Diastereoselectivity on attack to carbonyl groups

1. Sukumar Honkote Department of Chemistry, IIT Bombay Diastereoselectivity on attack to carbonyl groups Felkin- Anh method helps us determine the major product diastereomer on nucleophilic attack to a chiral carbonyl compound.

2. Master Layout The animation will be broken up into 4 sub animations: ani1, ani2, ani3 and ani4. The colours for the text, background and the various atoms is upto the discretion of the animator. The colour of the same atom or species should be same throughout the animation.

3. Definitions of the components: 1 1. Electrophile: is a reagent that participates in a chemical reaction by accepting an electron pair in order to bond to a nucleophile. 2. Nucleophile: is a reagent that participates in a chemical reaction by donating an electron pair in order to bond to n electrophile 3. Diastereoselectivity: the preference for the formation of one or more than one diastereomer over the other in an organic reaction. 4. Syn product: two substituents on adjacent carbons oriented in same direction 5. Anti product: The same substituents oriented in opposite direction. 6. Bürgi-Dunitz angle: the angle of attack of a nucleophile at a carbonyl center. It is 107° with respect to the carbonyl bond. 7.Conformers:The different shapes of an organic compound obtained due to its ability to rotate about single bonds 8. Prochiral Centre: The carbon having a C=X (where X= N, O or S) and the two other substituents attached are both different. Here if a nucleophile attacks this centre a chiral centre is formed. 2 3 4 5

4. Ani1

5. Master Layout (Ani2) Fig1 Fig1 Fig2 Fig3

6. In Fig2. and fig3. the angle between M & L , M & S and S & L is always 120° while the angle between R & O is always at 180°. In fig3, the angle between the balls blue & green, blue & red and red & green is always 120° while the angle between black & brown balls is always at 180°. In fig3, the sizes of the balls relative to others have to remain same with respect to others. Red ball will be the smallest and green the largest. In fir2 and fig3 initially the angles between O & L and black ball & green ball is 30°. The violet ball, nu denotes the nucleophile

7. Fig1 Fig2 Fig3

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15. Master Layout The angle between any 2 adjacent letters is 60°. Eg. Angle between L & R is 60°.

16. Ani 3

21. The following is the Summary : Using the Felkin–Anh model • Draw Newman projections of the conformations of the starting material that place a large group perpendicular to C=O • Allow the nucleophile to attack along the least hindered trajectory, taking into account the Bürgi–Dunitz angle • Draw a Newman projection of the product that arises from attack in this way. Rotate about the carbon (anticlockwise or clockwise) such that the longest chain is horizontal. This is considered the plane. • The bonds above the plane of longest chain (the horizontal plane) are denoted by a wedge bond and the bonds below the plane of longest chain (the horizontal plane) are denoted by a dash bond.

22. QUESTIONS 1.For the reaction of the following molecule with which nucleophile the percentage major product will be most compared with minor Product? A: Et- B: Me- C: nBu- D: H- answer is C as a bulky nucleophile is more stereoselective compared with other nucleophiles of similar reactivity. 2. The major product of the reaction of 1-phenyl, 1-methyl acetone with KCN in presence of hydrocyanic acid would be? A: B: answer is a 3. The relationship between the products formed in the previous question is that they are: A: enantiomers b: diastereomers c: anomers d: mesomers Answer is b

23. 4. The propensity to be attacked by a nucleophile is maximum for which of the following molecules: A: acetone b: 1 phenyl acetone c: 1,1 diphenyl acetone d: 1,1,1 triphenyl acetone

24. Links for further reading Books: Organic Chemistry by Clayden, Greevs, Warren and Wothers Thank You