Metalation vs Nucleophilic Addition in the Reactions of N-Phenethylimides with Organolithium Reagents. Ready Access to Isoquinoline Derivatives via N-Acyliminium Ions and Parham-Type Cyclizations

Abstract

Sequential carbophilic addition of organolithium reagents and N-acyliminium ion cyclization of N-phenethylimides 1 affords the substituted isoquinolones 3 in high yields, with the possibility of varying the substituent at the C-1 position of the isoquinoline ring by changing the organolithium reagent. Ready access to the isoquinoline nucleus via Parham-type cyclization of imides 2 is also described. We have shown that iodinated imides 2 tolerate the metal-halogen exchange in the presence of the imide group, and the intramolecular cyclization of the so-obtained aromatic organometallic derivatives leads to the corresponding enamides 4. Both approaches have allowed the efficient preparation of various types of the isoquinoline class of alkaloids, just by changing the substitution pattern on the readily available starting imides. Thus, we have developed convenient alternative routes for the synthesis of benzo[a]quinolizidones and their 2-oxa analogs, isoindoloisoquinolones, dibenzo[a,h]quinolizidones, and thiazolo- and oxazolo[4,3-a]isoquinolones.

1-Oxa-3-azapentalen-2-ones as precursors of cis-2-amino alcohols: synthesis from acetylenic alcohols, carbon dioxide and amines via intramolecular amidoalkylation of oxazolidinones

“…We did not attempt to identify the absolute configuration of compounds 4a-e. From the theoretical 5,8 and x-ray analysis data on compound 5' (see below), we suggest that these compounds should have the stereochemical structure presented in Scheme 2. The reaction proceeds through a standard mechanism, i.e.…”

“…4,5 However, this method has disadvantages such as by-product formation, moderate yields and a complicated procedure. There is also a technique to afford 4-methoxyoxazolidin-2-ones, compounds related to ours, via Sn-and Se-organics which provide good yields and stereo-control.…”

Zinc‐Catalyzed Selective Reduction of Cyclic Imides with Hydrosilanes: Synthesis of ω‐Hydroxylactams

“…The combined organic phase was dried over Na 2 SO 4 . After removing the solvent under vacuum, the residue was purified by column chromatography (DCM/ CH 3 OH = 20/1) to give 3 as a yellow oil; yield: 1.0 g (86% 5, 160.4, 70.3, 55.2, 38.7, 37.4, 30.3, 30.0, 24.6. Experimental Procedure for the Synthesis and Characterization Data of Racemic Crispine A N- (3,succinimide (1p): [35] To a solution of succinimide (5.0 g, 50.5 mmol) in DMF, was added sodium hydride (1.5 g, 60.5 mmol) carefully. After stirring for 1 h at r. t., the reaction mixture was added with 4-(2-bromoethyl)-1,2-dimethoxybenzene (14.8 g, 60.5 mmol) and stirred at 40 8C for 3 h. After DMF was removed under vacuum, water (30 mL) was added to the residue, and the mixture was extracted with CH 2 Cl 2 (50 mL 3).…”

Synthetic Chemistry with N-Acyliminium Ions Derived from Piperazine-2,5-Diones and Related Compounds

“…These hemiaminals, that may be obtained by alternative procedures (see Section 5), often exist as mixtures of cyclic and linear tautomers 16 and usually give N-acyliminium species of type 8 under acid catalysis (Scheme 2) [47][48][49]. Some synthetic applications of this method are shown in Section 8.…”