The Heck Reaction

by James

Description: The Heck Reaction is a means of forming C-C bonds between alkenyl or aryl halides and alkenes, using a palladium catalyst.


Notes: Although Br is shown as a leaving group, the reaction works with other leaving groups such as Cl, I, and OTf. For the alkene, the reaction works well when R is an electron-withdrawing group (such as an ester).

Examples:  2-examples Notes: Note that the C-C bond forms at the exact place where the leaving group is (OTf is “triflate”). The identity of the palladium source is ultimately unimportant for our purposes – Pd(OAc)2 works just as well as Pd2(dba)3 which is just as fine as Pd(PPh3)4. [Ultimately these can all be used create the same active catalyst]. A tertiary amine base such as NEt3 is usually added as well.

Editorial: First of all, an editorial. Personally, I hate that this is being taught in introductory organic chemistry, because full understanding of how these reactions work (oxidative addition, reductive elimination, ligand exchange, beta-hydride elimination, migratory insertion) requires considerable background in inorganic chemistry, which is not given in an introductory organic chemistry course. This means that typically instructors are expecting their students to memorize this material, rather than fully understand it, which is in stark contrast to their usual advice about “don’t memorize, learn the concepts”. However, this material is increasingly being asked on standardized exams like the ACS, so I would rather put it in than ignore it.

Mechanism: Transition metals such as palladium can participate in reactions such as oxidative addition, reductive elimination, ligand exchange, beta-hydride elimination, and migratory insertion – full understanding of which requires some background in inorganic chemistry. If your sole source of information is your instructor/course notes/ textbook, I guarantee you will be left with lots of unanswered questions. If you are interested in learning more deeply about these mechanisms I highly recommend Mike Evans’ The Organometallic Reader. A common catalyst for this reaction is Pd(PPh3)4, although other phosphines can be used (see below). For our purposes the identity of the phosphine does not matter – they all perform the same role. 3-mech-a-phosphines

Besides Pd(PPh3)4, it’s also common to start with Pd2(dba)3 [an alternative source of Pd(0), don’t worry about what dba is, it isn’t important for our purposes] or a Pd(II) source such Pd(OAc). You might reasonably ask,  “wait!  I thought we needed to start with Pd(0) in this reaction!”. Well, that’s part of the reason why you add NEt. You see, Pd(OAc)2 reacts with NEt3 to generate Pd(0) through a mechanism like this one [link to image,  because you don’t need to know this].

I know – obvious, right??? [sarcasm] Of course, this point is completely glossed over in textbooks like this one, which pisses me off so much. A prime example of why covering cross-coupling in introductory organic chemistry opens up a huge can of worms. There isn’t sufficient time in the course to deal with all these additional concepts properly.

Anyway. Once we get to Pd(PPh3)2,  Pd(0) performs oxidative addition on the alkenyl halide, giving a Pd(II) species (Step 1). Then, the alkene coordinates to palladium (Step 2, coordination of alkene), whereupon migratory insertion occurs (Step 3). In the fourth step, beta-hydride elimination occurs leading to formation of the new alkene, which then dissociates from Pd. Finally, reductive elimination results in the formation of HBr and Pd(0), which re-enters the catalytic cycle. Although not shown, the base that is added (usually NEtor similar tertiary amine base) reacts with the acid that is formed to generate a salt.

One note about the beta-hydride elimination step: it requires that the Pd and H are “syn” to each other. If there is an option of two hydrogens being eliminated, this reaction will generally proceed so as to form the least strained alkene. For example, beta-hydride elimination preferentially occurs with the “blue” hydrogen here, not the “red”, since it leads to the trans alkene. 3-mech-4

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Zachary Sweeney

The product of triethylamine ligation of Pd(OAc)2 in the image link to the mechanism of Pd(0) formation from triethylamine and Pd(OAc)2 is missing an ethyl group. This makes the illustration of the beta hydride elimination a little more confusing in my opinion.


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