eatles Oasis - 199

Transcription

1

2 eatles asis - 199

3 Biography 2001-present: University of : Professor, Shef : Various Reader : Post-doc with G : D at Universi 1983: Undergrad at Cambrid

4 Enantioselective Construction of Quaternary Stereogenic Centers from Tertiary Boronic Esters: thodology and Applications Ravindra P. Sonawane, Vshal Jheengut, Constantinos Rabalakos, Robin Larouche-Gauthier, elen K. Scott, and Varinder K. Aggarwal * Angew. Chem. Int. Ed. 2011, 50, Early View Bpin >99:1 e.r. M-Alk-LG Alk- >99:1 e.r. Sounds cool, but how do you make chiral tertiary boronic esters?

5 Tertiary Boronic Esters B oyori Asymmetric Transfer ydrogenation Cb s-buli Bpin Carbamate Formation >99:1 e.r. Bpin >99:1 e.r. From secondary chiral carbamates of course! e Cb sbuli Li Cb RB(R') 2 retention R B(R') 2 Cb Δ R B(R') a R Li ipr 2 91% (99:1) 95% (1:99) 69% (99:1) 94% (98:2) Aggarwal et al ature, 2008, 456,

6 Application of Matteson omologation Conditions Bpin a) LiC 2 Br TF, 78 o C b) 2 2, a 83% Br B 83%, >99:1 e.r. Cl 88%, >99:1 e.r. 62%, 99:1 e.r. 82%, >99:1 e.r. 37%, >99:1 e.r. 41%, 98:2 e.r.

7 Extention to Vinylation of Boronic Esters Bpin MgBr (n equiv) B B I 2 a I B I B 66%, >99:1 e.r. Cl 79%, >99:1 e.r. 62%, >99:1 e.r. 79%, >99:1 e.r. 66%, >99:1 e.r. a) Li b) I, a Bpin a) LiCCl 2 b) 2 2, a 68%, >99:1 e.r.

8 Applications Cb 98:2 e.r. a) s-buli b) Bpin c) MgBr 2, Bpin 69% a) MgBr MgI, neat 180 o C b) I 2 ; a 92%, 97:3 e.r. 91% (+)-(S)-sporochnol Cb a) s-buli Bpin pinb Allyl b) MgBr 2 b) 2 2, a Allyl >99:1 e.r. 92% >99:1 e.r. a) 3, 2 S ab(ac) 3 a) LCCl 2 63% over two steps a) MgBr b) PCC Allyl 70% from boronic ester >99:1 e.r. serotonin antagonist

9

10 Biography 2001-present: University of M : Post-doc with Pro : D at University 1968: Born: Kampala, Ugand

11 Enantioselective synthesis of tertiary thiols by intramolecular arylation of Lithiated thiocarbamates Paul MacLellan and Jonathan Clayden * Chem. Comm. 2011, 47,

12 Tet. Lett. 1976, 17, S R3 General Conundrum ucleophile Coordinating Chiral Ligand Enantiofacial selectivity in nucleophilic attack on a prochiral ketone u Zn 2 2 S S 2 Zn 2 MgBr t-bu Trt nbu S ucleophile Coordinating Chiral Ligand S u "A synthesis of thioacetone in Freiburg in 1889 was abandoned after widespread public protest and the evacuation of whole sectors of the city" J. Sulfur Chem. 2009, 30, 167 S umgx Su

13 General Strategy If: Cb sbuli Li ipr 2 Then: R 1 S aryl migration S base S

14 In Practice S LDA, DMPU 78 o C S a S 42-96% works with electron rich as well as deficient aromatics S 98:2 e.r. LiTMP, TF 78 o C 83% S 96:4 e.r. Li S

15 Substrates and Scope 1 R 1. ClC= 2 + Cl 2. CS 3. LiAl S 2 1. LiTMP 2.a 2 1 S I 2 Cl S S S S 97% 97% 51% 89%

16 A general synthetic approach to the amnesic shellfish toxins: total synthesis of ( )-isodomoic acid B, ( )-isodomoic acid E and ( )-isodomoic acid F Gilles Lemiere, Simon Sedehizadeh, Julie Toueg, adia Fleary-Roberts and Jonathan Clayden * Chem. Comm. 2011, Advanced ticle 2C C 2 t-bu R 2 C C 2 R = E Isomers Z Isomers 2 C 2 C 2 C isodomoic acid B isodomoic acid E isodomoic acid F isodomoic acid A domoic acid isodomoic acid D kainic acid

17 Li 67% 99:1 e.r. (after single recryst.) Clayden et al. Chem. Comm. 2002, rg. Lett. 2000, 2, e 3 ) 2 CuCLi 2, TMSCl 86% 3 Si Single Diastereomer acid; Boc 2 3 Si Boc 1. RuCl 3 (10 mol%) ai 4 2. t-bu, DCC 64% 3 Si Boc C2 t-bu Sharpless et al J. rg. Chem. 1981, 46, 3936 eduction xidation 3 Si Boc C2 t-bu mcpba 83% 3 Si Boc C 2 t-bu Boc TMS C 2 t-bu

18 Towards the Core 3 Si Boc C 2 t-bu 1. TBAF 2. Boc 2, t-bu 70% t-bu 2 C Boc C 2 t-bu 3 98% t-bu 2 C Boc C 2 t-bu P 2 Boc "the use of a...allowed us to avoid the epimerisation of the sensitive aldehyde which resulted when potassium carbonate in methanolwas used a base." a 89% t-bu 2 C C 2 t-bu 1. Bu 3 SnCu(Bu)CLi 2 2. I 1. PdCl 2 (C) 2 allylbromide 2. TFA 2 C ( )-isodo C C 2 )-kainic acid TFA Bu 3 Sn t-bu 2 C Boc C 2 t-bu Pd; TFA Pd; TFA 2 C 2 C 2 C C 2 C 2 ( )-isod 2 C 2 C C 2 ( )-isod