Enantioselective Total Syntheses of Pallambins A D

Presenter: Charles Anamoah

O Me H Me O O Me O Me pallambin D O Me H Me O O Me O Me pallambin B H H O Me H Me O O Me O Me pallambin C O Me H Me O O Me O Me pallambin A H H

O Me 8

O

Me

H

Me

MgBr

CuBr.Me

S

HMPA(3.0 equiv)

MeI(8.8 equiv)

(2 equiv)

( 1 equiv)

8(20 mmol)

THF, -40 °C, 20 min

55% (dr=3:1)

11

THF, 25 °C, 20 h

Conjugate addition followed by methylation

O Me H Me 13 O Me H Me O m-CPBA

1.0 mmol 40%, two steps

TsOH (0.5 equiv) MDI (2.0 equiv) CHCl₂, 30 °C, 2.5 h CHCl₂, 0 °C then rt (1.2 equiv) O Me H Me 17 OH MDI N N O

O

Me

H

Me

O

O

19

THF, -78 °C, 30 min

THF, -78 °C, 1 h

LIHMDS (3.0 equiv)

Davis reagent

Li+ N-Si Si O Me H Me O O Me H O Me H Me O O Me Li N Si Si H O N Ph SO₂Ph O Me H Me O O Me Li N Si Si H O Ph _N SO₂Ph O Me H Me O O Me N Si Si H O Li O Me H Me O O Me OH Li+ N-Si Si + Ph _N SO₂Ph

O Me H Me O O OH Me 21 0.95 mmol DMP (1.5 equiv) DCM, rt THF, -78 °C, 5 min O Me H Me O O OH Me _O Me H Me O O O Me LiAlH(Ot-Bu)₃ 28 89% 0.95 mmol (1.1 equiv) 15 99%

Time not stated

O Me H Me O O Me O Red-Al (16 equiv) THF,-10 °C, 30 min CuI (8.0 equiv) OH (16 equiv) 0.10 mmol O Me H Me O O Me 14 94% O THF,-20 °C, 30 min

O

Me

H

Me

O

O

OH

Me

15

0.080 mmol

C

O

C

Ph

P

(2.0 equiv)

m-xylene,145 to

160 °C, 30 min

O

Me

H

Me

O

O

Me

22

61%

O

Mechanism for step 9

CEM 850, Exam II key, Nov 15, 2019

O Me H Me O O Me O Me O Me H Me O O Me O Me pallambin C O Me H Me O O Me O Me O Me H Me O O Me O Me O Me H Me O O Me O Me O Me H Me O O Me O Me pallambin A 65% H H

Org. Lett., Vol. 14, No. 22,

2012

O O 23.78 mmol 92% i-BuOH (5.8 equiv) p-TsOH.H₂O (5 mol%) benzene, 104 °C, 3.5 h 25 g = $100.0 12 O i-BuO

Org. Lett.,Vol. 11, No. 2,

2009

O

i-BuO

O

i-BuO

O

O

2.19 mmol

MeI (3.0 equiv)

Cs

CO

(1.30 equiv)

CH

CN, 80 °C, 14 h

_SI-29

O

i-BuO

O

O

84%

Angew. Chem. Int. Ed.

2011,50, 2756 –2760,

Pd

_(pmdba)

N

O

t-Bu

PPh

(6.25 mol%)

(2.5 mol%)

Catalyst

toluene, 30 °C, 30 min

SI-29

O

i-BuO

O

O

Catalyst

(2.5 mol%)

0.68 mmol

O

i-BuO

8

97% ,86%ee

toluene, 50 °C, 22 h

Angew. Chem. Int. Ed.

2011,50, 2756 –2760,

O

O

O

+

O

OH

LiAlH

Et

92%, 84% ee

No observable

β-hydroxyketone

8

Starting material

0.66 mmol

(0.65 equiv)

aq. HCl