Organic Chemistry II - Reaction Mechanisms & Synthesis

A bimolecular nucleophilic substitution proceeding via a concerted, single-step mechanism. The nucleophile performs a backside attack ($180^{\circ }$ relative to the leaving group), causing complete inversion of stereochemistry (Walden inversion). Rate law: $\text{Rate}=k[\text{substrate}][\text{nucleophile}]$. Favored by unhindered primary ($1^{\circ }$) substrates, strong nucleophiles, and polar aprotic solvents.

A unimolecular nucleophilic substitution occurring in two main steps: (1) Rate-determining heterolytic cleavage of the leaving group to form a planar carbocation intermediate, and (2) Nucleophilic attack from either face, producing a racemic mixture. Rate law: $\text{Rate}=k[\text{substrate}]$. Favored by tertiary ($3^{\circ }$) substrates, good leaving groups, and polar protic solvents.

A bimolecular elimination mechanism where a strong base abstracts a $\beta$-proton simultaneously as the leaving group departs. Requires an anti-periplanar conformation (dihedral angle $\theta =180^{\circ }$) between the $\beta$-hydrogen and leaving group. Zaitsev's rule predicts the more substituted alkene as the major product unless a sterically hindered base (e.g., $t-\text{BuOK}$) yields the Hofmann product.

A unimolecular elimination proceeding in two steps: (1) Departure of the leaving group to form a carbocation intermediate, followed by (2) Deprotonation of a eta-hydrogen by a weak base to form a double bond. Always yields the most stable, hyperconjugated, and substituted alkene product according to Zaitsev's rule.

Spontaneous structural rearrangement of a carbocation intermediate to yield a more stable carbocation (e.g., $2^{\circ }\to 3^{\circ }$). Occurs via a 1,2-hydride shift ($:{\text{H}}^{-}$) or 1,2-alkyl shift ($:{\text{R}}^{-}$) prior to nucleophilic attack or elimination steps in $S_{N}1$ and $E1$ mechanisms.

Organometallic reagents prepared by reacting an alkyl/aryl halide with magnesium metal in anhydrous ether ($\text{R-X}+\text{Mg}\to \text{RMgX}$). The carbon-magnesium bond acts as a strong nucleophile and strong base. Reacts with aldehydes/ketones to form secondary/tertiary alcohols after acidic workup (${\text{H}}_3{\text{O}}^{+}$). Must be kept strictly free of protic species (${\text{H}}_2\text{O}$, $\text{ROH}$).

Esters react with two equivalents of a Grignard reagent ($\text{R’MgX}$). The first equivalent attacks the carbonyl carbon to form a tetrahedral intermediate that collapses, expelling an alkoxide leaving group to yield a ketone intermediate. The second equivalent immediately attacks the ketone, producing a $3^{\circ }$ alcohol after acidic workup.

A planar, cyclic, fully conjugated molecule (continuous ring of $p$-orbitals) is aromatic if it contains $(4n+2)$ $\pi$-electrons, where $n=0,1,2,\dots$. If it meets the cyclic, planar, and fully conjugated criteria but possesses $4n$ $\pi$-electrons, it is antiaromatic and exceptionally unstable.