Damand Dhla-AIdat lawitlons of 2.4.~-~(0c~c*rbony1~-1.3,5-rr~~Ln~ and 2.4.6-~(wchylthio)-l,3,5-rrfrKLar,: ?yTtildla* 1xltrodueticm~ D*le L. liog*r*' *nd Qun Dmg Dep*rtmmt of Chulatry Fur&a Univormlty u*st L4f*y*tt*, IH 67907 (Recciwdh C'SA 30 Drctndxr 1987) Abrcract : A full iw*sti&*cion of rho wzop* of the perticipeion of 2.&.6-Ufi(*thoxyc*tbonyl)-1.3.5.crl8rlru (la) and 2.4.6.Ul(uthylchio)-1,3,5trluin* (kb) in Invera* electron demand Dlrls-Al&r r**ctloru rutcebl* for tha preprr*cion of functlonalired 5.6.dlmbstltut*d pyrialdin*~ 1s &tall*d. The u** of th* rssulr1ng [t + 21 cyclodducta LS Imodl*ca pr*cursors to th* prrent 4.5.disub8tltutad pyrirldlnoo 1s descrlbsd. In recent efforts we h*v* d*t*llad the us* of l serl*s of lrrv*r** sleetron deeend Iti*lr Alder rt*ctions of *ltctron-dtflcl*nt h*c*rocytllc l radionrs in [b + 21 cycloe3dltfon r**ctlons ulch cl*ctron-rich dlmophllor comprlaing l genmwl approach to the lntroductlon of l full r*ng* of h*cero*routlc 8yscuu. Schow I. 2.16 Thi* l ppro*ch has prov*n v*ll-sulc*d for rho introduction of highly wbstltut*d and highly functionalltcd h*tcroaromtlc l y*tru dlfflcult LO l m*mbl* by l lt*nutlv* methodology and cons*quantly has found l pplicrtion in eh* tot*1 synches*a of l range of rutur*lly occurring Mceri~ls. *-13 In b continued l xpior*tion of ch* inv*r** l l*ctron dound Dlolr-Alder r**cclona of hstarocycllc l r*dlbrns l nd in efforta to oxtend the 1.3.5.trlbrllu bpyrloldln* Dlcls-Alder tt*CClOn 3 CO th* tor*l synth**te of pyrlmidoblufc l c1d, 15 rho h*t*ro8rom*tlc 8egmenc of the blsomycln. equation 1, the pot*ncl*l MO of 2.~.6-trfoubrcftut~-l,~,5~Crl*xfn*e has b*cn und*r lnv*stig*tion. Hsreln, va &c*il our effort8 on th* lnv*~tlg*tlon of the scope of the :o l 2; cyclo*dd1tlon rerctlorv of 2.G.6-~(athoxyc*rbon)rl~-1.3.)-trlullu (1a)3'16 *nd 2.4.6. ~(~thylthlo)-1.3,5.trl*zina (lb)l' vlth *l*ctron-rich dlmophilar l ultable for the pr*p*ratlon of funcciorulis*d 5.6.dl*ubstitut*d pyrl*idirw*. equation 2. + ml* p*per io Qdlc*t*d to Profemor C. C. Taylor on the occasion of hle 65th birthday. Ib8etlow of 2,~.6-~(.t~c~rb~1)-~,3~5-t?~8~~ (lo). Ynufruo, l l*ctron-rich l lkynw. and maminor. electron-rich alkenw. war. found co parclcipat. In well-defirwd 11 + 21 cyciowtdition r~ectloru with 2 o.6.ull(~thoxyc~rbonyl).l.3,S-tr~~c~~ (la). Table I. In th* cam of ynaminm. th rooa tuprracuro 14 l 2) cyclo~ddltion reaction ia followed by l wbaaqusnt rofro Dlola-Alder roactlon (GO-100'C) with low of ethyl cymoformte and wIch dlrocc ~anorrtion of the 5-8ubltltut& 2.4-Plt(sthoxyc~rbonyl)-b-dl~lkyl~lnopyrim~dl~~. Scheme II (Table I. antrier L-2). Tha 11 + 21 cycloaddltlon reaction of la vlth l uafnm Zc-2h -u found co proceed (25-1OO'C) In conwntforul orsanlc l olvmts (CH$?f. dioxana. dlglyw. C~2Cl2) co provlda tha stable. Leolable 10 + 2) cyclo&duc~s vhlch only slumtehly and poorly un&rgo l retro Dials-Alder r*rctton d ftrul l routlr*tion to prowl& rhb 5.6-diwbetirutod 2.*-~t8thoxyc~rbonyl)pyri~idlru8, Schwa XII. The lnltlal [G + 21 cycloaddwt8 proved remarkably b 2* b 3a 2*= 2bd 2 dloxxne. 1Ol'C. 2 h 2 dioxuu, 6O'C. 2Cr h 1.7 CHJQI, 82'C. 12 h b 2 2c* 2 2 c 2 d 2 269 2.9 5a 2 b 2 2te 2s* 2h' b 9& b c 10b b ll* 2c 26 2b dfo-.
101'C. 2L h dlo-. 101.C. 4 h 4i MCI. lOl'C, 12 h Qt2Cl. *O'C. 12 h CH2C12. Qi3COOH. lOO*C. 11 h cH2C12. CU3cooH. lOO*C. 20 h dioxmn. 25'C. 2 h lOl'C, 16 h CnjCn * 82'C. 1S h CH2C12. CH3CQOH. ES'C, 20 h Q(2c12. 00.C. 2 h a(2Cl2. CH3C00H. 100.C. 11 h 3c St dlo-. 1Ol'C. 12 h 4pI WCl. 1Ol'C. 24 h QI2c12. 4O'C. f h CH2C12. cH3CooH. fOO'C. 12 h cH2c12. CH3coOH. 9O'C. 17 h CH2C12. CH3COOH. IOO'C. 20 h a2c12. cH3cooH. 90'C. lb h diglyme. 12O.C. G h NS'C. 24 h CH2c12, ai3CoOH. PO'C. 13 h a3CN. 82.C. 12 h dlo-. 101'C. 6 h dloxana, 6S'C. 12 h Qljac * 82*C. lb h dloxme. 101'C. 16 h 3.