Abstract
The four-step conversion of a series of N-Boc-protected l-amino acid methyl esters into enantiopure N-Boc allylamines by a modified Julia olefination is described. Key steps include the reaction of a lithiated phenylalkylsulfone with amino esters, giving chiral β-ketosulfones, and the reductive elimination of related α-acetoxysulfones. The overall transformation takes place under mild conditions, with good yields, and without loss of stereochemical integrity, being in this respect superior to the conventional Julia reaction of α-amino aldehydes.
Highlights
OOnn tthhee ootthheerr hhaanndd, tthhee cchhaarraacctteerriissttiicc bbiiffuunnccttiioonnaall uunniitt ccaann uunnddeerrggoo aa wwiiddee rraannggee ooff cchheemmiiccaall ttrraannssffoorrmmaattiioonnss, ththuussmmakaiknigngallaylllaymlaimneisnevservsaetrisleatbilueildbuinilgdbinlogckbsloinckosrginaniocrgsyanntihc essyisn[t1h]e.sCishi[r1a]l
When the reaction was complete (TLC), the solvent was removed in vacuo; aqueous workup and extraction with ethyl acetate gave the β-hydroxysulfones 4 as mixtures of diastereoisomers, whose ratio was determined by NMR
Allylamines 6 were obtained from β-acetoxysulfones 5 following two methods
Summary
OOnn tthhee ootthheerr hhaanndd,, tthhee cchhaarraacctteerriissttiicc bbiiffuunnccttiioonnaall uunniitt ccaann uunnddeerrggoo aa wwiiddee rraannggee ooff cchheemmiiccaall ttrraannssffoorrmmaattiioonnss,, ththuussmmakaiknigngallaylllaymlaimneisnevservsaetrisleatbilueildbuinilgdbinlogckbsloinckosrginaniocrgsyanntihc essyisn[t1h]e.sCishi[r1a]l. Calhlyirlaaml ainlleysla, mininpesa,ritnicuplaarrt,icaurlear,vaarlueavballeuainblteerimnteedrimateedsiaftoers ftohre thsyenstyhnetshisesoisf oaf avvaraireiteytyooff cchhiirraall,, eennaannttiioommeerriiccaallllyy--ppuurree bbiiooaaccttiivvee ccoommppoouunnddss [[1144––1177]]. AtchonertaCdtcaChrhsos-ce-etyeHyIrHhhsnmrmpcieceIarhIahsmosnmanmnmippinrlrieseosiaitdaitpptntprnnlrelrioiaoiianditpctpsocteoteigiooiofnolohohoo-ognrαnyieflyfelsn-dr[dαcri[ai2es2eserser-m4cot4caonsrie]se]gmlgettintlnaienaiaelatlnitnnlancolndadaantdaaoadivatdtnontitivaachaovhonintaacnaeandetnit[cntrdtns2tnecaorcorsi5esiacebfatft]srctsbrcyi.iodtondtiyviiinsinsvsiveeoaeoeseaena-nse-vaesaeysvaaaeylnynmmlmtelrmteemteraeeiriamnrrmlnrrmnleneneereaaearaseoastcottcttrtuirtir[tui[viivi2ivitc2octoceee3ee3nnss,,s]s,s]y,y,y[aa[a[[2nn2nts2sts2h5th5t6t6hth]thet]e–h–.hh.eee22esteesst8r8iriisas]]sasss,.t.n,t,tnaataTtstTshrhrhriihtttehtteieiieiinnoeonooogngsnlglselyeeymfmmfnmmifinintnaaenhteaatathtteaetetataierestirloloiiis-ri-aosnacniiclsaanlasosootltofsaofacfcflalfcαaycαyhncnαa-z-zhaiane-erbmbimadadreebmlaiineanoaaloisoslbonaboylytylotabamalmallylitadiadnmanmlmleaeeidehnehmdeidetnyetyrhriedfdidfinrcysrceoeoedfsbsamrsameyloflflrbslrmyyotottyhflhhlmmirieceecotthhmee WicWtotirigrtte[isg2p9[o–2n39d1–i]3n,1gJ]u, αJlui-aalim[a3i[2n3–o23–4a3]c4ia]dnasdnbdyPPesteeetveresrrsoaonlnr[[o33u55]t]eosolle[e2fif6inn–aa2tt8ii]oo.nnTohofef ααs-y-aanmmthiniensooisaalodlfdechehhyidyraedlseashlalhysalabsmebeienneernseprbeoyprtotehrdet,ed, buWtbutihttteigsthe[e2as9pe–p3ar1op],apJcruholaeiacsh[ae3rs2e–3oa4rfe]teannofdltiemPneitelirdmsobitnyed[t3h5be] yoclhetefhimne aictciaholenamonifdcaαlc-oamannfiidngoucraoalndtifeoihgnyuadrlaeitsniohsntaaasbl bileiinetysntaorbefpilαoit-ryatemdoi,fno aldbαeu-hatymdtihenesos[ea2l7da]e.phpyrdoeasch[2e7s].are often limited by the chemical and configurational instability of α-aImn IitnnhoethacelldaceslhasyiscsdaieclasJl[u2Jlu7i]al.iareraecatcitoionn[3[366,3,377]]((SScchheemmee 11)),, aa lliitthhiiaatteeddaarryyl laalklkyyl lsusulflofnoeneisisadaddeddedtotaonan aldaelhdyehdInyedtheoetgocivglaeisvstehicteahlceoJcurorlriearseprseopanocndtidioninngg[α3α-6h-,h3y7yd]drr(oSoxcxyhysesumullfefoo1nn)ee, AAa l((ippthaaittahhtwwedaayyaaray)).l.TaThlhkisiy,sl,inisnutultfuronrn,nei,siscsocanodvndeverdeterdteoidnatinonto theathltdaeertghaeyrtgdaeeltktaoelnkgeeivnbeeytbhiyne icsnoitrsuriteauscpeaotcyneltdayitlniaogtnioαna-hnaydnddtrroetrxaeytamstumelnfeotnnotefoAtfht(ehperaertsheuswultalitnyingag)α. HiTaehtneedyslaapmlhkeeynlαsy-ulhalyflkodynrloesxuwylfsiotuhnlfeaonnweeistAhte, rah,nofowelsleotvewerr,e,dfcoablnlyobwteheeodbrebtadyiuntechdteion of itrnhedetuwccootrirosentsepopfostnhbdeyicntoghrerαea-skcpyeotlnaodtsiuionnlgfooαnf-ekte(hSteocshluietlhmfoiaentee1d,(Sppcahhtehemnwyealay1l,kbpy)a.ltsChuwhlfiaoryanleba)w.llCyithlhairmaanlinaeellssytlemarm,ayfiontlehlsouwmseabdyetbohybutstahbineeed staroretbditnuagicntfierodonmsotfartrehtaiendcgiloyfrr-raoevmspaoirlneaadbdilneilgyα-α-aa-vkmaeiitlnoasobulelfsoαten-raesm(tSihcnahotemaesreete1cr,shpetahmtahitwcaalrlyeybca)h.neCdmhciircoaanllfilayglluyanlraadmticoinonneasflimlgyuamryaottihrouenssatbllaeyble thaomnbotαar-ienamestdainbsloteaarttlhidnaegnhyfαrdo-aemms [irn4e0oa]d;aiflludy-erathhvyeadrilemasbo[lre4e0,α];t-hafeumraitndhoedriemtsiotoenrreas,lttshhtaetpaaodrfdepictaihotehnmawliacsaytlelbpyisaonfndoptactaohnlwifmiagyiutarbatitioisonnn,aoaltslyathe latlmtloieimnmorericitetsoaattmsteiitopoapnnb[o,2,luea6asn]st.hdtthhasenealrlaαaett-ttageemerrncicneoorommalappllyooduuepnhnrdeydpsdsaeaarsrreee[d4gg0efer]nn;oeemfruraarltltllhhyyeepprcmrroeeropprraaeerrs,eepdtdohfnefrrdooamimdndgttihhteieesotcnceooarrlrsrrseientssepppaootnnoldefdaiipnnsagtgtoheenswsteteaersrystsebiipnni[saa2ttn6ll]oee.atassatt one step [26] AtchonertaCdtcaChrhsos-ce-etyeHyIrHhhsnmrmpcieceIarhIahsmosnmanmnmippinrlrieseosiaitdaitpptntprnnlrelrioiaoiianditpctpsocteoteigiooiofnolohohoo-ognrαnyieflyfelsn-dr[dαcri[ai2es2eserser-m4cot4caonsrie]se]gmlgettintlnaienaiaelatlnitnnlancolndadaantdaaoadivatdtnontitivaachaovhonintaacnaeandetnit[cntrdtns2tnecaorcorsi5esiacebfatft]srctsbrcyi.iodtondtiyviiinsinsvsiveeoaeoeseaena-nse-vaesaeysvaaaeylnynmmlmtelrmteemteraeeiriamnrrmlnrrmnleneneereaaearaseoastcottcttrtuirtir[tui[viivi2ivitc2octoceee3ee3nnss,,s]s,s]y,y,y[aa[a[[2nn2nts2sts2h5th5t6t6hth]thet]e–h–.hh.eee22esteesst8r8iriisas]]sasss,.t.n,t,tnaataTtstTshrhrhriihtttehtteieiieiinnoeonooogngsnlglselyeeymfmmfnmmifinintnaaenhteaatathtteaetetataierestirloloiiis-ri-aosnacniiclsaanlasosootltofsaofacfcflalfcαaycαyhncnαa-z-zhaiane-erbmbimadadreebmlaiineanoaaloisoslbonaboylytylotabamalmallylitadiadnmanmlmleaeeidehnehmdeidetnyetyrhriedfdidfinrcysrceoeoedfsbsamrsameyloflflrbslrmyyotottyhflhhlmmirieceecotthhmee WicWtotirigrtte[isg2p9[o–2n39d1–i]3n,1gJ]u, αJlui-aalim[a3i[2n3–o23–4a3]c4ia]dnasdnbdyPPesteeetveresrrsoaonlnr[[o33u55]t]eosolle[e2fif6inn–aa2tt8ii]oo.nnTohofef ααs-y-aanmmthiniensooisaalodlfdechehhyidyraedlseashlalhysalabsmebeienneernseprbeoyprtotehrdet,ed, buWtbutihttteigsthe[e2as9pe–p3ar1op],apJcruholaeiacsh[ae3rs2e–3oa4rfe]teannofdltiemPneitelirdmsobitnyed[t3h5be] yoclhetefhimne aictciaholenamonifdcaαlc-oamannfiidngoucraoalndtifeoihgnyuadrlaeitsniohsntaaasbl bileiinetysntaorbefpilαoit-ryatemdoi,fno aldbαeu-hatymdtihenesos[ea2l7da]e.phpyrdoeasch[2e7s].are often limited by the chemical and configurational instability of α-aImn IitnnhoethacelldaceslhasyiscsdaieclasJl[u2Jlu7i]al.iareraecatcitoionn[3[366,3,377]]((SScchheemmee 11)),, aa lliitthhiiaatteeddaarryyl laalklkyyl lsusulflofnoeneisisadaddeddedtotaonan aldaelhdyehdInyedtheoetgocivglaeisvstehicteahlceoJcurorlriearseprseopanocndtidioninngg[α3α-6h-,h3y7yd]drr(oSoxcxyhysesumullfefoo1nn)ee, AAa l((ippthaaittahhtwwedaayyaaray)).l.TaThlhkisiy,sl,inisnutultfuronrn,nei,siscsocanodvndeverdeterdteoidnatinonto theathltdaeertghaeyrtgdaeeltktaoelnkgeeivnbeeytbhiyne icsnoitrsuriteauscpeaotcyneltdayitlniaogtnioαna-hnaydnddtrroetrxaeytamstumelnfeotnnotefoAtfht(ehperaertsheuswultalitnyingag)α. αT-a-haciceset,otionxxytyussurunlfl,fooinsneceowwnivitthehrstseoodddiiunumtmo or matohgrenmetasarigugnemet saailumkmeanlaegmabmyalgi[na3ms8i]tu[o3r8a]cSemotryISl2am[t3iIo92n][.3aT9n]hd. eTtrhseaeamstmaemeαne-thαoy-fhdtyrhdoexrroyexssyuuslluftoilnfnogenαeA-Aa, ch,eohtowoxweyvesvueerl,fro,cnacaennwbbeitehoobsbottadaiiinnueemdd in twooinrsmtewapogsnbsetyseiputhsmebaaycmytahlalegtiaaomcny[ola3ft8it]ohonerloSitfmhtiIha2et[e3dl9it]ph. hiTaehtneedyslaapmlhkeeynlαsy-ulhalyflkodynrloesxuwylfsiotuhnlfeaonnweeistAhte, rah,nofowelsleotvewerr,e,dfcoablnlyobwteheeodbrebtadyiuntechdteion of itrnhedetuwccootrirosentsepopfostnhbdeyicntoghrerαea-skcpyeotlnaodtsiuionnlgfooαnf-ekte(hSteocshluietlhmfoiaentee1d,(Sppcahhtehemnwyealay1l,kbpy)a.ltsChuwhlfiaoryanleba)w.llCyithlhairmaanlinaeellssytlemarm,ayfiontlehlsouwmseabdyetbohybutstahbineeed staroretbditnuagicntfierodonmsotfartrehtaiendcgiloyfrr-raoevmspaoirlneaadbdilneilgyα-α-aa-vkmaeiitlnoasobulelfsoαten-raesm(tSihcnahotemaesreete1cr,shpetahmtahitwcaalrlyeybca)h.neCdmhciircoaanllfilayglluyanlraadmticoinonneasflimlgyuamryaottihrouenssatbllaeyble thaomnbotαar-ienamestdainbsloteaarttlhidnaegnhyfαrdo-aemms [irn4e0oa]d;aiflludy-erathhvyeadrilemasbo[lre4e0,α];t-hafeumraitndhoedriemtsiotoenrreas,lttshhtaetpaaodrfdepictaihotehnmawliacsaytlelbpyisaonfndoptactaohnlwifmiagyiutarbatitioisonnn,aoaltslyathe latlmtloieimnmorericitetsoaattmsteiitopoapnnb[o,2,luea6asn]st.hdtthhasenealrlaαaett-ttageemerrncicneoorommalappllyooduuepnhnrdeydpsdsaeaarsrreee[d4gg0efer]nn;oeemfruraarltltllhhyyeepprcmrroeeropprraaeerrs,eepdtdohfnefrrdooamimdndgttihhteieesotcnceooarrlrsrrseientssepppaootnnoldefdaiipnnsagtgtoheenswsteteaersrystsebiipnni[saa2ttn6ll]oee.atassatt one step [26]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
