# Will "soft nucleophiles" undergo 1,4-conjugate addition even if the β-carbon is sterically hindered?

In general soft nucleophiles do 1,4 conjugate addition to a carbonyl carbon under thermodynamic control. Will soft nucleophiles like organocuprates still preferentially undergo 1,4 addition if the β-carbon is more sterically hindered than the carbonyl carbon?

For example, if I consider the following case

should I just accept it as a rule of thumb that these "soft nucleophiles" undergo 1,4-nucleophilic addition to the carbonyl group, or does it vary depending on the structure and the situation?

In addition to the example above, what happens if there is a methyl group at C-2 of the ring?

• I don't see much steric hindrance in the example case. May 19 at 22:47
• Regarding your edit: The terms 'ortho', 'meta', and 'para' are only applicable to benzene rings. You have a cyclohexane ring here, those terms are not correct. May 23 at 20:46
• @orthocresol Though I recall "ortho product" and "para product / selectivity" when describing the outcome of asymetric dienes (e.g., methacrylate) with asymetric dienes (e.g., 2-methyl-buta-1,3-diene) in the course of Diels-Alder reactions, too. May 23 at 20:50
• @Buttonwood Hmm, I recall Clayden uses these terms, but I think it's meant to be just a helpful mnemonic, not a serious scientific terminology. May 23 at 21:00

Your line of thought possibly is influenced by the Walden inversion which is characteristic for the nucleophilic substitution mechanism of $$\mathrm{S_N2}$$ where steric hindrance affects the rate when this umbrella-like structure flips upon entry of the nuclophile and departure of the nucleofuge around a formally $$\mathrm{sp^3}$$ hybridized center:
The reaction shown by you however is an addition on to a carbon with molecular orbitals formally hybridized as $$\mathrm{sp^2}$$. Similar to the Bürgi–Dunitz trajectory for the entry of a nucleophile on to a $$\ce{C=O}$$ bond a) it is plausible that the angle of attack for the 1,4-addition b) equally is tilted, rather than an attack from the back.