Literature Screening

1. Thibaud Gerfaud Literature Screening JACS Synthesis February 2nd 2009

2. Oxidative Pd(II)-catalyzed C-H bond amination to Carbazole at ambient temperature James A. Jordan-Hore, Carin C. C. Johansson, Moises Gulias, Elizabeth M. Beck and Matthew J. Gaunt • Classical disconnection in C-N bond formation: C-X + NH (Pd(0) and Cu(I) couplings) • This work: C-H + NH Pd(II) catalysis • Interest: No prefunctionalization of the aryl group with an halide • Carbazole motif present in a lot of natural products and medicines: Gaunt & al., JACS, 2008, 130, 16184-16186

3. Previous work on C-H amination: - Via nitrenes, Rh catalysis Driver & al., JACS, 2007, 129, 7500-7501 - Allylic C-H amination, heterobimetallic catalysis White & al., JACS, 2008, 130, 3316-3318 - Acetanilide amination, Pd catalysis Inamoto & al., Org. Lett., 2007, 9, 2931-2934 Gaunt & al., JACS, 2008, 130, 16184-16186

4. Mechanistic hypothesis: Optimized reaction conditions: Gaunt & al., JACS, 2008, 130, 16184-16186

5. Scope of the reaction Complex Isolation Gaunt & al., JACS, 2008, 130, 16184-16186

6. Application to complex substrates N-Glycosyl carbazoles Tandem para-iodination, C-H amination followed by Suzuki coupling to give highly functionalized cabazoles Conclusion • - New Pd(II) catalyzed intramolecular C-H amination to form carbazoles • Reaction occurs under mild conditions with a broad scope • - Rare exemple of reductive elimination from a high oxidation state transition • A non polar solvent seems necessary to promote polynuclear palladacycles • Useful in natural products synthesis Gaunt & al., JACS, 2008, 130, 16184-16186

7. Direct Catalytic Asymmetric Synthesis of Cyclic Aminals From Aldehydes Xu Cheng, Sreekumar Vellalath, Richard Goddard and Benjamin List • - Phosphoric acid catalyzed synthesis • Stereogenic cyclic aminals: very common in drugs, catalysts and pharmaceuticals • Common synthesis protocol for benzo(thia)diazines: use of an achiral catalyst and HPLC separation List & al., JACS, 2008, 130, 15786-15787

8. Catalyst Screening: List & al., JACS, 2008, 130, 15786-15787

9. Scope of the reaction: Aldehyde Aminobenzamide

10. Conclusion: • First enantioselective direct synthesis of aminals from aldehydes catalyzed by chiral phosphoric acid • Catalyst structure: • Good aldehyde tolerance • All investigated amides gave excellent enantioselectivities • - Methodology applied to different structures: List & al., JACS, 2008, 130, 15786-15787

11. Asymmetric Reductive Mannich Reaction to Ketimines Catalyzed by a Cu(I) Complex Yao Du, Li-Wen Xu, Yohei Shimizu, Kounosuke Oisaki, Motomu Kanai and Masakatsu Shibasaki • Asymmetric -aminoacids: Mannich reaction is the most straighforward method • Reaction was limited to the use of aldimines and iminoesters to form -amino acids • Low reactivity of ketimines • This work: expand the scope of previous work by the group Shibasaki & al., JACS, 2008, 130, 16146-16147

12. Previous work by the same group: Shibasaki & al., JACS, 2007, 129, 500-501 - Method limited to acetate-derived enolates as donors - New method required to achieve the catalytic asymmetric synthesis of -amino acids with a substituent at the -position Shibasaki & al., JACS, 2008, 130, 16146-16147

13. Catalytic Diastereoselective Reductive Mannich Reaction of Ketimines Shibasaki & al., JACS, 2008, 130, 16146-16147

14. Catalytic Asymmetric Reductive Mannich Reaction of Ketimines Conversion to 2,2,3-amino acids derivatives Without any racemization and epimerization Shibasaki & al., JACS, 2008, 130, 16146-16147

15. One-Pot Synthesis of -Siloxy Esters Using a Silylated Masked Acyl Cyanide Hisao Nemoto, Rujian Ma, Tomoyuki Kawamura, Kenji Yatsuzuka, Masaki Kamiya and Masayuki Shibuya - -Hydroxycarboxylic acids or esters usually prepared in multiple steps by C-C bond formation using carbanion chemistry Kirschning & al., Chem. Eur. J., 1999, 5, 2270 Nemoto & al., Synthesis, 2008, 23, 3819-3827

16. - Reminder on Passerini reaction: - One-pot reaction using MAC (Masked Acyl Cyanide) Nemoto & al., Synthesis, 2008, 23, 3819-3827

17. Esters and tertiary amides which cannot be directly synthesized by Passerini reactions can be synthesized using MAC reagents • Amines can be used directly: no need to form an isonitrile Scope of the reaction (selected examples) Nemoto & al., Synthesis, 2008, 23, 3819-3827

18. Electron density on aromatic rings did not influence the reaction • Sterically hindered aldehydes and ketones are not good substrates for the reaction • On cyclohexen-2-one; competition between 1,2 and 1,4 addition Alcohol scope • No reaction with hindered tert-butyl alcohol Nemoto & al., Synthesis, 2008, 23, 3819-3827

19. Conclusion • One-pot reaction to afford -siloxy esters • A tertiary amine is necessary, in case of sterically hindered substrates DMAP can improve the yield • Trialkylamines unsuitables for the reaction because of decomposition of the MAC reagents • MAC reagents are the only acyl anions equivalents that allow one pot reactions to create -hydroxy carbonyl compounds Nemoto & al., Synthesis, 2008, 23, 3819-3827

20. A Concise Asymetric Total Synthesis of Aspidophytine K. C. Nicolaou, Stephen M. Dalby and Uptal Majumber Haplophytine Haplophyton cimicidium • - Isolated from Haplophyton cimicidium in 1953 • Structure disclosed in 1973 • Acid-mediated degradation lead to the right-hand constituent aspidophytine: - First total synthesis: Corey 1999 Nicolaou & al., JACS, 2008, 130, 14942-14943

21. Retrosynthetic Analysis Nicolaou & al., JACS, 2008, 130, 14942-14943

22. Synthesis of A Nicolaou & al., JACS, 2008, 130, 14942-14943

23. Fragment coupling and elaboration to Aspidophytine Longest linear sequence: 12 steps 5% overall yield Nicolaou & al., JACS, 2008, 130, 14942-14943

24. Other interesting articles • Communications: • - Three Component Coupling of α-Iminoesters via Umpolung Addition of Organometals: Synthesis of α,α-Disubstituted α-Amino Acids • Kozlowski & al., JACS, 2008, 130,15794-15795 • Full Papers: • Total Synthesis of (−)-Pseudolaric Acid • Trost & al., JACS, 2008, 130,16424-16434