Synthesis of Strychnine

Structure of Strychnine

C21H22N2O2

Principal investigator	Masakatsu Shibasaki
Publication year	2002
Synthesis type	Total
Number of steps	31 (linear)
References	J. Am. Chem. Soc. 2002, 124, 14546. Tetrahedron 2002, 58, 2585.

Part 1 of 1

intermediate structure

Special reagent

KOt-Bu, Dimethyl malonate

4Å MS

THF

4 °C to RT, 24 h, 91%

See the Michael Addition

intermediate structure

2-Ethyl-2-methyl-1,3-dioxolane, TsOH

RT, 16 h

intermediate structure

LiCl

DMSO, H2O

140 °C, 17 h, 97% (2 steps)

See the Krapcho Decarboxylation

intermediate structure

+

intermediate structure

i-Pr2NLi

																	THF															

								-78 °C, 								19 h, 								72%
							
								See the Claisen Condensation
							
								"The yield was 82 % brsm."

intermediate structure

TiCl4, NaBH3CN

CH2Cl2, THF

-78 to -55 °C, 10.5 h

intermediate structure

DCC, CuCl

PhH

Reflux, 5 h, 70% (2 steps)

intermediate structure

i-Bu2AlH

CH2Cl2

-78 °C, 60 min

intermediate structure

Et3N, TIPSOTf

CH2Cl2

-78 °C, 10 min, 98% (2 steps)

intermediate structure

Camphorsulfonic acid

Acetone

RT, 2 d, 62%

"The yield was 90 % brsm."

intermediate structure

LiTMP, TMSCl

THF

-78 °C, 2 h

intermediate structure

Diallyl carbonate, Pd2(dba)3.CHCl3

MeCN

RT, 12 h, 90% (2 steps)

See the Saegusa-Ito Oxidation

intermediate structure

TMSCl, i-Pr2NLi

THF

-78 °C, 2 h

intermediate structure

Yb(OTf)3, CH2O

H2O, THF

RT, 3 d

See the Mukaiyama Aldol Addition

intermediate structure

DBU

CH2Cl2

RT, 60 min, 57% (3 steps)

intermediate structure

I2, DMAP

CH2Cl2

RT, 5 h, 89%

intermediate structure

+

intermediate structure

Ph3As, Pd2(dba)3.CHCl3, CuI

DMF

RT, 48 h, 100%

See the Stille Coupling

intermediate structure

TMS(CH2)2OCH2Cl, i-Pr2NEt

CH2Cl2

4 °C to RT, 24 h, 100%

intermediate structure

Et3N.3HF

THF

RT, 2.5 d, 100%

intermediate structure

+

intermediate structure

Tf2O, i-Pr2NEt

CH2Cl2

-78 °C, 90 min

See the Michael Addition

intermediate structure

Zn, NH4Cl

H2O, MeOH

RT, 2 h, 77% (2 steps)

intermediate structure

Me2SSMe+ BF4-

4Å MS

CH2Cl2

RT, 3 h, 86%

intermediate structure

NaBH3CN, TiCl4

CH2Cl2, THF

-78 °C, 65 min, 68%

intermediate structure

HCl

H2O, MeOH

55 °C, 3 h

intermediate structure

Ac2O

Pyr

RT, 36 h

intermediate structure

NaOMe

MeOH

RT, 30 min

intermediate structure

TIPSCl, Imidazole

CH2Cl2, DMF

4 °C, 2 h, 51% (4 steps)

intermediate structure

NiCl2, NaBH4

EtOH, MeOH

RT, 40 min, 33%

"The yield was 94 % brsm."

intermediate structure

Pyr.SO3, Et3N

DMSO

RT, 60 min

See the Parikh-Doering Oxidation

intermediate structure

Et3N.3HF

THF

RT, 12 h, 83% (2 steps)

intermediate structure

NaOMe

MeOH

40 °C, 2 d

intermediate structure

NaOAc, Malonic Acid

Ac2O, AcOH

110 °C, 2 h, 42% (2 steps)

See the Aldol Addition

intermediate structure

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