Umpolung reactivity

1
Umpolung reactivity

• Special Topic 27/02/09
• Anne Fournier

2
The synthetic problem
3
Definition
Seebach ACIEE 1979, 239
4
Carbonyl Umpolung
Patterns of Carbonyl Reactivity
5
Carbonyl Umpolung
Carbonyl Umpolung intermediates
6
Carbonyl Umpolung
Masked Acyl Anion Equivalents
Cyanide ion Catalyzed Addition

• 1a. Benzoin Condensation

• Must use aromatic or heteroaromatic aldehydes
  aliphatic aldehydes tend to undergo an aldol
  condensation
• Cannot selectivity cross couple of two different
  aldehydes

Lapworth JACS 1903, 995.
7
Carbonyl Umpolung
Masked Acyl Anion Equivalents
Johnson JACS 2005, 1833
8
Carbonyl Umpolung
Masked Acyl Anion Equivalents
(a) Breslow JACS 1958,3719. (b) Enders Acc.
Chem. Res. 2004, 534.
9
Carbonyl Umpolung
Masked Acyl Anion Equivalents
Enders ACIEE, 2002, 1743
10
Carbonyl Umpolung
Masked Acyl Anion Equivalents
(a) Stetter ACIEE 1976, 639. (b) Scheidt JACS
2004, 126, 2314
11
Carbonyl Umpolung
Masked Acyl Anion Equivalents
Rovis JACS, 2002, 10298
12
Carbonyl Umpolung
Masked Acyl Anion Equivalents
Rovis JACS, 2004, 8876
13
Carbonyl Umpolung
Masked Acyl Anion Equivalents
Johnson JACS 2004, 3070
14
Carbonyl Umpolung
Masked Acyl Anion Equivalents
1. HgCl2, H2SO4, H2O 2. NaIO4 or m-CPBA 3.
MeX (X I, OTs,)
(a) Corey, Seebach ACIEE 1965 1075 (b) Corey,
Seebach ACIEE 1965 1077
15
Carbonyl Umpolung
Masked Acyl Anion Equivalents
16
Carbonyl Umpolung
Unmasked Acyl Anion Equivalents
(a) Hanzawa ACIEE 1998, 1696 (a) Hanzawa TL 1998,
6249 (a) Guan Curr. Org. Chem. 2008, 1406
17
Carbonyl Umpolung
Unmasked Acyl Anion Equivalents
(a) Hanzawa TL 1998, 8141 (b) Hanzawa ACIEE,
1999, 2395 (c) Hanzawa T 2002, 8141
18
Carbonyl Umpolung
Acyl Anion Equivalents
19
Carbonyl Umpolung
?-Electrophile Equivalents
20
Carbonyl Umpolung
?-Electrophile Equivalents
Moller JACS 2003, 36
21
Carbonyl Umpolung
Homoenolate Equivalents
22
Carbonyl Umpolung
Homoenolate Equivalents
Bosch JOC 2003, 1919
23
Carbonyl Umpolung
Homoenolate Equivalents
Kuwajima Chem. Comm. 1979, 708
Corey Org. Lett. 2002, 2441
24
Carbonyl Umpolung
Homoenolate Equivalents
?-hydroxyesters
lactones

• (a) Nakamura, Kuwajima JACS 1977, 7360
• (b) Nakamura, Kuwajima JACS 1986, 3745

25
Carbonyl Umpolung
Homoenolate Equivalents
26
Carbonyl Umpolung
Homoenolate Equivalents

• 4b. Zinc Homoenolates Reactivity

• Copper-Catalyzed Conjugate Additions

Kuwajima JACS 1984, 3368

• Catalytic Homo-Reformatsky Reactions

Nakamura, Kuwajima JACS 1987, 8056
27
Carbonyl Umpolung
Homoenolate Equivalents
28
Thank you for your attention