- Email: [email protected]
A directed metalation route to the zwitterionic indole alkaloids.
TtWm Vol. 44, No. ll.PP. 3195 to 320% 1988 Printadin GIUI Britia.
A DIRECTED MEf’ALATiON ROUTE TO THE ZWlTTERIONH= INDOLE ALKALOIDS. SYNTHESIS OF ~UPE~Ul~~t Gordon W. Gribbk,* Timothy C. Bardtn, and Ihid
A. Joboaon
Deprtnnt of ckmisiq~ DartnwuthCollege Hsuwcr, New Haapdh (Receitwdin USA 14 OcrQbcr1987)
03755 USA
G. W. GJUSWE ci al.
31%
Scheme 3
30% l-92
N%=2
t 57% w 9
11
10
70-7996
CN
6 WI
Scheme
m N H
4
f.LDA
1. n-R&l
I-
2. Phso&I 03%
13 (12%)
m y S02Ph
2. t-BUNCO * a3%
NHtsu 0-7k ? PtIo$s
0
G. W. GIIBIIUI
3198
1. n-Bull
17
et al.
syntbcsis of scmpcrvirinc
3199
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ 6 138.1, 137.3, 135.9, 135.7, 125.7.27.7, 26.1, 21.9, 21.6. 3-Cy8a&,6,7,8-~y~noii~e
(4) =d
#t&8 (13). -To
l-Cy~n~5~,7~t~~~
N-oxide11~.6g,o.o51mof)ms~dropwistava35~~~~(~4&o.QT;1mol).
TkluultingIldxatn
wrubcatEdu~'C~Zb,awkd,pddirdvcdkr~(~~~lhirwrloriadElurstinn~~ovcr 30mintoasdatiaaotK~e),9~0.152mol)inmpa~mL)rt-5%
lEemctimnWu~~wm&mdov~&glttwI!ik
allowingittnwamDo2X)‘C ~wilh~~(3xIoO~),nubingbwcxrnctwib!~dspins(hdso~~md iXYmnu&oninvwcvlrgMaaiL
Cdmm dmmqp@ywusilicagd
withbMmImAc-HtjN(gndiaueludaa,
1~1~.~s~toprwkht(l;l0g(l%)ddrsu!dlyntidw~by0.92(12&)dWu&~wdidfmpS~C), ~dl.?g~~%~~by-~l~.
Nitrik:6s~fyc?rst*llia#toastandingto~cbkrkss~mg~C~~mp
65-66’C), and thet@Gomu
I3 was myWlix&
Data for 6: IR (neat) 3025,2925,2W,
from c&et-pemkum etherto fur&h colakse nccdks. mp 62-63-C
1590,1560,1455,1435,1390,13oa,
1265,lU70-lOlrr, 950,880,800 cm-‘; IH
NMR (CDCI3) zI8.9%(r. 1 ?I), 7.4%(5, 1 Hj, 3.1-2.6 (tn. 4 K), 2.1-M (m, 4-m MS m/r (relativeinmsityj 158 CM+,96). 157 (99), 143 WI), 143 (19), 130 (lOO), 103 (19). 77 (21), 76 (18), 63 (14X 51 (23). Datafcs U: lR (K&j 2935,2&60, 2220,1595,1580,
lildq 1450,f425,1400,1325,1255,
Il8S, 84S,8Wcm -~;~HNMRtCDQ3}b8.43(bJ-SHzlH),
7.2.8(d, J = 5 Hz, 1 Ii), 323-2.67 0~. 4 H), 223-1.63 {m, 4 H); 1% NMR (ClXi$ & 147.9, 147.1, 137.7, 133.5, 127.0, 116.0,2&5,25.8,21.7,21.4;
MS J& (rclathe inmmity) 15g (W, loo), 157 (98). 143 (33). 130 OIp), 118 (181,103 (a),
77 (19),Sl (21),41 (21). 39 (25). AnaL ofWCakdforCl~l~2:
C.75.92; H, 6.37; N, 17.71. Found: c, 75.97; H,
6.41; N, 17.62.
lqhe@sulfenyI)wok (14). - This xlmmial wm pepand in m% yield acemlhg to aa pbhsbed mcthodt3 bollI indole withn-bmyllithillmand bc~sulfonyl chloridezmp 76-77.5’c (lit.% mp 77.5-WC). 2~(+ButylaminocPrtnyl)-I-(p~~ylsulfongl)iadok
05). -To a sofutia~ of dihqnupylamhc
(0.865 g, 835
mmol) in THF (20 ML) under nitrog~ a! -78’C was added dropwiw OVQ10 tninn-butyllithium(1.45 M in hexam,5.63 mL,8.16umml). ~~~~stimdrt-78*C~15~irdthmau#i~cnarlSn6asrithr~utioo of l-~y~l)~
(14) (20 g, 7.8 mmc@ in ‘IHF (20 ml& After #irAg a -78’C fa 1 b, tbc rem&g milky-
whitesuripeasrmwaowarmdp,-5’cmaaominrrd~cooMco-78’cuadqucoc~veytqridly~r~ (1.16g,11.7masA). Thcmixaaewas~at-78’Cbar2huddPenrlbandtonrrm~~aomomrmpaUurtcrva 4b The~~~wurpaaedinKIrrrrrrucd~~~~~,nimdSminladwancbdwith~(3X50mL). nclImmbhd~erttaar,~warhd~brinc(2x5omW,dricd(MICSOSmdcaaccetnrezl yeuowoil. 0ymnimian~abcr~23g(83%~dlsumlorhpifols: 1:l) Rf0.38; IR @LBr)3370,3050,2960, l&Q 1555,1510,1445,1360.1315,127Q 910,870,830,755,720 NM2 (CD@)8
klMIc~togilmFlight mp162s165’csmC(Et~~, 1210~1170,116@1060,1045,920,
cm-‘; ‘H Nh¶R(Cm31 d 8.4-7.0 (HI,9 IQ, 6.87 (s, 1 HI, 6.1 (br s, 1 Hh 1.58 (s, 9 H); 1%
161.0. 137.3, 136.7, 136.7, 133.9, 129.0, 128.9, 127.5, 126.0, 124.2, 121.9,1152, 113.2,52.3,2$5;
MS m/e (ml int) 356 (hi+, 3),2&I (11). 144 (25)s 143 (48X 142 (100). 115 (19). 100 (16). 89 (13). 77 (32X 57 (42). 55 (11). 51 (12),45 (11). Anal. C&d forCI&,-,N$3$I: N, 7.86, S, 8.96,
C, 64.02; H, 5.66; N, 7.86; S,9.00. Founb: C, 63.96;H. 5.66;
lCI?Os 10!50,920,.845,?5Q~ 730 cm-l; lHNh@ (w 13W136.3.
d 8.X&7.9%(EB,3 I-I),7.83-7.27 (m, 7 J-J); 1% NMR (C!DCJ3)g
134.6. f29.4, 128.5, 12?.2, 126.8, 124.6, 123.1, 122.4, Jl4+3, 112.0, 108.7.
1-(l-()ha@~11lbmyi)JM~%)QeUmoJ
{ZO). - Th% wt9 pqmtd
S-(l-rPa~ybulf~~J))iadd-2-~J~-~~ormthiyJ-l~4-ttiuriac hydc 22 (1.98 g, 632 mmJ), m
ie 90% yield fmm 14 u dcmihcd.~~
(24). -A mixture of tfie oJigomuic kcaorl& -
hy&kdi&
(23) (1.67 g, 7.16 mm@, NaHWj (0.87 g, 10.4 lrampmm~~r.
anml~,~~3c3o~~radmgl.(10mL)wsr~y~rtrwm
-rblqcmrrar:
sepmrd,thtrqpwwr~mramnaad*liti~~(JOmt~mdbrt~~h~wrswubed~~water(2 IrrwmwtogJvcaaudeadJd.QryrPIlietlarJbnuJyJacuam
x20mL),brine@OmL),drkd(NQS0&Mdomcamund
[pve dmk @=a ~uims (2.01 g, 83%): mp l!J&lSl-c; JR 1610, J5?Q 1530,1495,1455,1380,
J260, JMOcm-‘; ‘H NMR
(CI=J3) I9.05 ts, 1 HI, 7.95 (d,,y = 6 HZ, 1 H); 6.9-7.S (m. 8 HI; 7.03 {r. 1 H), 2.67 (s, 3 H); 1% NJMR@ZDCJ$CL 172.8, 150.0, 145.6, 139.4, 136.0, 135.4, 136.1, 129.8, 128.8, 127.4, 126.9, 125.2, 122.4, 121.1, 116.4, 13.9; MS m/e 382 (M+), 3t8,281,242,156,149,140
WO%), 113,7?. Anal. Cakd fa C18H14N40&: C, 56.53; H, 3.69; N, 14.65;
S, 16.77. Found: C, 56,423 H, 3.72; N. 14.64, S, 16.67. 3~(l-(PhenyksoJ~oayJ)Jndd-2-yJ)~l~mttbab~lfoeyJ-5,6,7,8-taribJbrolsaqnodJnc
(27). - The triazine
~jl.Jbg,2.9%~J)inCH2Q2(SOiall)*rrs~dia~~~,lirid~~gsde(~S396)~~~d (1.608,>?.42nmd)was&kkdJnporcJomowr3min, pamm
S~gwrsciiiitfnrradu(YCfotlhfallauadby2hunxnmatm-
~briehtydlbw~wrsmrJb#)witht~rq~cauN~~(2x30mL)mrdbrine(30mL).
Afbdtying
~~4)*doaanfillionZlr~~r~.~baigtt~fmn~r*ur&eddiraityintfit~nrctian witlmt Rarba pttikuiti
(cJ.mmmik
lH.NMR mmaweis: 9.74(~1J-J),353(s,lH)).
wns~JvcdJnQJcJ3(5o~)at!wm#mqprrtnn
Tllecmdeeiaziacs~2!J
md,mtJdsiT&lion, amitk26@60ml+39?KKno1)nuiadd&
drqrwiseava2mia,whappatt&.#rfutiat~y~ud~~~~obsavcdAfDs1hd~8a lmrn~thebrir1#inrctiaa~ursburrdfor~Oha~ux,oooLdmdthtllollgionwrsccmocamwrdtn VM(O.~~wuprsstd~~r4Rmpsdafsilica~(QH2CIZ~d~t~,~artedEogircacrudcrolib;rad ~~~~1
IocQtdhcxint
(1:2) to sfikrd27 as tiny~wbus(0.62 g, 4596): mp MO-16f’CzlR 1610, WQ
1455,1440,1380,1310.1185,1160,1130,1095
cm-l; 1H NMR {CDCJ$ b 8.f3 (d, J = 7 Hz, 1 J-i), 7.0-7.6 (m, 9 HX
6.75 (s, J H), 323 (s, 3H), 3.0-35 (m, 2 H), 2.7-3.0 (m, 2 H). 1.6-2.0 (m, 4Jfj; ‘%ZNMR (CDCJ$ 8 155.1, 149.6, 146.1, 139.2, 138.1, 136.9, 133.6, 131.3, 129.9, 129.2, 128.6, 126.6, 125.6, 124.5, 121.3, 116.2, 115.6, 40.3, 29.6, 23.9,21.6,21.2;
MS mlc 466 0,325
flOO%),251,245,218,
?7. AnaL CM& for C!a(1&N@4S2: C, 61.783 H, 4.75;
N, 6.00; S, 13.74. Rmnd: C, 61.76; H, 4.78; N. 597; S, 13.68.
synw
of scmpcrvifine
3201
Shat-X)‘C,the~eyellowminantwasdrxanbad~tbtuartgamradfilad
‘Iltefil~was
tht~~was~betw&ncthylwxtwe(5o~)~wun~5omL). 50 UlL),brine(50 ml& dried (Na$30$, andCQactdtratEd in wcuo. Fkh wy c~~~~yl~~u(3:l~.
~inwcuoand
TbecKganicp~waswashedwithwater(2x (medtylenechloride- muhyicne
~~telurim)gvtalumwtrichsolidifKdrha!bcirytrtusdwithetbafollorwedbyslow
evaporationtodtyneas(0.1%g,91%). Rw
fromuhyl~~gavefltuprkts:
mp 159.5160.5’C(Iitp
mp 158-158.5.C); ‘H NMR (CIXJ$b 10.08 (br s, 1 H), 8.30 (5, 1 HJ,7.0-7.7 (m, 5 H), 493 (s, 1 H), 2.5-3.0 (m, 4 H), 1.8-2.0 (m, 4 I-Q;1% NMR (CDC&b 149.5, 147.4, 146.8, 137.2, 136.4, 131.9, 129.2, 122.6, 120.8, 119.9, 119.8.
111.3,99.4, 28.8,24.2,22.6, 22.4; MS mle 248 (M+, lo’&), 220, 117, 85. 3-(l-(Phcnylrulfonyl)iadol3-yI)_S,~7~t~~b~~~~uie~llsaqu
(17). -A 50% dispersion of N&i (19
mg,0.39maol)was~indrypadrat(lmL)fa30sec~draatbedid~rlkwatDoreetle. kcatttedandthensiduewasowendwidtTHF(4tnLr,
Therapidiystkdaqauiao
Tbtpartaatwas wascQo1aland8(16mg,0.06
rmaol)dissohredinTHF(O.5~~wluddaddFopwisc~2mia,md~wrscaatinutduo’Cfal
h. Pharylsul-
faaylchl~(0.07mL,0.55~~twutbendd#l~~lminro&nvadby~gat~Cfarl.Sh
Saturated
~N~(2mL)wrs~ddadQopwibw:andtbe~mi~~wrr~~for3ombnat(rc, ~~~~~~~
1)Ic~~wQt~llyIfht4uooua;phstwascxapcaadwithethcr(lomL~.
TheorganklrycXwaswashedwithllrittc(2xlOmL)Jrkd(K#O3)&ld praificationby flashcv
~&~togivea&Rntm
FLul
y(mthylencc~lacdib,~~)gsve17~a~eycllowxdid(18
mg, 72%) which gave off-white plaDtstfwr t=q&k&n
ftom ethyle
1480,1450,1370, 1185, 1170.1150an -l; *H NMR (CDU3) 6.80 (s, 1 H). 2.7-3.0 (m, 4 H). 1.7-U (IQ 4 H); ‘x
b
tnp 1X5-1595%
IR 1605,1585,
8.39 (s, 1 H), 8.20 (d, 3 3: 8 Hz, 1 H), 7.2-7.7 (m, 9 H-j,
NMR (CDCl,)a 149.4, 148.0, 145.7, 141.4, 137.9, 137.2, 133.5,
132.8, 130.5, 128.6, 127.0, 126.3. 125.0, 124.3, 121.2, 116.2, X14.5,28.7, 26.2, 22.5, 22.3;MS mlc 388 (M+), 324 (lClO%),295,247,219,77. 5.25; N, 7.17; S, 8.30.
Anal. Cakd for GfhnNfiS:
C, 71.11; H, 5.19; N, 7.21; S, 8.25. Found: C, 71.18; H,
G. w.
3202
ChIBBu!
CI d.
1.
Fm a mview, SIX: G.W. Gribble in “Studies in Nahnal Prodms (hcmishy.” in-s.
2.
RB. Woodward and WM. MC-
A. Rahman, FX, l%wim, Amstarlrm,
J, Am. Chem. Sue., 1949,72,379.
3. a) hf. Beljamki and M.S. Bc@mskj hp. CeU Biol., l%Q SO, 79; b) M. Bcl’mski and MS. Bcljmki, Oum&&y, lJ#16 43 19% c) R Basskcr, D. Qamart, J.M. Mpaatt, M. Qxassc, M. ha and L. Angarot, hc. Pkzm. Ft., 19&, 44, 83: 4.
D.A. Johnson and G.W. Gribbk, Heccrqc~~,
5. 0.W. &ibbk
md DA Johnma, T&&&m
l986,24,2127. f&z., 198f,28,5259.
6. R Bentky, T.8, Stevens, ad M. ‘IImqmq
1. Chcm Sue. (Cj, 1970,791.
7. F.W. viatqpcr
and EL. Eliel, I: Org. Ckm.. #975,40,2729.
8. A.L Myas.sad
TX. Baiky, 1. Org. C&m., 1986,51,872
9.
a} W.E. FaeJy md EM.. Bemrs, iwi. &pm? 19s9,7,130,
J. Am Chm. Sue., l9!!9,81,40(#,
10. I)D~~radG.W.OribMe,~.~drsenrtMas;b)form~~diwxmyatthis~ xe&oa, EC H Vcmhn88cn md K. Kmhhmwq SyntlreJLr, l#u, Il.
A. N&m
12. K. Tak&,
b) T. OtrmaaD md H Tani, Cht.
Phrm.
316,
and K.P.P.C Vollhanls Aiqew. Ckm. Iti. Ed En@., 1977,16,7U8. H Fujiwwa, ‘I-.Kaq$ri,
aad J. T&m&a,
13. M.G. Sanhicx and G.W. Gribble,1.0~.
Lcn., 1975,4375.
Chcm., 1982.47.757.
14. RB. pani and G.W. Gribbk, Org. Pnp. Pmxd 15. K.ii. Hardingti
Temkcdron
It% l!X% IS, 297.
1974,4, 297.
R.C. Ligon. &w. Co-.,
16. a) EC Taykx tnd J.E. Mawr, Tetmhe&u?~Lm., l9SS,26,2415,2439; h) EC. TaySor,K.F. MEDuritl, and J.C. wmer, 7iwuheon Lat., l96?, 28,1977, and ariicr pqms tied tbm!iE 17. 8) D.L.
Chcn.. % 1
ud J.S. Patek, 1. Org. C&m., lF81.46.2179; b) D.LmBqger, J.S. Pan& and MM Mcier, J. Org. c) D.L. Bow, Chcm. Rcu,, 1986,&I, 781; d) D.L Bcqcr, Temk&on, 1933,39,2865X
,47,895;
18. G.W. Gxibbk, M.G. Sauhicr, M.P. Sibi, J-AA.Obaza-Nutaitis, 1. Org. Chem., 1984,49,4518. 19. AlminumamlgamaRancynick~anlyclcawd ~~~~~~~~~b~~~~ ~~~~~~~~~n~~~~~~-7~ 8wasdcxctcdrmdaanyIeactimarndi~.
thqhe$+fcmylgmup~~kan&~~~qhpunrmtwchaL ~g~~~ Y? andsmppcd ofc%m&tm~ Notmeof
20.
GA. Kraus and P. Guttschalk, J, Org. Cht.,
21.
E schlitia andR M&n,
He&. C&t. AC&Z,194?,30,1339.
22.
J.Z. Ginos, 1. Org. Ch.,
1975.40,
23.
E. G&hi sad M. Ikeham, Ch.
24.
RJ. Sundbxg and HP. Russell, J. Org. Ch.,
25.
M.G. Sat&tier and G.W. Gribbk, unpubiishcd results; MO. Seulnier, Ph.D. II&s,
26.
KT. Potts and GA Mattingly,J. Org. Chm., l%8.33,3985.
l!M3,48,2111.
1191.
Phrm.
BJ& iqpan. l%4,2,109. l973,38,3724. E)rrhmath CofEtgc l982.
A DIRECTED MEf’ALATiON ROUTE TO THE ZWlTTERIONH= INDOLE ALKALOIDS. SYNTHESIS OF ~UPE~Ul~~t Gordon W. Gribbk,* Timothy C. Bardtn, and Ihid
A. Joboaon
Deprtnnt of ckmisiq~ DartnwuthCollege Hsuwcr, New Haapdh (Receitwdin USA 14 OcrQbcr1987)
03755 USA
G. W. GJUSWE ci al.
31%
Scheme 3
30% l-92
N%=2
t 57% w 9
11
10
70-7996
CN
6 WI
Scheme
m N H
4
f.LDA
1. n-R&l
I-
2. Phso&I 03%
13 (12%)
m y S02Ph
2. t-BUNCO * a3%
NHtsu 0-7k ? PtIo$s
0
G. W. GIIBIIUI
3198
1. n-Bull
17
et al.
syntbcsis of scmpcrvirinc
3199
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ 6 138.1, 137.3, 135.9, 135.7, 125.7.27.7, 26.1, 21.9, 21.6. 3-Cy8a&,6,7,8-~y~noii~e
(4) =d
#t&8 (13). -To
l-Cy~n~5~,7~t~~~
N-oxide11~.6g,o.o51mof)ms~dropwistava35~~~~(~4&o.QT;1mol).
TkluultingIldxatn
wrubcatEdu~'C~Zb,awkd,pddirdvcdkr~(~~~lhirwrloriadElurstinn~~ovcr 30mintoasdatiaaotK~e),9~0.152mol)inmpa~mL)rt-5%
lEemctimnWu~~wm&mdov~&glttwI!ik
allowingittnwamDo2X)‘C ~wilh~~(3xIoO~),nubingbwcxrnctwib!~dspins(hdso~~md iXYmnu&oninvwcvlrgMaaiL
Cdmm dmmqp@ywusilicagd
withbMmImAc-HtjN(gndiaueludaa,
1~1~.~s~toprwkht(l;l0g(l%)ddrsu!dlyntidw~by0.92(12&)dWu&~wdidfmpS~C), ~dl.?g~~%~~by-~l~.
Nitrik:6s~fyc?rst*llia#toastandingto~cbkrkss~mg~C~~mp
65-66’C), and thet@Gomu
I3 was myWlix&
Data for 6: IR (neat) 3025,2925,2W,
from c&et-pemkum etherto fur&h colakse nccdks. mp 62-63-C
1590,1560,1455,1435,1390,13oa,
1265,lU70-lOlrr, 950,880,800 cm-‘; IH
NMR (CDCI3) zI8.9%(r. 1 ?I), 7.4%(5, 1 Hj, 3.1-2.6 (tn. 4 K), 2.1-M (m, 4-m MS m/r (relativeinmsityj 158 CM+,96). 157 (99), 143 WI), 143 (19), 130 (lOO), 103 (19). 77 (21), 76 (18), 63 (14X 51 (23). Datafcs U: lR (K&j 2935,2&60, 2220,1595,1580,
lildq 1450,f425,1400,1325,1255,
Il8S, 84S,8Wcm -~;~HNMRtCDQ3}b8.43(bJ-SHzlH),
7.2.8(d, J = 5 Hz, 1 Ii), 323-2.67 0~. 4 H), 223-1.63 {m, 4 H); 1% NMR (ClXi$ & 147.9, 147.1, 137.7, 133.5, 127.0, 116.0,2&5,25.8,21.7,21.4;
MS J& (rclathe inmmity) 15g (W, loo), 157 (98). 143 (33). 130 OIp), 118 (181,103 (a),
77 (19),Sl (21),41 (21). 39 (25). AnaL ofWCakdforCl~l~2:
C.75.92; H, 6.37; N, 17.71. Found: c, 75.97; H,
6.41; N, 17.62.
lqhe@sulfenyI)wok (14). - This xlmmial wm pepand in m% yield acemlhg to aa pbhsbed mcthodt3 bollI indole withn-bmyllithillmand bc~sulfonyl chloridezmp 76-77.5’c (lit.% mp 77.5-WC). 2~(+ButylaminocPrtnyl)-I-(p~~ylsulfongl)iadok
05). -To a sofutia~ of dihqnupylamhc
(0.865 g, 835
mmol) in THF (20 ML) under nitrog~ a! -78’C was added dropwiw OVQ10 tninn-butyllithium(1.45 M in hexam,5.63 mL,8.16umml). ~~~~stimdrt-78*C~15~irdthmau#i~cnarlSn6asrithr~utioo of l-~y~l)~
(14) (20 g, 7.8 mmc@ in ‘IHF (20 ml& After #irAg a -78’C fa 1 b, tbc rem&g milky-
whitesuripeasrmwaowarmdp,-5’cmaaominrrd~cooMco-78’cuadqucoc~veytqridly~r~ (1.16g,11.7masA). Thcmixaaewas~at-78’Cbar2huddPenrlbandtonrrm~~aomomrmpaUurtcrva 4b The~~~wurpaaedinKIrrrrrrucd~~~~~,nimdSminladwancbdwith~(3X50mL). nclImmbhd~erttaar,~warhd~brinc(2x5omW,dricd(MICSOSmdcaaccetnrezl yeuowoil. 0ymnimian~abcr~23g(83%~dlsumlorhpifols: 1:l) Rf0.38; IR @LBr)3370,3050,2960, l&Q 1555,1510,1445,1360.1315,127Q 910,870,830,755,720 NM2 (CD@)8
klMIc~togilmFlight mp162s165’csmC(Et~~, 1210~1170,116@1060,1045,920,
cm-‘; ‘H Nh¶R(Cm31 d 8.4-7.0 (HI,9 IQ, 6.87 (s, 1 HI, 6.1 (br s, 1 Hh 1.58 (s, 9 H); 1%
161.0. 137.3, 136.7, 136.7, 133.9, 129.0, 128.9, 127.5, 126.0, 124.2, 121.9,1152, 113.2,52.3,2$5;
MS m/e (ml int) 356 (hi+, 3),2&I (11). 144 (25)s 143 (48X 142 (100). 115 (19). 100 (16). 89 (13). 77 (32X 57 (42). 55 (11). 51 (12),45 (11). Anal. C&d forCI&,-,N$3$I: N, 7.86, S, 8.96,
C, 64.02; H, 5.66; N, 7.86; S,9.00. Founb: C, 63.96;H. 5.66;
lCI?Os 10!50,920,.845,?5Q~ 730 cm-l; lHNh@ (w 13W136.3.
d 8.X&7.9%(EB,3 I-I),7.83-7.27 (m, 7 J-J); 1% NMR (C!DCJ3)g
134.6. f29.4, 128.5, 12?.2, 126.8, 124.6, 123.1, 122.4, Jl4+3, 112.0, 108.7.
1-(l-()ha@~11lbmyi)JM~%)QeUmoJ
{ZO). - Th% wt9 pqmtd
S-(l-rPa~ybulf~~J))iadd-2-~J~-~~ormthiyJ-l~4-ttiuriac hydc 22 (1.98 g, 632 mmJ), m
ie 90% yield fmm 14 u dcmihcd.~~
(24). -A mixture of tfie oJigomuic kcaorl& -
hy&kdi&
(23) (1.67 g, 7.16 mm@, NaHWj (0.87 g, 10.4 lrampmm~~r.
anml~,~~3c3o~~radmgl.(10mL)wsr~y~rtrwm
-rblqcmrrar:
sepmrd,thtrqpwwr~mramnaad*liti~~(JOmt~mdbrt~~h~wrswubed~~water(2 IrrwmwtogJvcaaudeadJd.QryrPIlietlarJbnuJyJacuam
x20mL),brine@OmL),drkd(NQS0&Mdomcamund
[pve dmk @=a ~uims (2.01 g, 83%): mp l!J&lSl-c; JR 1610, J5?Q 1530,1495,1455,1380,
J260, JMOcm-‘; ‘H NMR
(CI=J3) I9.05 ts, 1 HI, 7.95 (d,,y = 6 HZ, 1 H); 6.9-7.S (m. 8 HI; 7.03 {r. 1 H), 2.67 (s, 3 H); 1% NJMR@ZDCJ$CL 172.8, 150.0, 145.6, 139.4, 136.0, 135.4, 136.1, 129.8, 128.8, 127.4, 126.9, 125.2, 122.4, 121.1, 116.4, 13.9; MS m/e 382 (M+), 3t8,281,242,156,149,140
WO%), 113,7?. Anal. Cakd fa C18H14N40&: C, 56.53; H, 3.69; N, 14.65;
S, 16.77. Found: C, 56,423 H, 3.72; N. 14.64, S, 16.67. 3~(l-(PhenyksoJ~oayJ)Jndd-2-yJ)~l~mttbab~lfoeyJ-5,6,7,8-taribJbrolsaqnodJnc
(27). - The triazine
~jl.Jbg,2.9%~J)inCH2Q2(SOiall)*rrs~dia~~~,lirid~~gsde(~S396)~~~d (1.608,>?.42nmd)was&kkdJnporcJomowr3min, pamm
S~gwrsciiiitfnrradu(YCfotlhfallauadby2hunxnmatm-
~briehtydlbw~wrsmrJb#)witht~rq~cauN~~(2x30mL)mrdbrine(30mL).
Afbdtying
~~4)*doaanfillionZlr~~r~.~baigtt~fmn~r*ur&eddiraityintfit~nrctian witlmt Rarba pttikuiti
(cJ.mmmik
lH.NMR mmaweis: 9.74(~1J-J),353(s,lH)).
wns~JvcdJnQJcJ3(5o~)at!wm#mqprrtnn
Tllecmdeeiaziacs~2!J
md,mtJdsiT&lion, amitk26@60ml+39?KKno1)nuiadd&
drqrwiseava2mia,whappatt&.#rfutiat~y~ud~~~~obsavcdAfDs1hd~8a lmrn~thebrir1#inrctiaa~ursburrdfor~Oha~ux,oooLdmdthtllollgionwrsccmocamwrdtn VM(O.~~wuprsstd~~r4Rmpsdafsilica~(QH2CIZ~d~t~,~artedEogircacrudcrolib;rad ~~~~1
IocQtdhcxint
(1:2) to sfikrd27 as tiny~wbus(0.62 g, 4596): mp MO-16f’CzlR 1610, WQ
1455,1440,1380,1310.1185,1160,1130,1095
cm-l; 1H NMR {CDCJ$ b 8.f3 (d, J = 7 Hz, 1 J-i), 7.0-7.6 (m, 9 HX
6.75 (s, J H), 323 (s, 3H), 3.0-35 (m, 2 H), 2.7-3.0 (m, 2 H). 1.6-2.0 (m, 4Jfj; ‘%ZNMR (CDCJ$ 8 155.1, 149.6, 146.1, 139.2, 138.1, 136.9, 133.6, 131.3, 129.9, 129.2, 128.6, 126.6, 125.6, 124.5, 121.3, 116.2, 115.6, 40.3, 29.6, 23.9,21.6,21.2;
MS mlc 466 0,325
flOO%),251,245,218,
?7. AnaL CM& for C!a(1&N@4S2: C, 61.783 H, 4.75;
N, 6.00; S, 13.74. Rmnd: C, 61.76; H, 4.78; N. 597; S, 13.68.
synw
of scmpcrvifine
3201
Shat-X)‘C,the~eyellowminantwasdrxanbad~tbtuartgamradfilad
‘Iltefil~was
tht~~was~betw&ncthylwxtwe(5o~)~wun~5omL). 50 UlL),brine(50 ml& dried (Na$30$, andCQactdtratEd in wcuo. Fkh wy c~~~~yl~~u(3:l~.
~inwcuoand
TbecKganicp~waswashedwithwater(2x (medtylenechloride- muhyicne
~~telurim)gvtalumwtrichsolidifKdrha!bcirytrtusdwithetbafollorwedbyslow
evaporationtodtyneas(0.1%g,91%). Rw
fromuhyl~~gavefltuprkts:
mp 159.5160.5’C(Iitp
mp 158-158.5.C); ‘H NMR (CIXJ$b 10.08 (br s, 1 H), 8.30 (5, 1 HJ,7.0-7.7 (m, 5 H), 493 (s, 1 H), 2.5-3.0 (m, 4 H), 1.8-2.0 (m, 4 I-Q;1% NMR (CDC&b 149.5, 147.4, 146.8, 137.2, 136.4, 131.9, 129.2, 122.6, 120.8, 119.9, 119.8.
111.3,99.4, 28.8,24.2,22.6, 22.4; MS mle 248 (M+, lo’&), 220, 117, 85. 3-(l-(Phcnylrulfonyl)iadol3-yI)_S,~7~t~~b~~~~uie~llsaqu
(17). -A 50% dispersion of N&i (19
mg,0.39maol)was~indrypadrat(lmL)fa30sec~draatbedid~rlkwatDoreetle. kcatttedandthensiduewasowendwidtTHF(4tnLr,
Therapidiystkdaqauiao
Tbtpartaatwas wascQo1aland8(16mg,0.06
rmaol)dissohredinTHF(O.5~~wluddaddFopwisc~2mia,md~wrscaatinutduo’Cfal
h. Pharylsul-
faaylchl~(0.07mL,0.55~~twutbendd#l~~lminro&nvadby~gat~Cfarl.Sh
Saturated
~N~(2mL)wrs~ddadQopwibw:andtbe~mi~~wrr~~for3ombnat(rc, ~~~~~~~
1)Ic~~wQt~llyIfht4uooua;phstwascxapcaadwithethcr(lomL~.
TheorganklrycXwaswashedwithllrittc(2xlOmL)Jrkd(K#O3)&ld praificationby flashcv
~&~togivea&Rntm
FLul
y(mthylencc~lacdib,~~)gsve17~a~eycllowxdid(18
mg, 72%) which gave off-white plaDtstfwr t=q&k&n
ftom ethyle
1480,1450,1370, 1185, 1170.1150an -l; *H NMR (CDU3) 6.80 (s, 1 H). 2.7-3.0 (m, 4 H). 1.7-U (IQ 4 H); ‘x
b
tnp 1X5-1595%
IR 1605,1585,
8.39 (s, 1 H), 8.20 (d, 3 3: 8 Hz, 1 H), 7.2-7.7 (m, 9 H-j,
NMR (CDCl,)a 149.4, 148.0, 145.7, 141.4, 137.9, 137.2, 133.5,
132.8, 130.5, 128.6, 127.0, 126.3. 125.0, 124.3, 121.2, 116.2, X14.5,28.7, 26.2, 22.5, 22.3;MS mlc 388 (M+), 324 (lClO%),295,247,219,77. 5.25; N, 7.17; S, 8.30.
Anal. Cakd for GfhnNfiS:
C, 71.11; H, 5.19; N, 7.21; S, 8.25. Found: C, 71.18; H,
G. w.
3202
ChIBBu!
CI d.
1.
Fm a mview, SIX: G.W. Gribble in “Studies in Nahnal Prodms (hcmishy.” in-s.
2.
RB. Woodward and WM. MC-
A. Rahman, FX, l%wim, Amstarlrm,
J, Am. Chem. Sue., 1949,72,379.
3. a) hf. Beljamki and M.S. Bc@mskj hp. CeU Biol., l%Q SO, 79; b) M. Bcl’mski and MS. Bcljmki, Oum&&y, lJ#16 43 19% c) R Basskcr, D. Qamart, J.M. Mpaatt, M. Qxassc, M. ha and L. Angarot, hc. Pkzm. Ft., 19&, 44, 83: 4.
D.A. Johnson and G.W. Gribbk, Heccrqc~~,
5. 0.W. &ibbk
md DA Johnma, T&&&m
l986,24,2127. f&z., 198f,28,5259.
6. R Bentky, T.8, Stevens, ad M. ‘IImqmq
1. Chcm Sue. (Cj, 1970,791.
7. F.W. viatqpcr
and EL. Eliel, I: Org. Ckm.. #975,40,2729.
8. A.L Myas.sad
TX. Baiky, 1. Org. C&m., 1986,51,872
9.
a} W.E. FaeJy md EM.. Bemrs, iwi. &pm? 19s9,7,130,
J. Am Chm. Sue., l9!!9,81,40(#,
10. I)D~~radG.W.OribMe,~.~drsenrtMas;b)form~~diwxmyatthis~ xe&oa, EC H Vcmhn88cn md K. Kmhhmwq SyntlreJLr, l#u, Il.
A. N&m
12. K. Tak&,
b) T. OtrmaaD md H Tani, Cht.
Phrm.
316,
and K.P.P.C Vollhanls Aiqew. Ckm. Iti. Ed En@., 1977,16,7U8. H Fujiwwa, ‘I-.Kaq$ri,
aad J. T&m&a,
13. M.G. Sanhicx and G.W. Gribble,1.0~.
Lcn., 1975,4375.
Chcm., 1982.47.757.
14. RB. pani and G.W. Gribbk, Org. Pnp. Pmxd 15. K.ii. Hardingti
Temkcdron
It% l!X% IS, 297.
1974,4, 297.
R.C. Ligon. &w. Co-.,
16. a) EC Taykx tnd J.E. Mawr, Tetmhe&u?~Lm., l9SS,26,2415,2439; h) EC. TaySor,K.F. MEDuritl, and J.C. wmer, 7iwuheon Lat., l96?, 28,1977, and ariicr pqms tied tbm!iE 17. 8) D.L.
Chcn.. % 1
ud J.S. Patek, 1. Org. C&m., lF81.46.2179; b) D.LmBqger, J.S. Pan& and MM Mcier, J. Org. c) D.L. Bow, Chcm. Rcu,, 1986,&I, 781; d) D.L Bcqcr, Temk&on, 1933,39,2865X
,47,895;
18. G.W. Gxibbk, M.G. Sauhicr, M.P. Sibi, J-AA.Obaza-Nutaitis, 1. Org. Chem., 1984,49,4518. 19. AlminumamlgamaRancynick~anlyclcawd ~~~~~~~~~b~~~~ ~~~~~~~~~n~~~~~~-7~ 8wasdcxctcdrmdaanyIeactimarndi~.
thqhe$+fcmylgmup~~kan&~~~qhpunrmtwchaL ~g~~~ Y? andsmppcd ofc%m&tm~ Notmeof
20.
GA. Kraus and P. Guttschalk, J, Org. Cht.,
21.
E schlitia andR M&n,
He&. C&t. AC&Z,194?,30,1339.
22.
J.Z. Ginos, 1. Org. Ch.,
1975.40,
23.
E. G&hi sad M. Ikeham, Ch.
24.
RJ. Sundbxg and HP. Russell, J. Org. Ch.,
25.
M.G. Sat&tier and G.W. Gribbk, unpubiishcd results; MO. Seulnier, Ph.D. II&s,
26.
KT. Potts and GA Mattingly,J. Org. Chm., l%8.33,3985.
l!M3,48,2111.
1191.
Phrm.
BJ& iqpan. l%4,2,109. l973,38,3724. E)rrhmath CofEtgc l982.