It always works on paper..
I took 3-methylglutaric anhydride and treated it with 1 eq of isopropenylmagnesium bromide at -78 (ref ACIE 41(6) 2002 p. 1057, they use PhMgBr). I expected the conjugated ketone, but found a mixture (3:2) of the 1,4-addition product to the conjugated ketone. There was also hydrolyzed starting material (diacid). So I decided to try the reaction using 0.5 eq of Grignard to see if I could mitigate 1,4-addition.
Nope. A mixture still. This time 1:1. All products were confirmed with 2D NMR experiments (HSQC, HMBC, and COSY)
My question is does anyone have any ideas as to why this is happening without copper? Also, does anyone have any ideas on how to possibly get the product I want?
I think the 1,4-addition is happening due to sterics. The 1,2-addition of a second Grignard is too crowded, so 1,4-predominates. Still doesn't make sense to have 1,4 over addition to an anhydride though. I think there may be some Lewis acid activation of the carbonyl from magnesium and is activating the conjugate product to afford 1,4 addition. My idea is to change to isopropenyl lithium.
What y'all think?