Synthesis of Okilactomycin

Structure of Okilactomycin

C24H32O6

Principal investigator	Amos B. Smith, III
Publication year	2007
Synthesis type	Total
Number of steps	37 (3 parts)
References	J. Am. Chem. Soc. 2007, 129, 14872. J. Am. Chem. Soc. 2009, 131, 2348.

Part 1 of 3

intermediate structure

+

intermediate structure

i-Pr2NLi, LiCl

THF

-78 °C to RT, 24 h, 95%

See the Myers Asymmetric Alkylation

intermediate structure

BH3.NH3, i-Pr2NLi

THF

0 °C to RT, 3 h, 94%

intermediate structure

Pyr.SO3, Et3N, DMSO

CH2Cl2

0 °C, 30 min, 90%

See the Parikh-Doering Oxidation

intermediate structure

Ph3P+CH3 Br-, n-BuLi

THF

0 °C, 3 h, 96%

See the Wittig Reaction

intermediate structure

n-Bu4N+ F-

THF

0 °C to RT, 5 h, 97%

intermediate structure

Pyr.SO3, Et3N, DMSO

CH2Cl2

0 °C, 30 min, 93%

See the Parikh-Doering Oxidation

intermediate structure

+

intermediate structure

n-Bu2BOTf, Et3N

CH2Cl2

-78 to 0 °C, 3.5 h, 93%

See the Evans Asymmetric Aldol Addition

intermediate structure

H2O2, LiOH

H2O

0 °C to RT, 2 h, 97%

intermediate structure

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Part 2 of 3

intermediate structure

+

intermediate structure

PhMe

90 °C, 24 h, 88%

See the Diels-Alder Reaction

intermediate structure

LiAlH4

Et2O

-78 °C to RT, 90 min, 97%

intermediate structure

TMS2NNa
n-Bu4N+ I- , BnBr

THF

0 °C to RT, 70 min

See the Williamson Ether Synthesis

intermediate structure

HF

MeCN

RT, 60 min, 90% (2 steps)

intermediate structure

Li(s-Bu)3BH
PhNTf2

THF

-78 °C to RT, 7.5 h, 82%

intermediate structure

Pd(PPh3)4, LiCl, CO, n-Bu3SnH

THF

70 °C, 5 h, 87%

intermediate structure

Special reagent

CH2Cl2

-78 °C, 60 min, 71%

intermediate structure

KH , 18-Crown-6
Me2SO4

THF

0 °C to RT, 22 h, 96%

See the Cope Rearrangement

intermediate structure

mCPBA

MeOH

0 °C, 30 min, 91%

See the Rubottom Oxidation

intermediate structure

NaH
n-Bu4N+ I- , 2-Bromomethylnaphthalene

DMF

0 °C to RT, 36 h, 96%

See the Williamson Ether Synthesis

intermediate structure

Cp2ZrHCl
NBS

CH2Cl2

0 °C to RT, 40 min, 98%

intermediate structure

PhSeH, Cs2CO3

MeCN

RT, 60 min, 93%

intermediate structure

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Part 3 of 3

intermediate structure

+

intermediate structure

TMSOTf, i-PrOTMS

CH2Cl2

0 °C, 30 min

intermediate structure

Cp2TiMe2

THF

60 °C, 24 h

See the Tebbe-Petasis Olefination

intermediate structure

Me2AlCl

CH2Cl2

RT, 5 min, 42% (3 steps)

See the Petasis-Ferrier Rearrangement

intermediate structure

Special reagent

Pyr

CHCl3

RT to 60 °C, 2.5 h, 94%

intermediate structure

DDQ

CH2Cl2, MeOH

RT, 60 min, 84%

intermediate structure

TMS2NK
ClCO2Me

THF

-78 to 0 °C, 65 min, 99%

intermediate structure

NaOMe

THF

0 °C, 60 min

intermediate structure

K2CO3, MeI

MeCN

70 °C, 2 h, 88% (2 steps)

intermediate structure

Grubbs-Hoveyda catalyst (2nd gen.)

PhH

80 °C, 24 h

See the Olefin Metathesis

intermediate structure

Pd/C, H2

1 atm

EtOAc

RT, 15 h, 84% (2 steps)

intermediate structure

o-NO2PhSeCN , n-Bu3P
H2O2 , H2O

Pyr, THF

0 °C to RT, ON, 90%

See the Grieco Dehydration

intermediate structure

SeO2, t-BuOOH

CH2Cl2

10 °C, 40 min, 54%

"The yield was 62 % brsm."

intermediate structure

SOCl2, Propylene oxide

Et2O

0 °C, 4 h, 74%

intermediate structure

TMS2NNa
PhSeCl

THF

-78 °C, 30 min, 83%

intermediate structure

Et3NO

DMSO

RT, 12 h, 65%

See the Ganem Oxidation

intermediate structure

NaIO4

H2O, THF

RT, 5 h, 90%

intermediate structure

2-Methyl-2-butene, NaH2PO4, NaClO2

H2O, t-BuOH, THF

RT, 60 min, 80%

See the Pinnick-Lindgren Oxidation

intermediate structure

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