M ECHANISMS OF N UCLEOPHILIC S UBSTITUTION : S TEREOCHEMISTRY PREPARED BY: MRS. SHUBHRA CHAUDHURI K. V. BARRACKPORE (ARMY)

2 All S N 2 reactions proceed with backside attack of the nucleophile, resulting in inversion of configuration at a stereogenic center. Mechanisms of Nucleophilic Substitution: Stereochemistry Figure 7.9 Stereochemistry of the S N 2 reaction Alkyl Halides and Nucleophilic Substitution

3 Figure 7.10 Two examples of S N 2 inversion of configuration Alkyl Halides and Nucleophilic Substitution Mechanisms of Nucleophilic Substitution: Stereochemistry

S TEREOISOMERISM AND C HIRALITY Stereoisomers: Stereoisomers: isomers with the same connectivity but a different orientation of their atoms in space

C HIRAL C ENTER *The most common (but not the only) cause of chirality in organic molecules is a tetrahedral atom, most commonly carbon, bonded to four different groups chiral cente. *A carbon with four different groups bonded to it is called a chiral cente. *Enantiomers: *Enantiomers: stereoisomers that are nonsuperposable mirror images -refers to the relationship between pairs of objects

6 Mechanisms of Nucleophilic Substitution: Stereochemistry To understand the stereochemistry of the S N 1 reaction, we must examine the geometry of the carbocation intermediate. Alkyl Halides and Nucleophilic Substitution

7 Loss of the leaving group in Step [1] generates a planar carbocation that is achiral. In Step [2], attack of the nucleophile can occur on either side to afford two products which are a pair of enantiomers. Because there is no preference for nucleophilic attack from either direction, an equal amount of the two enantiomers is formed called a racemic mixture. We say that racemization has occurred. Alkyl Halides and Nucleophilic Substitution Mechanisms of Nucleophilic Substitution:

8 Figure 7.16 Two examples of racemization in the S N 1 reaction, due to C + Alkyl Halides and Nucleophilic Substitution Mechanisms of Nucleophilic Substitution:

9 Alkyl Halides and Nucleophilic Substitution Kinetics: SN1rate = k[RX] SN2rate = k[RX][Nu:] Stereochemistry: SN1both inversion and retention (racemic) SN2inversion only Rearrangements: SN1rearrangements common SN2rearrangements not possible Results of SN1 vs SN2 mechanisms:

WWU -- Chemistry S N 1 R EACTION : STEREOCHEMISTRY With chiral R-X compounds, the product will be racemic (50% of each enantiomer).

WWU -- Chemistry F OR AN S N 2 R EACTION : EVERY REACTION EVENT ALWAYS LEADS TO INVERSION OF CONFIGURATION