamine nitrogen atom. cally, the epoxidation of the enamines 1 c -f resulted in the In a recent publication [11 we have demonstrated that dimethyldioxirane reacts with enamines, which bear an a-hydrogen atom at the C -C double bond, to form amino-substituted 1,Cdioxanes. Unfortunately, the intermediary epoxides could not be detected spectroscopically even at low temperatures. The oxygen transfer by dimethyldioxirane occurred selectively at the double bond independent of the amino group, and the observed 1,4-dioxanes result from dimerization of the labile enamine oxides through the mesomerically stabilized 1,3-dipoles. Alternatively, analogous to epoxides which bear a + M substituent, a-amino epoxides should rearrange by an 1,2-hydride shift to the corresponding carbonyl products [*]. Indeed, such rearrangement is observed in the oxidation of enamines by tripletIn this case, attack of molecular oxygen at the C-C double bond forms, besides C-C cleavage products, also a-amino ketones, which have been postulated to be derived from their intermediary a-amino epoxides. Moreover, the formation of the indolinone in the deoxygenation of an indole dioxetane[61 can be interpreted in terms of the corresponding epoxide as intermediate. To date, no direct experimental evidence for u-amino epoxides has been published. Presumably, the destabilizing effect of the a-amino substituent is responsible and, thus, it is not surprising that recently an a-amino epoxide was reported"', in which the destabilizing effect of the electron-rich amino group was arrested through substitution by an electron-withdrawing group.Since silylation is known to diminish dramatically the basicity and nucleophilicity of amines [loal, it was of interest to assess whether such substitution is sufficient to observe N-silylated a-amino epoxides and, if successful, explore the chemical behavior of such hitherto unknown epoxides. Herein we demonstrate that the novel concept of stabilizing a-amino epoxides through disilylation of the enamine nitrogen atom is indeed an effective tool to observe labile enamine oxides. Furthermore, an effort was made to detect intact Nacylated indole epoxides. Results and DiscussionEpoxidation of the bis(trimethy1sily)-substituted enamines 1 a, b by dimethyldioxirane (DMD) afforded the corresponding a-amino epoxides 2a,b (Scheme l), as manifested by low-temperature NMR spectroscopy. The characteristic 'H chemical shifts at 6 = 2.74 for 2 a (R3 = H) and 2.80 ...

Incorporation of an indole-containing diarylbutylamine pharmacophore into furo[2,3-a]carbazole ring systems

“…[12][13][14][15] Instead of being converted to the stabilised 3-hydroxyindolium ion 13 (see Scheme 3 before), the protonated epoxide intermediate 19 is subject to an alternative ring cleavage process, which is assisted by the vicinal OH group. The resulting enol intermediate 20 is then converted into the corresponding lactam carbonyl product 21 or can be further oxidized to give the 3-OH product 22.…”

“…11 Initially, we assumed that hydroxylation at the 3-position of the indole moiety of 12 would trigger a similar rearrangement of the cation intermediate 13 to form the spiro product 14 (Scheme 3). For both compounds the presumed spiro structure, however, was refuted based on the observation of three carbonyl signals in each of the 13 C NMR spectra. This finding suggested the existence of the ring-opened indolone structures 16 and 17, which could be formed via an acidcatalysed retro-aldol reaction of b-hydroxy ketone 14 .…”

“…11 There is ample precedent for the oxidative cleavage of the indole ring system to form the corresponding keto amide, for example, tryptophan has been converted into a mixture of products which included N-formylkynurenine, 16 whereas tetrahydrocarbazole and the octahydroindolo[2,3-a]quinolizine ring system afforded the corresponding nine-membered ring keto-lactams. 17,18 The keto lactam structure of 29 is indicated by two relevant carbonyl signals in the IR (1666, 1596 cm K1 ) and 13 C NMR spectra (d 198.4,172.2). The correlations found in the HMBC spectrum confirm the proposed 8-membered keto lactam ring.…”

“…The residue was purified by column chromatography (silica gel, heptane/ethyl acetate, 3/22) to give 0.019 g of 26 and 0.068 g of 27. 13 4.6.2. 1,4,4-Trimethyl-3-phenyl-4,5-dihydro-1H,3H-benzo[b]azocine-2,6-dione (29).…”

Asymmetric Synthesis of Isoquinoline Derivatives from Amino Acids

“…The configuration of 9 was tentatively assigned on the basis of the NMR data, where the total number of resonance signals is half the number of H-atoms or C-atoms, respectively, and doublets are seen in the 1 H NMR spectra for the cyclobutane H-atoms. Scheme 4 Dimethyldioxirane [19,20] has become a reliable reagent in epoxidation of N-acylenamine moieties. [21][22][23][24] Its reaction with dihydroimidazo[2,1-a]isoquinolines 5 was highly stereoselective (dr Ͼ 95:5) affording excellent yields of the oxiranes 8a,b (see Scheme 2).…”