S1 Copper-Catalyzed Asymmetric Conjugate Additions of bis(pinacolato)diboron and Dimethylzinc to Acyl-N-Methylimidazole Michael Acceptors: A Highly Stereoselective Unified Strategy for 1,3,5,..n (OH, Me) Motifs Synthesis. Jimmy Lauberteaux, Christophe Crévisy, Olivier Baslé, Renata Marcia de Figueiredo, Marc Mauduit, and Jean-Marc Campagne 1. GENERAL CONSIDERATIONS .......................................................................................................................... S2 2. GENERAL PROCEDURES ................................................................................................................................. S3 2.1 Homologation to α,β-unsaturated Weinreb amide ........................................................................................ S3 2.2 Addition of NMI to Weinreb Amide ................................................................................................................ S3 2.3 Addition of NMI to aldehydes ......................................................................................................................... S4 2.4 Allylic alcohol oxidation .................................................................................................................................. S4 2.5 Oxidation of alcohol to aldehyde .................................................................................................................... S4 2.6 Transformation of the imidazole moiety to an ester ...................................................................................... S5 2.7 ACA of B 2 Pin 2 to α,β-unsaturated 2-acyl-N-methylimidazole ketones ........................................................... S5 2.8 Reduction of ester to aldehyde ...................................................................................................................... S6 2.9 ACA of Me 2 Zn to α,β-unsaturated 2-acyl-N-methylimidazole ketones........................................................... S6 3. PREPARATION OF THE DIETHYL 2-(METHOXY(METHYL)AMINO)-2-OXOETHYLPHOSPHONATE 12 ................... S7 4. PREPARATION OF NON-COMMERCIAL ALDEHYDES ........................................................................................ S7 5. PRELIMINARY EXPERIMENTS ......................................................................................................................... S8 6. PREPARATION OF SUBSTRATES- EARLIEST STAGES....................................................................................... S10 7. PREPARATION OF SUBSTRATES- LAST STEP : IMIDAZOLE INTRODUCTION PROCEDURE ................................ S11 8. ASYMMETRIC CONJUGATE BORYLATION (ACB) ............................................................................................ S14 8.1 Preliminary studies ....................................................................................................................................... S14 8.2 Substrate scope ............................................................................................................................................ S15 9. EXPERIMENT AT LARGER SCALE ................................................................................................................... S20 10. DETERMINATION OF ABSOLUTE CONFIGURATION ....................................................................................... S21 11. ITERATION STUDY........................................................................................................................................ S22 11.1 Post-transformation of the β-boryl acyl imidazole to the β-OTBS ester (3R,5S)-11 .................................... S22 11.2 Synthesis of the α-β-unsaturated acyl imidazole (5R,7S)-13 ....................................................................... S24 11.3 Iteration OTBS-CH 3 ........................................................................................................................................ S25 11.4 Iteration OTBS-OH ........................................................................................................................................ S27