A regio- and stereoselective synthesis of the tertiary chloride 7 is described, involving the Lewis acid catalysed addition of the allyl chloride 6 to isobutene as a key step. Acid catalysed cyclisation of 7 yields the damasconoid compounds 12–15

Bäuml, Englbert

Heilmann, Werner

Mayr, Herbert

Rahman, Azizur

English

Open Access LMU ( Ludwig-Maximilians-Univ. München)

Werner Hellmnn, klmr-Rm, wlbert Blluml. and Herbert Meyr* Itutitut Rlr Tommie her Medlzlnlxhen Unlvenltiit p1 L&beck Ratzeburger Allee 160, D-Z’WI LUbeck 1, Federal RepJbllc of Germany ( Rtchtrd m Grmuy I 5 July 1988) hblltlmA: A raglo- and strreoselectlve synthesis of the tertiary chlwl6s 7 1s described. lnvolvlw the Levis acid catalysed addltlon of the ally1 chloride 6 to lsbutene m a key step. Acid catalywd cycllsatlon of 7 ylelas the damasamold antpomds 12-15. Aa c,, ampounds, the damasamee 1, llke the lonmes 2 am not members of the terpene fenlly. Their structural relatloruhlp to terpsnes 1s obvious, houever, and they hwe been suggested to be metabolltes ol carotenes.’ Because of their occurenoe as natural fragrance and am anutl- t.uentS, they are of casmerclal interest, and several symthsses ampounds have ken developed, often based m Intermediates synthesis.*-‘9 to Omimxnca and dmiuamold of the techn1ca1 vltamln A In thls tark, ye report cm the synthesis of the dlenyne 7, a ww precursor of dMlascmol0 compounds. Its acid catalysed cycllsatlcm 1s fomd to give mlxtur03 of oooparnds, a of utllch are kmm az. axutltuents of black tsa arcma (13)**, of Omanthus absolute (II)“, and of Vlrglnla tabacm (14)*’ tille othen hwe been used a9 precursm for the synthesis of arcma cunpowlds (8, 12).“@” barlts. Pd(II) catalysed mupllng **e” of 3-methyl-pent-2(g)-an-b-yn-l-01 (4) (trade w: 1 ‘-panto ulth l(Z)-bnaropmpene (3) gavs 83$ of 5 ln a stemmelectlve mactlm. Slncc the ccmflgwatlcw of the 6.7~double bond 1s loat ln the cyclimd pmducte. the w of sWlcally pure 3 1s qot necemary, Ma it tms been &o&l tJnt the Mae cy6llsatlan prcclucts am obtalmcl. when a mlxtun of 1-brcmopmpenes 1s u!M instead of the pum (L)-1-r. Treatant of 5 ulth conoentr8te4 hydmchlorlc acid in petmlem ether ylelOe4 961 of 6, vhlch shwa a hl@er Snl reactlvlty th3n tertiary alkyl chlorides ma, therefore, gives the 1:1 pm&et 7 ulth leobutene ‘*-” ln presence of the weak Leuls acid ZnCl,~Et,O.‘* 6047 6048 w. HCILMANS <*I <I/ 831. , 961: 60% 4 5 8 1 Attwps to cycllse 7 with BCl, or SnC1, at -78’C w wlth ZnCl, at O°C yielded complex mlxtw of products uhlch hsve not been lbentlfled. Tn~tment of 7 with sliver trlrluoroacetate In hexane and successive workup with ethanollc KOH afforded the cyclic allene alcdd 8 along with the acyclic ccu~pands 9-l 1. fhe prekdnnnt fonuetlon of cyclfsed -rmQs was observed when the tertiary chlorlda 7 YBS heate in aqueous folalc acid. Yhlle the tertlary alcohol 9 was isolated with the cycllsed ozqwu~Us 12-14 tin&r rrlatlvely mild condltlons (HUl,H:H,O:THF -2:1:2). only cyclic acid under rpflux. oompwnds were observed (13-15). when 7 was heated In 901 aqxms fomlc Scheme 1 a+FJ r+ 8 8’ 10 FI: 47X \ 4 1)X 1’ 9x tr / / 11 8: : 12 13 43x 6X c: - 17x fl :l.figCF3COC/h~xana, 2 .EtO-; B:HCOrH/~rO/THF-2/1/2, 19h rmflux, c: HCOeH/HtO-9:l; 0.5h rmfluxl 7x 1cx 38X St~tulal A88lgarLs. Gmpmlds 7 and 9-11 shov "C NM spectra closely slmllar to that of thelr precursor 5, lndlcntlng that the conflguratlon at the tug double bonds had renalned tmchanged. H r.rrc 1 ‘;:‘;.” n.” 1n.b tr “.U eJ.w* n.n 0 u0.w ‘-.='u.lo Cyclsationr and rcarwqanenlr in the damrsconc sefks 6049 Ths ‘H NM spctra of (&6)-12 era In 0cwM ulth the specttu rrported for the mlxtw of the two dlastereol~n. ’ Tt10@ differences In the “C M spectra Oetuwn the lsae~ can be fouxl. the relatlve stereochsmlstry could not be assigned on thls baals. 6M.U) (R3.31) JO.11 ac.3t 0 as.44 4 9s.a1 Lt.97 - lR4.bl :r1.s1> 1O.M 134 .bO l’e*es (LO.O?> (El-12 (ZI-12 NOE IEI-12 Nuclear Overhauser effects between the allyllc ethyl pmtuu (6 I.611 and the rnethyl doublet at 6 1.31 aa well BJ an WE between 2-H and the methyl ~PXIP at 6 0.94 suggested the stereoche0lcal assignment of the (E)-1-r. 5he cyclopentenone structure of 13 MU derived from, the strong infrared atuorptlons at 1689 and 1619 cm-’ and the UV absorption at Amax - 223.0 (log E - 0.03). Its ‘H NMl and 1~85s spectmxoplc data are In accord with literature raport~.’ The tnJteny1-cyclohexe 14 has previously been detected as a oxutltwnt of -thus absolute.” bfa have now corroborated the suggested structure by ‘H NW spln &xxx~pllng experlmts and a “C NM spectnm. W absorptlons at 229, 267 and 276 m ma an AB system at 6 6.91 and 7.01 (a-7.6 Hz, 2 H) ln the ‘H NM spectNm lndlcated 15 to be a axipound wlth two adjaoent aramatlc protons. Since 15 85 uell M stNctura1 altematlves had been syntheslsed by cycllalkylatlon pcwxdures,‘* an unequlvccal asslgrnent on the Msls of ‘H tM chemical shifts vas posslble. Reactlar -la. The formation of compunds 9-15 1s ratlonallsed by Scheme 2. Ionlsstlon of 7 ylelds the tertlary carbenlun lcm 16 from vhlch oompowxls 9-11 am derived. Cycllaatlon of 16 affords the anbldent methyleneallyl - allenylcarblnyl cation 17 uhlch may be attacked by nucleophlles at tw different posltlciw. Canpound 8, the only cyclic prcduct famed in the sllver trlflLoFosoet.ate lnltlated reactlm. arises km attack of CF,cO; at 17 and hydrolysis of the resulting ester. h?wn the reaction 1s carried Out In formic acid, 8 1s not isolated; under these condltlons, the central allenlc posltlon of 8 Is protonated to yleld the sterwolwrlc pentadlenyl catlcxw 18 and Zl. the fomer of tilch nay cycllse ulth fmtlon of the theasplrenes 12. In accord with this ,wchanlsn acid treatment of 8 has been reported to yleld the theasplrenea 12.” Canpomds 12 are not observed when the cycllsatlcn or 7 1s carried out in Sor rmlc acid. It can be assrmd, them, that u&r are acldlc cwdltlorw the dlhydroruran ring 0r 12 1s cleaved agaln, and the regenerated ostlon 18 undergoes steracuwtatlon with fonratlon of 21, which can alx, be rc+ued fmn 8 directly. Cation 2l then oosbl~s ulth a nucleopllle to glve the allyllc formste 25 (or the oorrespondlng alcohol), uhlch 1s converted lnto 27 by acid catalyzed behydratlon. lhe trlenyl rotate 27 may elther be hydrolysed to glve 11 or pmtonated to arrord the pentadlenyl cation 2% uhlch Lndergoes electraycllc ring closure and depmtonation. 6050 w. titlLUNN Cl 01. The seoondlry fomate 21, thus famed, 1s suggested to solvolyse bflth sl~~~lt.aneow 1,2-vinyl shift to give the benzmlm lon 23. the prwursor of 15. Compound 8 as well as the products 12, II, and 15 are thu explained vla attack of a nucleophlle at the sp’ temlnue of the allyllc cation 17. The altematlve nucleophlllc attack at the sp carbon of 17 yields an mol of the daaasoone 1. uhlch afford 13 In a Harmor type cycllsstlm, as deacrlbed pr8vloualy. I’ Scheme 2 7 16 / / 9.10.11 1 -H' 16 H +H,O -ti* 87 OH / 6 OH 21 I +HCO,H -H4 OH OCHO 26 6CHO I IH’I -H,O 1 (enol) I +H' OH 19 I a>cyc 1. b) -H+ OH w / 22 0 w / 13 Cycl~retionsrndramngmvnuinthcd ama¶axuvner 6051 Qaalrslan. The rwdlly available chlowlfslyne 7 represents a w prwursor to draaearrold m, but condltlona for the seleotive cycllsatlon have not yet bean land. Slnoe in pnsence of Brkrstad acids, pt‘otanatlon of 8 to give 18 or 21 appears to be faster than the relcmlsatlal II - 17. ths eelectlve fmtlon of 1 probably requ11~ solvents of lac acidity and high lonlslng pacsr. (hraal. IR: ShlDsdzu M-435. - MM: Varlan XL 200; chemloal shifts (6) refer to internal Rc;. - Hase Spectra: VC 70-250. - UV: Kontran Uvlkon MO. - The pcepnantlve l+%C eeparatlofu were carried out on 30 x 2.5 cm glass ml- filled ulth Llch~~prep S! 60, 15-25 u (SlO, or RP 18) partlclss using a Cllson &de1 302 pmp, a Rheodyne 7125 lnjectlon valve, and a Iatek RI 201 dlfrenatlal rafrectaactar. 3-~t~I-2(Z).6(t)-octadian-4_mtsl (5). 3-Cbthyl-2(2)-LEnt~-4-vn-1-o1 (4) (19.3 u. 200 -1, FWKA~andi(Z)+nnop&ene (22.5 g, 186 nmoi, J+ -mdej - _. YBR dkolved in 300 mL of dlethyl~lne (nlr&m atmos&ere). A mlxtlw of Cu,X. (0.33 g. 0.87 mol) and Pd (PPh.).CI. (0.59 g, 0.84 -1) Y&Y added slculy with stlrrlng (exothetic &ctlonl). A clear solution 1; funed fron tilch a colcurlsss ealt preclpftetes after several minutes. After 2 h at amblent temperature, the mixture uIu pcuzwd Onto 500 d. of Ice/water. The layers were separated, and the aweoue layer m extracted with two 100 mL wrtluu of ether. The cc&lned oraanlc lavere were &shed s&era1 tlmee wlth 50 I& portions of’ 31 aqueous HCl until the aqueaG Yayer had a pH < 7. After dryly over Na,SO. and evaporatla! of the solvent. dlstlllatlon gave 5 (20.9 g, 8%). a colourless 011 with bp. 48-49*C/O.l nbar. ‘H JM (CDCl,): 6 1.89 (da. -J - 6.8 Hz, 1.7 ttz, 3 H. 8-H). 1.92 (dt, J - 1.5 Kziz, 1.1 H, 3-CM,). 4.34 (dq, J - 6.8 Kz, 5.86 (ta, J - 6.6 M.-l.5 Hz. 1 1.1 Hz. 2 H, 1-H). 5.62 (dq, J - 10.8 J - 10.8 Hz: 6.8 Hz. Ri, 1.7 Hz, Hz, 3 1 ~-HI. H, H. 2-H). 6.01 (da. 1 H. 7-H). - “C MI: see YGuKural Asslgfxnentsw. - 1360, 1085. 1036, IR-neat:.3301, 30%,-2912, 2850; 218o,~i630, ‘143j; 1400, 13?i, 1323, 997, 707, 762. n9 cm-‘. 1+1law-3athjlr2(2).6(~~&~ (6). Wtreted agueoLu HCl (371. 14.2 & 171 -1) was added drop&e to a well stlrred mlutlon of 5 (10.5 g, 77.1 -1) ln 62 mL of petrolarm ether (bp. 40-6WC) at 0% The mixture NM stirred at 0% for 17 h, and the wlc layer ybs dried over Na,SO,. After evapbratlan of the solvent. g, 96$), a colourlejs 011 with bp. 30-31 Y/4 mbnr. the reeldue uaz~ dlstllled to give 6 (11.4 ‘H NWI (CDcl,): 6 1.92 (dd, J - 6.9 Hz, 1.7 Hz, 3 H, 8-H). 1.s (dt, J - 1.5 Hz, 0.8 Hz, 3 H, 3-a(,). 4.29 (dq, J - 5.83 (ta, J - 7.8 i&iz. 0.8 Hz. 2 H. I-H), 5.66 (dq, J - 10.7 %, 1.7 Hz, 1 H, 6-H). 7.8 Hz, 1.5 Hz, 1 H, 2-H). 6.05 (dq, J - 10.7 ti 6.9 Hz. 1 H. 7-H). - “C NWt (CDCl,): 676.11 (q. C-8). 23.18 (q. 3-W.). 42.57 Ct; C-11, 91.15, 92.64 (2 s, C-4.5). 109.83 (d, C-6). 123.88 (s, C-3). 130.77 (d, C-21, 139.26 (d, C-7). - IR (neat): 3023, 2940, 2913, 2950, 2180, 1666, 1626, 1435, 1400, 1375, 1365, 1346, 1257, 1235, 1217, 1155, 1032. 1000, 920, 832, 720 cm-‘. lWav-6.l odlruul-Z(Z) ,60 solutlcn of ZnCl, (5.18 g)in et i -wle=u&7ne (7). Isobutene (17.8 g. 317 amol) and a r (6.2 at) uep~ dlsaolved In CH,C1,(133 mt) which wu preoooled at -78T.** A solution of 6 (7.73 g. 50.0 -1) In CH,C1,(6OmL) wee added dropwise within 2 h. llm mixture Y- kept at -78% for 16 h and WM then washed wlth 100 mL of 251 am NH.Cl solutlcn. The organic layer MU dried over C&l, and the eolvent uas eva &T rated. Dlstlllatlon of the residue yielded 7 (6.34 g. 60$), a slightly yellou 011 with bp. 50 l C (beth)/O.l mbar. ‘H !M (al,): 6 1.59 (5, 6 H, 11-H, 10-M.). 1.80 - (PI, 2 H, 8-H). 5.60 - 2.02 (m, 8 H, 1,9-H, 6-a.). 2.40 - 2.52 5.70 (m, 2 H, 3.7-H). 5.99 (dq, J - 10.7 Hz, 6.8 Hz, 1 H, 2-H). - “C NM: see %ructural Ase@mentsn. - IR (neat): 3020, 297%, 2920, 2180, 1724, 1670. 1448, 1400, 1385, 1370, 1215. 11%). 1160. 1114, 1077, 1034, 820, 719 cm-‘. m-t d 7 uith Sllnr MILuomatat4. A solution of 7 (2.11 g, 10.0 mol) in 300 ti of ary hemne was mAed at -1QOC and protected from, ll*t (almlnllar foil). ApproxlaPstely 20 portlone. of AgcF,CO, (total: 2.21 g, 10.0 -1) uem added to the well stirred solution wlthln 2 h. ‘The ooollng bath WM r*rmoved. and stlrrlna was oontlnued for 17 h. 7he ausmwlcn m flltered, the Gl was wutwd vlth 20 mL of he&, end the solvent w&evaporated to give 3.06 g of a yellcu 011, which uas added dropulee to a well-stlrtvd solution of KW (5.0 u. 89 -1) in 70 ti of ethanol. After 1 h, 150 & of water wm added, and the mutts W(P ext&ted with tw 75 mL portluu of pentane. The organic layen uere dried over Na,SD.. and the solvent KM evaporated to afford 1.75 g of a yeller 011, uhlch UM separated by CPU: (RP 18, aC,aC : It.0 - 10 : 1). We obtained 904 w (47%) of 8. 365 w (191) of 9, end 194 eg (11s) of a 4:l mixture of 10 and 11. 6.7-D&yWcw-laaol [4-(2*.6’.61-Trlmu@-2’-ap l&.xm-1*71lbrre)-3-euw-2-01] (8, 1:1 - mlxtum of dlaetemolsaaers): &. 35-4OY (tnth)/O.l abar (lit.” ca 44-46q/O.O1 Torr). - ‘H M (CDCl,): 6 1.06. 1.07, 1.07 (3 s, 6 H, 6’-Q(,), 1.31 (d, J- 6.4 Hz, 3 H, 1-H). 1.49 (t, Cyclivtioor and mmngcmea0 in tbc duarmae wria 6053 (371, 41 (43). - Anal. Cdod for C,,H,,O (192.3)1 C, 81.20; H, 10.48. F-0: C. 80.76; H, 10.44. !3olvnlJ8lB d 7 in poz ?awo b1ubt.u. Gapam 7 (1.05 g, 5.00 -1) wan inled Qppwlae to a refluxlng solution of 905 fdc acid/w&or (50 mL) to give a dar(c W dxtwo. Aftw 0.5 h, the heat- yu lla~ved, and 100 d. of uater ufu adbsd. The pfudwta wm extmoted with tm zo d. portlum of pstlwlBn ether. Ths extrscta WXY! dried over Na,So., and the sol-t ras evaporated ln vacua to glve 0.760 g of a yellcnf oil, which wan pWaed over Sllla (ptrolerP ether :et.hw - 98 : 2) to give 330 w (38s) of 15 with ep. 5055% bnth)/9.1 du‘. w?nl the alllca colwm wae ueahed wlth ether, 420 (ps of a mlxtum was obtdned rchloh whB aeparatad by WLC (silica @l, twana : etJw - 80 : 20) to give 160 a (17s) of 13 an4 150 m of allBht.ly ccn- tamlnatcd 11. IQU: of tJ11a fraction (RP 18, CH,W : H,O - 85 : 15) &avs 112 * (12s) of plre 14. 1.1.1.5-Tet~ll1x~a (15)". - 'H NM (CDCl,): 6 - 1.24 (a, 6 H, l-CH,), 1.91 (t, J - 7.2 Hz, 2 H, 2-H). 2.17 (d, J - 0.4 Hz, 3 H. aryl-Qt.), 2.25 (d, J - 0.3 Hz, 3 Ii, aryl-o(,T, 2.83 ft. J - 7.2 Hz, 2 H. 3-HT. 6.91, 7.01 (A&system, J - 7.6 ttzb, 1 H. 6,7-H). All 6 values In t.ha ~~refo;alys dascrlbed apectrd’ (ccl., 60 Mtz) KappPxlmtely 0.07 pp tiler. - “C Nl4R I : - 15.78, 19.59 (2 Q, 4.5~CM,), 28.88 (q, I-CXH,), 29.00 (t, C-31, 41.19 (t, C-2). 44.05 (a, C-l), 119.01 (d, C-7). 128.14 (d, C-6). 132.28 (a, C-5). 134.23 (a, C-4), 141.76 (a, C-9). 150.05 (a, C-8). - IR (neat): 3001, 2950. 2856, Iboo, 1476, 1453. 1380, 13&I, 1313, 1120, 1100, 998, 811, 785. 762 an”. - W (pentane): A Naas apecttun (70 eV): m/z - 17’( (191, K’), 159 Cl%+, (log c) - 229.0 (2.84). 267.0 (2.74). - 144 (7), 129 (7). 128 (8). 119 (4). 115 (51, 91 (4). 77 (3). --il. Calcd for C,,H,, (174.3): C. 89.59; H. 10.41. Feud: C. 89.33; H, 10.59. Adawl_t. Ye thank Roawltha m for experiDsnta1 aaalatance for the N?fl apectmplc atrvctural eluclclatluu. A.-R. thanks the A.v. a fellwshlp. and Ralner Koechlnaky Hu&oldt Stlftung for 1) 2) 3) 10 5) 6) 7) 8) 9) 10) 11) 12) 13) 14) 15) 16) 17) 18) 19) 20) 21) R. Kaiser, D. Lgpsmky, Helv. Chlm. Aeta 61, 2328 (1978). 22) K. !%xqa&~lra, Y. Tohds, N. Haglhara, Tetmhadmn Lott. 4467 (1975). 23) E.N. Mrvell, C. Hilton, M. Tilton. J. w. Chm. 46, 5379 (1983). C. tXloff, V. Reutenatrauch, K.H. Schulte-Elte, Helv. Calm. Acta 56, 1503 (1973). E. Desnole. P. -1st. U. Slluberll, H. Stall, E. as. Kovbta, Hslv. 0110. Acta 53, 91 (1970). C. Mchl, J.C. Vederaa, J. &I. Chem. SW. 94, 9128 (1972). K.H. SchultbElte, B.L. Miller, C. chloff, Helv. Chlm. Acta 56, 310 (1973). C. CWoff, G. Uhcle, Helv. Chlm. Acta 53, 531 (1970). S. Yamada. U. ShlbsMkl, S. Terashlm, Tet mhedron Lett. 381 (1973). t!. Ktuano, Y. Mtaubara. Klnkl Dalgaku Rlkogakubu Kenkyu Hokoku 13, 37 (1978); chea. Abatr. 09, 163794 p (1978). R.L. snowden, B.L. MJller, K.H. Schulte-Elte, Tetrahedron Lett. 23, 335 (1982). C. Fehr. J. Gallndo, Hclv. Chlm. Acta 69. 228 (1986). H.J. LOU. H.K. w. C.L. w&e. H.L.D. Yelnberg. can. J. Cheat. 56, 1368 (1978). K.H. Schulte-Elte, H. Strlckler, F. Cautachl, Y. Plckenhagsl, t4. CnOola, J. Llmcher, B.L. Miller. F. Wuffll. C. chloff. Lleblgs Ann. than. 484 (1975). T. Mar&l, K. ~lz&uchi, t4. Kavada, J. Otera, J. Crg. Chc~. 49, 3403 (1984). F. Naef, R. Deconant.. Tetrahedm7 &?, 3245 (1986). I% Zaldlwlcz. Tetrahedron L&t. a, 5135 (1986). E. Bbuml, H. Ebyr, Ger. Pat. P 3402 993.1; Um. Abatr. 101, 207490 u (1986). K.H. Schulte-Elte, F. Cautschl, V. Renold, A. Hniausar, P. PankMuser, J. Llmcher, C. CMoff. Hslv. Chlm. Acta 61, 1125 (1978). C. Chloff. K.H. Schulte-Elte. E. -le. Helv. Chlm. Acta 9, 2913 (1971). K. Uneyama, S. Fujlbayaahl, S. Tori!, Tetduwlron Lett. 4637 (1985). R. Pelllcclarl, E. Caatagnlno, R. Frlnguelll. S. Cocrano, Tetrahedron l&t. @1 (1979). U. Ranold, R. NM-Wller, U. Keller, B. Wlllhalm, C. CWoff, Helv. Chlm. Acta !V, 1301 (1974). 6054 W. HMINA~ l I al 24) H. bfl, m. Qlso. 93, 202 (1981): h@f. chsm., ht. Ed. -1. 20, 181( (1981). 25) H. chyr, V. Strlepe, .I. Ox& chso. 16, 1159 (1993). 26) H. klaryr, H. Klein, C. Koltnwg, Chm. Bar. 117, 2555 (1984). 27, H. Mayr, C. S&a&, M. RU~CN. R. SchnOi&W. h@V. cm. 9. 1059 (1987): h&V. -. xnt. Ed. hgl. 26, 1029 (1987). 28) H. Hayr, U. Strlepe, J. Urg. chso. 9, 29% (1985). 29) E.J. Elambram, J.R. Mttox, R.C. Baned, I4.A. WlhOh P.U.K. Fh’UWfI, LB. -1, ~.e. ~aramy, n.c. mhg, J. erg. Ch. 33, ~OOO (1968). 

Carbocationic cyclisations and rearrangements in the damascone series

Universität München: Elektronischen Publikationen

Werner Hellmnn, klmr-Rm, wlbert Blluml. and Herbert Meyr* 
Itutitut Rlr Tommie her Medlzlnlxhen Unlvenltiit p1 L&beck 
Ratzeburger Allee 160, D-Z’WI LUbeck 1, Federal RepJbllc of Germany 
( Rtchtrd m Grmuy I 5 July 1988) 
hblltlmA: A raglo- and strreoselectlve synthesis of the tertiary chlwl6s 
7 1s described. lnvolvlw the Levis acid catalysed addltlon of the ally1 
chloride 6 to lsbutene m a key step. Acid catalywd cycllsatlon of 7 
ylelas the damasamold antpomds 12-15. 
Aa c,, ampounds, the damasamee 1, llke the lonmes 2 am not members of the terpene fenlly. 
Their structural relatloruhlp to terpsnes 1s obvious, houever, and they hwe been suggested to 
be metabolltes ol carotenes.’ Because of their occurenoe as natural fragrance and am anutl- 
t.uentS, they are of casmerclal interest, and several symthsses 
ampounds have ken developed, often based m Intermediates 
synthesis.*-‘9 
to Omimxnca and dmiuamold 
of the techn1ca1 vltamln A 
In thls tark, ye report cm the synthesis of the dlenyne 7, a ww precursor of dMlascmol0 
compounds. Its acid catalysed cycllsatlcm 1s fomd to give mlxtur03 of oooparnds, a of utllch 
are kmm az. axutltuents of black tsa arcma (13)**, of Omanthus absolute (II)“, and of 
Vlrglnla tabacm (14)*’ tille othen hwe been used a9 precursm for the synthesis of arcma 
cunpowlds (8, 12).“@” 
barlts. Pd(II) catalysed mupllng **e” of 3-methyl-pent-2(g)-an-b-yn-l-01 (4) (trade w: 
1 ‘-panto ulth l(Z)-bnaropmpene (3) gavs 83$ of 5 ln a stemmelectlve mactlm. Slncc the 
ccmflgwatlcw of the 6.7~double bond 1s loat ln the cyclimd pmducte. the w of sWlcally 
pure 3 1s qot necemary, Ma it tms been &o&l tJnt the Mae cy6llsatlan prcclucts am obtalmcl. 
when a mlxtun of 1-brcmopmpenes 1s u!M instead of the pum (L)-1-r. Treatant of 5 ulth 
conoentr8te4 hydmchlorlc acid in petmlem ether ylelOe4 961 of 6, vhlch shwa a hl@er Snl 
reactlvlty th3n tertiary alkyl chlorides ma, therefore, gives the 1:1 pm&et 7 ulth leobutene 
‘*-” ln presence of the weak Leuls acid ZnCl,~Et,O.‘* 
6047 
6048 w. HCILMANS <*I <I/ 
831. , 961: 60% 
4 5 8 1 
Attwps to cycllse 7 with BCl, or SnC1, at -78’C w wlth ZnCl, at O°C yielded complex mlxtw 
of products uhlch hsve not been lbentlfled. Tn~tment of 7 with sliver trlrluoroacetate In 
hexane and successive workup with ethanollc KOH afforded the cyclic allene alcdd 8 along with 
the acyclic ccu~pands 9-l 1. fhe prekdnnnt fonuetlon of cyclfsed -rmQs was observed when 
the tertiary chlorlda 7 YBS heate in aqueous folalc acid. Yhlle the tertlary alcohol 9 was 
isolated with the cycllsed ozqwu~Us 12-14 tin&r rrlatlvely mild condltlons (HUl,H:H,O:THF 
-2:1:2). only cyclic 
acid under rpflux. 
oompwnds were observed (13-15). when 7 was heated In 901 aqxms fomlc 
Scheme 1 
a+FJ r+ 8 8’ 10 
FI: 47X \ 4 1)X 1’ 9x 
tr / / 
11 
8: : 
12 13 
43x 6X 
c: - 17x 
fl :l.figCF3COC/h~xana, 2 .EtO-; 
B:HCOrH/~rO/THF-2/1/2, 19h rmflux, 
c: HCOeH/HtO-9:l; 0.5h rmfluxl 
7x 
1cx 38X 
St~tulal A88lgarLs. Gmpmlds 7 and 9-11 shov "C NM spectra closely slmllar to that of thelr 
precursor 5, lndlcntlng that the conflguratlon at the tug double bonds had renalned tmchanged. 
H 
r.rrc 1 ‘;:‘;.” 
n.” 1n.b tr “.U eJ.w* n.n 0 u0.w 
‘-.='u.lo 
Cyclsationr and rcarwqanenlr in the damrsconc sefks 6049 
Ths ‘H NM spctra of (&6)-12 era In 0cwM ulth the specttu rrported for the mlxtw of the 
two dlastereol~n. ’ Tt10@ differences In the “C M spectra Oetuwn the lsae~ can be 
fouxl. the relatlve stereochsmlstry could not be assigned on thls baals. 
6M.U) 
(R3.31) 
JO.11 
ac.3t 
0 as.44 4 9s.a1 Lt.97 - lR4.bl :r1.s1> 1O.M 134 .bO 
l’e*es (LO.O?> 
(El-12 (ZI-12 NOE 
IEI-12 
Nuclear Overhauser effects between the allyllc ethyl pmtuu (6 I.611 and the rnethyl doublet 
at 6 1.31 aa well BJ an WE between 2-H and the methyl ~PXIP at 6 0.94 suggested the stereoche0lcal 
assignment of the (E)-1-r. 
5he cyclopentenone structure of 13 MU derived from, the strong infrared atuorptlons at 1689 and 
1619 cm-’ and the UV absorption at Amax - 223.0 (log E - 0.03). Its ‘H NMl and 1~85s spectmxoplc 
data are In accord with literature raport~.’ The tnJteny1-cyclohexe 14 has previously been 
detected as a oxutltwnt of -thus absolute.” bfa have now corroborated the suggested 
structure by ‘H NW spln &xxx~pllng experlmts and a “C NM spectnm. W absorptlons at 
229, 267 and 276 m ma an AB system at 6 6.91 and 7.01 (a-7.6 Hz, 2 H) ln the ‘H NM spectNm 
lndlcated 15 to be a axipound wlth two adjaoent aramatlc protons. Since 15 85 uell M stNctura1 
altematlves had been syntheslsed by cycllalkylatlon pcwxdures,‘* an unequlvccal asslgrnent 
on the Msls of ‘H tM chemical shifts vas posslble. 
Reactlar -la. The formation of compunds 9-15 1s ratlonallsed by Scheme 2. Ionlsstlon of 
7 ylelds the tertlary carbenlun lcm 16 from vhlch oompowxls 9-11 am derived. Cycllaatlon of 
16 affords the anbldent methyleneallyl - allenylcarblnyl cation 17 uhlch may be attacked by 
nucleophlles at tw different posltlciw. 
Canpound 8, the only cyclic prcduct famed in the sllver trlflLoFosoet.ate lnltlated reactlm. 
arises km attack of CF,cO; at 17 and hydrolysis of the resulting ester. h?wn the reaction 1s 
carried Out In formic acid, 8 1s not isolated; under these condltlons, the central allenlc 
posltlon of 8 Is protonated to yleld the sterwolwrlc pentadlenyl catlcxw 18 and Zl. the 
fomer of tilch nay cycllse ulth fmtlon of the theasplrenes 12. In accord with this ,wchanlsn 
acid treatment of 8 has been reported to yleld the theasplrenea 12.” 
Canpomds 12 are not observed when the cycllsatlcn or 7 1s carried out in Sor rmlc acid. It 
can be assrmd, them, that u&r are acldlc cwdltlorw the dlhydroruran ring 0r 12 1s 
cleaved agaln, and the regenerated ostlon 18 undergoes steracuwtatlon with fonratlon of 21, 
which can alx, be rc+ued fmn 8 directly. Cation 2l then oosbl~s ulth a nucleopllle to glve 
the allyllc formste 25 (or the oorrespondlng alcohol), uhlch 1s converted lnto 27 by acid 
catalyzed behydratlon. lhe trlenyl rotate 27 may elther be hydrolysed to glve 11 or pmtonated 
to arrord the pentadlenyl cation 2% uhlch Lndergoes electraycllc ring closure and depmtonation. 
6050 w. titlLUNN Cl 01. 
The seoondlry fomate 21, thus famed, 1s suggested to solvolyse bflth sl~~~lt.aneow 1,2-vinyl 
shift to give the benzmlm lon 23. the prwursor of 15. 
Compound 8 as well as the products 12, II, and 15 are thu explained vla attack of a nucleophlle 
at the sp’ temlnue of the allyllc cation 17. The altematlve nucleophlllc attack at the sp 
carbon of 17 yields an mol of the daaasoone 1. uhlch afford 13 In a Harmor type cycllsstlm, 
as deacrlbed pr8vloualy. I’ 
Scheme 2 
7 16 
/ 
/ 
9.10.11 
1 -H' 
16 H 
+H,O 
-ti* 
87 
OH 
/ 
6 
OH 
21 
I 
+HCO,H 
-H4 
OH 
OCHO 
26 
6CHO 
I 
IH’I 
-H,O 
1 (enol) 
I +H' OH 
19 
I a>cyc 1. b) -H+ 
OH 
w 
/ 
22 
0 w / 13 
Cycl~retionsrndramngmvnuinthcd ama¶axuvner 6051 
Qaalrslan. The rwdlly available chlowlfslyne 7 represents a w prwursor to draaearrold 
m, but condltlona for the seleotive cycllsatlon have not yet bean land. Slnoe in 
pnsence of Brkrstad acids, pt‘otanatlon of 8 to give 18 or 21 appears to be faster than the 
relcmlsatlal II - 17. ths eelectlve fmtlon of 1 probably requ11~ solvents of lac acidity 
and high lonlslng pacsr. 
(hraal. IR: ShlDsdzu M-435. - MM: Varlan XL 200; chemloal shifts (6) refer to internal Rc;. 
- Hase Spectra: VC 70-250. - UV: Kontran Uvlkon MO. - The pcepnantlve l+%C eeparatlofu were 
carried out on 30 x 2.5 cm glass ml- filled ulth Llch~~prep S! 60, 15-25 u (SlO, or RP 18) 
partlclss using a Cllson &de1 302 pmp, a Rheodyne 7125 lnjectlon valve, and a Iatek RI 201 
dlfrenatlal rafrectaactar. 
3-~t~I-2(Z).6(t)-octadian-4_mtsl (5). 3-Cbthyl-2(2)-LEnt~-4-vn-1-o1 (4) (19.3 u. 200 
-1, FWKA~andi(Z)+nnop&ene (22.5 g, 186 nmoi, J+ -mdej 
- _. 
YBR dkolved in 300 mL 
of dlethyl~lne (nlr&m atmos&ere). A mlxtlw of Cu,X. (0.33 g. 0.87 mol) and Pd (PPh.).CI. 
(0.59 g, 0.84 -1) Y&Y added slculy with stlrrlng (exothetic &ctlonl). A clear solution 1; 
funed fron tilch a colcurlsss ealt preclpftetes after several minutes. After 2 h at amblent 
temperature, the mixture uIu pcuzwd Onto 500 d. of Ice/water. The layers were separated, and 
the aweoue layer m extracted with two 100 mL wrtluu of ether. The cc&lned oraanlc lavere 
were &shed s&era1 tlmee wlth 50 I& portions of’ 31 aqueous HCl until the aqueaG Yayer had a 
pH < 7. After dryly over Na,SO. and evaporatla! of the solvent. dlstlllatlon gave 5 (20.9 g, 
8%). a colourless 011 with bp. 48-49*C/O.l nbar. 
‘H JM (CDCl,): 6 1.89 (da. -J - 6.8 Hz, 1.7 ttz, 3 H. 8-H). 1.92 (dt, J - 1.5 Kziz, 1.1 
H, 3-CM,). 4.34 (dq, J - 6.8 Kz, 
5.86 (ta, J - 6.6 M.-l.5 Hz. 1 
1.1 Hz. 2 H, 1-H). 5.62 (dq, J - 10.8 
J - 10.8 Hz: 6.8 Hz. 
Ri, 1.7 Hz, 
Hz, 3 
1 ~-HI. H, 
H. 2-H). 6.01 (da. 1 H. 7-H). - “C MI: 
see YGuKural Asslgfxnentsw. - 
1360, 1085. 1036, 
IR-neat:.3301, 30%,-2912, 2850; 218o,~i630, ‘143j; 1400, 13?i, 
1323, 997, 707, 762. n9 cm-‘. 
1+1law-3athjlr2(2).6(~~&~ (6). Wtreted agueoLu HCl (371. 14.2 & 171 
-1) was added drop&e to a well stlrred mlutlon of 5 (10.5 g, 77.1 -1) ln 62 mL of petrolarm 
ether (bp. 40-6WC) at 0% The mixture NM stirred at 0% for 17 h, and the wlc layer ybs 
dried over Na,SO,. After evapbratlan of the solvent. 
g, 96$), a colourlejs 011 with bp. 30-31 Y/4 mbnr. 
the reeldue uaz~ dlstllled to give 6 (11.4 
‘H NWI (CDcl,): 6 1.92 (dd, J - 6.9 Hz, 1.7 Hz, 3 H, 8-H). 1.s (dt, J - 1.5 Hz, 0.8 Hz, 3 
H, 3-a(,). 4.29 (dq, J - 
5.83 (ta, J - 
7.8 i&iz. 0.8 Hz. 2 H. I-H), 5.66 (dq, J - 10.7 %, 1.7 Hz, 1 H, 6-H). 
7.8 Hz, 1.5 Hz, 1 H, 2-H). 6.05 (dq, J - 10.7 ti 6.9 Hz. 1 H. 7-H). - “C NWt 
(CDCl,): 676.11 (q. C-8). 23.18 (q. 3-W.). 42.57 Ct; C-11, 91.15, 92.64 (2 s, C-4.5). 109.83 
(d, C-6). 123.88 (s, C-3). 130.77 (d, C-21, 139.26 (d, C-7). - IR (neat): 3023, 2940, 2913, 2950, 
2180, 1666, 1626, 1435, 1400, 1375, 1365, 1346, 1257, 1235, 1217, 1155, 1032. 1000, 920, 832, 
720 cm-‘. 
lWav-6.l odlruul-Z(Z) ,60 
solutlcn of ZnCl, (5.18 g)in et i 
-wle=u&7ne (7). Isobutene (17.8 g. 317 amol) and a 
r (6.2 at) uep~ dlsaolved In CH,C1,(133 mt) which wu preoooled 
at -78T.** A solution of 6 (7.73 g. 50.0 -1) In CH,C1,(6OmL) wee added dropwise within 2 h. 
llm mixture Y- kept at -78% for 16 h and WM then washed wlth 100 mL of 251 am NH.Cl 
solutlcn. The organic layer MU dried over C&l, and the eolvent uas eva 
&T 
rated. Dlstlllatlon of 
the residue yielded 7 (6.34 g. 60$), a slightly yellou 011 with bp. 50 l C (beth)/O.l mbar. 
‘H !M (al,): 6 1.59 (5, 6 H, 11-H, 10-M.). 1.80 - 
(PI, 2 H, 8-H). 5.60 - 
2.02 (m, 8 H, 1,9-H, 6-a.). 2.40 - 2.52 
5.70 (m, 2 H, 3.7-H). 5.99 (dq, J - 10.7 Hz, 6.8 Hz, 1 H, 2-H). - “C 
NM: see %ructural Ase@mentsn. - IR (neat): 3020, 297%, 2920, 2180, 1724, 1670. 1448, 1400, 
1385, 1370, 1215. 11%). 1160. 1114, 1077, 1034, 820, 719 cm-‘. 
m-t d 7 uith Sllnr MILuomatat4. A solution of 7 (2.11 g, 10.0 mol) in 300 ti of 
ary hemne was mAed at -1QOC and protected from, ll*t (almlnllar foil). ApproxlaPstely 20 
portlone. of AgcF,CO, (total: 2.21 g, 10.0 -1) uem added to the well stirred solution wlthln 
2 h. ‘The ooollng bath WM r*rmoved. and stlrrlna was oontlnued for 17 h. 7he ausmwlcn m 
flltered, the Gl was wutwd vlth 20 mL of he&, end the solvent w&evaporated to give 3.06 
g of a yellcu 011, which uas added dropulee to a well-stlrtvd solution of KW (5.0 u. 89 -1) 
in 70 ti of ethanol. After 1 h, 150 & of water wm added, and the mutts W(P ext&ted with 
tw 75 mL portluu of pentane. The organic layen uere dried over Na,SD.. and the solvent KM 
evaporated to afford 1.75 g of a yeller 011, uhlch UM separated by CPU: (RP 18, aC,aC : It.0 - 
10 : 1). We obtained 904 w (47%) of 8. 365 w (191) of 9, end 194 eg (11s) of a 4:l mixture of 
10 and 11. 
6.7-D&yWcw-laaol [4-(2*.6’.61-Trlmu@-2’-ap l&.xm-1*71lbrre)-3-euw-2-01] (8, 1:1 - 
mlxtum of dlaetemolsaaers): &. 35-4OY (tnth)/O.l abar (lit.” ca 44-46q/O.O1 Torr). - 
‘H M (CDCl,): 6 1.06. 1.07, 1.07 (3 s, 6 H, 6’-Q(,), 1.31 (d, J- 6.4 Hz, 3 H, 1-H). 1.49 (t, 

Cyclivtioor and mmngcmea0 in tbc duarmae wria 6053 
(371, 41 (43). - Anal. Cdod for C,,H,,O (192.3)1 C, 81.20; H, 10.48. F-0: C. 80.76; H, 10.44. 
!3olvnlJ8lB d 7 in poz ?awo b1ubt.u. Gapam 7 (1.05 g, 5.00 -1) wan inled Qppwlae to 
a refluxlng solution of 905 fdc acid/w&or (50 mL) to give a dar(c W dxtwo. Aftw 0.5 h, 
the heat- yu lla~ved, and 100 d. of uater ufu adbsd. The pfudwta wm extmoted with tm 
zo d. portlum of pstlwlBn ether. Ths extrscta WXY! dried over Na,So., and the sol-t ras 
evaporated ln vacua to glve 0.760 g of a yellcnf oil, which wan pWaed over Sllla (ptrolerP 
ether :et.hw - 98 : 2) to give 330 w (38s) of 15 with ep. 5055% bnth)/9.1 du‘. w?nl the 
alllca colwm wae ueahed wlth ether, 420 (ps of a mlxtum was obtdned rchloh whB aeparatad by WLC 
(silica @l, twana : etJw - 80 : 20) to give 160 a (17s) of 13 an4 150 m of allBht.ly ccn- 
tamlnatcd 11. IQU: of tJ11a fraction (RP 18, CH,W : H,O - 85 : 15) &avs 112 * (12s) of plre 14. 
1.1.1.5-Tet~ll1x~a (15)". - 'H NM (CDCl,): 6 - 1.24 (a, 6 H, l-CH,), 1.91 (t, J - 7.2 
Hz, 2 H, 2-H). 2.17 (d, J - 0.4 Hz, 3 H. aryl-Qt.), 2.25 (d, J - 0.3 Hz, 3 Ii, aryl-o(,T, 2.83 
ft. J - 7.2 Hz, 2 H. 3-HT. 6.91, 7.01 (A&system, J - 7.6 ttzb, 1 H. 6,7-H). All 6 values In t.ha 
~~refo;alys dascrlbed apectrd’ (ccl., 60 Mtz) KappPxlmtely 0.07 pp tiler. - “C Nl4R 
I : - 15.78, 19.59 (2 Q, 4.5~CM,), 28.88 (q, I-CXH,), 29.00 (t, C-31, 41.19 (t, C-2). 
44.05 (a, C-l), 119.01 (d, C-7). 128.14 (d, C-6). 132.28 (a, C-5). 134.23 (a, C-4), 141.76 (a, 
C-9). 150.05 (a, C-8). - IR (neat): 3001, 2950. 2856, Iboo, 1476, 1453. 1380, 13&I, 1313, 1120, 
1100, 998, 811, 785. 762 an”. - W (pentane): A 
Naas apecttun (70 eV): m/z - 17’( (191, K’), 159 Cl%+, 
(log c) - 229.0 (2.84). 267.0 (2.74). - 
144 (7), 129 (7). 128 (8). 119 (4). 115 
(51, 91 (4). 77 (3). --il. Calcd for C,,H,, (174.3): C. 89.59; H. 10.41. Feud: C. 89.33; 
H, 10.59. 
Adawl_t. Ye thank Roawltha m for experiDsnta1 aaalatance 
for the N?fl apectmplc atrvctural eluclclatluu. A.-R. thanks the A.v. 
a fellwshlp. 
and Ralner Koechlnaky 
Hu&oldt Stlftung for 
1) 
2) 
3) 
10 
5) 
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8) 
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18) 
19) 
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Carbocationic cyclisations and rearrangements in the damascone series

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