Question

2. When both the diene and dienophile are unsymmetrical, then regiochemistry becomes an issue. In this case, it is helpful to remember that when you number the diene and dienophile, that carbon 1 of the diene can either attach to carbon 6 or to carbon 5 of the dienophile: 1 1 2 4 2 6 2 5 1 5 3 3 5 3 6 4 4 In on top of this, you still need to think about the different possible stereochemical outcomes (from endo or exo addition). This will lead to eight possible products which are actually 4 pairs of enantiomers. Noting that the diene is the nucleophile and the dienophile is the electrophile, you want to identify the carbon of the diene with high electron density (this will be the one that does the attacking) and the carbon of the dienophile with low electron density (this will be the one that gets attacked. For the example below: i) Draw four possible products. Make sure none of the products you draw are an enantiomer of another product you've drawn (these should be 4 unique products related as either diastereomers or constitutional isomers). Use dashes and wedges for each chiral center in the product (there are two chiral centers in this product). ii) Identify which products are exo and which products are endo Draw the relevant resonance contributors of the diene and dienophile to explain the preferred regiochemistry expected in this reaction iv) Identify the one structure that represents the major product :0:

Answer 1

2. i) and ii) 5 + 6 C-1 is attached to C-5 C-1 is attached to C-6 exo mode endo mode exo mode endo mode NMez NMez NMez NMez CO2Me ...CO2Me 6 2 1 2 2 2 1 5 5 5 5 3 6 3 6 3 3 CO2Me ""CO Me 4 4 4 4 iii) Resonance structure analysis of diene and dienophile Resonance structure of the diene Resonance structure of the diene 2 2 3 6 6 NMez 1 NMe2 CO2Me 2 N ...CO2Me 2 1 2 1 + 5 + 3 5 6 3 6 3 4 4 4 exo product endo product lowest electron density highest electron density preferred mode of interaction Hence according to the resonance structure analysis the preferred regiochemistry of prouct formation will one in which C-1 is attached to C-5 to afford the above exo and/or endo product. iv) Among exo and endo products endo will be the major product due to the presence of stabilizing secondary orbital interaction. Hence the structure that represents the major product is: NMez ...CO2Me 2 5 6 3 4 endo product