Difficulty: Intermediate | Prerequisites: Organic Chemistry I (alkene chemistry, substitution/elimination basics, stereochemistry fundamentals)
This material covers six named reactions used to form carbon-carbon bonds and new alkenes in Organic Chemistry II. These reactions, including organocuprate coupling, Suzuki, Heck, carbene addition, olefin metathesis, and Wittig, are the backbone of synthetic organic chemistry and appear heavily on exams. You should already be comfortable with alkene structure, E/Z nomenclature, and basic stereochemistry (R/S, cis/trans) from Orgo I. Understanding the stereochemical and regiochemical outcomes of each reaction is just as important as knowing the reagents themselves.
Six palladium-catalysed and organometallic reactions let you build new C-C bonds or convert carbonyls into alkenes. Each one has a specific stereochemical fingerprint (syn addition, retention, trans selectivity, or a mixture of E/Z) and, in some cases, predictable regiochemistry. Knowing which reagents give which geometry is the core exam skill here.
Organocuprate (Gilman reagent)
A reagent of the form R'₂CuLi used to couple an alkyl, vinyl, or aryl group to an organic halide via a new C-C bond. Think of it as a way to swap out a halide leaving group for a carbon group, but it will not work on tertiary halides.
Suzuki reaction
A palladium-catalysed cross-coupling between a vinyl or aryl halide and a vinyl or aryl organoborane, forming a new C-C bond. In simple terms, you are stitching two carbon fragments together using a boron partner and a palladium catalyst.
Heck reaction
A palladium-catalysed coupling of an aryl or vinyl halide with an alkene, producing a substituted alkene with trans geometry. Think of it as bolting an aryl or vinyl group onto an alkene, with the new bond landing on the less substituted carbon.
Carbene
A neutral, divalent carbon species (R₂C:) that adds across a double bond to form a cyclopropane ring. In simple terms, a single carbon (with two substituents or two hydrogens) bridges across both carbons of an alkene in one step.
Olefin metathesis
A reaction in which two alkenes exchange their substituents around the double bond, catalysed by Grubbs' catalyst. Think of it as cutting two double bonds in half and reassembling the pieces, which can close rings or swap groups.
Wittig reaction
The reaction of a phosphorus ylide (a Wittig reagent) with an aldehyde or ketone to form an alkene and triphenylphosphine oxide as a byproduct. In simple terms, you are replacing a C=O with a C=C.
Ylide (phosphonium ylide)
Another name for the Wittig reagent. It is a species with adjacent positive (phosphorus) and negative (carbon) charges, written Ph₃P⁺-C⁻R₂.
Stereospecific
A reaction whose stereochemical outcome is determined by the geometry of the starting material. A cis starting material gives one product geometry; a trans starting material gives another.
Syn addition
Both new bonds form on the same face of the double bond. The classic pattern for carbene additions to alkenes.
Regiochemistry
Which carbon of an unsymmetrical substrate gets the new bond. In the Heck reaction, the new C-C bond forms on the less substituted carbon of the alkene.
General reaction: R-Br + R'₂CuLi → R-R'
Replaces a halide with an alkyl, vinyl, or aryl group from the cuprate
Limitation: Does not work with tertiary halides (too sterically hindered for the coupling to proceed)
Stereochemistry: Stereospecific. A trans vinyl halide gives a trans alkene product; a cis vinyl halide gives a cis alkene product. The geometry of the starting material is preserved in the product.
Regiochemistry: Not applicable (the halide is simply replaced).
General reaction: Vinyl or aryl halide + vinyl or aryl organoborane → R-R', catalysed by Pd(PPh₃)₄ with OH⁻ base
Both coupling partners must be sp² carbons (vinyl or aryl). You cannot use an sp³ alkyl borane in a standard Suzuki coupling.
Stereochemistry: Maintains the stereochemistry of both coupling partners. A cis vinyl halide gives a cis-configured product; a trans vinyl halide gives a trans-configured product.
Regiochemistry: Not applicable.
General reaction: Aryl or vinyl halide + alkene → substituted alkene, using Pd(OAc)₂, P(o-tolyl)₃ or PPh₃, and Et₃N (a base)
The aryl or vinyl group from the halide attaches to the alkene
Stereochemistry: Favours trans (E) geometry in the product alkene. Vinyl halide starting materials maintain their own stereochemistry through the coupling.
Regiochemistry: The new C-C bond forms on the less substituted carbon of the alkene. This is a key distinction from the other reactions in this set.
In the practice problems, note that electron-withdrawing groups (like -CN, -OEt on an ester) on the alkene do not change this regiochemical outcome.
There are two variants to know, and both add a :CR₂ unit across a double bond to form a cyclopropane.
Variant 1 (dihalocarbene): Alkene + CHX₃ / tBuO⁻ → dichlorocyclopropane (or dibromo, depending on X). The carbene carries two halogen substituents.
Variant 2 (Simmons-Smith): Alkene + CH₂I₂ / Zn(Cu) → cyclopropane with two H substituents on the new carbon. This is the classic method for adding a simple CH₂ unit.
Stereochemistry: Syn addition and stereospecific. Both new C-C bonds form on the same face of the alkene. The alkene's geometry is preserved: a cis alkene gives a cis-substituted cyclopropane, and a trans alkene gives a trans-substituted cyclopropane.
For trans alkenes, the carbene can attach from either face, producing a racemic mixture of enantiomers.
Regiochemistry: Not applicable.
Uses Grubbs' catalyst (a ruthenium carbene complex) to redistribute alkene fragments
Intramolecular (ring-closing metathesis): A diene cyclises to form a ring, releasing ethylene (H₂C=CH₂) as a small-molecule byproduct
Intermolecular (cross metathesis): Two alkenes swap substituents. Can also be performed with WCl₆/CH₃Li as the catalyst system.
Stereochemistry: Produces a mixture of E and Z isomers (or a cycloalkane if ring-closing). You cannot predict which geometric isomer will dominate.
Regiochemistry: Not applicable.
General reaction: Phosphorus ylide (Ph₃P=CR₂) + aldehyde or ketone → alkene + Ph₃P=O (triphenylphosphine oxide)
The C=O of the carbonyl is replaced by a C=C. The two R groups on the ylide carbon end up on the same carbon of the product alkene.
A Wittig reagent is also called a ylide (or phosphonium ylide).
Stereochemistry: E/Z isomers are possible. You may get a mixture unless stabilised or non-stabilised ylide conditions are specified.
Regiochemistry: Particularly useful for forming terminal alkenes (place the =CH₂ from the ylide onto an aldehyde carbonyl).
When predicting products, identify which groups came from the ylide and which came from the carbonyl. The carbon that was C=O becomes one end of the new C=C.
This table is worth memorising. Exams frequently ask you to state the stereochemical or regiochemical outcome of a given reaction.
Reaction | Stereochemistry | Regiochemistry |
|---|---|---|
Organocuprate | Stereospecific; trans reactant → trans product, cis → cis | N/A |
Suzuki | Maintains stereochemistry of both partners | N/A |
Heck | Favours trans (E) product; vinyl halides maintain their geometry | New C-C bond on less substituted carbon |
Carbene | Syn addition, stereospecific; racemic mixture for trans alkenes (attack from either face) | N/A |
Olefin metathesis | Mixture of E and Z (or cycloalkane) | N/A |
Wittig | E/Z isomers possible | Useful for forming terminal alkenes |
Students often assume organocuprate reagents work with all halides. They do not. Tertiary halides are too hindered, and the reaction fails.
Students sometimes confuse the Suzuki and Heck reactions because both use palladium catalysts. The key difference: Suzuki couples two sp² partners via a borane, while Heck couples a halide with an alkene and has distinct regiochemistry (less substituted carbon).
Carbene addition is syn, not anti. Students who default to anti addition (from experience with halogenation or epoxidation opening) sometimes get this wrong. Both bonds form on the same face.
The Wittig reaction replaces C=O with C=C. Students occasionally draw the product with the oxygen still present or place the new double bond in the wrong position. Track which carbon was the carbonyl carbon: that carbon becomes one end of the new alkene.
⚠️ "Predict the product" questions are the bread and butter of this topic. You need to identify the reaction type from the reagents, then apply the correct stereochemistry and regiochemistry.
⚠️ The stereochemistry summary table is almost certainly testable. Be ready to fill it in from memory or apply it to a specific substrate.
⚠️ Knowing that organocuprates fail with tertiary halides is a common bonus or trick question.
⚠️ For Heck reactions, always check regiochemistry: the new bond goes to the less substituted carbon of the alkene.
⚠️ Wittig products: trace which fragment came from the ylide and which from the carbonyl. This is where students lose marks on product-prediction questions.
⚠️ Carbene reactions: remember there are two variants (dihalocarbene and Simmons-Smith). The exam may specify one and expect you to draw the correct cyclopropane product.
These reactions are workhorses in pharmaceutical synthesis and materials science. The Suzuki and Heck reactions won the 2010 Nobel Prize in Chemistry (awarded to Heck, Negishi, and Suzuki). Olefin metathesis, developed by Grubbs and others, earned the 2005 Nobel Prize. If you go into medicinal chemistry or process chemistry, you will use these transformations regularly.
True or False: Organocuprate reagents can couple with tertiary alkyl halides.
False. They do not work with tertiary halides.
Fill in the blank: The Heck reaction forms the new C-C bond on the ______ substituted carbon of the alkene.
Less substituted.
True or False: Carbene addition to an alkene is an anti addition.
False. It is a syn addition.
Fill in the blank: Another name for a Wittig reagent is a(n) ______.
Ylide (phosphonium ylide).
True or False: Olefin metathesis with Grubbs' catalyst always gives the E isomer selectively.
False. It gives a mixture of E and Z.
Organocuprate, Gilman reagent, R₂CuLi, Suzuki coupling, Suzuki-Miyaura, Heck reaction, palladium-catalysed cross-coupling, Pd(OAc)₂, Pd(PPh₃)₄, carbene addition, cyclopropanation, Simmons-Smith, dihalocarbene, CHX₃/tBuO⁻, CH₂I₂/Zn(Cu), olefin metathesis, ring-closing metathesis, RCM, Grubbs' catalyst, WCl₆/CH₃Li, Wittig reaction, phosphonium ylide, Ph₃P=CR₂, triphenylphosphine oxide, stereochemistry, regiochemistry, syn addition, stereospecific, E/Z isomers, cis/trans, terminal alkene, Orgo II, Organic Chemistry II, named reactions, C-C bond formation