(a) Distinguish clearly between general- and specific-acid catalysis. Hand-draw two simple graphs that illustrate the dependence of kobs on pH for an acid catalysed reaction. The first graph should illustrate the dependence for a specific-acid catalysed reaction, and the second graph for a general-acid catalysed reaction. Include any relevant slopes on the graphs. (4 marks) The data in the table below were obtained for an acid-catalysed reaction with p- nitrophenol as the general acid in the buffer system. Treat the data to obtain a value for each of kha, kuo- and khao (where HA = p-nitrophenol). [HA]/M 0.010 0.029 0.058 0.004 0.030 0.049 pH 5.70 5.70 5.70 5.24 5.24 5.24 104 x kobs / min-1 2.00 2.60 3.50 4.50 5.30 5.90 (8 marks) Page 5 of 10 SPRING 2019 CH4008 - Organic Pharmaceutical Chemistry 2 QUESTION 2 - continued: (b) The CBS catalyst (structure shown below) facilitates the reduction by borane of the prochiral ketone, PhC(O)Me, to the corresponding alcohol with a high degree of enantioselectivity (Scheme 1). 1. BH, CBS HO H yield - 93% Phi ( CH 60 = 84% Ph . 2 H / HO Scheme 1 Corey-Bakshi-Shibata (CBS) catalyst With the aid of a reaction scheme (including curly arrows) describe how the complex that borane forms with the CBS catalyst asymmetrically catalyses the reduction. (6 marks) Use the ee quoted in Scheme 1 to calculate the percentage of (R) and (S) enantiomers formed (2 marks) Undesired side reactions are possible when sterically hindered ketones undergo Grignard reactions. Provide mechanistic detail (including curly arrows) to show how the undesired reactions in Schemes 2 and 3 below may occur. CH, 1. Big HC CH, whe CH, mylo H.C .CH CH CH, CH . 2 H7HO Scheme 2 CH 1. SAMO OH CH H.C. . HC CHE CH + HC CH, HC CH, CH2 2 H7H,O Scheme 3 (4 marks)