Massachusetts Institute of TechnologyOrganic Chemistry 5.511

October 19, 2007Prof. Rick L. Danheiser

Carbanionic Synthons

Lecture 6

Reading Assignment

Background: Clayden et al. Sections of Chapters 9, 21, and 26

Carey and Sundberg Part B, Chapters 1, 7 (Sections 7.1, 7.2, and 7.3.1), and 8 (Section 8.1) Note: some stereochemical features of this chemistry will not be covered until later units

1. Metalation with base (deprotonation) 2. Oxidative addition (reductive metalation) 3. Halogen-metal exchange 4. Transmetalation 5. Addition to π-bonds 6. Fragmentation and cleavage

Introduction to General Reactivity and Overview ofGeneral Methods for the Generation of Carbanionic Synthons

Unit 2 Outline

Case Study

Total Synthesis of Cecropia Juvenile HormoneKondo, K.; Negishi, A.; Matsui, K.; Tsunemoto, D.; Masamune, S. Chem. Commun. 1972, 1311Stotter, P. L.; Hornish, R. E. J. Am. Chem. Soc. 1973, 95, 4444Demoute, J. P.; Hainaut, D. Toromanoff, E. C. R. Acad. Sci., Ser. C 1973, 277, 49

CO2Me

O

S

OHS

S

S

O

OHCl

+

+

OH

1) Li, EtNH2, -78 °C2) RaNi, EtOH Δ 4 h

Hyalophora cecropia

Henry Gilman1893-1986

"Henry Gilman: American Pioneer in the Rise of Organometallic Chemistry in Modern Science and Technology" Eisch, J. J. Organometallics 2002, 21, 5439

Umpolung Reversal of polarity