Lecture 6 Flashcards
What is the easiest way to make nucleophilic carbon?
one way to create a nucleophilic carbon is to bond the carbon to a metal (M). This is because metals will always have lower negativities than carbon. This sis shown in digital notes.
What are organometallic compounds?
An organometallic compound is a compound that contains a carbon-metal bond. The name of an organometallic compound usually begins with the name of the alkyl group, followed by the name of the metal (E.x: butyllithium)
What are the two most common organometallic compounds?
The two most common organometallic compounds are organolithium and organomagnesium (Grigards regents).
How are organolithium metals prepared?
Organolithium compounds are prepared by adding lithium metal to an alkyl halide in a nonpolar solvent such as hexane.
How are Organomagnesium compounds prepared (we know)? What is the role of the solvent (new info)?
Organomagnesium compounds are prepared by adding an alkyl halide to magnesium metal shavings being stirred
in an ether—usually diethyl ether or tetrahydrofuran (THF)—under anhydrous conditions.
The solvent plays a crucial role in the formation of a Grignard reagent. The magnesium atom is surrounded by only four electrons, so it needs four more to form an octet. Solvent molecules
provide these electrons. Sharing electrons with a metal is called coordination. Coordination of the solvent molecules with the magnesium atom allows the Grignard reagent to dissolve in the solvent, preventing it from coating the magnesium shavings, which would make them unreactive. This is shown in digital notes
What are the different Alkyl halides used to make organolithium and organomagnesium compounds and which is most often used?
Alkyl halides, vinylic halides, and aryl halides can all be used to form organolithium and organomagnesium compounds. Alkyl bromides are used most often because they react more readily than alkyl chlorides and are less expensive than alkyl iodides.
Gaining some intuition from the slides
Okay, when you choose your alkyl halide you have to keep in mind that Grigard regents aren’t selective like organolithium compounds, y3ani as we saw before regards regents will react with C=O carbonyls so if you use an alkyl halide with a carbonyl group you will form a suicide molecule that always cyclizes! This is shown in digital notes.
What is an important condition of organolithium and organomagnesium compounds?
Due to Organomagnesium and organolithium compounds being very strong bases, they will react immediately with any acid present in the reaction mixture, even with very weak acids such as water and alcohols. When this happens, the organometallic compound is converted to an alkane.
This means that Grignard reagents and organolithium compounds cannot be prepared from compounds that contain acidic groups (such as OH, NH2, NHR, SH, C‚CH, or COOH). Because even trace amounts of moisture can convert an organometallic compound into an alkane, it is important that all reagents are dry when organometallic compounds are synthesized and when they react with other reagents. This is shown in digital notes.
What is an application for organometallic compounds given their high basic nature?
We can prepare deuterated hydrocarbons by washing the Organometallic compound with D2O. This will allow for the possibility of so much isotope analysis. This is shown in digital notes under flashcard 8
What is the organometallic compound reactivity dependent on?
The reactivity of an organometallic compound depends on the polarity of the carbon–metal bond: the greater the polarity of the bond, the more reactive the compound is as a nucleophile. The polarity of the bond depends on the difference in electronegativity between the metal and carbon. As seen in digital notes under Flash card one the most reactive carbon nucleophile is C-Li followed by C-Mg
What is transmetallation and when does an organometallic compound undergo it?
Transmetallation is a metal exchange reaction and an organometallic compound transmetallation if it is added to a
metal halide whose metal is more electronegative than the metal in the organometallic compound. In other words, transmetallation occurs if the alkyl group can be transferred to a metal with an electronegativity closer to that of carbon, thereby forming a less polar carbon–metal bond and, therefore, a less reactive nucleophile. (principle of lower reactivity applies)
What are coupling reactions?
They are reactions upon which CH-containing groups are joined (coupled) together.
What are the different coupling reactions that involve organometallic compounds?
- Grigards Rregents (Learnt)
Before the rest, it is important to note that new carbon-carbon bonds can be made using an organometallic reagent that has a transition metal as its metal atom:
- Gliman regents (Organocuprates) (Discussed next)
- Suski reaction (Discussed in this lecture)
- Heck reaction (Discussed in this lecture)
What are organocuprtes?
The first organometallic compounds used in coupling reactions were copper-containing organocuprates (R2CuLi), also called Gilman reagents. Organocuprates are less reactive than organolithium reagents or Grignard reagents because a carbon–copper bond is less polar than a carbon–lithium or carbon–magnesium bond—that is, Cu is closer in electronegativity to C. Only one of the two alkyl groups in an organocuprate is used as a nucleophile in reactions
How are organocuprates prepared?
An organocuprate is prepared by the reaction of an organolithium compound with cuprous iodide in diethyl ether or in THF. Notice that because Cu is more electronegative (1.8) than Li (1.0), transmetallation occurs. This is shown in digital notes.
How are organocuprates used in coupling reactions?
The organocuprate reacts by coupling one of its alkyl groups to the alkyl group of an alkyl halide (with the exception of alkyl fluorides, which do not undergo this reaction) and displacing the halogen. This means that an alkane can be formed from two alkyl halides—one alkyl halide is used to form the organocuprate, which then reacts with the second alkyl halide in a coupling reaction. The precise mechanism of the substitution reaction is unknown but is thought to involve radicals. The reaction is shown in digital notes
note that the R groups of the organocuprate and the alkyl halide can be primary alkyl, methyl, aryl, vinylic, or allylic. In other words, any R group except secondary or tertiary alkyl.
What is the “advantage” of using organocuprates?
- Because organocuprates can react with vinylic halides and aryl halides, they can be used to prepare compounds that cannot be prepared by SN2 reactions with Grignard reagents or organolithium compounds. (Remember that vinylic and aryl halides cannot undergo nucleophilic attack. This is shown in digital notes. Notice that The substitution reaction is stereospecific. In other words, the configuration of the double bond is retained in the product.
- Organocuprates can even replace halogens in compounds that contain other functional groups such as compounds with a bromo or chloro substituent attached to a carbon adjacent to a carbonyl group. This is a follow-up from the “initiation form slides” FC
What is the disadvantage of organocuprates?
Bad atom efficiency as shown in digital notes under flash card 16.
What are some final notes about organocuprates and some not so final notes about organometallic compounds?
- When doing retrosynthesis know that the a smaller alkyl chain on the organocuprate is favoured.
- Because organocuprates are nucleophiles, they react with electrophiles (no shit). For example (imp!!), in the reaction shown in digital notes), the organocuprate reacts with an epoxide in a nucleophilic substitution reaction to form an alcohol after washing with HCl
- tert-Butyllithium (𝑡-BuLi) is more reactive than n-butyllithium (n-BuLi) due to its steric bulk, stronger basicity, and less thermal stability (as tert has the negative carbon surrounded by 3 electron donating alkyl groups making it less stable)
- In all organometallic reactions a stoichiometric amount of metal is used which can be nice if a cheap metal but not so nice if an expensive metal
What is the Suzuki reaction?
The Suzuki reaction couples the R group of a vinylic or aryl halide with the R′ group of an organoboron compound in a basic solution in the presence of a palladium catalyst (PdL2). The general reaction is shown in the notes. Notice that the carbons that were bonded to the halogen and to the boron are joined by a new C-C bond.
The R′ group of the organoboron compound can be either an alkyl group, an alkenyl group, or an aryl group. When an alkenyl-organoboron compound is used, the new double bond in the product is always trans because an alkenyl-organoboron compound always has a trans configuration. This is shown in digital notes.
Note If the catalysts are modified, halides other than vinylic or aryl can be used
What are some notes about the Suzuki mechanism?
Okay before we start note that this mechanism is asked in the exam, and a nice FC coming up (“What are the several common features of the Suzuki and Heck reactions?”) shows almost everything, buttt i still want to highlight some things (the mech is also in notes nice to look at):
- The mechanism for the Suzuki reaction is under active investigation; it has been found to depend on the ligand (L) and the base
- Pd is an active species that allows R and Br to bind to it in OXIDATIVE ADDITION.
- The base substitutes the Br
- Finally, the formation of the B-OH bond is the driving force of this reaction.
What is oxidative addition and reductive elimination?
The insertion of a metal between two atoms is called oxidative addition—two new groups are added to the metal; it is an oxidation because the oxidation state of palladium is 0 in L2Pd and +2 in L2Pd(X)R. (Recall that oxidation is loss of electrons; reduction is gain of electrons.) Reductive
elimination eliminates two groups from the metal. Thus, the first step in a Suzuki reaction is an oxidative addition, and the last step is a reductive elimination.
How are Organoboron Compounds for Suzuki reaction prepared?
The alkyl- or alkenyl-organoboron compound used in a Suzuki reaction is prepared by hydroboration of a terminal alkene or a terminal alkyne, respectively. Often the boron-containing compound is catecholborane. The boron in an the alkenyl-organoboron compound is always trans to the substituent on the adjacent sp2
carbon (Recall that boron adds to the triply bonded carbon that is bonded to the hydrogen and that B and H add to the same side of the triple bond). This is shown in digital notes.
An aryl-organoboron compound is prepared from an organolithium compound and trimethylborate. also shown in digital notes
Note that these compounds are generally hard to make which is a disadvantage of the Suzuki reaction. (STILL BETTER THAN HECK)
What is The Heck reaction?
The Heck reaction couples a vinylic or an aryl halide with an alkene in the presence of a base (such as triethylamine) and a palladium catalyst (L2Pd). Like the Suzuki reaction, the Heck reaction is a substitution reaction: the R group of the halide replaces a vinylic hydrogen of an alkene. If there is a substituent attached to the alkene (Z), the R group will be trans to that substituent in the product. Notice in the reactions shown in digital notes that the new C¬C bond joins two sp2 carbons. When the reactant is a vinylic halide,the configuration of its double bond is retained in the product.
What is the Mechanism of Heck’s reaction?
Shown in digital notes
How do you obtain a high yield of a single product in a heck reaction?
The nucleophilic R group can add to either sp2 carbon of the alkene. Therefore, the reaction leads to a high yield of a single product only in the following situations:
■ if the alkene is symmetrical.
■ if one of the sp2 carbons is sterically hindered to the addition of the nucleophile. Therefore, internal alkenes are much less reactive than less sterically hindered terminal alkenes, so internal alkenes are generally not employed in Heck reactions.
■ if one of the sp2 carbons is bonded to a group that can withdraw electrons by resonance (such as C“O or C‚N), causing the other sp2 carbon to have a partial positive charge that makes it more susceptible to nucleophilic addition. This is shown in the digital notes
What are the several common features of the Suzuki and Heck reactions? long srry also take some things with a grain of salt
■ Both use a palladium catalyst (L2Pd)!!
■ Both reactions form a new C-C bond by replacing a halogen of a vinylic halide or an aryl halide (only vinylic and aryl halide explained why next FC) (bromides and iodides work best) with a carbon-containing group (R). Thus, they are substitution reactions. Shown in digital notes
■ The palladium atom of the catalyst is coordinated with ligands (L2Pd). Several different ligands (L) can be used; a common ligand is triphenylphosphine [P(C6H5)3].
■ Both reactions occur via a catalytic cycle in which the palladium atom participates in breaking bonds in the reactants and forming the new C¬C bond in the product (this might not fully be accurate).
■ The first step of each cycle is the insertion of palladium between the carbon and halogen to form an organopalladium compound. This is shown in digital notes
■ The reactions can be carried out if the reactants have other functional groups.
■ The reactions are stereospecific: the configuration of the double bond in a vinylic halide is retained in the product.
■ The reactions are very efficient, often requiring less than 0.1% of the palladium catalyst (compared to the reactants) and giving high yields of products (80–98%).
Why do Suzuki and Heck’s reactions only happen with vinylic or aryl halide? (Remember than if PdL2 is modified Suzuki can react with other compounds bas out of our scope)
If the organopalladium compound (firmed after the first step of the cycle after insertion of pd) has a b-hydrogen on an sp3 carbon, the organopalladium compound will rapidly undergo an elimination reaction before the coupling reaction has a chance to occur. This is shown in digital notes
This explains why vinylic and aryl halides are the reactants in these reactions—they cannot undergo an elimination reaction under the conditions used to carry out the coupling reactions.
