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: Enolate anions: Try to see what factors promote the formation of the negative charge on the carbon atoms: hybridization, resonance. Synthetic Thinking: This offers many opportunities provided you can work with the two carbon straight chain segment. or

We examine two types of organometallics: RMgX, a Grignard reagent, and RLi, an organolithium compound Preparation  +  -  + Solvated by ether, aprotic solvent

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

Reactivity patterns Recall the S N 2 reaction where the alkyl group, R, is part of the electrophile. Electrophile Nucleophile 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 -+ Nucleophile 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 and a larger molecule. Problem is that a terminal alkyne is needed.

Recall an earlier Example of Retrosynthesis Analysis A  blocker The Main Point: nucleophilic reactivity provided by oxygen or nitrogen. We are not forming new C-C bonds.

A Grignard has a reactive, negative carbon. Now examine reaction of Grignard and oxirane ring. Net results 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 -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. Now a substituted oxirane… Note attack on less hindered carbon 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) Gilman Preparation of Gilman Reagents

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: 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 electrophile

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

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

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

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 E2.

Carbenes, :CH carbene Preparation of simple carbenes Mechanism of the  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 ZnI Carbenoid, properties similar to carbenes.

Template for Reactions Why stereospecific, why from same side as OH group? Interaction with metal holds the carbenoid on the top side.

Electronic Structure Electrons paired, singlet

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