The document summarizes the Brook rearrangement reaction. It was discovered in 1957 by Adrian Brook and involves the migration of a silyl group from carbon to oxygen under basic conditions. The mechanism proceeds through the formation of a pentavalent silicon intermediate. The rearrangement has various applications in synthesis, such as constructing 8-membered rings and chiral silyl ethers. It has been used to synthesize compounds like gamma-amino-beta-hydroxy amides and alpha-hydroxy acid derivatives.

1. Presentedby,
Priyadarshini. R
M.Pharm(sem-I)
DEPT OF PHARM.CHEMISTRY

2. CONTENTS
Introduction
Reaction
Mechanism
Application
Scope
Conclusion
Reference

3. INTRODUCTION
First observedby Henry Gilman in early 1950 -
Suggestedthe migration of the Si group.
Extensively developedin 1957 by Adrian G. Brook -
Proposed a nucleophilic attack of oxygen to α-silicon
atom.

4. INTRODUCTION
Adrian Gibbs Brook discovered the
rearrangement in 1974.
Brook did mechanistic studies as well.
He was first to synthesis a silicon-carbon
double bond

5. DEFINITION
The 1,2- migration of a silyl group from carbon to
oxygen under basic conditions is known as Brook
rearrangement.
Rearrangement of α- silyl oxyanion to α-silyl
carbanions involving a penta coordinate silicon
intermediate.

7. Amines
Sodium
hydroxide
Organolithi
um reagent
Alkali
metal alloy
BASE

8. METHODSGENERATIONOF α - SILYLALKOXIDES:

9. METHOD 1:
Reaction of acylsilanes with a nucleophile
METHOD 2:
Although deprotonation of the corresponding α-silyl
alcohols
METHOD 3:
Addition of silyl metallic reagents to aldehydes or
ketones

10. DRAWBACK:
 Organosilyl metal reagents are only readily generated
when there is atleast one anion stabilizing group such as
phenyl attached to the silicon.
METHOD 4:
Regioselective β-ring opening of α,β-epoxysilanes can also
same as a source of α-silyl alkoxides.

11. CHARACTERISTICS
Depends on the amount of base added.
 Pseudofirst order kinetics.
A silyl shift from oxygen to carbon, the reverse
process is called retro-Brook rearrangement.
Aza- or Thia- variants of the rearrangement have
also been observed

12. OUTLINE Of REARRANGEMENT MECHANISM:

13. MECHANISM-STEPS INVOLVED
The mechanism as described by Brook includes the
formationof a cyclic pentavalent silicon species .
Immediately following the deprotonation.
Subsequentring opening and irreversible.
Fast protonation of the carbanion by the starting alcohol
or the conjugate base leads to the corresponding silyl
ether.

14. MECHANISM OF REACTION

15. SYNTHETIC APPLICATIONS
APPLICATION 1:
K. Takeda and co-workers synthesized the tricyclic core
of the cyanthins using a Brook rearragement reaction.

16. APPLICATION 2
 K.Takeda developed a new synthetic strategy for the
stereoselective construction of 8 membered carbocycles
utilizing a Brook rearrangement.

17. APPLICATION3
E.J. Corey synthesized (+)- Onocerin from farnesyl
acetate- derived acyl silane via four-component
coupling and tetracyclization steps.

18. APPLICATION 4
Brook rearrangement is used for another
important name reaction called vinylogues
Michael-cascade reaction.(vinylation and 1,2-
brook rearrangement reaction is used).

19. APPLICATION-5
 It is used in the synthesis of alpha hydroxyl acid derivatives
are important in the cosmetic industry.

20. APPLICATION6
1,4 Brook rearrangement –wittingreaction-
synthesis of silyl dienol ether.

21. APPLICATION 7
For the preparation of functionalised,stereo
defined 8-membered ring.
APPLICATION 8
Silyl ethers are used as protecting agents for
alcohols.

22. APPLICATION 9
Synthesis of gamma amino β-hydroxy
amines(lactum synthesis).

23. APPLICATION 10
Useful in tandem with other reactions via the
addition of electrophile.

24. SCOPE
Brook rearrangements are known in acylsilanes. Beyond
that, acylsilanes are well known for their hydrolysis in
basic solution to a silanol and an aldehyde – initiated by
attack-carbonyl group.
A related reaction, involving initial attack at the silicon
center, causes migration of one of the silicon groups to
the carbonyl carbon, which initiates a Brook-
Rearrangement. If the silicon group was chiral, the end
product is a chiral silyl ether, as the migration occurs
stereo specifically.

25. Conclusion
 The Brook rearrangement has been applied widely since its discovery in
1957.
 some of which have been used as tools in the synthesisof structurally
challenging organic compounds.
 Useful reaction in tandem with others to form bonds.
 Several one-pot synthesis in recent literature.
 Recent literature have used this chemistry to synthesize the following
1. γ-amino-β- hydroxy amide
2. α- hydroxy acid derivatives
3. Aryl vinyl ketones
4. Eight-membered rings

26. REFERENCE
1.Jie Jack Li:Name Reactions Third Edition;Springer
Science & Bussiness Media, 2006:Page no:83-84
2. Brook, A. G. (1958). "Isomerism of some α-
hydroxysilanes to silyl ethers". J. Am. Chem. Soc. 80:
1886–1889.
3.Laszlo Kurti,Barbara Czako:Strategic Applications of
Named Reactions in Organic Synthesis;Elsevier,29-
Apr-2005;page no:64-65
4.Christian M. Rojas:Molecular Rearrangements in
Organic Synthesis:Wiley,March-2015,Page no:207-
241

27. 5.A. Hassner, I.Namboothiri;Organic Syntheses Based
on Named Reactions, Third Edition;Elsevier;Page
no:62
6. : Boyce, Gregory R. and Johnson, Jeffery S., J. Org.
Chem. 2016, 81, 1712-1717