Azetines alkyl

Shu Kobayashi of the University of Tokyo found Organic Lett. 2008,10, 807) that the conjugate addition of 25 to 24 mediated by a chiral Ca catalyst proceeded with high enantiocontrol at both of the newly formed stereogenic centers, to give 26. In a chiral auxiliary based approach, Dennis C. Liotta foimd J. Org. Chem. 2008, 73,1264) that condensation of 27 with 28 gave predominantly just two of the possible four diastereomeric azetines. Alkylation of the cis diastereomer, followed by benzoylation and hydrolysis, then delivered the a-quatemary 3-amino acid derivative 29 as a single enantiomerically-pure diastereomer. 

O-Alkylation of the readily available iV-unsubstituted azetidin-2-ones (/3-lactams) constitutes a versatile route to 2-alkoxy-l-azetines (cf. Section 5.09.3.2.3). Thus treatment of the /3-lactams (266) with trialkyloxonium tetrafluoroborates followed by basification affords the 2-alkoxy-l-azetines (267) in moderate yields (67JHC619,69LA(725)124). Similar treatment of the azetidine-2-thiones (268) (available from thiation of the corresponding /3-lactams with phosphorus pentasulfide) affords the analogous 2-ethylthio-1-azetines (269) (67JHC619), which are generally more stable than their 2-alkoxy analogues. 

Cyclization of 3,3-dimethyl-2-hydroximino-4-tosyloxybutane (272) with 1,6-bis-(dimethylamino)naphthalene is reported to occur via iV-alkylation to give the 1-azetine Af-oxide (273) as an unstable oil which decomposes over a few days at room temperature (74TL4283). 

The reaction of 4-(phenylsulfonyl)azetidin-2-one (128) with nucleophiles such as dialkylcopper lithium and Grignard reagents gives 4-alkyl, 4-allyl, 4-vinyl or 4-ethynyl-azetidinon-2-one (129) in good yields (equation 99)83. The yields of several azetidin-2-ones obtained by this method are given in Table 10. The reaction apparently proceeds through an intermediate azetin-2-one 131 derived from the five-membered coordination complex (equation 100). 

O-Alkylation of 7V-unsubstituted /3-lactams to give the corresponding 2-alkoxy-l-azetines can be achieved by reaction of the azetidin-2-ones with hard electrophiles (trialkyloxonium tetrafluoroborates) followed by treatment with base (c/. Section 5.09.4.3.1) (67JHC619, 69LA(725)124). In contrast, reaction of the Af-unsubstituted azetidin-2-ones (73) or their derived anions with a variety of softer electrophiles results in Af-substitution, and some representative reactions are illustrated in Scheme 7. 

The 4-thioxoazetidin-2-one (281) (cf. Section 5.09.3.3.5) is reported to undergo exclusive 5-alkylation on treatment with methyl iodide in the presence of base to yield the 2-methylthio-l-azetin-4-one (282) (80TL4247). 

Thermal ring expansion of cyclopropyl azides provides a general route (95 — 96) to alkyl- and aryl-azetines (79CB3914). 

Heating of a mixture of polyfluoro amines 636 and 637 resulted in a mixture in which azetine 638 was present in 15% yield (Equation 242), whereas heating of fluorinated alkenyl amines 639 furnished IV-alkyl azetines 640 selectively in excellent yields (Equation 243) <1996JFC(79)97>. 

Treatment of /vam-.Vhydroxyazctidinc with methane sulfonyl chloride or phosphoryl chloride in the presence of triethylamine afforded 2-azetine 646 (Equation 246) <2006TL6377>. Interestingly, the //war-relationship between the hydroxyl group and the alkyl substituent is crucial for effective elimination since the rM-3-hydroxyazetidine failed to give the 2-azetine. 

A synthesis of 2-aryl-3,3-dichloroazetidines 2, a relatively unexplored class of azaheterocycles, was accomplished by reduction of the corresponding 4-aryl-3,3-dichloro-2-azetidinones with monochloroalane. Reacting these 3,3-dichloroazetidines with sodium hydride in DMSO, followed by aqueous work up, afforded l-alkyl-2-aroylaziridines, by hydrolysis of the intermediate 2-azetines <02JOC2075>. 

In contrast, the photolysis of these azides at 350 nm leads only to the corresponding nitriles and olefins in yields of 90 l-(Alkylthio)cyclopropyl azides (164), readily accessible from the corresponding chlorides and bromides, are smoothly decomposed at ITC with nitrogen evolution. The main process is a ring enlargement to 2-(alkylthio)azetines (165), accompanied by cleavage to an alkyl thiocyanate and an alkene (equation 114). ... 

---