A Diversity-Oriented Approach to Spirocyclic and Fused Hydantoins via Olefin Metathesis

Abstract

An efficient and general method is reported to prepare a diverse series of 5,5-spirocyclic and 1,5-, 4,5-, and 3,4-fused bicyclic imidazolidinone derivatives based on selective alkylation and ring closing metathesis (RCM) by exploiting the four possible points of diversity in the hydantoin ring. Hydantoins containing trienes and tetraenes undergo selective RCM and cross metathesis to afford functionalized spirohydantoins. A tandem metathesis sequence involving ring closing-ring opening-ring closing and cross metathesis (RC-RO-RC-CM) occurred with a hydantoin triene to give a bicyclic hydantoin dimer in high yield. The fused bicylic dimer could participate in cross metathesis to produce a functionalized fused hydantoin derivative. The methodology establishes novel routes to unnatural amino acids, proline homologues, and cyclic vicinal diamines.

Chemoselective Electrosynthesis Using Rapid Alternating Polarity

“…After concentration, the resulting residue was purified by silica gel column chromatography (CH2Cl2/hexane = 1:1 → CH2Cl2/hexane/AcOEt = 5:5:1) to furnish 23 (662 mg, 24%). The spectral data matched with the reported values 14.…”

“…An additional layer of difficulty stems from the lack of readily available instrumentation to generate a suitable AC for evaluation by synthetic organic chemists. 14 Herein we disclose a practical implementation of a unique form of AC electrolysis that uses a square waveform, rapid alternating polarity (rAP), which enables precise control of specific reaction pathways and remarkable chemoselectivity in synthetically relevant reduction processes for which no known direct chemical alternative currently exists.…”

Recent Advances in the Synthesis of Hydrogenated Azocine-Containing­ Molecules

“…Dash and co-workers constructed imidazo[1,5- a ]azocine 163 from commercially available hydantoin 162 via a four-step procedure involving selective N-allylation and C5-alkylation and with the key step being RCM (Scheme 48 ). 58…”

Synthesis, NMR analysis and applications of isotope-labelled hydantoins

“…A hydantoin with a 123mtellurium labelled 5-substituent (23) has been synthesised starting from [ 123m Te]diphenyl ditelluride (20) (Figure 4, Scheme 6). This compound was reduced by sodium borohydride to generate [ 123m Te]phenyltellurol (21), which was then reacted with 5-(β-bromoethyl)hydantoin (22) to give [ 123m Te]-5-[β-(phenyltelluro)ethyl]hydantoin (23). The hydantoin was hydrolysed to [ 123m Te]-DL-α-amino--(phenyltelluro)-butyric acid, which was used as a potential pancreatic imaging agent [80].…”

“…The chemical properties, methods of synthesis and reactivity of hydantoin and its derivativies have been reviewed extensively [10][11][12][13][14][15]. For synthetic chemistry applications, hydantoin is a useful centre in combinatorial chemistry [16], multicomponent reactions [17,18] and in diversity-oriented synthesis [19][20][21]. Hydantoins substituted at the 5-position are precursors to optically pure natural and unnatural α-amino acids, which is achieved through their chemical or enzymatic hydrolysis [22][23][24][25][26][27][28][29][30].…”