Reactions with azetidines

Ring expansion of activated aziridines (43) with sulfur ylides also provides a synthesis of azetidines (75JOC2990, 58BSF345, 81CC417). The highly reactive sulfonium methylide (44 R = R = H) undergoes further reaction with the azetidines (46), but the reaction is satisfactory for substituted methylides. The less reactive sulfoxonium methylide (45 R = R = H)... 

Af-Halogeno-, fV-nitroso- and hence fV-amino-azetidines have been prepared from azetidines by reaction with positive halogen reagents and nitrosating agents, respectively (Section 5.09.2.2.3). 

H-pyran synthesis from, 3, 759 bis(trimethylsiloxy) in pyrrole synthesis, 4, 333 chromene synthesis from, 3, 750 cycloaddition reactions with isocyanates, azetidin-2-ones from, 7, 261 dihydropyran synthesis from, 3, 771 fuiyl... 

The electrophilicity of alane is the basis for its selective reaction with the amide group. Alane is also useful for reducing azetidinones to azetidines. Most nucleophilic hydride reducing agents lead to ring-opened products. DiBAlH, A1H2C1, and A1HC12 can also reduce azetinones to azetidines.100... 

During the stereoselective synthesis of azetidin-2-ones the reaction with 1 atm hydrogen over 10% Pd/C hydrogenated the double bond and hydrogeno-lyzed the benzyl group (Scheme 4.37).173... 

The reaction of aziridines and azetidine heterocycles with dinitrogen pentoxide in chlorinated solvents yields 1,2-nitramine nitrates and 1,3-nitramine nitrates respectively. In most cases yields are good to excellent, but, reactions are not as general as with the oxygen heterocycles the outcome of reactions is heavily dependent on the nature of the substituent on the exocyclic nitrogen. Some of the products from these reactions find use as melt-castable explosives i.e. Tris-X (46) and energetic plasticizers e.g. Bu-NENA (48) the latter is a component of some LOVA (low vulnerability ammunition) propellant formulations. 

Treatment of Af-phenylazetidine 315 with lithium and a catalytic amount of DTBB (5%) in THF at — 15°C led to a solution of the corresponding y-functionalized organohthium intermediate 316, which by reaction with different electrophiles at temperatures ranging between —78 and 20 °C, and final hydrolysis, afforded the expected functionalized amines 317. The same reaction using azetidine 318 yielded products 320, functionalized at the benzylic position, intermediates 319 being involved in the process (Scheme 93) . ... 

Indium mediated allylation of 4-acetoxy-2-azetidinones gave the products 57 in high yield <99SL447> and similar reactions with azetidin-2,3-diones gave 3-substituted 3-hydroxy-P-lactams 58 <98H97>. 

Woodward s synthesis, 4, 416-419 Chlorophyll b, 4, 382 Chlorophyll c, 4, 382 Chlorophyll d, 4, 382 Chlorophylls, 4, 378 biosynthesis reviews, 1, 99 structure, 4, 370 substituents reactions, 4, 402 Chloroporphyrin e6, 4, 404 Chloroprothixene pharmacology, 3, 942 Chloropyramine as antihistamine, 1, 177 Chloropyrifos synthesis, 2, 201 Chloropyrifos-ethyl as insecticide, 2, 516 Chloropyrifos-methyl as insecticide, 2, 516 Chloroquine, 1, 145 adsorption on nucleic acids, 1, 179 as antimalarial, 1, 173, 2, 517 Chloroquine, hydroxy-as antimalarial, 2, 517 Chlorosulfonyl isocyanate cycloaddition reactions with alkenes, azetidin-2-ones from, 7, 261 reactions... 

The synthesis of antiviral spiro-(3-lactam 51 begins with the benzylation of isatin 45 to give 1-benzylisatin 46, which affords Schiff s base 47 on reaction with anisidine in ethanol. The Schiff s base 47 on treatment with methoxyacetyl chloride by the chloride-imidate cycloaddition [85] route afforded a mixture of spiro E- and Z-azetidin-2-ones 48 and 49, which were separated by chromatography. The (Z)-N-arylazetidin-2-one 49 was further converted to desired 4-spiro-(3-lactam 51 by treatment with ceric ammonium nitrate and subsequently with tetrabutylammonium bromide in THF in the presence of pulverized KOH (Scheme 13). 

Chlorophenyl)glutarate monoethyl ester 87 was reduced to hydroxy acid and subsequently cyclized to afford lactone 88. This was further submitted to reduction with diisobutylaluminium hydride to provide lactol followed by Homer-Emmons reaction, which resulted in the formation of hydroxy ester product 89 in good yield. The alcohol was protected as silyl ether and the double bond in 89 was reduced with magnesium powder in methanol to provide methyl ester 90. The hydrolysis to the acid and condensation of the acid chloride with Evans s chiral auxiliary provided product 91, which was further converted to titanium enolate on reaction with TiCI. This was submitted to enolate-imine condensation in the presence of amine to afford 92. The silylation of the 92 with N, O-bis(trimethylsilyl) acetamide followed by treatment with tetrabutylammonium fluoride resulted in cyclization to form the azetidin-2-one ring and subsequently hydrolysis provided 93. This product was converted to bromide analog, which on treatment with LDA underwent intramolecular cyclization to afford the cholesterol absorption inhibitor spiro-(3-lactam (+)-SCH 54016 94. 

They have employed the strategy of intramolecular trans alkylation of azetidin-2-ones since C-4 substituted azetidin-2-one enolates, predominantly yield the C-3, 4-frans-diastereomer upon reaction with electrophiles, [45] thus, providing control of stereochemistry of substituents at the cyclohexyl ring (Scheme 25). 

For example (+)-43a was obtained after two purifications at 55 % ee and 10 % yield. Treatment of (+)-43a with hydrazine and KOH gave (+)-45a at 55 % ee and 40 % yield. The chiral host (S)-(—)-40 has been found to be extremely effective as a chiral selector towards comparatively bulky molecules of the phthalimide formed from of l- < r -butyl-3-chloro-azetidin-2-one, 47. A crystalline inclusion complex of 1 1 stoichiometry was formed between one mole of (S)-(—)-40 and two moles of rac-47 dissolved in benzene/hexane 1 1 solution. After one recrystallization, the complex was chromatographed on silica gel, and the crystalline product was treated with hydrazine. Optically pure (—)-3-amino-l-ieri-butyl-azetidin-2-one (—)-47, was obtained at 100% ee and 44% yield [51]. Primary diamines, like 1,3-dibromobutane (49), can undergo a similar reaction with potassium phthalimide, yielding diphthalimide, 50. The complexation process between rac-diphthalimide 50 and host (S,S)-(—)-6 gave a 1 1 complex containing (—)-50... 

Regiospecific, Pd(II) catalysed, cycloaddition reactions of azetidines to yield ring-enlarged products include the formation of tetrahydro-2-iminopyrimidines (e.g. 10) by reaction with carbodi-imides (95JOC253) and tetrahydro-l,3-thiazin-2-imines (e.g. 11) from isothiocyanates (95JOC3092). 

The azetidinium acetates 18 are suitable substrates for the synthesis of 1-arylazetidines 19 <2000EJ01815>. The palladium-catalyzed coupling reaction of azetidines 18 with aryl bromides has led to the synthesis of 1-arylazetidines 19 (Equation 1). This reaction required the presence of a strong base such as /-butoxide. 

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