Organometallic Compounds Chapter 15 Carbon Nucleophiles Critical in

Organometallic Compounds Chapter 15

Carbon Nucleophiles: Critical in making larger organic molecules. Review some of the ones that we have talked about…. Cyanide ion: CN- + RX RCN RCH 2 NH 2 Acetylide anions: Synthetic Thinking: This offers many opportunities provided you can work with the two carbon straight chain segment. Enolate anions: or Try to see what factors promote the formation of the negative charge on the carbon atoms: hybridization, resonance.

We examine two types of organometallics: RMg. X, a Grignard reagent, and RLi, an organolithium compound Preparation d-d+ dd+ Solvated by ether, aprotic solvent

Basicity Recall that a carbanion, R 3 C: -, is a very strong base. So also Grignards and alkyl lithiums. Ethane, a gas. Bottom Line: Grignards are destroyed by (weak) protic acids: amines, alcohols, water, terminal alkynes, phenols, carboxylic acids. The Grignard, RMg. X, is converted to a Mg salt eventually and RH. The liberation of RH can serve as a test for protic hydrogens.

Reactivity patterns Recall the SN 2 reaction where the alkyl group, R, is part of the electrophile. Nucleophile Electrophile Forming the Grignard converts the R from electrophile to a potential nucleophile. A wide range of new reactions opens up with R as nucleophile. - + RX + Mg R-Mg-X Electrophile Electrostatic potential maps. + -

Recall Reactions of Oxiranes with Nucleophiles Recall opening of oxirane with a strong, basic nucleophile. The next slides recall the diversity of nucleophiles that may be used. Observe that there is limited opportunity of creating new C-C bonds, welding together two R groups. We seem to be somewhat lacking in simple carbon based nucleophiles.

Recall Synthetic Applications nucleophile Only reaction with the acetylide anion offers the means of making a new C-C bond a larger molecule. Problem is that a terminal alkyne is needed.

A Grignard has a reactive, negative carbon. Now examine reaction of Grignard and oxirane ring. Net results Newly formed bond The size of the alkyl group has increased by 2. Look at this alcohol to alcohol sequence R-OH R-X R-Mg-X R-CH 2 -OH. The functionality (OH) has remained at the end of the chain. We could make it even longer by repeating the above sequence. Note attack on less hindered carbon Now a substituted oxirane… Newly formed bond

Synthesis Example Retrosynthesize the following Recall reaction of a nucleophile with an (oxirane) epoxide to give a HO-C-C -Nu pattern. Back side attack gives anti opening. Trans geometry suggests trying an oxirane. What should the nucleophile be? The allyl group should be the nucleophile. This is done by using a Grignard (or Gilman).

Gilman Reagent (Lithium diorganocopper Reagents) Preparation of Gilman Reagents Gilman

Reactions of Gilman Reagent Coupling Reaction Used to create new C – C bonds. . Overall result. R-X + R’-X R – R’ Necessary details As before: electrophile Next step: Restrictions on the process. Caution. R group which goes into Gilman may be methyl, 1 o (best not 2 o or 3 o), allylic, vinylic (unusual), aryl Alkyl (not 3 o), vinylic nucleophile

Particularly useful, reaction with vinyl halides to make an alkene. trans Note that the stereochemistry of the alkene is retained.

Gilman and oxiranes R of the Gilman reagent is the nucleophile, typical of organometallics. Because in basic media (acid destroys Gilman) oxygen of oxirane can not be protonated. Less hindered carbon of oxirane is attacked.

Synthetic Analysis Similar to Grignard analysis. Newly formed bond. Note its position relative to the OH.

Example of Retrosynthetic Analysis Design a synthesis using oxiranes The oxirane ring could be on either side of the OH. Look at both possibilities. Nucleophile can come in on only one position of oxirane, on the C to which the OH should not be attached… or On the left, located here. Open oxirane here. Nucleophile makes this bond. On the right, located here. Open oxirane here. Nucleophile makes this bond. 2 synthetic routes available

Synthesis Example Carry out the following transformation in as many steps as needed. target Remember oxidation of a secondary alcohol can produce a ketone. Note pattern of a nucleophile (OCH 3) then C-C then OH. Use an epoxide. Epoxides can come from alkenes via peracids. Alkenes can come from halides via E 2.

Carbenes, : CH 2 Preparation of simple carbenes 1. carbene 2. Mechanism of the a elimination.

Reactions of Carbenes, : CH 2 (not for synthesis) Addition to double bond. Insertion into C-H bond Formation of ylide (later) liquid

Simmons Smith Reaction (for synthesis, addition to alkenes to yield cyclopropanes) CH 2 I 2 + Zn(Cu) ICH 2 Zn. I Carbenoid, properties similar to carbenes.

Electronic Structure Electrons paired, singlet

Triplet and Singlet Methylene Dominant form in solution Gas phase Rotation can occur around this bond.