Synthesis of Kendomydin

Structure of Kendomydin

C29H42O6

Principal investigator	Johann Mulzer
Publication year	2009
Synthesis type	Total
Number of steps	39 (7 parts)
References	Angew. Chem. Int. Ed. 2009, 48, 6032. Org. Lett. 2014, 16, 4276.

Part 1 of 7

intermediate structure

Sn(OTf)2
Acrolein

CH2Cl2, Et3N

-20 °C, 60 min, 91%

"87:17 d.r."

intermediate structure

Me4N+ BH(OAc)3-

AcOH, MeCN

-32 to 0 °C, 3 h, 70%

See the Evans-Saksena Reduction

intermediate structure

LiOH, H2O2

H2O, THF

RT, 1 h, 72%

intermediate structure

Me2C(OMe)2, Camphorsulfonic acid

RT, ON, 91%

intermediate structure

LiAlH4

Et2O

0 °C, 30 min, 96%

intermediate structure

Pyr.SO3, Et3N, DMSO

CH2Cl2

-5 °C, 90 min, 99%

See the Parikh-Doering Oxidation

intermediate structure

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Part 2 of 7

intermediate structure

mCPBA, NaOAc

CH2Cl2

-20 to 0 °C, 90 min

See the Prilezhaev Reaction

intermediate structure

H5IO6

Et2O

0 °C

intermediate structure

LiAlH4

Et2O

0 °C, 3 h, 77% (3 steps)

intermediate structure

Imidazole, TBDPSCl

DMF

0 °C to RT, 1 h, 90%

intermediate structure

O3
Ph3P

CH2Cl2

-78 to 0 °C, 2 h, 99%

intermediate structure

TMSCHN2, n-BuLi

-78 to 0 °C, 3.5 h, 83%

See the Peterson Olefination

See the Fritsch-Buttenberg-Wiechell Rearrangement

intermediate structure

Cp2ZrHCl
I2

THF

-78 to 0 °C, 1 h, 76%

intermediate structure

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Part 3 of 7

intermediate structure

PhI(OAc)2

H2O, MeOH

RT, 16.5 h

intermediate structure

Na2S2O4

Et2O, H2O

RT, 3 h, 72% (2 steps)

intermediate structure

MeOCH2Cl, NaH

THF

0 °C to RT, 24 h, 94%

intermediate structure

NBS

THF

0 °C, 16 h, 89%

intermediate structure

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Part 4 of 7

intermediate structure

+

intermediate structure

ZnCl2 , t-BuLi
Pd(PPh3)4

Et2O, THF

-78 to 0 °C, 3.5 h, 67%

See the Negishi Coupling

intermediate structure

DMDO

Acetone

RT, 15 min, 99%

intermediate structure

Pd(OAc)2, n-Bu3P

t-BuOH

reflux, 90 min, 81%

See the Semi-Pinacol Rearrangement

intermediate structure

TfOH

4A MS

EtOH, PhMe

80 °C, 5 min, 95%

intermediate structure

NaH, MeOCH2Cl

DMF

RT, 1 h, 95%

intermediate structure

n-Bu4N+ F-

THF

RT, ON, 89%

intermediate structure

IBX

DMSO

RT, 2 h, 97%

intermediate structure

2-Methyl-2-butene, NaClO2, NaH2PO4

H2O, t-BuOH

0 °C, 70 min, 99%

See the Pinnick-Lindgren Oxidation

intermediate structure

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Part 5 of 7

intermediate structure

+

intermediate structure

Special reagent

Et2O

-78 °C, 52%

"d.r. 50:1, 86% ee"

intermediate structure

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Part 6 of 7

intermediate structure

+

intermediate structure

DMAP, EDC

CH2Cl2

RT, 81%

intermediate structure

TBSCl, TMS2NLi

HMPA, THF

-78 °C to RT

intermediate structure

uW

DMF

180 °C, 10 min

intermediate structure

LiAlH4

Et2O

0 °C, 89%

intermediate structure

MsCl

CH2Cl2

0 °C

intermediate structure

LiAlH4

Et2O

0 °C, 89%

intermediate structure

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Part 7 of 7

intermediate structure

+

intermediate structure

n-BuLi, (CH2NMe2)2

THF

-78 to -25 °C, 3.5 h, 90%

"76:24 S/R at C6"

intermediate structure

Grubbs catalyst (2nd gen.)

20 mol%

CH2Cl2

reflux, 16.5 h, 62%

See the Olefin Metathesis

intermediate structure

N2(COOK)2, AcOH

CH2Cl2

reflux, 36 h, 60%

intermediate structure

HCl

H2O, MeOH

RT, 4 h, 96%

intermediate structure

TESOTf, Et3N

CH2Cl2

0 °C to RT, ON, 82%

intermediate structure

IBX

DMF

RT, 24 h

intermediate structure

HF

H2O, MeCN

RT, 4 h, 30% (2 steps)

intermediate structure

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