Alkyne Technology from GFS Chemicals

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ALKYNESALKYNES

THE HYPER-VERSATILE BUILDING THE HYPER-VERSATILE BUILDING BLOCKS OF CHEMISTRYBLOCKS OF CHEMISTRY


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%


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


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


EneynesEneynes OligomerizationOligomerization

I

R2

R1

Si + OH1. K2CO3

2. Sonogashira rxn

Repeat

R2

R1

Si

HO

n

Org. Lett., 2003, 5 (3) 365


1,3-butadienes1,3-butadienes

BnO+ C6

BnO C6

82%

Ru cat

C2H4 rt

Org. Lett., 2003, 5 (11), 1855


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


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)


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


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


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


[4]-radialenes[4]-radialenes

Org. Lett., 2003, 5 (19), 3371

Br

Br

X

X

2 Steps

X = S, -CMe2, none


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


CarbocyclesCarbocycles 2-cyclopentenones2-cyclopentenones

N-Boc

O

TMS 2 StepsO

TMS

Boc-HN

HO

Tetrahedron. Lett., 2000, 41, 9393


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


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

+


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


HeterocyclesHeterocycles Maleic AnhydridesMaleic Anhydrides

OO O

HPdCl2, CuCl2

CO (1 atm), rt

Tetrahedron Lett., 2001, 42 (39), 6923


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


HeterocyclesHeterocycles pyrrolespyrroles

ClH2C CH2Cl +

COOEt

COOEt

CH3CONH

HN COOEtNaOMe

EtOH

38%

J. Org. Chem., 1996, 61, 9068


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


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


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


HeterocyclesHeterocycles IsoquinolinesIsoquinolines

NI2, CH2Cl2

rt

N

R

R

Org. Lett., 2003, 5 (7), 1055


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


HeterocyclesHeterocycles 2,3-dihydrofurans2,3-dihydrofurans

O

OH

80 - 98%

Et3N, Mo(CO)5

Et2O

Org. Syn., 79, 27

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