Problema 21 Pyrrolizidine alkaloids 1.

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47 IChO 2015 Baku – Azerbaijan Soluzioni preliminari dei problemi preparatori 1 Problema 21 Pyrrolizidine alkaloids

1. The synthesis of dihydroxypyrrolizidine alkaloid, (±)-turneforcidine, is given in the

Scheme 1. In this scheme E is an unstable intermediate which spontaneously undergoes the Claisen rearrangement producing F. Write down the structural formulae of compounds A–J.

Scheme 1

H3N CO2Et ^CO2Et A B ClCO2Et

K2CO3

C₁₂H₂₁NO₆ EtONa

C

10% H2SO4

D C₇H₁₁NO₃

HO OBn

TsOH,∆

E F

NaBH4

G ^BnBr

NaH H

KOH

∆ I

C₂₅H₃₁NO₄

PhSCl

C₂₈H₃₁NO₂S J

1) Raney Ni

2) H2, Pd/C N

HO H OH

(±)-turneforcidine Et = C2H5; Bn = CH2C6H5

1

Cl ^{K2CO3 EtOH}

Solution 1:

N

H₂ COOEt

COOEt

NH COOEt

COOEt

COOEt Cl

N COOEt

COOEt

COOEt B A

K₂CO₃ K₂CO₃

EtONa EtOH

N O

COOEt

COOEt

N O

COOEt O

H OBn

N COOEt

O

OBn 10% H₂SO₄

C D

TsOH, ∆

[ E ] ..

N O

H

OBn COOEt

N OH

H

COOEt

OBn _N

H

COOEt

OBn OBn

F

NaBH₄

G

BnBr NaH

KOH

∆

H

NH

OBn OBn H

NH

OBn OBn H

S Ph

N OH

H OH N

OBn OBn H

S Ph PhSCl

I

1) Ni Raney 2) H₂ Pd/C

(+ - )-turneforcidine +

J

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47 IChO 2015 Baku – Azerbaijan Soluzioni preliminari dei problemi preparatori 2 2) Epimer of turneforcidine at C(7) atom, (±)-platynecine, was synthesized by the reaction sequence given in Scheme 2. It is noteworthing that K is the product of [2+2]-cycloaddition.

Write down the structural formulae of compounds K–M as well as of (±)-platynecine.

Scheme 2

N

O O

Cl COCl

Et₃N,∆ K Bn

C₁₆H₁₈ClNO₃ RCO3H

L

H_2,Pd(OAc)₂ then base to neutralization

M

LiAlH₄

(±)-platynecine

Solution 2:

N

BnO O

Cl COCl

N

O BnO

O

Cl

N

O BnO

O

NEt₃ , ∆ + Cl

RCO₃H

K

N

O BnO

O O

Cl H

N

O O

H

N H OH OH

H₂ Pd(OAc)₂

L

LiAlH₄

M then base to

neutralization

(+ -)-platynecine

Soluzione proposta da

Mauro Tonellato - ITI Marconi - Padova