R.A. Rodriguez Leo Armand Paquette Baran GM 2011-08-20 ...

R.A. Rodriguez

Born in Worcester, Mass., July 15, 1934

1390 publications (111 reviews)

42 patents

17 books

38 book chapters

Research interests

Heterocyclic chemistry

Hydrocarbon chemistry

Natural product synthesis

Synthetic methodology

Catalytic asymmetric methods

Organoetallic chemistry

Organosulfur reagents

Leo Armand Paquette

B.S., Holy Cross College, 1956

Ph.D., MIT, 1959 synthesis of azasteroids

and regioselectivity in Baeyer-Villiger

(Adv. Norman A. Nelson)

Upjohn, medicinal chemist, 1959-63

Prof. Ohio State University, 1969-present

Honors and Awards

1965 Alfred P. Sloan Fellow

1971 Morley Medalist Cleveland Section

1976 Guggenheim Fellow

1979 Columbus Section Award

1980 Senior Research Award, OSU

1981 Kimberly Professorship in Chemsitry

1987 Arthur C. Cope Scholar

1984 National Award for Creative Work

in Synthetic Organic Chemistry

1989 Senior Humboldt Fellow

1990 Sullivant Medal, OSU highest honor

1992 Awardee of the Japanese Society for

the Promotion of Science

1992 Ernest Guenther Award

2002 S.T. Li Prize Science and Technology

Syntheses Discussed

[4]peristylane

Elassovalene

OH

Dodecahedron

[22](1,5)Cycloctatetraenophane

Me

Me

H

O H H Me

Me

Me

Me

Me

Me

Pentalene

Me

OAc

Me

Me

Me Salsolene oxide

4a¦Â, 10¦Â-doladiol acetate

Me

HO

Me

Me

O

O

Me

O

Me

Me

O

MeO

Me

O

O

OMe

Me

H

HO 3

C(3) OH ¦Á; C(3) OH ¦Â

(-)-Austalide B

Timeline: Career in review

Natural Product Synthesis 1979-present

Gymnomitrol and Isocomene 1979

55 total syntheses to date

Hydrocarbons 1974-1990

Dodecahedrane 1982

Heterocyclic chemsitry

1962-1975

Azepine 1962

Oxy-Cope RR 1978-2000

Ag(I) cat. RR di-¦Ð?methane RR

1975-1984

1970-75

Postdoctoral Researchers

from the Paquette group:

Steven Ley (1972-1974)

Louis Barriault (1997-1999)

(-)-polycarvernoside A

Baran GM

2011-08-20

1962

1968

1975

Organosulfur 1964-74

¦Á-Halosulfones 1964

1981

Squarate esters Indium reagents

1993-97 1995-2000

1987

1993

2000

Silicon chemistry

Polyspiro tetrahydrofurans

1977-1984

1981-2004

2006

2011

Leo Armand Paquette

R.A. Rodriguez

Heterocyclic and Carbocycle Chemistry 1962-1975

Upjohn and OSU

Syntheses and derivatives:

N

H

Azepine

Baran GM

2011-08-20

MeO

N

N

Syntheses and derivatives:

JACS 1962, 84, 4987

JACS 1963, 85, 4053

JACS 1964, 86, 4092

JACS 1964, 86, 4096

JACS 1965, 87, 1718

JACS 1965, 87, 3417

JACS 1968, 90, 6148

JACS 1972, 94, 6751

O

Oxepin

MeO

Azabullvalene

1967

Azasemibullvalene

1969

Bullvalene

Semibullvalene

e.g. phenol and chloramine

A Synthetic Entry into the Azasemibullvalene System

Photochemistry of Carbocycles

O

O

Me

H

hv

hv

H

1/4 products

acyclic

¦Á,¦Â-cyclopropane

ester

Me

Me

Me

O

Me

Me

ClO2SN

Me

C O

Me

Me

Me O

O

JACS 1969, 91, 7108

ClO2SN

Me

Me

The Protonation of Hexamethyl Dewar Benzene and Hexamethylprismane

in FSO3H?SbF5?SO2 "magic acid"

Me

Me

Me

HN

Me NaOH Me

Me

Me

1.

Me

Me

Me

Me

Me

Me

JACS 1968, 90, 7147

Me

Me 2. K2CO3

Protonation of cis-Bicyclo[6.1.0]nona-2,4,6-trienes in superacidic media

H

?95 ¡ãC

H

JACS 1973, 95, 3386

Me

Me

Me

Me

Me

Me

N

MeO

Novel aromatics 1976

The First 8C-6¦Ð Huckeloid System:

1,3,5,7- Tetramethylcyclooctatetraene Dication

Me

FSO3H?SO2ClF

Me

Me

Me

Me3O+BF4-

JACS 1969, 91, 6107; JACS 1967, 89, 5480;

JACS 1975, 97, 6124; JACS 1970, 92, 4338

Me

Me

Me

O

Identification of cationic species 1968 (collaboration with Olah)

Me

Me

trans-Bicyclo[6.1.0]nonan-2-ones

2,3 Homotropone

JACS 1967, 89, 5633

Me

Me

Me

NSO2Cl

Me

Me

Me

ClO2SN

+

initial trans cation

JACS 1976, 98, 1267

Me

2+

Me

Me

Me

+

+

Me

Me

Me

Me

JACS 1976, 98, 4327 Bis(tetramethylhomocyclopropenyl) Dication

Leo Armand Paquette

R.A. Rodriguez

Synthetic Methods:

1. Ramberg-Backlund 1964-74

Baran GM

2011-08-20

3. di-¦Ð-methane RR 1975-80

Upjohn: Conversion of Mercaptans to Homologous Terminal Olefins

1989 [3]peristylane

HO

O

[O]

SH

SCH2Cl

90%

SO2CH2Cl

97%

4. Silanes 1977-84

- cyclopentanone synthesis

Cl

S

O

S

O

O

O

Me

O

HO

X

SO2CH2Cl

base

Cl

R

S

-HCl

O

JACS 1967, 89, 4487

O

TMS

+

base

-SO2

-HCl

Me

Me

Me

Me

Me

Me

Me

Me

Me

¦Á?Vetispirene

Tet.Lett 1982, 23, 3227

Ag

Ag

Ag

H

(AgBF4)

vs >150 ¡ãC w/o Ag (I)

Br

Br

H

Me

TMS

2. Ag I cat. RR 1970-75

Ag+

O

Me

SnCl4

TMS

TMS

Me

O

Me

R

AlCl3

Cl

Me

Me

JOC 1980, 45, 3017

Chem. Rev. 1986, 86, 733

(silyl cylopropanes)

RR of ¦Á,¦Á-Dichloromethyl Sulfones

CH2SO2CHCl2

O

Me

2. nBuLi

3. TMSCl

O

JACS 1964, 86, 4383

R

1. PhSO2NHNH2

O

oxydi-¦Ð-methane

Tetrahedron 1989, 45, 3099

OH-

OH

hv

Diels-Alder equivalents

Phenyl Vinyl Sulfoxide as

Acetylene Equivalent

trans-1-(Phenylsulfonyl)-2-(TMS)ethylene as

Ethylene Equivalent

H

O

SO2Ph

H

H

H

H

PhS

MeLi

80%

JACS 1971, 93, 1288; JACS 1980, 102, 637

Ag+

(AgBF4)

40 ¡ãC

H

via ene-type

quant. clean

non-conjugated triene

JACS 1978, 100, 1597

? Indium 1995

? Zr 2002

TMS

* cis found to be less reactive

JACS 1980, 102, 4976

Leo Armand Paquette

R.A. Rodriguez

Baran GM

2011-08-20

Men of learning in ancient Greece took especial concern for "the putting together of cosmic figures.' their regular polyhedra whose mathematical elegance inspired

considerable wonder. The heritage of that wonder inevitably passed into the realm of synthetic organic chemistry and attracted the practitioners of this science to

apply their skills to the construction from carbon and hydrogen of such strained molecules...

A journey to dodecahedron: selected syntheses of hydrocarbons

[4] peristylane

octahedrane

[8 faces]

decahedrane

[10 faces]

top view

[5] peristylane

Eaton and Muller

dodecahedrane

[12 faces]

X

Tetrahedron, 1989, 45, 3099

[3] peristylane

"triaxane"

JACS, 1983, 105, 4113

[4] peristylane

top view

R

R

1. SeO2 H

2. Al2O3,

quinoline

H

1. BF3,

Et3SiH

I

[3+2]

N

wurtz

O

CO2H

Cl

O

80%

2.

CO2H

Br

S

I

O

Ts

O O

O

OH

TsOH

63% 2 steps

O MsCl/TEA 0 ¡ãC;

rt NO GOOD!!

85%

H

H

Cl

10%aq

MeOH

95%

O

O

quant [5 gram] 1. hv

76% 2. H+,¦¤

O

I 1. sulfene

N NHTs

N

SOCl2

Cl

O

O

O

HO

OH

H

HIO4,

Me

HO2C

1.

N

NaK-alloy

54% wurtz-type

¦¤

O

Ts

77%

O

O

TS

hv

quant

acetone

3.H3O+

69% 3 steps

NaOEt,

EtONO

OH

2. I2, PPh3

N NHTs

1.eth.gly., H+

2. Li, EtNH2

Hypostrophene

1. hv

¦¤

O

N OH

Several years later, Garratt and White noted that the top row (vide supra)

hydrocarbons constitutes a series of compounds characterized by the

interconnection of a smaller n-memberd ring to one twice the original size at

alternate carbons of the latter and the community decided to generalize the

Eaton nomenclature.

O

O

98%

2 steps

Ts

2. TsCl, py

3. LAH, ¦¤

64% 3 steps

After successful preparation of one of these hydrocarbons, Eaton named it

"peristylane" after a Greek word hat alludes to the similarity to "a group of

columns arranged about an open space in a manner designed to support a roof".

I

mCPBA

PhH, ¦¤

Ts

It was initially named "triaxane" in an effort to capture the C3v symmetry of its

tetracyclic framework and to depict that the cyclopropane ring rests on three

axial pillars fixed to a cyclohexane chair.

OH

O

H

When first synthesized, trixane was viewed predominantly as a chemical curiosity.

[3] peristylane

"triaxane"

? molecular modeling shows

serious nonbonded steric strain

H

I

Tet. Lett., 1974, 17, 1615

2. NaI

90%

OH LAH

O

84%

HO

O

O

Leo Armand Paquette

R.A. Rodriguez

Baran GM

2011-08-20

B

JACS, 1990, 112, 1258; Tetrahedron, 1981, 37, 4521

Br

A

B

Br

A

45 ¡ã

E

[22](1,5)Cyclooctatetraenophane

The Weiss-Cook reaction:

E

E

R

+

O

2 equiv

O

O

E

aq. buffer

O

R

E

E

2 equiv

O

1.LAH

2.NaH,

CS2, MeI;

¦¤

O

70%

1.

O

O

R

2. HCl, ¦¤

85%

- 4CO2

O

HCl, ¦¤

92%

E

O

HO

O

Br

3.Ph3PBr2

66% 3 steps

ether, rt

two-fold

Br cation-olefin

cyclization

CO2Me

1. OsO4

2.HO

OH

TsOH

OH 1.LAH

2.NaH, CS2

MeI; ¦¤

SiO2

(10X weight)

1.LAH

2. DHP/H+

83%

83%

Me

Me

O

O

H

H

Br

AgClO4

H

Br

H

PhH/pentane

Br

Br

Bu3SnH

3.TsOH

56%

69%

O

A

B

O

minor

Br

+

(~ 1:2)

major

B

Ni(CO)4

DMF

34%

Br 2 steps

all mixtures

O

all mixtures

NBS 4 eq

AIBN/CCl4

CO2Me

E

(COCl)2,

DMSO

2 eq E

E

O

E

all mixtures

Br

O

cis-bicyclo[3.3.0]

octanedione

O

85%

O

- 4CO2

E

pH = 5.6

+

E

Br

R

E

O

R

O

E

O

E

R

[3,3]

H2, Pt

EtOAc

500 ¡ãC

40%

brsm

bicyclo

[3.2.1]octane

A

JACS, 1979, 101, 4773

bicyclo

[2.2.2]octane

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