BROOK REARRANGEMENT

BROOK REARRANGEMENT AND ITS APPLICATION

1. BROOK REARRANGEMENT Presented by, Priyadarshini. R M.Pharm ( sem -I) DEPT OF PHARM.CHEMISTRY

2. CONTENTS Introduction Reaction Mechanism Application Scope Conclusion Reference

3. INTRODUCTION First observed by Henry Gilman in early 1950 - Suggested the migration of the Si group. Extensively developed in 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 .  

6. BASE

7. METHODS GENERATION OF α - SILYL ALKOXIDES:

8. 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

9. 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 .

10. 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 .

11. OUTLINE Of REARRANGEMENT MECHANISM:

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

13. MECHANISM OF REACTION

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

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

16. APPLICATION 3   E.J. Corey synthesized (+)- Onocerin from farnesyl acetate- derived acyl silane via four-component coupling and tetracyclization steps.

17. 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).

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

19. APPLICATION 6   1,4 Brook rearrangement – wittingreaction -synthesis of silyl dienol ether .

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

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

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

23. 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 .

24. 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 5. Silyl dienol ethers

25. 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

26. 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