M.Periasamy,M.Thirumalaikumar/JournalofOrganometallicChemistry609(2000)137–151141

TheNaBH4–I2reagentsystemhasalsobeenusedforthisapplication.Itreadilyreducescarboxylicacidestersunderre uxconditionsingoodyields(Eq.(36))[21].PhCHNaBH4–I2,THFH2O

2COOEt 70°C,0.5h

PhCH2CH2OH

(36)

85%

6.Reductionofcarboxylicacidamides

Numerouschemicalsofimportanceinmedicinalchemistryhavebeenpreparedthroughreductionofamides[45].ItwasfoundthattheamidescanbeeasilyreducedtoprimaryaminesusingNaBH4–CoCl2systemingoodyieldsinhydroxylicaswellasinnon-hydrox-ylicsolvents(Eq.(37))[46].

n-CNaBH4–CoCl2

3H7CONH2 n-C3H770%

CH2NH2

(37)

TheNaBH4–I2systemisalsousefulforthereductionofamides(Eqs.(38)–(40))[21].PhCONH2 NaBH4–I2

NaOH

THF,D

PhCH70%

2NH2

(38)PhNHCOCH3 PhNHCH75%

2CH3

(39)Ph(CH3)NCOCH3 Ph(CH3)NCH74%

2CH3

(40)

Further,reductionofamidescontainingsensitivefunctionalgroupscanalsobecarriedoutusingNaBH4–I2reagentsystemunderambientconditions(Eq.(41))[47].

(41)

AnewprocedureforthehighlyselectivereductionoftertiaryamidestoaminesusingNaBH4–bis(2-bro-moethyl)seleniumdibromide4hasbeenreported(Eq.42)[48a,b].

(42)

Atahighertemperature,thisreactiontakesplacesmoothlyinashorterperiod.However,reductionofsecondaryandprimaryamideswiththissysteminTHFfailed.Also,withouttheseleniumcompound,thereac-tiondidnottakeplace.IthasbeenobservedthatthereactionofNaBH4with4producesborane(5)andbis(2-bromoethyl)selenide(6).

(BrCH2CH2)2Se–BH3(BrCH2CH2)2Se

56

7.Reductionofnitriles

TheCoCl2–NaBH4reagentsystemeffectivelyre-ducesthenitrilesingoodyields[46]inhydroxylicas

wellasnon-hydroxylicsolvents(Eq.(43)).

CNaBH4–CoCl2

6H5CH(OH)CN C6H5CH(OH)CH80%

2NH2

(43)MandelonitrileissmoothlyreducedusingtheNaBH4–CoCl2system[49].ItisofinteresttonotethatreductionbyLiAlH4givesthea-hydroxy-b-phenylethyl-amineinlowyields.Cupricsalts–NaBH4combinationsarealsoeffectiveforreductionofnitriles.Thehalo-genides,sulfates,carboxylatesofcobalt,nickel,iridium,rhodium,osmiumandplatinumwerealsousedalongwithNaBH4inseveralapplications.Also,ZrCl4–NaBH4reagentsystemhasbeenusedforthereductionofnitrilesinexcellentyields(Eq.(44))[31].PhCHNaBH4–ZrCl4

2CN THF,r.t.

PhCH2CH2NH2

(44)

91%

NitrilesarealsoreducedbyNaBH4–I2systeminTHFunderre uxingconditions(Eq.(45))[21].PhCN NaBH4–I2

NaOH

THF

PhCH2NH2

(45)

72%

Also,nitrilesonreactionwithamixtureofNaBH4andbis(2-bromoethyl)seleniumdibromide(4),inboil-ingTHFgivethecorrespondingprimaryamines(Eq.(46))[48].

RCN 1.NaBH4–4,THF

2.HCl

RCH(46)

R=2NHalkyl/aryl2.HCl

35–73%

Thisreagentsystemdoesnotaffectmanyothersub-stituentsthataresusceptibletoH3B–THF[48b].

8.Reductionofacidchlorides

Theacylchloridesareef cientlyreducedtothecor-respondingalcoholsonreactionwithZn(BH4)2inpres-enceofTMEDA(Eq.(47))[50].Electronwithdrawinggroupinthesubstratesenhancestherateofreduction.Itisofinteresttonotethattheselectivereductionofacylchloridesinthepresenceofotherfunctionalgroups,suchaschloro,nitro,esterandconjugateddoublebondcanbeachievedusingthisreagentsystem.RCOCl NaBH4–ZnCl2

TMEDA

RCH2OH

(47)

R=alkyl/aryl86–98%