✍ Scribed by James A. Ciaccio; Catherine Stanescu; Jongnic Bontemps
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Functionalir@d epoxides are easily and efficiently converted lo P-hydroxy nitnles In good yield with high fegio-and stereoselectivity upon treatment with lithium cyanide in rcfluxing anhydrous THF The conditions described permit a one-pot conversion of epoxide to 1 J-amino alcohol via hydnde reduction of the nitrile.
As part of a project directed toward the synthesis of tunchonalized azacycles, we required an ellicient and convenient method for the preparation of substituted 1,3 ammo alcohols. These can be obrained hy lilhiuni aluminum hydride (LAH) reduction of the corresponding fl hydroxy nitriles which. in turn, are afforded upon epoxlde rtng opening with cyanide 4
The use of an apfotic. inert solvent would allow for a one-pot conversion 01 epoxido to 1,3 amino alcohol upon treatment of the ring-opened intermediate with LAH. However, since cyanation of epoxides is commonly accomplished with either HCN or an alkali metal cyanida in protic solvents (H2O,5 FKI)H,~ (CH3)2C(OH)CN7), DMSOa or Cti$N,g in situ hydride reduction ol the nittile intermediate is precluded. Alternatively, trimcthylsilyl cyanide (TMSCN) can be used to convert epoxides to nitriles either neati or in halo-or hydrocarbon solvent 11112 However, a suitable acid or base catalyst IS required, and moderate regloselectivity and/or isonitrile formation can occur under acid catalyzed conditions. Moreover, as reaction with 1 MSCN affords the 0-silylated Jl-hydroxy nItrIle, selcctlve hydrolysis of the silyl ether may be required if the epoxide itself possesses a silyl protecting group or other sensitive functionality.
We wish to report an extremely simple, general procedure lor Me converston of epoxides to I$-hydroxy nitriles under neutral, aprotic conditions using lithium cyanide in relluxing anhydrous THF 13 1) 3-4 equiv.
RfkJX 2) Hz0 (60.88% yields)
As shown in the TABLE. functionalized mono-, di-and trisubstituted epoxides undergo highly regio-and chemoselective reaction with 3-4 equivalents of lilhium cyanide to afford the corresponding fi hydroxy nitriles in good yield.
Gycloalkene oxides are stereoseleciively converted to the corresponding trans hydroxy nitriles By contrast, reachon of cyclohexene oxtde with aqueous HCN for seven days afforded 60% of the rrans hydroxy nitrile along with up to 10% of
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## Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
## Abstract Halohydrin dehalogenases (HheA, HheB and HheC) were found to efficiently catalyse a carbon‐carbon bond forming reaction between terminal aliphatic epoxides and cyanide, yielding β‐hydroxy nitriles. With all three enzymes nucleophilic ring opening of epoxides proceeds with high regiosele
## Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable v