rhodomolleid XX rhodomolleid XXII · 2020. 2. 24. · Rhodomolleins XX and XXII 5 OMe OTiPS O OEt O...

1

Presenter: Behrad Masoudi 02/15/2020

rhodomolleid XXIIrhodomolleid XXH

OH

H

HO

OOH

HO

H

OH

H

HO

OOH

HOHO

Rhodomolleins XX and XXII


Pearson, D. E.; Cowan, D.; Beckler, J. D., A Study of the Entrainment Method for Making Grignard Reagents. The Journal of Organic Chemistry 1959, 24 (4), 504-509

i-PrSii-Pr

Cli-Pr

TiPSCltriisopropylsilyl chloride

3

OMeOOH

TiPSCl (1.1 equiv.)Et3N (1.5 equiv.)

CH2Cl2, 0 to 30 °C, 6h

OMeOOTiPS

OMeOHOTiPS

CBr4 (1.5 equiv.)PPh3 (1.5 equiv.)

CH2Cl2, 0 °C to rt, 30 min

OMeBrOTiPS

OMeOOTiPS NaBH4 (1.1 equiv.)

MeOH, 0 °C, 30 min

OMeOHOTiPS

OMeOOH

OMeBrOTiPS

64%over 3 steps

OH

0.25 mol

Br

HH

H

BrH

Mg (10.0 equiv)MgBr2

0.1 mol+ C2H2

Et2O, rt, 30 min

OMeBrOTiPS

OMeMgBrOTiPS

Et2O, rt, 1 h

(1.0 equiv.)

0.10 M749 mL= 7.49 mmol

(0.95 equiv.)OMe

OTiPS

HO

Et2O, 0 °C, 2 h

88%

alcohol protection

reduction

Appel reaction

Grignard reaction


4

Li, W.; Wang, J.; Hu, X.; Shen, K.; Wang, W.; Chu, Y.; Lin, L.; Liu, X.; Feng, X. Journal of the American Chemical Society 2010, 132, 8532.

Hg(OAc)2 (0.1 equiv.)AcONa (0.1 equiv.)

n-Bu O

(5.0 equiv.)

CH2Cl2, rt to 94 °C, 24 h

OMeOTiPS

OH

OMeOTiPS

OMeOTiPS

O O OEtO

N2 OEtO

(1 equiv.)SnCl2 (0.1 equiv.)

CH2Cl2, rt, 24 h

72%over 2 steps

104.6 mmol

OAc

n-Bu OHg OAcAcO

n-Bu O

HgOAc

OAc

ROH

n-Bu O

HgOAcO

R

H

OAc

P.T.

n-Bu O

HgOAcO

R

H n-BuOH

HgOAcO

R

Hg(OAc)2

O

R

O

R Claisen Rearrangement

O

ROMe

OTiPSR =

Claisen Rearrangement

R

OSn Cl

Cl

R

OSnCl Cl

NEtO

O

N

R

OSn

Cl

ClOOEt

OSnO

EtON2

R

Cl

Cl

N2

H

R

O

O OEt

+ SnCl2 + N2

Roskamp homologation


5

OMeOTiPS

O OEtO

OMeOTiPS

O

OEtO

N2

TsN3 (1.0 equiv.)Et3N (1.2 equiv.)

71.3 mmol

MeCN, 30 °C, 12 h

97%

László Kürti and Barbara Czakó; Strategic Applications of Named Reactions in Organic Synthesis: Background and Detailed Mechanisms;; Elsevier Academic Press

R

O

OEt

O

Regitz diazo transfer

P.T.R

O

OEt

O

R

O

OEt

ON N N S

O

O

R

O

OEt

O

N N N SO

OH R

O

OEt

O

N N NHS

O

OR

O

OEt

O

NN

NHSO

O


O

NCuN

O

t-Bu

t-BuCu(tbs)2

tbs = N-t-butylsalicylaldiminato

OMeOTiPS

O

OEtO

N2

OMeOTiPSO

OEtO

HH

69.1 mmol

Cu(tbs)2 (5 mol%)toluene, 115 °C, 2h

90%

R

O

OEt

O

NN

R

O

OEt

O

NN

Cu(II)R

O

OEt

O

NN

Cu(I)

π-back donation

N2

R

O

OEt

O

Cu(II)

R’OOEt

OCu(II)

≡R’O

OEt

O OMeOTiPSO

OEtO

HH

≡

Cu(II)

pseudo-Simmons-Smith Cyclopropanation

6



OMeOTiPSO

OEtO

HH

MeOOTiPS

OEtO

H

OO

(CH2OTMS)2 (1.5 equiv.)TMSOTf (1.0 equiv.)

CH2Cl2, 0 °C, 2 h

pyridine(1.5 equiv.)

15 min

62.0 mmol 70%

7

ROOEtO

HH

SiOSO

OCF3

ROOEtO

HH

SiOTf

ROOEtO

HH

Si

OTMSTMSO

RTMSOOEtO

HHO

TMSO H

P.T. RTMSHOOEtO

HHO

TMSO

ROEtO

HH

O

TMSO

HOTMS

ROEtO

HH

O

OTMS

OTf

OTf OTf OTf

OTf

ROEtO

HH

O

O

TMSOTf

NH

ROEtO

H

O

O

HN

P.T.

ROEtO

H

O

O

H


RCO2Et

H

OO

N

O

O

Br RCO2Et

H

OO

Br OH2R

CO 2Et

H

OO

Br

OH

t-BuOK

P.T. RCO 2E

t

H

OO

Br

O

RCO 2Et

H

OO O

8

MeOOTiPS

OEtO

H

OO

19.7 mmol

NBS (1.1 equiv.)

THF/H2O, 0 °C, 10 h

MeOOTiPS

OEtO

H

OO

OHH

OO

OH

MeOOTiPS

O OEt t-BuOK (1.1 equiv.)Pd/C, H2 (atm)

-78 to 30 °C, 1.5 h

65%over 2 steps

Br

didn’t report dr


9

PO

MeOOMe

H P.T.PO

MeOOMe

RHO O

H

OO

HO

RO

H

OO

OH

POMeO

OMe

ROHO

H

OO

OH

POMeO

MeO

P.T. RO

H

OO

OH

P OMeO

MeO

H H

O

RO

H

OO

OH

P OMeO

MeOO

RO

H

OO

OH

POMeO

MeOO

RO

H

OO

OH

Horner-Wadsworth-Emmons Reaction


MeOOTiPS

OEtO

H

OO

OH

MeOOTiPS

O

H

OO

OH

18.2 mmol

i-Pr2NH (3.1 equiv.)n-BuLi (3.0 equiv.)

-78 to 0 °C, 15 min

PO

OMeOMe

(1.1 equiv.)

THF, 0 °C, 30 min

(CH2O)n(19.9 equiv.)

0 °C, 1 h

82%


MeOOTiPS

O

H

OO

OH

TBAF (1.1 equiv.)

28.2 mmol

0 °C, 10 min

MeOOH

O

H

OO

OH

PhI(OAc)2 (1.5 equiv.)

MeOH, 65 °C, 10 h

OO

HO

HH OH

MeO OMeO

HO

OH

HH OH

H

OMeO OMe

O

+

a70%

b25%

I OO

OO

(diacetoxyiodo)benzene

MeOOH

O

H

OO

OH

I OOOO MeO

O

O

H

OO

OH

IPh

OAc

MeOO

O

H

OO

OH

MeOO

O

H

OO

OH

MeOH P.T.

OAc

MeOO

O

H

OO

OH

MeO

≡

O

H

OO

OH

OMeO

MeO

Oxidative dearomatization-induced Diels-Alder Reaction

10Harned, A. M. Tetrahedron Letters 2014, 55, 4681.


OO

HO

HH OH

MeO OMeO

H SmI2 (3.0 equiv.)

THF/MeOH (10:1)0 °C to rt, 1 h

OO

HO

HH OH

OH

12.3 mmol 90%

O O

DMDOdimethyldioxirane

11

OO

R

OH

’R

OO

HO

HH OH

OH

DMDO (4 equiv.)

CH2Cl2 , 0 °C to rt, 8 h

OO

HO

HH OH

OH

O

92%12.3 mmol

https://en.wikipedia.org/wiki/Epoxidation_with_dioxiranes

OO

HO

HH OH

OH

O

5.8 equiv

Cp2TiCl2 (0.1 equiv.)Mn (8 equiv.)

2,4,6-collidine

DCE, rt to 50 °C, 12 h

OO

H O

HH OH

OH

OH

OO

HO

HH OH

OH

OH

61% 15%

+


N

2,4,6-collidine R

O

O M

’RR

O

OM

’RR

O

OM

’RR

O

OM

’R

Dowd-Beckwith ring expantion

12

Jie Jack Li, A Collection of Detailed Mechanisms and Synthetic Applications, Springer-Verlag Berlin Heidelberg 2009


Petasis olefination

OO

H O

HH OH

OH

OH

OO

H

HH OH

OH

OH

H

HH OH

HO H

OH

O

4.9 mmol 67%

Cp2TiMe2(3.0 equiv.)

toluene, 85 °C2 h

p-TsOH H2O(2 equiv.)

rt, 2 h

13



H

HH OH

HO H

OH

O PhSeCl (3.0 equiv.)pyridine (3.1 equiv.)

CH2Cl2, 0 °C, 18 hH

OH

O H

HO

O

1.6 mmol 93%

H

OH

O H

HO

O

H

OH

O H

HO

O

OHO

Co(acac)2 (0.2 equiv)PhSiH3 (2 equiv.)

O2 (1 atm)

i-PtOH, 0 °C, 3 h

65%0.32 mmol

14

O OCo

O O

Cobalt(II) acetylacetonate

H

OH

O H

HO

O

OH

TBSOTf (5.0 equiv.)Et3N (1.1 equiv.)

CH2Cl2, 0 °C, 15 min

H

OH

O H

TBSO

TBSO

OH

0.32 mmol 92%


15

H

OH

O H

TBSO

TBSO

OH MeMgBr (1.7 equiv.)toluene, 0 °C, 1 h

H

OH

H

TBSO

TBSOOH

HO

H

OH

H

HO

OOH

HOHCl (2 N)

0 °C, 2 h

77%rhodomollein XXII


16

MeReO3 (0.25 equiv.)H2O2 (2.5 equiv.)

pyridine (2.5 equiv.)

MeCN/AcOH (19:1)0 °C, 15 hH

OH

H

TBSO

TBSOOH

HO

H

OH

H

HO

OOH

HO

rt, 2h

rhodomollein XX

HOPPTS (5.0 equiv.)

64% over 3 steps

H

OH

H

TBSO

OOH

HOHO

0.4 mmolPPTS

Pyridinium p-toluenesulfonate

NH

SO O

O

Thank you.

rhodomolleid XX rhodomolleid XXII · 2020. 2. 24. · Rhodomolleins XX and XXII 5 OMe OTiPS O OEt O...

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Transcript of rhodomolleid XX rhodomolleid XXII · 2020. 2. 24. · Rhodomolleins XX and XXII 5 OMe OTiPS O OEt O...