~~ Ylides are defined as compounds ia which a S) is connected te acarbon carrying a negative jomic (Le.. with positive and negative cherg ‘three main type ef ylices ed hetere atom harge. They are also referred as y § on acjacent 2toms) intermed’ates. Ti phosphorus, nitrogen ard sulfur, although arsen ¢, selene etc., ylides are also known. Phosphors and sulfur yldes can be represented in two cenonical forms but nitrogen ylides have only one structures. Phosphorus ylices are much more stable than nitrogen ylides. Sulfur ylides have a lew stability. The three yl'des are represented as shown below: (R)N— CH Nitroger ylide ‘R)pS == CHCH2R'<——> ——- R,S— CHCH AR Sulfur ylideidles 28.1 Generation of nonjurn salt by treatment with a strong hase f tes om etre CK (CH) anirogon ye (a) Nitrogen ylid ‘These are prepare Clty + Libs (CHa)gNCH3Br iy + Libr Totramethylamniosin bromido mira J-lithium) eliminate an a-hydrogen in treatment with a base (like alkyl-ithiun Pane ealfotam methyhde (a sulfur ylide) This is the most Commonly used method for the preparation of sulfur ylides. +. ——» (CH3)9S! (Clig2S | CHsl Sulfonium salt Dimethyl sulfide CH, SCH + > (CHs)2S + Rou z (CH3)g8 — CH3 ——*> (Ci ls)28 ‘Sulfur ylide Sulfur ylides can also be prepared by the reaction of a carbene with a sulfuide. The required carbene is generated by any of the methods given earlier. N: . & 3 N\, (©) Phosphorus ylides Phosphorus ylides are prepared from phosphonium salts by deprotonating them with a strong hase. The method consists in the alkylation of triphenylphosphine with methyl iodide. The resulting phosphonium salt is treated with a strong base to give a phosphorus ylide. CHol * ~ Gobbi (CeHs)3P —» (CeHs)3P — CHs | ——> (CeHs)s} Triphenybhosphine Phosphonium salt Cots (CotHs)3P — CHa Phosphorus ylive 2.8.2 Reactions of ylides A number of ylides have been isolatcd in crystalline state. However, some of the ylides are transient intermediates in some of the reactions. Most of the yides are strong nucleophiles or bases and are very important in organic synthesis,Peyton Imermediotes 129 (a) Nitrogen ylides ‘The nitrogen ylides are formed as intermediate method is used for the conversion of the tctra-alkyh in a csposition to N) into a fertiary amines (sce see. 6.4.3). the § LC -NICHayT Noble ie h | dis tants WIS, ung Hees : — oe Aiton vida & . cn aw ols ah gare ] — a et Ch Ap crticton ‘CHN(CH)2 st found that pyridine -carboxylie wed undergoes deearboxylatiog readily compared 10 ‘ts 3- or 4-isonief. This 18 due to stabilization of carbanion by N* which is adjacent to the carbon carrying negative charge in the intermediate ylide. Or OL #=©O.=O hee 8 ) & ylide 7 (intermediate) Pyridine-2-carbonylic acid OL Qu CeHsCOCH Q he J cit bn 3 cts Addition product formation of ylide intexnediate has been confirmed by its trapping with carbonyl cetophenone to yield the addition product. Avy Sulfur vides x Sulfur ylides have nvf 126 Onganiec Reaction Mechanisms Ye er. 7 DSC 7 . Jes are unstabilized sulfonium ylides, Two ofthe mest widely wed te of sli fides ave namin a such as dimethylsulfonium methylide ((CHs)28'-C such as dimethyloxosulfoninmn methylide. oO _ bon (Clis)8—CH (CHa)o— CHa the fated carbonyl compounds, These ylides show different reactions with o,-unsaturated carbonyl cloproy the absence of the double former give epoxides snl she Ine lve op lop Prateeniy lial atete el er epoxide, The epoxide formation (i.e, hand, both give at qi eee favourable while cyclopropane formation (ic, 1,4-addition, Michael energetically favourable. The former reaction (epoxide formation, which eee is faster with the unstabilized ylides. But, the stabilized ylides is sufficently Eas Gods ite wsPrursaurated Ketone mn @ Inttashion to give eyelopropane, which is te thermodynamic product (1.4-addition, althaugh slower, is energetically more Sapien because the new C-C bond is formed at the expenses of a, relatively, weak C=C bon rather than, relatively, stung C=O bond). 9 (Cs)eS— CH st Ae — Se The sulphur ylide is a very important class of stabilized sulfur ylide and reacts with cx B-unsamurated carbonyl compounds to give cyclopropane derivatives. However vith unsaturated cumpouuls, sulfoxonium ylides react in the same way as the stabi 800G Hs (CHS — Og ; Cc’ ee ae co0Cs Hs Hye’ Nc (0%) cetones (unsaturated ketones) give cpoxides while The sulphur ylides ou reaction with k Phosphorus vlides give alkenes “9 L oN (CHta)sS— CH Cohan? — CO (J wena ) emsel une in both reactions. However, the intermediate decomposes by hilio substitution uf (CHa)x5 by the oxyanion to give the epoxide, the intermediate eyclizes to give a four-membered ring, which The first step is. sa intramolecnlar nucleop! Instead, in Wittig reac decomposes to give alkene,+. ~ (CHa)eS—- Clty + ome > (CHy)ed oH, J o-¢— tntram Substitution eT No 2 the above reaction is useful for the preparation of epoxides and heterocyclic compounds from appropriate substrates. : Hq 1 or (CHs):8—cHi, See NH Cr ~ = Sulfur ylides undergo a number of rearrangements, one such rearrangeme! below: ‘S-KOC¢H-t ~ deere lke” |—-L s_) Sutfonium sait (72%) Reerranged product A useful sulfonium ylide is diphenylsulfonium cylopropylide. It is usually generated in situ by the action of potassium hydroxide on cyclopropyldiphenylsulfonium fluorobarate. The attack of ylide at the C-C double bond of an a, B-unsatutated ketone, followed by rearrangement with acid or lithium fluoroborate in refluxing benzene gives cyclobutanone. The cyclobutanones are also valuable intermediates. + KOH, DMSO (CeHs)S—] BF; =——= (CoHg)2SKOHL DMs (c) Phosphorus ylides ‘The phosphorus yhdes (or the phosphoranes) ha t well known reaction of phosphorous compounds to give olefins (Wittig reaction). The phosphorus ylide reacts with aldehyde ‘or ketone to form an intermediate betain, which eliminates triphenylphosphine oxide to give an alkene. Wittig reaction is very useful for the introduction of exocyclic double bond. For example, cyclohexanone is converted into methylenceyclohexane in 99% yield. For other applications and properties of phosphorus ylides see sec. 8.14. ie tremendous synthetic potentialities ylides is their reaction with carbonyl Presec Yiige bog 2 L R—cCH==CR, + O—=PPh, Tripheny! phosphine Oxide Oxaphosphetane a - 2.9 Enamines _ famines are 0, Beunsaturated amines, |Resetion Intermediates 129 Enamines are obtained by the reaction of an carbonyl compound (aldehyde or a Ketone) Witla secandary amine in presence of a suitable dehydrating agent such as potassium carbonate, or better by refluxing in beizene solution in presence of catalytic amount of p- rnesulfonic-aéid with azcotropic removal of the formed water. The secondary amines which are commonly used are pyrrolidine, morpholine and piperidine in descending order of reactivity, The reaction proceeds through the intermediacy of iminium ion which loses a proton from a carbon atom B to the nitrogen resulting in the formation of a double bond ‘between a and B-carbon atoms. ~ Oo ‘OH ti i Cs + CHs— ¢ + NH(CHs)2 <== Gly UE NCHe H 4 H Acetaldehyde Dimethyl amine (sec-amine) {tno H + =CH—N(CI =—s [cH 7 cre ettaa| (CH2==CH—N(CHa)2 [cg uM is)2 An enamine Iminium salt Enamines can be considered as nitrogen analogues of enolates. Their reactivity 2s rrucleophiles is due to the dipolar character of one of the resonating structures which ‘show that the carbon to the nirtrogen has a partial negative charge. Hie Pore N(CHy)2 < — H 2.9.1 Generacon of enamines imimines ae generated from a carbonyl compound and a secondary amine (see sec. AZ 59), Synthesis of cyclohexanone-morpholine enamine is described below. 0 fe} a Np —TawenesH aS Vey reflux Cyelchexanone Morphotine cyclohexanone ‘morpholine enamine 2.9.2 Reactions af enamines The enamine reaction was introduced: by Stork and his coworkers (1963) and provides a valuable alternative method for the selective alkylativu and acylation of aldehydes and ketones.fa) Alkylation of ketones 1 is found that the reaction of enamines with alkyl halides initially formes the C- alkylated intnium salt, which pives the a-alkylated ketone. The N-alkylated product is also formed, but it is water soluble and is unaffected by hydrolysis. CN C\ [ C-Alkylation | a snatiocted by hydrolyse 9 A cy 2 Methyleyeiohoncnene The above principle is used for the synthesis of 2-allyleyclopentanone. a-O- Cyclopentanone Morpholine 9 oN ovo “Lie 2.Allylcyclopentanone ay The alkylation procedure has also been used for the synthesis of bicyclic compounds. The following example is illustrative, - “0 ices AL (i) Ho” OO iis that it is regioselective, Thus, in the ‘-methyleyclohexanone), the substitution However, direct base catalysed re of products, Also in the ‘A valuable feature of the enamine reaction alkylation of an unsymmetrical ketone (C2. takes place at the less substituted or-carbon atom, alkylation of unsynunctiical ketones gives usually a mixtu tine reactions, since no alkali is used, there is no possibility of side products, which sre normally obtained from carbonyl compounds. or example; he reaétion of enamine Sere Grelohexanone with methyl iodide gives almost exclusively 2 dimethyleyelohexanone 5 OO Hoc. 3 pon kL. UO Ove 2-Methy! H (85-90%) (10-15%) cyachexanine Pyrotdine [ov ° + “ye yt Hee “CHa 2,6 Dimethyl cyclohexanone trical ketone, the selectivity ofthe reaction is due to the fact inly of the more reactive isomer in which the double bond is, Thus, in the case °F uns} That the enamine vonsisté directed towards the less hifidered carbon. (b) Formylation Formylation cau be achieved with dimethylformamide o. CJ oO i POCIs CHO [0 # HGON(CH:)2, —>©) Acylation uf ketones : The above principle is used for the synthesis of 2-acetyleyelohexanone. Co (d) Arylation Arylation can be achieved by activated aryl halides NO SS 2.4 - Dinitrochiorobenzene 2.9.3 Metalloenamines It is found that many imines, formed from enolizable aldehydes and ketones on reaction with aliphatic primary amines, can be easily deprotonated on treatment with lithium di- isopropylamide ur Griynusd reagents, The metal salts so formed are called metalloenamines. The metal salts on reaction with primary or secondary alkyl halides give manoalkylated carbonyl compounds.139 RH e RK eno" a sont Amine salt R peHO ) CeHs (75-80%) Metalloenanire The metalloenamine reaction is used for enantioselective alkylaticn of ketones, using optically active amine. A typical example is given below. 0 Ce H Cyclohexanone Optically active 80% yield amine (94% enantiomenic excess) It is found that the methoxy group in -netalloenamine plays an important role in asymmetric induction, in its absence optica. yields ere much lower.