Tebbes reagent

Tebbes reagent , chemistry reagent

1. TEBBE’S REAGENT 1

2. TEBBE’S REAGENT The tebbe reagent is the organometallic compound .It is used in the methylenation of carbonyl compounds ,that is it converts organic compounds containing the R 2 C=O group into the related R 2 C=CH 2 derivative. Formula : C 13 H 18 Al Cl Ti 2

3. Reagents for Alkylidenations O 3

4. Why use Titanium-based Reagents? 4 Non-basic, reactive reagent More reactive to the sterically hindered carbonyl group

5. Comparison of Tebbe and Wittig Reagents O 5 97% 8 9% T e b b e W i t t ig O 77% 4% Ph Ph O Ph Ph 63% 3 8%

6. Why use Titanium-based Reagents ? Non-basic, reactive reagent More reactive to the sterically hindered carbonyl group Alkylidenate carboxylic acid and carboxylic acid derivatives Ti Cl Al Cl Cl Tebbe Reagent Ti Ti Grubbs Reagent Ti Me Me Petasis Reagent Takeda Reagent 6 Ti P ( O Et ) 3 P ( O Et ) 3 + RS R 1 SR R 2 Zn, TiCl 4 , TMEDA, PbCl 2 (cat), RCHBr 2 Takai Re a g e nt

7. Tebbe Reagent Ti 7 Cl Al Cl Cl Ti C l Al R R O R + Cp 2 TiMeCl R + (MeAlO) n R R O Without Base

8. Tebbe Reagent Ti 8 Cl Al Cl Cl Ti R + R R In the presence of base O Pyridine Ti C H 2 R O R R Ti O

9. Tebbe Reagent with Ketone and aldehyde Didemnenones O O O O EtO O O O EtO Tebbe, PhMe 71% M eN 9 C H O O C H 2 OH O MOM N Tebbe,THF 65% M eN O C H 2 OH O MOM N

10. Tebbe Reagent: Esters and Lactones Atrochrysone Steglich, W. et. al. JCS. Pekin Trans I 2000 , 2483 Polyhydroxylated Molecules CO 2 Me CO 2 TBDMS O T BD M S Me CO 2 TBDMS O T BD M S Me Tebbe,THF 61-85% M eO O 10 O O O O O O Tebbe,THF/PhMe 69% O O O O O O

11. Tebbe Reagent: Acid Chlorides and Enol ethers R C l O Tebbe C p 2 Ti O Cl R R O T i C l C p 2 R O R 1 T ebbe C p 2 Ti O O R 1 R R T i C l C p 2 Ph C H O R P h OH 55-78%

12. Tebbe Reagent: Alkenes Aplysins O 12 O Cp 2 TiCl 2 (2.8 eq) AlMe 3 (7.8 eq) Cp 2 TiCl 2 (6 eq) AlMe 3 (12 eq) O O O T i C p 2

13. Summary of the Tebbe Reagent 13 Tebbe methylenation of esters has been accomplished in the presence of many functional groups. Alkenes including dienes, Vinyl fluorides, vinyl chlorides, aryl bromides, and aryl iodides Ethers including benzyl,and trityl ethers, Silyl ethers including TMS,TBDMS,and di- tert butylsilylene, Acetals including benzylidene acetal,MOM, and acetonides Selenoglycosides and thioglycosides Carbamates including NHBoc,and sulfonamides The key advantage of the Tebbe reagent over other titanium reagents used in alkylidenations is that the reactive titanium methylidene is generated and reacted at low temperature. Its disadvantages are its high sensitivity to both moisture and air, its Lewis acidic character, and the fact that it is limited to methylenation.