Organometallic Chemistry - Organic Chemistry - Lecture Notes, Study notes of Organic Chemistry

Download Organometallic Chemistry - Organic Chemistry - Lecture Notes and more Study notes Organic Chemistry in PDF only on Docsity! 1 Organometallic Chemistry Organometallic compounds are those that have a carbon-metal bond such as sodium acetylide. C C:- Na+H Nomenclature: name as a substituted derivative of a metal: Li H Cyclopropyl lithium C H H H Na+ vinyl sodium CH3CH2 Mg CH2CH3 diethyl magnesium CH3MgI methylmagnesium iodide Carbon-Metal Bonds Most metals are less electronegative than carbon and therefore the carbon will have a negative charge. A carbon with a negative charge is called a carbanion. Therefore the organometallic compounds that we will talk about have a carbanion character. As the metal becomes more electropositive, the ionic character of the carbon increases. C Na+ C K+organosodium organopotassium Organosodium and organopotassium compounds are essentially ionic. These compounds are very unstable and they are also not very soluble in common organic solvents and so are not very useful in organic synthesis. Organolithium and organomagnesium compounds have a covalent bond between the carbon and the metal but the bond is highly polarized with the carbon having lots of negative charge and the metal lots of positive charge. C Li C MgX X= halogen Preparation of Organolithium Compounds We make organolithium compounds by reaction of alkyl or aryl or vinyl halides with lithium metal. This is an electron transfer process, not a substitution reaction. As we know, lithium is in the far left column of the periodic table and has an electronegativity (Pauling scale) of 0.98. It has one valence electron that it easily gives up to form Li+. Lithium metal is highly reactive and in fact is pyrophoric in air (i.e. it burns) and must be kept in an inert solvent at all times. We need two equivalents of the lithium to contribute the two electrons needed to form the C-X bond since each lithium atom has one valence electron and the halogen, X, ends up with a full negative charge. docsity.com 2 RX + 2Li R Li + LiX CH3 R = alkyl, vinyl, aryl Cl 2Li+ CH3 Li + LiCl X= Cl, Br, I The alkyl halide may be primary, secondary or tertiary. Alkyl iodides are the most reactive, then alkyl bromides, then the chlorides. Alkyl fluorides are relatively unreactive. C I > C Br > C Cl >> C F This correlates with the strength of the C-X bond. As mentioned above, vinyl and aryl halides also react but do so more slowly than alkyl halides since the C-X bonds are stronger. Br + 2Li Et2O 35°C Et2O = diethyl ether Li C C Cl H CH3 CH3CH2 + 2Li 35°C C C Cl H CH3 CH3CH2 + + LiClLiBr THF THF = tetrahydrofuran OCH3CH2 O CH2CH3 Two good solvents for these reactions are diethyl ether (Et2O) and tetrahydrofuran (THF). Both of these are moderately polar due to the oxygen lone pair (for example, both are miscible with water) and they do not have acidic protons. Organolithium reagents are very strong bases and will react with compounds like alcohols that have relatively acidic protons (pKa’s ~16) and also with water. So it is very important that the solvents be anhydrous. Organolithium reagents react with alcohols and water to form insoluble lithium alkoxides and lithium hydroxide that coat the surface of the lithium and make it unreactive. Mechanism of Organolithium formation: H CCH3 H Br + Li H CCH3 H Br H CCH3 H + Br Li H C:LiCH3 H + Li+ ! Preparation of Organomagnesium Compounds (Grignard Reagents) docsity.com 5 Both organolithium and organomagnesium reagents are excellent nucleophiles and will attack several kinds of electrophile as we will see. The most important of these is the carbonyl group. Grignards and organolithium reagents both attack the carbonyl group with cleavage of the C=O bond to form alcohols with formation of a new C-C bond. This is a very, very important reaction. First, look at the carbonyl group. C O C O Oxygen (electronegativity 3.44) is more electronegative than carbon (electronegativity 2.55) and so the C=O bond is strongly polarized toward oxygen as shown by the resonance structure shown on the right. This means that nucleophiles will be attracted toward the carbonyl carbon. We will see a variety of nucleophiles that attack the carbonyl carbon. Our first example is the Grignard and the organolithium reagent. O + R M C O- M+ R H O H H C OH R Alcohol, may be primary, secondary or tertiary M = Mg or Li tetrahedral intermediate Acidic work-up anhydrous solvent The organometallic reagent (M = Mg or Li) attacks the carbonyl carbon and the C=O bonds breaks at the same time to give the tetrahedral intermediate with a negative charge on the oxygen. The organometallic reagent is often generated in situ (i.e. in place) and then the electrophilic carbonyl is then added usually at low temperature and with care taken that anhydrous conditions are maintained. Then, once the reaction has gone to completion, a solution of dilute acid is added so as to protonate the oxygen to make the neutral alcohol. With Aldehydes: we form primary and secondary alcohols MgBr + H C O H Et2O C H H O- MgBr+ H3O+ C H H OH formaldehyde CH3CH2CH2 Li CH3CH2 C O H + THF CH3CH2CH2 C O- Li+ H CH2CH3 H3O+ CH3CH2CH2 C OH H CH2CH3 With Ketones: we form tertiary alcohols. docsity.com 6 CH3CH2MgCl + O THF MgCl+ -O CH2CH3 H3O+ HO CH2CH3 CH3CH2CH2 Li + CH3 C O CH3 CH3CH2CH2 C O- Li+ CH3 CH3 H3O+ CH3CH2CH2 C OH CH3 CH3 Acetylenic Alcohols Anions of acetylene can be prepared using a strong base such as NaNH2 or CH3Li or CH3MgBr. CH3CH2MgBr + C C CH3H pKa 62 pKa 26 THF CH3CH3 + C C CH3MgBr+ Keq = 1036 C C CH3HNH2- Na+ THF C C CH3Na+ Both of these can attack carbonyls to make acetylenic alcohols. CCCH3 MgBr+ CH3CH2 C O H + CCCH3 C O- MgBr+ H CH2CH3 H3O+ CCCH3 C OH H CH2CH3 C C CH3Na+ O + Li+ -O C C CH3 H3O+ HO C C CH3 Retrosynthetic Analysis This is a method of analysis that involves reasoning backward from the target molecule. Sometimes in a synthesis problem it is not obvious what the first step of the synthesis should be when looking at the starting material. The technique of retrosynthetic analysis is a way of helping find the best route to the target molecule (T.M.) from the starting material (S.M.). docsity.com 7 What we do is look at the target molecule first and in our minds say if I had molecule X, then I could make the T.M. using a reaction that I know and that we have studied. Then we work one more step backward until we come to the starting material. (S.M.) (T.M.) known reaction backward arrow X known reaction Y known reaction S.M. Starting Material Target Molecule forward arrows unknown number of steps Here are some examples using the chemistry we have studied in this chapter. Our first step in this process is to imagine which bond we are going to form. In order to break this bond hypothetically in our minds, we must have a clear method for forming it in the forward direction. Breaking this bond is called a “disconnection” and we represent this typically by making a wavy line through the bond that we will break. Remember this is purely an imaginary exercise as we work backward step-by-step from the target molecule to the product. We do not have to do this and many times we can do it in our minds without actually writing it down but sometimes it is helpful, especially when the target molecule does not look similar to the starting material. C OH CH3 CH2CH3 CB A C CH2CH3 O + CH3MgBr MgBr CH3 C O CH2CH3 C C CH3 O + CH3CH2MgBr + acetophenone butanone ethyl phenyl ketone A B Here we are not given the starting material but the target molecule is a tertiary alcohol and we have just learned that we can make tertiary alcohols using Grignard reagents in reaction with ketones. So, looking at the formation of bond A (the backward disconnection represented by the wavy line) we know that we could form the target molecule if we had the methyl magnesium bromide and ethyl phenyl ketone. In this example we see that there are three possible disconnections that we could make and they are all about the same. Again, we do not have to perform the retrosynthetic analysis but sometimes in more complicated examples it is a useful technique, as we will see in later chapters. Here is another example, using chemistry from Chem. 121. docsity.com