Both E‐ and Z‐N′‐alkenyl urea derivatives of imidazolidinones may be formed selectively from enantiopure α‐amino acids. Generation of their enolate derivatives in the presence of K+ and [18]crown‐6 induces intramolecular migration of the alkenyl group from N′ to Cα with retention of double bond geometry. DFT calculations indicate a partially concerted substitution mechanism. Hydrolysis of the enantiopure products under acid conditions reveals quaternary α‐alkenyl amino acids with stereodivergent control of both absolute configuration and double bond geometry.
N-Chloroformyl imidazolidinone derivatives of enantiopure amino acids may be deprotonated to give remarkably well-behaved enolates with both nucleophilic and electrophilic character. The enolates undergo diastereoselective C-alkylation with benzylic halides. A Bischler-Napieralski-like cyclization reaction onto the chloroformyl group, induced by either nucleophilic (KI, 2,6-lutidine) or Lewis acid (AlCl3) catalysis, gives substituted 3,4-dihydroisoquinolone derivatives in enantioenriched form. The reaction sequence constitutes a formal [3+3] route to the 6-membered lactam ring of the dihydroisoquinolones.
Steroids are highly prevalent structures in small‐molecule therapeutics, with the level of oxidation being key to their biological activity and physicochemical properties. These C(sp3)‐rich tetracycles contain many stereocentres, which are important for creating specific vectors and protein binding orientations. Therefore, the ability to hydroxylate steroids with a high degree of regio‐, chemo‐ and stereoselectivity is essential for researchers working in this field. This review will cover three main methods for the hydroxylation of steroidal C(sp3)−H bonds: biocatalysis, metal‐catalysed C−H hydroxylation and organic oxidants, such as dioxiranes and oxaziridines.
The first total synthesis of (+)-lophirone H (1) and its pentamethyl ether 29, featuring an oxonium-Prins cyclization/benzylic cation trapping reaction, is described.
N-Acyl imidazolidinones, which are key intermediates in the stereoselective synthesis of amino acids by 'self-regeneration of stereochemistry' methods, are classically made by only moderately diastereoselective methods. We now report that cyclisation of pivaldimino-amides with phosgene in the presence of pyridine may be made fully diastereoselective for the trans-N-chloroformylimidazolidinones, and we detail the conformational features of the products. We show that despite the presence of the electrophilic carbamoyl chloride function, the products show remarkable stability, and may be deprotonated to form enolates with useful reactivity for the synthesis of amino acid derivatives. toluene -60 40 95:5 2 toluene -100 20 57:43 3 CH2Cl2 -rt 48 96:4 4 THF -rt 70 91:9
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