Mohammad Movassaghi,* Meiliana Tjandra, and Jun Qi Reporter: ZhiYong Han 2009-07-06 Total Synthesis of (-)-Himandrine J. AM. CHEM. SOC ASAP.

Mohammad Movassaghi,* Meiliana Tjandra, and Jun Qi

Reporter: ZhiYong HanReporter: ZhiYong Han2009-07-062009-07-06

Total Synthesis of (-)-Himandrine

J. AM. CHEM. SOC ASAP

2

Hzy-090706Author

•Mohammad Movassaghi

•Associate Professor of Chemistry

•Massachusetts Institute of Technology

B.S. University of California at Berkeley 1995 Ph.D. Harvard University 2001

3

Hzy-090706Origin

Galbulimima belgraveana

Cannabis(大麻 )

Similarity

Hallucinogen(迷幻剂 )

Popuans(巴布亚人 )

Sleeping Popuan

Boil

4

Hzy-090706Structure

5

Hzy-090706Retro synthesis

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7

Hzy-090706

Tetrakis(triphenylphosphine)palladium (1.54 g, 1.30 mmol, 8.00 mol%) and thalliumcarbonate (15.7 g, 33.0 mmol, 2.00 equiv) were added sequentially

OTBS

B(OH)2

OMe

OTBS

BrOMe

BrBr

+

MacMillan -hydroxylation

Pd(PPh3)4,Tl2CO3

97%

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Hzy-090706

O H

H

H

OMeN

H

H

O

>50%

N

Me

nBuLi;CuBr·SMe2

OH

H

H

OMeN

H

H

O

NMe

H

OH

H

H

OMeN

H

H

O

NMe

H

H

H

H

H

OMeN

H

H

O

N

OHH

Me

H

H

HH

(-)-15

(-)-19

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Hzy-090706

H

H

H

H

OMe

H

HN

OHH

MeH

H

OZ

H

H

H

OMe

H

HN

OHH

MeH

H

OHZ

H

H

H

H

OMe

H

N

H

MeH

H

OZ

H

Cl

N

H

O H

H

H

H

OMe

H

NMe

H

H

OZ

OH

NMe2

71%

POCl3DMF

Vilsmeier’sreagent

(-)-21

(+)-23

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Hzy-090706

H

H

H

H

OMeNH

H

MeH

H

OH

OH

OOMe

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Hzy-090706