Catalytic Enantioselective Construction of AllCarbon Quaternary Stereocentres

1
Catalytic Enantioselective Construction of
All-Carbon Quaternary Stereocentres

• Anna Innitzer
• 05.04.2006

2
Introduction

• asymmetric construction of all-carbon
  quaternary stereocentres
• as challenge in organic synthesis
• need for atom-economic process
• high enantioselectivity
• synthecially useful yields

Methods discussed

• Cycloadditions
• Michael Additions and Direct Alkylations
• Allylation via Palladium p-Allyl Intermediates
• Copper Catalysed SN2Allylations
• Intramolecular Heck Reactions
• Enyne Reactions
• Metathesis

3
Cycloadditions 42
(1) Wulff et al. J.Am.Chem.Soc. 1993, 115, 3814
(2) Yamamoto et al. J.Am.Chem.Soc. 1994, 116,
1561 (3) Bernardinelli et al. Angew. Chem. Int.
Ed. 1994, 33, 1856 (4) Corey et al. Org. Lett.
2003, 5, 2466
4
Cycloadditions 42Total Synthesis of
()-Cassiol
Synthesis was achieved in 9 steps with 40
overall yield
Potent anti ulcer agent
Key-Step
(5) Corey et al. J. Am. Chem. Soc. 1994, 116,
3611
5
Cycloadditions 42DA reactions of
Benzoquinone Derivatives
Iodide controls regioselectivity
(6) Corey et al. J. Am. Chem. Soc. 2003, 125,
6388 (7) Evans et al. J. Am. Chem. Soc. 2003,
125, 10162
6
Cycloadditions 32Synthesis of
Isoxazolidines
(8) Yamada et al. Org. Lett. 2002, 4, 2457
7
Cycloaddtions 22Kinugasa Reaction
Synthesis of b-Lactams
I
(9)Fu et al. Angew. Chem. Int. Ed. 2003, 42, 4082
8
CyclopropanationsIntermolecular Cyclopropanation
R aryl 83 94 ee, only E-isomer, 41-91
yield R alkyl gt90 ee, E/Z 81 161, 58-65
yield10
R aryl, alkyl 74 96 de, 74 88 ee 63
90 yield11
R Ph 97 ee, 83 yield R Me E/Z 32, 88
yield,85 ee (E), 81 ee (Z)12
(10) (a) Davies et al. Tet. Lett. 1993, 34, 7243
(b) Davies et al. J.Am.Chem.Soc. 1996, 118, 6897
(c) Corey et al. Tet. Lett. 1994, 35, 5373 (11)
Davies et al. Tet. Lett. 1996, 37, 4133 (12)
Doyle et al. Tet. Lett. 1996, 37, 4129
9
CyclopropanationsIntramolecular Cyclopropanation
R1 Me, R2 Me2CCH(CH2)2 93 ee, 79 yield R1
Me2CCH(CH2)2 R2 Me 95 ee, 88 yield13
Total synthesis of presqualene diphosphate14
(13) Doyle et al. J.Am.Chem.Soc. 1995, 117, 5763
(14) Poulter et al. J.Org.Chem. 1995, 60, 941
10
Michael AdditionMichael Reaction with Enones
R H, alkyl, aryl 94 ee, up to 99 yield X
OR, NMe(OMe)15
(15) Ito et al. J.Am.Chem.Soc. 1992, 114, 8295
11
Michael AdditionUse of Chiral Palladium
Enolates from 1,3-Dicarbonyls
100 mol c 97 ee, 99 yield 10 mol c 90 ee,
89 yield16
(16) Sodeoka et al. J.Am.Chem.Soc. 2002, 124,
11240
12
a-AlkylationAlkylation of Tributyltin Enolates
(17) Jacobsen et al. J.Am.Chem.Soc. 2005, 127, 62
13
Allylation via Pd p-Allyl IntermediatesQuaternar
y Stereocentre on the Nucleophile Side
946 dr, 97 ee, 71 yield
R1 Me, benzyl 86 - 95 ee, 80 - 100 yield R2
H, Me, CH2OAc16
n 1 R Me, 991 dr, 96 ee, 87 yield n 2 R
OMe, 982 dr, 99 ee, 91 yield
(18) Trost et al. J.Am.Chem.Soc. 1997, 119, 7879
14
Allylation via Pd p-Allyl IntermediatesQuaternar
y Stereocentre on the Nucleophile Side
91, 89ee

• Trimethylsilylenolethers can also be used!

n 2 94, 86ee n 3 90, 79 ee
(19) Stoltz et al. J.Am.Chem.Soc. 2004, 126, 15044
15
Allylation via Pd p-Allyl IntermediatesTotal
Synthesis of Hamigeran B
(20) Trost et al. J.Am.Chem.Soc. 2004, 126, 4480
16
Allylation via Pd p-Allyl IntermediatesQuaternar
y Stereocentre on the Electrophile Side
(21) Trost et al. J.Am.Chem.Soc. 2001, 123, 12907
17
Allylation via Pd p-Allyl IntermediatesSynthesis
of the Cyclopentyl Core of Viridenomycin
(22) Trost et al. Org. Lett. 2003, 9, 1563
18
Copper Catalysed SN2Allylation
a (CuOTf)2.C6H6 b CuCl2.2H2O
P
(23) Hoveyda et al. Angew. Chem. Int. Ed. 2001,
40, 1456 (24) Hoveyda et al. J.Am.Chem.Soc. 2004,
126, 10676 (25) Hoveyda et al. J.Am.Chem.Soc.
2004, 126, 11130
19
Intramolecular Heck Reactions Synthesis of
Decalin Systems, Bicyclic Enones and Dienones
R1 CH2OPG R2 H, CH2OAc X I, OTf
67 90 yield, 80 90 ee
(26) Shibasaki et al. J.Am.Chem.Soc. 1994, 116,
11737 (27) Shibasaki et al. Synthesis 1993, 920
20
Enyne Cyclisations Cyclisations of 1,6- and
1,7-Enynes
(28) Mikami et al. J.Am.Chem.Soc. 2003, 125, 4704
(29) Mikami et al. Angew. Chem. Int. Ed. 2001,
40, 249
21
Asymmetric Ring Closing Metathesis Synthesis of
Cyclic Enol Ethers
S
(30) Hoveyda et al. J.Am.Chem.Soc. ASAP,
24.3.2006
22
References
review Catalytic Enantioselective Construction
of All-Carbon Quaternary Stereocentres Trost et
al. Synthesis 2006, 369.
Cycloadditions (1) Wulff et al. J.Am.Chem.Soc.
1993, 115, 3814 (2) Yamamoto et al.
J.Am.Chem.Soc. 1994, 116, 1561 (3) Bernardinelli
et al. Angew. Chem. Int. Ed. 1994, 33, 1856 (4)
Corey et al. Org. Lett. 2003, 5, 2466 (5) Corey
et al. J. Am. Chem. Soc. 1994, 116, 3611(6)
Corey et al. J. Am. Chem. Soc. 2003, 125,
6388 (7) Evans et al. J. Am. Chem. Soc. 2003,
125, 10162 (8) Yamada et al. Org. Lett. 2002, 4,
2457 (9)Fu et al. Angew. Chem. Int. Ed. 2003,
42, 4082 (10) (a) Davies et al. Tet. Lett. 1993,
34, 7243 (b) Davies et al. J.Am.Chem.Soc. 1996,
118, 6897 (c) Corey et al. Tet. Lett. 1994, 35,
5373 (11) Davies et al. Tet. Lett. 1996, 37,
4133 (12) Doyle et al. Tet. Lett. 1996, 37, 4129
(13) Doyle et al. J.Am.Chem.Soc. 1995, 117, 5763
(14) Poulter et al. J.Org.Chem. 1995, 60,
941 Michael Additons/Direct Alkylation (15) Ito
et al. J.Am.Chem.Soc. 1992, 114, 8295(16) Sodeoka
et al. J.Am.Chem.Soc. 2002, 124, 11240 (17)
Jacobsen et al. J.Am.Chem.Soc. 2005, 127,
62 Allylation via Palladium p-Allyl
Intermediates (18) Trost et al. J.Am.Chem.Soc.
1997, 119, 7879 (19) Stoltz et al. J.Am.Chem.Soc.
2004, 126, 15044 (20) Trost et al. J.Am.Chem.Soc.
2004, 126, 4480 (21) Trost et al. J.Am.Chem.Soc.
2001, 123, 12907 (22) Trost et al. Org. Lett.
2003, 9, 1563 Copper Catalysed
SN2Allylations (23) Hoveyda et al. Angew. Chem.
Int. Ed. 2001, 40, 1456 (24) Hoveyda et al.
J.Am.Chem.Soc. 2004, 126, 10676 (25) Hoveyda et
al. J.Am.Chem.Soc. 2004, 126, 11130
Intramolecular Heck Reactions (26) Shibasaki et
al. J.Am.Chem.Soc. 1994, 116, 11737 (27)
Shibasaki et al. Synthesis 1993, 920 Enyne
Reactions (28) Mikami et al. J.Am.Chem.Soc. 2003,
125, 4704 (29) Mikami et al. Angew. Chem. Int.
Ed. 2001, 40, 249 Metathesis (30) Hoveyda et al.
J.Am.Chem.Soc. ASAP, 24.3.2006