Beruflich Dokumente
Kultur Dokumente
Andrew McClory Monday March 16, 2009 8:00 pm, 147 Noyes
S S S
S S S
'Attempts to make thioacetone by the cracking of trithioacetone gave rise to an offensive smell which spread rapidly over a great area of the town causing fainting, vomiting and a panic evacuation'...'the laboratory work was abandoned.' -Researcher, Freiburg, 1889
S S S
'Attempts to make thioacetone by the cracking of trithioacetone gave rise to an offensive smell which spread rapidly over a great area of the town causing fainting, vomiting and a panic evacuation'...'the laboratory work was abandoned.' -Researcher, Freiburg, 1889
'Recently we found ourselves with an odour problem beyond our worst expectations. During early experiments, a stopper jumped from a bottle of residues, and, although replaced at once, resulted in an immediate complaint of nausea and sickness from colleagues working in a building two hundred yards away. Two of our chemists who had done no more than investigate the cracking of minute amounts of trithioacetone found themselves the object of hostile stares in a restaurant and suffered the humiliation of having a waitress spray the area around them with a deodorant. The odours defied the expected effects of dilution since workers in the laboratory did not find the odours intolerable...and genuinely denied responsibility since they were working in closed systems. To convince them otherwise, they were dispersed with other observers around the laboratory, at distances up to a quarter of a mile, and one drop of either acetone gem-dithiol or the mother liquors from crude thioacetone crystallizations were placed on a watch glass in a fume cupboard. The odour was detected downwind in seconds.' -Esso Researcher, Oxford, 1967
Seminar Overview
1. Nomenclature 2. Selected Properties 3. Elimination
A. Burgess B. Martin C. Sulfoxide D. Chugaev
6. Olefination
A. Julia B. Ramberg-Backlund C. Eschenmoser D. Corey-Winter E. Nicolaou
7. Oxidation
A. Kornblum B. Moffatt-Swern
4. Radical Reaction
A. Barton B. Zard
8. Functionalization
A. Mislow-Evans B. Pummerer C. DMTSF D. Diels-Alder E. Total Synthesis
9. Allium Chemistry
Sulfoxide
Sulfone
Disulfide
S SR' RO SR' R
O S S O
Thionoester
Thioester O
Dithioester
Xanthate Ester R S S
Sulfine
Sulfene
Sulfonium Salt O O S
S Sulfonium ylide
O X S
S Sulfoxonium Ylide
Thiirane (Episulfide) X
Episulfonium Salt
Episulfone
Sulfolane
S R S R
S S
S N
Cl
OH
OR'
Thioacetal (1,3-Dithiane)
Ketene Thioacetal
R Thiazolium Salt R N O R S Cl
Sulfenyl Chloride
Sulfenic Acid
Sulfenate Ester
S O
R'
S O
R' O
S R
R'
O R S N R' R
O S NH2 R
O S OR'
Thiosulfinate
Thiosulfonate
Sulfilimine
Sulfinyl Chloride
Sulfinimine
Sulfinamide
Sulfinate Ester
S 25
O Ph S 1
O OH
18
10
A-Values (kcal/mol)
Me: 1.7 OMe: 0.6 SMe: 0.7 SOMe: 1.2 SO2Me: 2.5
Elimination
Burgess Dehydration
O O MeO2C S N NEt3
OH
60$ / gram
MeO2CNH2
Et3NH
O O MeO2C S N O H
TESO
TESO
TBSO O O H O OTMS OH
O O
H O
Atkins, G. M.; Burgess, E. M. J. Am. Chem. Soc. 1968, 90, 4744-4745. Burgess, E. M.; Penton, H. R.; Taylor, E. A. J. Org. Chem. 1973, 38, 26-31. Holton, R. A. et al. J. Am. Chem. Soc. 1994, 116, 1599-1600.
Elimination
Martin Dehydration
OH
F3C F3C Ph
Ph Ph
57$ / gram
F3C CF3 O Ph Ph Ph S Ph OH F3C O CF3 CF3 Ph CF3 O Ph Ph S O H O CF3 CF3 Ph S
Ph
Ph
OH
F3C F3C Ph
Ph Ph
Elimination
Sulfoxide
Ph R
O Benzene 25 -> 80 C
Ph R
O H R' R R'
R'
O LiCA; PhSSPh
O SPh
O Ph S O
mCPBA;
CCl4, 70 C H
(+/-)-Acorenone
Trost, B. M. Acc. Chem. Res. 1978, 11, 453-461. Oppolzer, W.; Mahalanabis, K. K.; Bttig, K. Helv. Chim. Acta. 1977, 60, 2388-2401.
Elimination
Xanthate Ester
S O SMe 250 -> 300 C Ph S C O MeSH
Ph
OH
MeS HO O O N Cbz NaH, THF, CS2; then MeI, -30 C (92% yield) O O N Cbz O S NaHCO3 Ph2O, 260 C (72% yield)
N H H
(-)-Kainic Acid
Chugaev, L. Ber. Dtsch. Chem. Ges. 1899, 32, 3332. Nakagawa, H.; Sugahara, T.; Ogasawara, K. Org. Lett. 2000, 2, 3181-3183.
Radical Reaction
Barton
O R Cl NaO N R S O AIBN, Bu3SnH N S Benzene, 80 C
RH
H SnBu3 NC N N CN CN
Bu3Sn
H SnBu3
O R O N S SnBu3
OH
S O
SMe
RCH3
Barton, D. H. R.; Serebryakov, E. P. Proc. Chem. Soc. 1962, 309. Barton, D. H. R.; McCombie, S. W. J. Chem. Soc., Perkin Trans. 1 1975, 1574-1585.
O O
HO HO HO
O SCoA Alkaloids
HO2C
CO2H HO CO2H
FADH2
NADH
ATP Synthesis
RCHO
O R R' Pd (0) R
O SEt
O R Pd R'
R' = H, R R
O Pd SEt
MSEt O
R'M O
O O
O O
O O
tBuO2C
HO2C
Phomoidride B
Fukuyama, T.; Lin, S-C.; Li, L. J. Am. Chem. Soc. 1990, 112, 7050-7051. Hayashi, Y.; Itoh, T.; Fukuyama, T. Org. Lett. 2003, 5, 2235-2238. Fukuyama, T.; Tokuyama, H. Aldrich. Acta. 2004. 37, 87-96.
HO
S N
Cl Ph
1.30 $ / gram
OH
HO
S N
Cl Ph
O CN
O CN
Stetter, H.; Kuhlmann, H. Org. Syn. 1984, 62, 170. Stetter, H.; Kuhlmann, H.; Haese, W. Org. Syn. 1987, 65, 26.
O Ph * Ph OH R R' S Ph NBn
S OH N
Cl
HO S R R'
Ph Ph R
S NBn R'
Ph 6% yield 52% ee
Breslow, R. J. Am. Chem. Soc. 1958, 80, 3719-3726. Sheehan, J.; Hunnemann, D. H. J. Am. Chem. Soc. 1966, 88, 3666-3667. Sheehan, J.; Hara, T. J. Org. Chem. 1974, 39, 1196-1199.
CN H MeO2C O HO2C H
H OH
(+/-)-Hirsutic Acid
O BzO O
HO
S N
Cl Ph
O O BzO
N 6 steps NH O Cl
OMe Roseophilin
Trost, B. M.; Shuey, C. D.; DiNinno, F. J. Am. Chem. Soc. 1979, 101, 1284-1285. Harrington, P. E.; Tius, M. A. J. Am. Chem. Soc. 2001, 123, 8509-8514.
nBuLi
THF, -78 C
MeS R
SMe
SMe
nBuLi
S R S THF, -78 C S R S
S R
CH2CH2
SH O R H
SH
BF3Et2O CH2Cl2
nBuLi
S R S THF, -78 C
S R
S R
E+ S R S E
PhI(CF3CO2)2 CH3CN, 25 C R
O E
O H R'
O R''
O R'
O R'
Corey, E. J.; Seebach, D. Angew. Chem. Int. Ed. Engl. 1965, 4, 1075-1077. Stork, G.; Zhao, K. A. Tetrahedron Lett. 1989, 30, 287-290.
TBSO
TBSO BnO
OH HO
OTBS OBn
HO
OH OBn
HO
OH
OH
OH
OH
OH
HO HO (+)-Mycoticin A
O O
Smith, A. B. III; Pitram, S. M. Org. Lett. 1999, 1, 2001-2004. Smith, A. B. III, Adams, C. M. Acc. Chem. Res. 2004, 37, 365-377.
nBuLi
THF, -78 C S
O S
NaH DMSO, 25 C O
O S
THF
0 C -> 25 C
87 : 13
O B Ratio (A/B)
Temperature
THF
0 C -> 25 C 25 C -> 50 C
100 : 0 0 : 100
BF4 Ph2S O
O Ph2S
BF4
Eu(fod)3 CDCl3, 37 C O
Bogdanowicz, M. J.; Trost, B. M. Org. Syn. 1974, 54, 27. Trost, B. M.; Bogdanowicz, M. J. J. Am. Chem. Soc. 1971, 93, 3773-3774. Trost, B. M.; Bogdanowicz, M. J. J. Am. Chem. Soc. 1973, 95, 5311-5321. Trost, B. M.; Bogdanowicz, M. J. J. Am. Chem. Soc. 1973, 95, 5321-5334.
(56% yield)
Trost, B. M.; Nishimura, Y.; Yamamoto, K.; McElvain, S. S. J. Am. Chem. Soc. 1979, 101, 1328-1330.
Ph
O Ph PhCHO
Ph *R S R* PhCH2Br
Ph *R S R* *R S
Ph R*
KOH
Ph Ar OH SMe Furukawa 1989 43% ee Dai 1996 42% ee Saito 2001 56% ee Metzner 1999 85% ee SMe OH OH S S O
O HH O
Ph O
H O O S H Ph Ph
Na S R* MLn Ph N N Ts or PhCHN2
R*2S
LnM Ph
N2
5% O
Na RCHO Ph N N Ts
O R
R Ph Ph
Yield (%) 82 70 46
ee (%) 94 87 89
h O O
Ph Ph S O H O Ph H S H Ph R
SR*2 H
H R
Ph Ph
O R'
H SR*2
SR*2 R
H R
Ph Ph
O R'
H SR*2
Aggarwal, V. K.; Harvey, J. N.; Richardson, J. J. Am. Chem. Soc. 2002, 124, 5747-5756.
OMe O O N trans/cis 70:30 98% ee OMe (85% yield) PhMgBr, CuI THF, -40 C
then
CDP-840
20% O O Na Ph N N Ts 1% Rh2(OAc)4 20% BnEt3NCl Dioxane, 40 C (55% yield) EtO2C N O Ph 7:1 dr 91% ee (90% yield) 6N HCl (aq) EtO2C NH3Cl
O CO2Et
Ph
Aggarwal, V. K. et al. Angew. Chem. Int. Ed. 2003, 42, 3274-3278. Aggarwal, V. K. et al. Angew. Chem. Int. Ed. 2001, 40, 1433-1436.
3. Et3N Cl OtBu
S N H S O O R N H S N H Et3N S Cl O NH2 R
O R
S R O NH
Gassman, P. G.; van Bergen, T. J.; Gilbert, D. P.; Cue, B. W. J. Am. Chem. Soc. 1974, 96, 5495-5508.
TMS O Ph H N H O
TMS OAc Ph O H N H O
S O
TMS 1. Me3OBF4 2. Zn, HOAc (92% yield) Ph H N H O OAc 1. mCPBA 2. CaCO3, Xylenes, 140 C 3. BF3Et2O, HOAc, 0 C O (73% yield) Ph OAc H N Bz O O
SMe
Cytochalasan Vedejs, E.; Reid, J. G. J. Am. Chem. Soc. 1984, 106, 4617-4618. Vedejs, E. Acc. Chem. Res. 1984, 17, 358-364.
R'
iPrOH, CH2Cl2
O S
O Cl HO
ArO2S N S O
NHSO2Ar OH
Zhao, S. H.; Samuel, O.; Kagan, H. B. Org. Syn. 1989, 68, 49-56. Andersen, K. K. Tetrahedron Lett. 1962, 3, 93. Klunder, J. M.; Sharpless, K. B. J. Org. Chem. 1987, 52, 2598-2602. Senanayake, C. H. et al. Aldrich. Acta. 2005, 38, 93-104.
pTol
S O
pTol
pTol
pTol
MeO
MeO
(89% yield)
MeO
Reider, P. J. et al. Tetrahedron Lett. 1997, 38, 7131-7134. Posner, G. H.; Mallamo, J. P.; Miura, K. J. Am. Chem. Soc. 1981, 103, 2886-2888.
pTol O Ar S O
HN
Ar HN
pTol
CO2Et CO2Et O
AcO
pTol
OEt
pTol
pTol
Ruano, J. L. G. Tito, A.; Peromingo, M. T. J. Org. Chem. 2003, 68, 10013-10019. Lopez, F.; Castedo, L.; Mascarenas, J. L. J. Org. Chem. 2003, 68, 9780-9786. Carreno, M. C.; Conzalez-Lopez, M.; Urbano, A. Chem. Commun. 2005, 611-613.
O S
N NH2
S O
O S NH2
tBu
Exo/Endo 93:7
0.25%
tBu
N OH
OH
tBu
tBu
tBu
tBu
tBu
tBu
NH2
91% ee
Davis, F. A. et al. J. Org. Chem. 1999, 64, 1403-1406. Senanayake, C. H. et al. Aldrich. Acta. 2005, 38, 93-104. Ellman, J. A.; Owens, T. D.; Tang, T. P. Acc. Chem. Res. 2002, 35, 984-995.
tBu
tBu
H N R
H R' N H R
tBu
tBu S N
R Mg O R'
tBu
HCl MeOH
R Et Et Et Ph
R' Me iPr Ph Me
Ellman, J. A.; Owens, T. D.; Tang, T. P. Acc. Chem. Res. 2002, 35, 984-995.
tBu
O R' S tBu N H
R'' R
HCl MeOH
R'
R''
H2N R HCl
R' Me Me
R''
nBu
Ph Me
nBu
Me
nBu
2.5% [Rh(OH)cod]2 5% dppbenz Et3N (2 equiv) N KF3B DMF, H2O, 60 C (72% yield)
H N H 98:2 dr
tBu
tBu
Ellman, J. A.; Owens, T. D.; Tang, T. P. Acc. Chem. Res. 2002, 35, 984-995. Brak, K.; Ellman, J. A. J. Am. Chem. Soc. asap.
Ph N H CO2Et
tBu
tBu
HCl EtOH
84:16 dr
tBu
O NC Me S tBu N Ph H 12:1 dr
tBu
O OTi(OiPr)3 N Ph OMe THF, -78 C (81% yield) MeO Ph O S O Ti N O Ph S tBu N H O OMe
tBu
91:9:0:0 dr
Davis, F. A.; McCoull, W. J. Org. Chem, 1999, 64, 3396-3397. Davis, F. A.; Lee, S.; Zhang, H.; Fanelli, D. L. J. Org. Chem. 2000, 65, 8704-8708. Ellman, J. A.; Owens, T. D.; Tang, T. P. Acc. Chem. Res. 2002, 35, 984-995.
tBu
LiBEt3H (2 equiv) THF, -78 C S O HN OH Ph 99:1 dr
tBu
N Ph S O LDA, MgBr2 THF, -78 C; C2H5CHO (84% yield) Ph
tBu
S O N OH
(69% yield)
tBu
S O HN OH
Kochi, T.; Tang, T. P.; Ellman, J. A. J. Am. Chem. Soc. 2002, 124, 6518-6519.
tBu
N N O (82% yield) S O KHMDS THF, -78 C; N Br O N
tBu
S O MeLi, CeCl3 THF, -48 C (82% yield) >20:1 dr
tBu
N S O 2% Grubbs II CH2Cl2, 40C (87% yield) N
tBu
S O
HCl H2N
Olefination
Julia
R SO2Ph 1. nBuLi; R'CHO 2. Ac2O 3. Na/Hg, MeOH R R' -AcO
nBuLi; R'CHO
R'
-SO2; -ArO
O O N N N N
S O O N N Ph N N
Julia, M.; Paris, J. M. Tetrahedron Lett. 1973, 4833-4836. Kocienski, P. J. et al. Synlett. 1998, 26-28.
Olefination
Julia
Ph HO N SH H H H O 1. PPh3, DEAD THF, 25 C 2. H2O2, (NH4)6Mo7O24 EtOH, H2O (82% yield)
N N N
N N N N
Ph H S O O H H O
OH OH O H H O
H (+)-Ambruticin
Olefination
Ramberg-Backlund
O KOtBu THF
I O
S O O
S O X-Ray
O S O Cl
NCO2tBu
NCO2tBu
Ramberg, L.; Backlund, B. Arkiv. Kemi, Minerat. Geol. 1940, 13A, 50. MaGee, D. I.; Beck, E. J. Can. J. Chem. 2000, 78, 1060-1066.
Olefination
Eschenmoser Sulfide Contraction
S N Ph S Ar P S N Ph S O Ar P S O S P Ar S Ar O MeO P S S P OMe Toluene 110 C N Ph O P S
S 92 / gram
N Ph
CO2Me
Ph3P=S DABCO
N Bn
S CO2Me
N Bn
S CO2Me
S N Bn CO2Me
Lawesson, S. O.; Perregaad, J.; Scheibye, S.; Meyer, H. J.; Thomsen, I. Bull Soc. Chim. Belg. 1977, 86, 679. Eschenmoser, A. Angew. Chem. Int. Ed. Engl. 1973, 12, 910.
Olefination
Nicolaou Ring Contraction
H H O O O O O H (78% yield) H H S O O O S H O Lawesson's Reagent Toluene, 110 C O H S O O S H O 1. NaNaphthalenide THF, -78 C 2. MeI -78 C -> 25 C (80% yield) H AIBN, Bu3SnH Toluene, 110 C O (99% yield) BnO H O H H O OTIPS H O O
O H
O O O O H
O O
O H H Brevetoxin B
Nicolaou, K. C. et al. J. Am. Chem. Soc. 1986, 108, 6800-6802. Nicolaou, K. C. et al. J. Am. Chem. Soc. 1990, 112, 3040-3054.
Olefination
Corey-Winter
OH OH 1. (Im)2C=S 2. P(OMe)3 (75% yield) P(OMe)3 O S O O P(OMe)3
O S O
P(OMe)3
O O
P(OMe)3
OH
(+)-Swainsonine
Corey, E. J.; Winter, R. A. E. J. Am. Chem. Soc. 1963, 85, 2677-2678. Corey, E. J., Carey, F. A.; Winter, R. A. E. J. Am. Chem. Soc. 1965, 87, 934-935. Fleet, G. W. J. Tetrahedron Lett. 1996, 37, 8565-8568.
Oxidation
Kornblum
O S Cl Na2CO3 100 - 150 C CHO
H O S O S
NO2
NO2
NH2 N O
-O
N N
N H O H H OH H H
P O O-
NO2 O
-O
N N H O H H OH H H N
P O O-
Kornblum, N. et al. J. Am. Chem. Soc. 1957, 79, 6562. Fischer, B.; Kabha, E.; Gendron, F-P.; Beaudoin, A. R. Nucleosides, Nucleotides & Nucleic Acids 2000, 19, 1033-1054.
Oxidation
Moffatt-Swern
RCHO
O O S Cl O Cl R H O S
R O O S Cl O Cl
OH Cl S R O
Corey, E. J.; Kim, C. U. J. Am. Chem. Soc. 1972, 94, 7586. Mancuso, A. J.; Swern, D. J. Org. Chem. 1978, 43, 2480. Mancuso, A. J.; Swern, D. Synthesis. 1981, 161-185.
Functionalization
Mislow-Evans Rearrangement
P(OMe)3 MeOH
OH
Ts
pTol
Ts N
Na Cl
pTol
pTol
Ts
HO HO HO
nBuLi;
PhSCl HO O S Ph
O S Ph Me2NH H2O
HO
HO
Bickart, P.; Carson, F. W.; Jacobus, J.; Miller, E. G.; Mislow, K. J. Am. Chem. Soc. 1968, 90, 4869-4876. Evans, D. A.; Andrews, G. C.; Sims, C. L. J. Am. Chem. Soc. 1971, 93, 4956-4957.
Functionalization
Pummerer Rearrangement
O Ph S CO2Et OAc Ac2O Ph S H CO2Et OAc Ph S CO2Et Ph S CO2Et OAc
AcO
RO
RO
O OH
OH RO O RO
OH SPh OH RO
DIBALH RO POCl3 O Me2C(OMe)2 O SPh 1. mCPBA, -78 C 2. Ac2O, NaOAc O O K2CO3 MeOH, 25 C (100% yield) O O RO CH2Cl2, -78 C OAc SPh RO (91% yield) O O
CHO
(D)-Hexoses
CHO
Pummerer, R. Chem. Ber. 1909, 42, 2282. Ko, S. Y.; Lee, A. W. M.; Masamune, S.; Reed, L. A. III, Sharpless, K. B.; Walker, F. J. Science. 1983, 220, 949.
Functionalization
DMTSF
MeS SMe OTMS DMTSF (2 equiv) CH2Cl2, -20 C -> 0 C O S S S SMe OTMS H O S S S S S (63% yield) S
S BF4 DMTSF
TMSO
TMSO
MeS
SMe
S BF4
TMS
CH2Cl2, 25 C
Functionalization
DMTSF
S
S BF4 DMTSF
O SPh SPh
1.
Lebsack, A. D.; Overman, L. E.; Valentekovich, R. J. J. Am. Chem. Soc. 2001, 123, 4851-4852.
Functionalization
DMTSF
S SMe NH2 [Me2S-SMe]BF4 NH4OH CH3CN, H2O, 25 C (92% yield) CH3CN, 25 C (94% yield) SMe OH [Me2S-SMe]BF4 NaHCO3 CH3CN, H2O, 25 C (92% yield) [Me2S-SMe]BF4 1-heptyne nBuLi, Me3Al DCE, THF, 80 C (88% yield) O then iPr2NEt, 25 C (72% yield) CN Episulfonium [Me2S-SMe]BF4 NaCN
SMe
SMe
SMe
[Me2S-SMe]BF4 DMSO;
Trost, B. M.; Shibata, T. J. Am. Chem. Soc. 1982, 104, 3225-3228. Trost, B. M.; Shibata, T.; Martin, S. J. J. Am. Chem. Soc. 1982, 104, 3228-3230. Trost, B. M.; Martin, S. J. J. Am. Chem. Soc. 1984, 106, 4263-4265.
Functionalization
Diels-Alder Controlling Group
5:1 regioselectivity
18 / gram
H O
Buss, A. D.; Hirst, G. C.; Parsons, P. J. J. Chem. Soc. Chem. Commun. 1987, 18360-1837. Winkler, J. D.; Kim, H. S.; Kim, S. Tetrahedron Lett. 1995, 36, 687-690.
O O O
Cantharidin
Cantharus vesicatoria
Dauben, W. G.; Kessel, C. R.; Takemura, K. H. J. Am. Chem. Soc. 1980, 102, 6893-6894.
S O
OLi
(90% yield)
S OH
Li EtNH2, -70 C
SH
SH OH
Kondo, K.; Negishi, A.; Matsui, K.; Tunemoto, D.; Masamune, S. J. Chem. Soc. Chem. Commun. 1972, 1311-1312. Stotter, P. L.; Hornish, R. E. J. Am. Chem. Soc. 1973, 95, 4444-4446.
Allium Chemistry
Garlic
Alliinase
OH S S HO (sulfenic acid)
SN2
O S
H S
O S S
OH S S
[4+2]
S S
Allium Chemistry
Onion
O O S S ((Z)-sulfine) onion lachrymator factor [3+2] S O O S O S (thiosulfonate ester) non-lachrymator
O S
B O S S HO SN2 O S H S
Alliinase
(sulfenic acid)
S [2+2] S O trans-zwiebelane
O S
O [3,3] S S O S [Ox] S
Organosulfur Compounds
O CH3SH methylmercaptan (natural gas additive) MeS SMe S O SH 1-p-menthene-8-thiol (grapefruit) O HN H S biotin NH H CO2H Ph O O penicillin G (antibiotic) H2N SO2NH2 sulfanilamide (antibiotic) H N H S N CO2H O S N O N Viagra (erectile dysfunction) EtO HN O N N NH O
saccharin (sweetener)
Summary
Nomenclature Elimination Radical Reaction C-C Bond Formation Olefination Oxidation Functionalization Allium Chemistry