Wittig Reaction

Wittig Reaction — Ph₃P Ylide → Alkene (Wittig Olefination)

Wittig Reaction — Alkene Formation from Aldehydes/Ketones via Ph₃P and Alkyl Halides

Triphenylphosphine (PPh₃) displaces halide from an SN2‑compatible alkyl halide to give a phosphonium salt. A base then removes the α‑hydrogen to generate the phosphonium ylide, which adds to an aldehyde or ketone, passing through an oxaphosphetane and collapsing to an alkene plus triphenylphosphine oxide (Ph₃P=O). Non‑stabilized ylides normally deliver Z‑alkenes; stabilized ylides (bearing EWG on the ylide carbon) favor E‑alkenes. Aldehydes react faster than ketones, and forming the ylide is usually the rate‑determining gate.

Introduction

Two-stage logic: (1) Ylide generation — PPh₃ + primary/allylic/benzylic R–X → phosphonium salt; base → ylide. (2) Carbonyl coupling — ylide + aldehyde/ketone → oxaphosphetane → alkene + Ph₃P=O.
Driving force: Formation of a strong P=O bond when the oxaphosphetane collapses.
Halide scope: Primary (best), allylic, or benzylic halides give clean SN2. Unactivated secondary halides are unreliable; tertiary/vinyl/aryl halides fail.
E/Z heuristic: Non‑stabilized ylides → Z‑alkenes. Stabilized ylides (ylide carbon bears EWG) → E‑alkenes.
Substrate reactivity: Aldehydes > ketones. Hindered ketones may require heating or Horner–Wadsworth–Emmons alternatives.

Quick Summary

Salt formation (SN2): PPh₃ + primary/allylic/benzylic R–X → R–PPh₃⁺ X⁻. Avoid unactivated secondary halides (SN2 too slow; elimination).
Ylide generation: Strong base (n‑BuLi, NaHMDS, t‑BuOK) for non‑stabilized salts; milder bases (NaH, NaOMe) suffice for stabilized salts.
Carbonyl coupling: Add aldehyde/ketone in dry ether solvent (THF/Et₂O) at 0–25 °C → betaine/oxaphosphetane → alkene + Ph₃P=O.
Stereochemistry rule-of-thumb: Non‑stabilized ylides → Z. Stabilized ylides → E. (Schlosser modification can invert the unstabilized case but is advanced.)
Common pitfalls: Attempting to form salts from simple secondary halides, choosing a base that cannot deprotonate the salt, or forgetting that cyclic ketones deliver exocyclic alkenes.

Mechanism — Ylide Generation then Carbonyl Coupling

Part A — Ylide Generation (optional display in the Mechanism Solver)

Step 1: Triphenylphosphine performs SN2 on a primary/allylic/benzylic alkyl halide to form the phosphonium salt. — **Step A‑1 — SN2 to the phosphonium salt:** PPh₃ attacks the alkyl halide (primary/allylic/benzylic), displacing X⁻ to give [Ph₃P–R]⁺ X⁻. Tertiary, vinyl, or aryl halides cannot take part; generic secondary halides are too sluggish.

Step 2: Base deprotonates the phosphonium salt to yield the ylide. — **Step A‑2 — Deprotonation to the ylide:** A base removes the α‑H next to phosphorus, generating the ylide (Ph₃P=CR¹R²). Non‑stabilized salts need strong base (n‑BuLi, NaHMDS); stabilized salts can be handled with NaH/NaOMe.

Part B — Carbonyl Coupling

Ylide carbon attacks the carbonyl carbon. — **Step B‑1 — Ylide attack:** The nucleophilic ylide carbon performs a backside addition into the aldehyde/ketone while the carbonyl π bond shifts onto oxygen.

Betaine shows O− adjacent to P+. — **Step B‑2 — Betaine capture:** Oxygen bonds to phosphorus (O⁻ → P⁺), giving the zwitterionic betaine that positions all four atoms for ring closure.

**Step B‑3 — Oxaphosphetane collapse:** The betaine closes to the neutral P–O–C–C ring, then concerted arrows push the C=O electrons into the P–O bond while the P–C bond forms the new alkene.

Final alkene (Ph3P=O left the frame). — **Step B‑4 — Alkene + Ph₃P=O:** Only the alkene remains in the teaching panel (Ph₃P=O is implicit). The highlighted C=C joins the former carbonyl carbon with the ylide carbon.

Mechanistic Checklist (Exam Focus)

Confirm the alkyl halide partner is SN2‑compatible (primary or allylic/benzylic); do not draw SN2 at a simple secondary/tertiary center.
Match base strength to the ylide (strong base for non‑stabilized salts, milder base for stabilized salts).
Depict the addition → betaine → oxaphosphetane → alkene + Ph₃P=O sequence with closed-shell arrows.
Predict Z for non‑stabilized ylides, E for stabilized ylides (unless the prompt specifies Schlosser conditions).
For cyclic ketones, show exocyclic alkenes (the new double bond leaves the ring).

Worked Examples

Benzaldehyde — **Non-stabilized case (methylenetriphenylphosphorane):** A primary halide (MeBr) forms the ylide, which reacts rapidly with benzaldehyde to furnish styrene. Only the terminal =CH₂ carbon delivered by the ylide appears in seafoam-teal Color 1.

PPh3 + R–X reagent button — **Non-stabilized case (methylenetriphenylphosphorane):** A primary halide (MeBr) forms the ylide, which reacts rapidly with benzaldehyde to furnish styrene. Only the terminal =CH₂ carbon delivered by the ylide appears in seafoam-teal Color 1.

Cyclohexanone — **Exocyclic benzylidene:** Benzylidenetriphenylphosphorane adds to cyclohexanone, giving the exocyclic alkene directly. The seafoam-teal Color 1 highlight marks the benzyl ring plus the benzylic carbon imported from benzyl bromide.

PPh3 + R–X button — **Exocyclic benzylidene:** Benzylidenetriphenylphosphorane adds to cyclohexanone, giving the exocyclic alkene directly. The seafoam-teal Color 1 highlight marks the benzyl ring plus the benzylic carbon imported from benzyl bromide.

Scope & Limitations

Best halides for salt formation: Primary > allylic ≈ benzylic ≫ simple secondary (poor). Tertiary/vinyl/aryl halides fail (no SN2).
Carbonyl partners: Aldehydes are fast; ketones may need heat or different ylides. Conjugated carbonyls work but may give blends.
Ylide classes: Non‑stabilized (alkyl/benzyl) require strong bases and typically give Z. Stabilized ylides (CO₂R, COR, CN, SO₂R) are easier to form and give E.
Selectivity tweaks: Schlosser modifications (n‑BuLi then strong alkoxide at low T) can invert the non‑stabilized case to E, but this is beyond the introductory scope.

Practical Tips & Pitfalls

Form the phosphonium salt cleanly (heat/polar solvents help) before you add strong base.
Keep all ylide steps dry and under inert atmosphere; moisture/protic solvents quench both base and ylide.
Choose the base based on ylide acidity: n‑BuLi/NaHMDS for non‑stabilized salts, NaH/NaOMe for stabilized salts.
Expect triphenylphosphine oxide as a stoichiometric byproduct; plan for its removal (crystallization, silica plug).
If you truly need an E‑alkene from a hindered ketone, consider Horner–Wadsworth–Emmons or Julia–Kocienski routes instead.

Exam-Style Summary

PPh₃ + primary/allylic/benzylic alkyl halide → phosphonium salt; strong/mild base → ylide; ylide + aldehyde/ketone → oxaphosphetane → alkene + Ph₃P=O. Unstabilized ylides give Z (major), stabilized ylides give E (major), and simple secondary halides are not reliable ylide precursors.

Interactive Toolbox

Mechanism Solver — Toggle halide class (primary vs allylic/benzylic vs blocked secondary), ylide type (non‑stabilized vs stabilized), and carbonyl to see every RDKit-rendered frame.
Reaction Solver — Compare predicted outcomes for different carbonyls or ylides and log any warnings about the halide input.
IUPAC Namer — Confirm systematic names of the alkene products shown in the worked examples (no SMILES exposed to users).

FAQ

Which alkyl halides can I use to make the phosphonium salt?
Primary, allylic, and benzylic halides work well through SN2. Simple secondary halides usually give low conversion or elimination, and tertiary/vinyl/aryl halides fail.

How do I choose the base for ylide formation?
Match it to the salt: non‑stabilized salts need strong bases (n‑BuLi, NaHMDS, t‑BuOK), whereas stabilized salts (with EWG) can be deprotonated by NaH/NaOMe.

How do I predict the alkene geometry?
Use the intro rule: non‑stabilized ylides → Z, stabilized ylides → E. Aldehydes give cleaner selectivity than ketones. Schlosser conditions can invert the unstabilized case but are beyond this course.

Do ketones behave the same as aldehydes?
They’re slower and more sterically hindered. Exocyclic alkenes form when cyclic ketones are used.

Where does the oxygen go?
Into the triphenylphosphine oxide byproduct (Ph₃P=O). The alkene product contains only the carbon framework from the carbonyl carbon and the ylide carbon.

Study Tools