Chemical Forums
Chemistry Forums for Students => Organic Chemistry Forum => Topic started by: glycogrl07 on January 23, 2008, 09:07:38 PM
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So I understand clearly the nucleophilic substitution reactions, but I am wondering if anyone is familiar with any sn2 reaction that can be forced into a retention of stereochemistry? I am speaking of ring substituents, mainly. Is there a possiblity of having a large enough substiuent to cause the ring to change its shape(say a 1c4->4c1)to keep Nu- in the same stereochemistry as the leaving group? I am thinking maybe a nucleophile that would be so stable as axial, the ring would not want to have it equitorial, as an Sn2 product would give.
R2-LG + NU- ---> R2-Nu + LG
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This is a unique topic. I'm not sure how you want to approach this problem. Your nucleophile would have to be bulky enough or sterically hindered to cause the ring to flip back to a more energetically desired conformation after inversion. (I haven't seen this before) This being said it is unlikely that your nucleophile would attack in an SN2 if it were so big. Devise a specific reaction and you will get more theoretical analysis. For example, substitution of a halogen at C-1 of chair cyclohexane would be dependent on the C-4 substituent. ???
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I think SN2 always goes by inversion, by consideration of the mechanism. However, if you have excess of a large incoming group is it possible you could get a second attack at that centre (a bit like an SNi reaction http://en.wikipedia.org/w/index.php?title=SNi&oldid=169573366 (http://en.wikipedia.org/w/index.php?title=SNi&oldid=169573366)), simply to get the more stable diasteromer?
Mad thoughts early in the morning, may need another cup of tea to wake up.
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If you just want to have the nucleophile in the same configuration as the leaving group, you might be able to do this via an Sn1 mechanism but not an Sn2.
If the carbocation that forms prefers attack from the same side as the departing leaving group, you will get retention.
A true Sn2 reaction cannot give retention.
If you provide the structure of the compound and the product you want I might be able to give more specifics.
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Can't you do some sort of double mitsunobu to lead to overall retention of stereochem?
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Two Sn2 processes mean retention. A classic example of this is found in the synthesis of alpha-carboxylic acids from amino acids. One diazotizes the amino acid, typically with sodium nitrite in water. This species is quickly attacked by the carboxylate group of the diazonium derivative, expelling nitrogen and resulting in the formation of a three-membered alpha lactone. Water is easily a good enough nucleophile to open this highly strained ring by a second Sn2 process, resulting in retention of stereochemistry at the alpha-carbon (say, 20:1 dr for the reaction run in water with a sulfuric acid catalyst). This is all one pot, of course... and moreover, the intermediates are not isolable.
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neighbouring group participation is retention of the configuration. It undergo via SN2 Mechanism
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Yes, I suppose that would work the best for me.