A Sakurai-Prins-Ritter Sequence for the Three-Component ...ccc.chem.pitt.edu/wipf/Current...
15
A Sakurai-Prins-Ritter Sequence for the Three-Component Diastereoselective Synthesis of 4-Amino Tetrahydropyrans Oleg L. Epstein and Tomislav Rovis* Colorado State University J. Am. Chem. Soc. 2006, 128, 16480-16481. Current Literature Presentation on Jan. 6 th , 2007 Shuli Mao Shuli Mao @ Wipf Group 1 1/14/2007
Transcript of A Sakurai-Prins-Ritter Sequence for the Three-Component ...ccc.chem.pitt.edu/wipf/Current...
A Sakurai-Prins-Ritter Sequence for the Three-ComponentDiastereoselective Synthesis of 4-Amino Tetrahydropyrans
Oleg L. Epstein and Tomislav Rovis*Colorado State University
J. Am. Chem. Soc. 2006, 128, 16480-16481.
Current Literature Presentation on Jan. 6th, 2007Shuli Mao
Shuli Mao @ Wipf Group 1 1/14/2007
Tetrahydropyrans as Backbones of Natural Products
Potent antimitotic agents Mean GI50 value: 1.58 X 10-9 M
against NCI panel of 60 tumor cell lines
Potent cytotoxicity against KB and P388 tumor cell lines
IC50=1-5 nM against several tumor cell lines(-)-Zampanolide
Shuli Mao @ Wipf Group 2 1/14/2007
Approaches to Tetrahydropyran Skeleton
• Cyclizations onto Oxocarbenium Ions (C-C formation)
• Hetero-Diels-Alder Cyclizations (C-C and C-O formation)
• Cyclizations onto Epoxides (C-O formation)
• Other Methods
Review: Clarke, P. A.; Santos, S. Eur. J. Org. Chem. 2006, 2045.Shuli Mao @ Wipf Group 3 1/14/2007
[4+2] Hetero-Diels-Alder Approach
OTBS
OBn
O
H OTBDPS+
RT O
OBn
OTBS
TBDPSO64%
97%ee
O
OBn
OTBS
TBDPSO
OH1) BH3
.THF, THF, 0oC
2) 30% H2O2,
3N NaOH,
0oC to RT
94%
(1S, 2R)-1
Liu, P.; Jacobsen, E. N. J. Am. Chem. Soc. 2001, 123, 10772.
(+)-Ambruticin
Shuli Mao @ Wipf Group 4 1/14/2007
Cyclizations onto Epoxides
McDonald, F. E.; Wei, X. Org. Lett. 2002, 4, 593.
Thyrsiferol
Venustatriol
Shuli Mao @ Wipf Group 5 1/14/2007
Cyclizations onto Oxocarbenium Ions
TsO
O
OBn
OAc
SnBr4, CH2Cl2, -78oC
84%TsO
Br
O
OBn
MeO
O
OH
(-)-Centrolobine
Marumoto, S.; Jaber, J. J.; Vitale, J. P.; Rychnovsky, S. D. Org. Lett. 2002, 4, 3919. Shuli Mao @ Wipf Group 6 1/14/2007
[3+3] Cyclocondensation Approach
O O
R2
R1
OAc
O
R
R
R
A
BOH O
R1 R
3
NHCOR4
R2
13
O O
R2
R1
LA1 R
3
SiR32
O O
R2
R1
R3
LA2
O O
R1
LA
R3
R2
Sakurai Reaction
Prins and Ritter Reaction
Epstein, O. L.; Rovis, T. J. Am. Chem. Soc. 2006, 128, 16480.
A: Biselectrophile “1”B: Bisnucleophile “2”
Shuli Mao @ Wipf Group 7 1/14/2007
Sakurai Reaction
O O
tBu
C6H13 OAcTMS
BF3.OEt2
CH3CN, -30oC
O O
tBu
C6H13
1:196%
O O
R2
R1 R
3
SiR32
O O
R2
R1
R3
O O
R2
R1
OAc
1
LA1
Rychnovsky, S. D.; Skalitzky, D. J. Synlett 1995, 555. Boons, G.-J.; Eveson, R.; Smith, S.; Stauch, T. Synlett 1996, 536.
1,3-anti relationship
In this paper:
TMSOTf
CH2Cl2, -78oC
single diastereomer86%
O O
tBu
OAc TMS
O O
tBu
O
R2R1
ketone or aldehyde
+R3 SiMe3
R4
Lewis acid, CH2Cl2R4
R3
R1
HO R2
R4
R3
R1
R2 OH
+
Homoallylic alcohol Homoallylic alcohol
When R2=H: Syn-diastereomer When R2=H: Anti-diastereomer
Temp range: -78oC to RT
favored
Shuli Mao @ Wipf Group 8 1/14/2007
Prins ReactionO
HR5
Protic or Lewis acid
R2
R3R1
R4
+
R2
R3R1
R4
R5
HHO
R2
R3R1
R5
HHO
and/or
R2
R3R1
R4
R5
HHO
Nu
Allylic alcohol 3-Substituted alcohol
+ other products
OH O
R1 R
3
Nu
R2
3
O O
R2
R1
R3
LA2
O O
R1
LA
R3
R2
Rational for 2,6-cis tetrahydropyran formation:
In this paper:
OR
R3
OR
R3
R2 R2
Shuli Mao @ Wipf Group 9 1/14/2007
Ritter Reaction
C NR1 + R4
R3
R2
X R3NR2
R4CR1
XH2O C
O
NH
R1
R2
R4
R3
N-Alkyl carboxamide
R3NR2
R4CR1
Nitrilium ion
OH O
R1 R
3
NHCOR4
R2
3
OH O
R1
R2
R3
N C R4 H2O
Stereochemistry depends on R3
In this paper:
Shuli Mao @ Wipf Group 10 1/14/2007
Sequential Sakurai-Prins-Ritter Reactions
Shuli Mao @ Wipf Group 11 1/14/2007
Stereochemistry RationalAlder’s model:1) THP cation 4 has an increased stability relative to the open-chain oxocarboniumion due to delocalization. The calculated optimal geometry for delocalizationplaces the H atom at C4 in a pseudoaxial position.
2) 4-Methyl substituted THP cation 5 is much more stable than 4.
Epstein, O. L.; Rovis, T. J. Am. Chem. Soc. 2006, 128, 16480.
3) Destabilization of the intermediate tertiary cation was observed if 4-methylwas replaced by 4-acetoxymethyl substituent.
Alder, R. W.; Harvey, J. N.; Oakley, M. T. J. Am. Chem. Soc. 2002, 124, 4960.
Shuli Mao @ Wipf Group 12 1/14/2007
Nitriles Scope
Epstein, O. L.; Rovis, T. J. Am. Chem. Soc. 2006, 128, 16480. Shuli Mao @ Wipf Group 13 1/14/2007
Extension of Sakurai-Prins-Ritter Reactions
Epstein, O. L.; Rovis, T. J. Am. Chem. Soc. 2006, 128, 16480.
Shuli Mao @ Wipf Group 14 1/14/2007
Conclusions
• Another THP formation method was developed using a sequential Sakurai-Prins-Ritter Reactions
• Reactions involved are all diastereoselective
• The introduction of the amide made further functionalization possible
• Up to four new stereocenters may be controlled from a single stereocenter present in the starting material
Shuli Mao @ Wipf Group 15 1/14/2007
