Chirality Transfer from Guanidinium Ylides to 3-Alkenyl (or 3-Alkynyl) Aziridine-2-carboxylates and Application to the Syntheses of (2R,3S)-3-Hydroxyleucinate and d-erythro-Sphingosine

Abstract

[Reaction: see text]. Reaction of chiral guanidinium ylides with alpha,beta-unsaturated aldehydes gives 3-(alpha,beta-unsaturated) aziridine-2-carboxylates in high diastereo- and enantioselectivities (up to 93% diastereomeric excess and 98% enantiomeric excess). 3-(1-methylvinyl)- and 3-[(E)-pentadec-1-enyl]aziridine-2-carboxylates were successfully employed to prepare (2R,3S)-3-hydroxyleucinate and d-erythro-sphingosine, respectively.

Synthesis of novel 5-alkyl/aryl/heteroaryl substituted diethyl 3,4-dihydro-2H-pyrrole-4,4-dicarboxylates by aziridine ring expansion of 2-[(aziridin-1-yl)-1-alkyl/aryl/heteroaryl-methylene]malonic acid diethyl esters

“…They are versatile electrophiles and notably undergo regioselective ring opening via addition at either the vinyl terminus [2–5] or directly at the aziridine ring carbon depending on the reagents employed [6–7]. Vinylaziridines have also been exploited in a variety of ring expansion reactions to afford a range of heterocyclic products, including piperidines [8–9], pyrrolines [10–14], imidazolidinones [15], β-lactams [16–18] and azepines [19–21].…”

Ring‐Opening Reactions of 3‐Aryl‐1‐benzylaziridine‐2‐carboxylates and Application to the Asymmetric Synthesis of an Amphetamine‐Type Compound

“…; the former category includes electron-withdrawing substituents such as tosyl or acyl functions, whereas a H-atom and alkyl substituents are typical for the latter one. Although the reactivity of activated aziridines has been well investigated, there are only limited reports [6 -9] on unactivated aziridines.Recently, we have reported an atom-economical aziridine synthesis from guanidinium salts 1 (obtained from the ureas 4) and arenecarboxaldehydes 2 [10] (or unsaturated aldehydes [11]) applicable to asymmetric synthesis, in which 1-alkyl-3-arylaziridine-2-carboxylates 3 (or the corresponding unsaturated derivatives) are produced, as shown in Scheme 2. In this paper, we present the ring-opening reactions of N-benzylaziridine-2-carboxylates, prepared by the above reaction, with O-nucleophiles and aromatic C-nucleophiles and application to the asymmetric synthesis of an amphetaminetype compound from the reductively ring-opened product.…”

“…Shiba and coworkers [13] had assigned the configuration of diastereoisomeric a-amino-b-hydroxy acids by cyclization to oxazolidinones; the obtained cis-derivative showed a large coupling constant (J = 9.6 Hz) between HÀC(4) and HÀC(5), whereas the trans-isomer showed a small coupling constant (J = 5.0 Hz). We have independently determined the relative configuration of a-amino-b-hydroxy esters derived from 3-vinylaziridine-2-carboxylates in the synthesis of hydroxyleucinate and sphingosine [11] by application of Shibas procedure. This technique was also applied to product 5c obtained in the reaction of Entry 6 of Table 1 (Scheme 3).…”

Synthesis and Structure-Activity Relationships of Skin Ceramides

“…Disadee and Ishikawa utilized alkenyl aziridines as key intermediates in the preparation of D-erythro-sphingosine (Scheme 18) [103]. Treatment of (S,S)-guanidinium salt (109) with (E)-hexadec-2-enal in the presence of TMG yielded in the formation of cis-and trans-isomers with a good combined yield and enantioselectivity.…”