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Copyright GFS Chemicals 1/08 www.gfschCopyright GFS Chemicals 1/08 www.gfschemicals.comemicals.com
ALKYNESALKYNES
THE HYPER-VERSATILE BUILDING THE HYPER-VERSATILE BUILDING BLOCKS OF CHEMISTRYBLOCKS OF CHEMISTRY
Copyright GFS Chemicals 1/08 www.gfschCopyright GFS Chemicals 1/08 www.gfschemicals.comemicals.com
CyclopropanationCyclopropanation Modified Simmons-Smith reactionModified Simmons-Smith reaction
R1 R2 + CH2I2 + Et3AlR2
Et
R1
Et20 - 25o C
hexane
J. Organometallic Chem., 2001, 636 91-95
38 - 58%
Copyright GFS Chemicals 1/08 www.gfschCopyright GFS Chemicals 1/08 www.gfschemicals.comemicals.com
AllenesAllenes HomologousHomologous
OH OHCH2O, (i-Pr)2NH
CuBr
65% (Ref. 1)
R
OH
+
OEt
OEt
OEt
R
H CH2COOEt
H
82 - 91% (2)
CH3CH2COOH
1. Org. Syn. Coll., 7, 2762. ibid., 8, 251
Copyright GFS Chemicals 1/08 www.gfschCopyright GFS Chemicals 1/08 www.gfschemicals.comemicals.com
EneynesEneynes ConjugatedConjugated
H
H3C H
X
+ X Zn C CRH3C
R
Pd cat
THF
X = halogen, OTf
H
H
I
R
+ HC CO
OCH3
R
O
OMe
87%R = CH3(CH2)5
Org. Lett., (2003) 5 (10), 1597
Copyright GFS Chemicals 1/08 www.gfschCopyright GFS Chemicals 1/08 www.gfschemicals.comemicals.com
EneynesEneynes OligomerizationOligomerization
I
R2
R1
Si + OH1. K2CO3
2. Sonogashira rxn
Repeat
R2
R1
Si
HO
n
Org. Lett., 2003, 5 (3) 365
Copyright GFS Chemicals 1/08 www.gfschCopyright GFS Chemicals 1/08 www.gfschemicals.comemicals.com
1,3-butadienes1,3-butadienes
BnO+ C6
BnO C6
82%
Ru cat
C2H4 rt
Org. Lett., 2003, 5 (11), 1855
Copyright GFS Chemicals 1/08 www.gfschCopyright GFS Chemicals 1/08 www.gfschemicals.comemicals.com
AminesAmines HydroaminationHydroamination
R1 R2
Ph Ph
NH2
+ R1R2
NH21. Ti cat, 100o
2. H2, Pd/C
R1 = R2 = phenyl 67%
R1 = R2 = ethyl 59%
R1 = phenyl; R2 = H 41%
Org. Lett., 2000, 2 (13), 1935
Copyright GFS Chemicals 1/08 www.gfschCopyright GFS Chemicals 1/08 www.gfschemicals.comemicals.com
Aldehydes/Carboxy AcidsAldehydes/Carboxy Acids AllylicAllylic
EtOC CMgBr
O
R2R1
+R1 OH
R2 C COEt
R1 OH
R2 C COEt
COOHR1
R2
CHOR1
R2
H2SO4
Pd-Pb-CaCO3
(1)
(2)
1. J. Chem. Soc., 1949, 18232. Rec. Trav. Chim., 1963, 82 (305)
Copyright GFS Chemicals 1/08 www.gfschCopyright GFS Chemicals 1/08 www.gfschemicals.comemicals.com
DiketonesDiketones 1,4- and 1,5- disubstituted1,4- and 1,5- disubstituted
OR
O
R
O
R
O
H2O
Pd(II)
H2O
Pd(II)
R
O
O
Tetrahedron Lett., 1987, 28 (27), 3127
Copyright GFS Chemicals 1/08 www.gfschCopyright GFS Chemicals 1/08 www.gfschemicals.comemicals.com
1,3,5-triketones1,3,5-triketonesO
HR1
2 steps
-78o C
2 steps
-78o C
O
R1
H
O
R1 R2
O
R1 R2
O
S
S
R2
S
SR1
R1 R2
OO O
HS SH
cleave
Org. Lett., 2003, 5 (7), 1147
Copyright GFS Chemicals 1/08 www.gfschCopyright GFS Chemicals 1/08 www.gfschemicals.comemicals.com
HexaethynylbenzenesHexaethynylbenzenesCl
ClCl
I
Cl
I
Cl
I
Cl Cl
Cl Cl
H5IO6
H2SO4
R R
R
TMS acetylene
Pd, 30 hr
(I)
ZnCl
+ (I)
R R
R
Ph
PhPh
R = Si(CH3)3Org. Lett., 2001, 3 (15), 2419
Pd, THF
4 days
Copyright GFS Chemicals 1/08 www.gfschCopyright GFS Chemicals 1/08 www.gfschemicals.comemicals.com
[4]-radialenes[4]-radialenes
Org. Lett., 2003, 5 (19), 3371
Br
Br
X
X
2 Steps
X = S, -CMe2, none
Copyright GFS Chemicals 1/08 www.gfschCopyright GFS Chemicals 1/08 www.gfschemicals.comemicals.com
CarbocyclesCarbocycles Conjugated 2- substituted cycloheptadienesConjugated 2- substituted cycloheptadienes
R H +
(excess)
R
Ru cat, AgI
50o
R = phenyl, -CCl3, -CO2Bz, -C(R1)(OR2)H
Org. Lett., 2003, 5 (19), 3463
Copyright GFS Chemicals 1/08 www.gfschCopyright GFS Chemicals 1/08 www.gfschemicals.comemicals.com
CarbocyclesCarbocycles 2-cyclopentenones2-cyclopentenones
N-Boc
O
TMS 2 StepsO
TMS
Boc-HN
HO
Tetrahedron. Lett., 2000, 41, 9393
Copyright GFS Chemicals 1/08 www.gfschCopyright GFS Chemicals 1/08 www.gfschemicals.comemicals.com
CarbocyclesCarbocycles 9-alkylidene-99-alkylidene-9H-H-fluorenesfluorenes
I
+
R
Pd cat
R
R = t-butyl, phenyl, -C(CH3)2OH
Org. Lett., 2000, 2 (21), 3329-3332
Copyright GFS Chemicals 1/08 www.gfschCopyright GFS Chemicals 1/08 www.gfschemicals.comemicals.com
CarbocyclesCarbocycles Synthesis of civetone via ring-closing metathesisSynthesis of civetone via ring-closing metathesis
O OO
H2, Lindlar-Pd
quinoline, CH2Cl2
2 Steps
O
cat. (10%)
toluene
W CC(CH3)3(tBuO)3cat =
J. Organometallic Chem., 2000, 606, 75-78
MgBr
+
Copyright GFS Chemicals 1/08 www.gfschCopyright GFS Chemicals 1/08 www.gfschemicals.comemicals.com
HeterocyclesHeterocycles Pyrazoles & IsoxazolesPyrazoles & Isoxazoles
FloHet V Conference Proc. 4-16
R1 R1
NN
R1
R1 R2
R1 R1 N+ O-R2+
ON
R1
R1 R2
+ R2CHN2
Copyright GFS Chemicals 1/08 www.gfschCopyright GFS Chemicals 1/08 www.gfschemicals.comemicals.com
HeterocyclesHeterocycles Maleic AnhydridesMaleic Anhydrides
OO O
HPdCl2, CuCl2
CO (1 atm), rt
Tetrahedron Lett., 2001, 42 (39), 6923
Copyright GFS Chemicals 1/08 www.gfschCopyright GFS Chemicals 1/08 www.gfschemicals.comemicals.com
HeterocyclesHeterocycles 1,2,3-triazoles (‘click chemistry’)1,2,3-triazoles (‘click chemistry’)
R1 + NR2 N NNN
NN
N
NR1
R2
R1
R2
+
syn anti
Chem. & Eng. News, 2002, 80 (6), 29-34
Copyright GFS Chemicals 1/08 www.gfschCopyright GFS Chemicals 1/08 www.gfschemicals.comemicals.com
HeterocyclesHeterocycles pyrrolespyrroles
ClH2C CH2Cl +
COOEt
COOEt
CH3CONH
HN COOEtNaOMe
EtOH
38%
J. Org. Chem., 1996, 61, 9068
Copyright GFS Chemicals 1/08 www.gfschCopyright GFS Chemicals 1/08 www.gfschemicals.comemicals.com
HeterocyclesHeterocycles Benzofurans, indoles, isocoumarinsBenzofurans, indoles, isocoumarins
I
Z
R1 R2
Z
R1
R2
Pd(II)-L
LiCl2, DMF
I
COOCH3O
+
+
O
70 - 90%
72%
Pd(II)-L
LiCl2, DMF, Na2CO3
Z = OH, NH2, NHR3
R1 = alkyl, aryl
R2 = H, alkyl, aryl
J. Amer. Chem. Soc., 1991, 113, 6689Angew. Chem. Int'l. Ed., 2000, 39, 2488J. Chem. Soc. Perkin. 1, 1997, 2815Org. Syn. Coll., 6, 916
Copyright GFS Chemicals 1/08 www.gfschCopyright GFS Chemicals 1/08 www.gfschemicals.comemicals.com
HeterocyclesHeterocycles Benzopyrans and coumarinsBenzopyrans and coumarins
O O
PtCl4
OO
dioxane, rt
PtCl4
dioxane, rt
O
O
O O
92%
89% ee
PtCl4
dioxane, rt
73%
Org. Lett., 2003, 5 (7), 1055
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HeterocyclesHeterocycles 2-substituted furo[3,2-b]pyridines2-substituted furo[3,2-b]pyridines
N N
O
R H
OH
I
+ RCu+
pyridine
89%
N
OH
I
+
OEt
OEt
N
O OEt
OEt82%
Pd(II)-L
Cu+, piperidine
Org. Syn. Coll., 6, 916Heterocycles, 2002, 56, 613
Copyright GFS Chemicals 1/08 www.gfschCopyright GFS Chemicals 1/08 www.gfschemicals.comemicals.com
HeterocyclesHeterocycles IsoquinolinesIsoquinolines
NI2, CH2Cl2
rt
N
R
R
Org. Lett., 2003, 5 (7), 1055
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HeterocyclesHeterocycles bispyrrolopyrimidinesbispyrrolopyrimidines
N NN N
RBr
Br
R
Base 50oC
N N
R
N N
R
N N
RH H
H
CuBr
Et3N, DMA
CH3+Pd cat, Cu cat
H
reduction
2 steps
single diastereomer
R = (CH2)4CH3
Org. Lett., 2002, 4 (26), 4697
Copyright GFS Chemicals 1/08 www.gfschCopyright GFS Chemicals 1/08 www.gfschemicals.comemicals.com
HeterocyclesHeterocycles 2,3-dihydrofurans2,3-dihydrofurans
O
OH
80 - 98%
Et3N, Mo(CO)5
Et2O
Org. Syn., 79, 27