ogi Sin oliw Reactions Te @ Catalytic Hydrogenation @Nuaeophilie Reactions of Acetylenie Anions @Reduction of Alkynes with Sodium in Liquid Armonia. @tydration of Alkynes @ tydroboration- Oxidation of Alkynes @ Cronolysis of Alkynes @ralogenation of Alkynes @Hydroryhalogenation & Alcoryhalogenation of Alkynes @tydrnalogenation of Alkynes @Free-Radical Hydrohalogenation of Alkynes Code: ATIEEReactions of Alkynes m8 A) Catalytic Hydrogenation HH Sterec: Ph-C=c-H —“2 me" He Ph-¢-¢-H Sut * ~ Pd W7 ~ Say Pa i Qddition catalyst (can be isolated with, Lindlars cat. instead of Pd) 2) Nucleophitic Reactions of Acetylenic Anions © R-CH,-x — NaNH Ph-c=c-H ———*> Ph-cec: Ph-Cac—cH,R SN2 Mechanism &) Partio® Reduction with Sodism in Liquid Ammonia, H NaCmetag) PAY Sterevepecific Ph-C=C-CH, cae : : 8 Ns @ HA Ney, Anti-Gddition A) Hydration of Cekynes 2s Hg" HO Ph AH eto-ence PRY Ph-C=C-H Aes cag —> C- CH, catalyst = HOT SH tautomerianion Gv enol intermediate, ketone product Markoonikou Regioselectivitiy 5S) Hydroboration- Oxidation of’ Cekynes 5 4. BHS Pr H t Ph-c=c-H ASK THE Sc=el es PSY 2.4,0,/0H 4 OH autPmenization sy enol intermediate aldehyde product Anti-Markounikoo Regioselectioity, ©) Ozonolysis of Atkynes Ph-C=C-CH oO ©. 2 < Ph- ce + Te-cHs OH HO’ carborytic acids as products 3 20 single step process NO additional workup wired. Ashiasis Tyg Sov “s Code’ ATIEE@® Hatogenation of Olkynes alin Ce an koe xx 2! Ph-cec-cn, 2 Nee OS® bl, Cay vc, ri x inert solvent Onti- addition. double-addition is typicad in Add, to C&C @ Hyaronyhacogenation of Atkyres x Ph, x . Ph % Ph-Cee-H —S YeneQ ee EH 20 Ho’ 4 o 4 anti-addition Rebone prodicct halchydrin intermediate Marrkounikoo Cnet isotated) Regiosellectivity @ Gthonyhatogenation Of tkynes Ph. Xx ‘ Ph-c=sc-h —% Nec’ Second. addition products are ROH aoe SH Posibte as tet anti-addition Markoonikov Regioselectintys Hydiohaogenation. nes eminad GO) Hysronateg oF Oey Ot ionice H-Br Coq) Ph Ho H-Be eg) \ Ph-c=c-H Nese Pr-E-C-H Be H 4 anti-addition Be Markounikov product double Addition product Free- Radical Hydrchologenation. nes. 8 8 7 H-@r Pa Ph-c=c-H C=CHBe —— Radicat mechanism ! ROOR ,o Hn? Onty works Anti-Markounikov fer Her! Regioselectivity, Ashiasis Tyg Sov Code: ATIEECatalytic Hi Hydrogenation of Olkynes not Stereosp. H yi H Ph-C=C-H iO Nc=c0 ——2—> Pr G- ¢ H Syn ho Pa "s Nu Pa 7 i Oddition catalyst intermediate Cnot isolated) Mechanism: Reaction starts by absorbtion of H, on the surface, of the metal. | . We can represent HH Dbsertotion H 4 this as ine “falousing: 7 777 WITT Ho a Me Pt Typical metal catalysts are: Pt, Pd, Pale, Ni CHa-Cac-cH, _San Hac CH, _S" HC CH Xe H7 i H-e- 4 “a. mono-hydrogenated HOH product Cnot tsotated) & complete reduction H. a Ph 2 = Pa pn Oe complete reduction of C=C Bsr he ee xh Pa Ph HH Notice: all It-bonds are reduced in this reaction. Partial reduction is possible when you use the Lindlars catalyst instead of a bypicod heterogeneous catatyet ence as Pt or Pa Lindlars (5% Pd on CacOs catalyst Pb COAc)2 ~ poison responsible fir the catalysts activity S : . wbouces cee EIS) qurotine farther deackuates the Pd catadyst bout is inactive towards C=C or other double bonds. Examples: Reaction is stereospecific givin Hy Pho Ph a strict oe addiction yielding =C-Ph Trata® Gl ec the cis Ne AS A Product. Ashiasis Tyg Sov Code’ ATIEEFormation of O.cetyvenic Cnions Terminal R-C=C-H is weakly acidic CpKkan 25) & can be deprotonated bby using a sbong base: er aesenic. ton R-ce CH Base R-Cec? + H-Base Conjugate. acid.) Common bases in Conjugate acids organic. chemistry they make ° pKa of the cont acids Hydroxide OH wa HO water Methouide CHA @| weaker bases 85 CHgOH methanod Ethoxide CHgCH,O” } cart deprotenate ~ 49 CHsCHOH — ethano? tert-butprids RCREH ~ - e Xe 48 K oy trbutanct Omide NH, ~ Be NH Ammonia, stronger bases >a AwAd € ~3 . She | Hat can be And diisopropytamine used to depret: H Butyttythium “SLi | R-CaC-H 788 ~ butane iytride eH 785 Hy hyarogen. Resuvting Acetyvenic ions are very basic! “Typical reactions thot give acetytenic anions are done in such a 80 that the conjugate ocid is gaseous & is ically removed from the reaction drivi the g to womptetion. me 3 i) Examples: De Ph-CSC-H + NaNH, ————> Ph-CSCNa * NH, Cees) ‘e ammonia. is often dissclved in Uquid ammonia whic we easity evaporate “%s at the end oP run. Out DAN ——> )-escui + ~~ Gas) butane yece Alternatively, 0 brans-metattodion with the Grignard agent gives an inert product which will not interfere with the towing s-berzene + Pho or a Neo 2 Mae PH Oe hclve H ether oc THE Magee Side-~product) Ashiasis Tyg Sov Code’ ATIEEReactions of Ocetytenic Qunions” Rca? &S mucleophitic & can react with various elecbophites. Nani, Ph-ce OH Br Note: reaction ONLY works for # RX Se Acetyfenic anions yield E2 products with Z & 5 RX ar product, Su2 product is NOT observed. CK oncec? 1H ® Reaction with epoxides 2 & “Rakin, Ph-ce@y OSS p,- ca ES Ph- cc oe Su2 a Ho. The Sn2 attack of the acdytenic ton aloays workup oa occurs from the Less Substitiied side of the epoude ring. — Ph-C=C News bond Reaction ONLY works for non-stericatly hindered epoxides Qiring an epoxide opening via EZ for more sud. epoxides: ) Ph HO Ph ‘ PSS eS Nae eT ae hs C=C-Ph ® Reaction woth aldehydes & ketones s RlanH, Ph- csQH ——— Ph- cece ——— Pr- ec 8. Bw New bend, Hic? H P were Reaction works well with aldehydes CR-C ) & is less productive with ketones CR. -R) ~H Ph-C=c Just Uke in the previous cases, stericatly hindered ketones moy give Side products or not react at atl. We generally treat ony reaction of an Onetytenic ions with aldehydes & ketenes as vidBle C-C bend formation method Ashiasis Tyg Sov Code’ ATIEEPartial Reduction of Gtkynes“ with Na in Uiquid NH, = Nd (metab RY 8 Qnki- Addition R-c=c-R Nis Gaga wore + 2NONH, — trans-aDkene product Notes: Na Cmetat) is most commonty used but Li (metat) can also be used Reaction is usually done at ~34°C CO.p. of Uiquid ammonia) Otternativery , reaction can be done at -38°C in a mixture of CH30H & NH Mechannise: vadicad Cc a E-trancfer PAL? Hebransfer PAL Ne Ph-CaC- Ph —__ cc ae 3 anion’ CP H Ph Na H. aH nt E-bransfec Trans anion-radical is H aH more therm namical Ph HH Hetransfer Ph 28 HAN stable ijecerd the Newel = ca trans alkene™ product, H Ph H Ph trans-atkene Examples: 4 Reaction is stereospecific KEE VAS oe s 4 H Abwsays wing the trans Ovs- cts SS < Santorini, ObRERE for a product. NHs, CH, H Note: this reaction produces NaNH, a8 a Side-product , Which is extremely basic, which easily deprotonates terminal alkynes making them unreactive to Na. 4 Ra Hoe 4 H _ Na ere he o ~ —“ S — ; SP Ns i workup Ay intemad hing Note that white the internal akyne was reduced, the internal alkyne was deprotonated &, aS a result, stays unaffected. Ashiasis Tyg Sov Code’ ATIEEHydration of” Qteynes (isons e R H _ RW a RecEcHH H® Coat), H2O Nee? keto-enct Ne-duy or Ha*ccat)sH2 pyc” Ny tautomerization 7 4 Pv eno’ intermediate Hg tegpicat comes, Cnot isotated) ketone product from IgcOAc 2 OF Hg S04 Markovnikoo Tegioselectinity Mechanism with H® catatyst: more stable C° (markoonikos Rule) 6 JH Ph-Cec-H — Electrophitic Ph-c=cK Nucleoghitig hy Oxttack $ Attack, N“, S 2 Je He HO: H-O@ se ? Yo fore Note: hike the carbotation” intermediate is postulated, theres little evidence it actually forms. H- bransfer vbetone product Pr Pr = ence Ne- H- beans Ne- H- beans Ses i A Zo Os eg Hs icbransfec_ THe intermediate, ° Hoo H-O eH ¢ HOC H,0: H Mechanism with Hg" catalyst: — 8 Mackounikoo Eepicselectivity Ph 4 Ph H -H Etectophivic Sc=c% — Nucleophitic Neac¢ 3 g Ostack. Cafe Citak de —H a+ Lo ia mereugic ion intermediote H0:_A Important: mercuric ton always opens from the H-bransfc more substituted side of the ring. Ph oe Ph _ Ph Ho? NcecHy <—g__ Seger, i transfie Scael ‘4 H-oF S, Hssodationy oS Sho 4-55 GSH eno HH erg H intermediate Se & H-transfie 4 Wry Ph. _ Ph. = ketone product Ne-ch, Hoban "Nc ~cu, * a 3 a 3 H-O °o oe HO: Ashiasis Tyg Siv Code’ ATIEEExamples: a) cbeto-ence, = a. Xe te paoreteaon oore substituted C’ Avon (Marrkoonikos Regioselectivity) (foot oes product) > 3° HO CH _ keto-enol. Crees SS quate, OX enot ketone Cfina® product) Tf you have a non-terminal Cinternal) C=C bond , the reaction Loses regidselectivity & gives muuttiple products: Hg’ HO CH _keto-enct o oe oO taudomerizakion oe constibitional Both i are 2 OL os isomers =F no oselectivi ~ reg g im d eno ketone intermediates products On acid- catatyzed keto-ence tautomerization TTautomerization is an equilibrium between two constitutional isomers, one & an. enot, the other one is an aldehyde or a ketone. 7 This equitibrium generat ors the, R-c=C-R R-C-C-R formation of the Carbo: ng & C=O) containis wo 4 64 Constitutional isomer os te iS more thermody enok ketone stable. General mechanism: a i ‘ a-céc-R oC Hibensin RCo oo R Aebeansfie R-C-C-R HOH Se 4 $H ot. We on HO ketone Note: multiple enots can give the same ketone: CH ° oH A a= ~~ == 1 Sy keton 0 Asli Tyas Sw a oe Code ATIEEOkkousmercuration of nes “ a R RacacH HELEN “Sea ct, — Markonikoo Regioselechinity vingtic ether Mechanism: — Pa aeomte PPS ae He Ph-CEC-H Etectophitic: C=C% Nudleophiti C=C Gita = Ch /, Gitack ~ Hic-08 | H Hg casoH 7 Hg® Q pmercuric don HOH A Opening of the mercuric ibn occurs from the H+transfer more substituted side of the S-membered ring HH. @ Ph Hetranspie PR [Hee GO- Cs Ne Noe < Ned H = CHe Fescciakion, < He £ Sy Cc CH,-O cH go 4 Hge Hsc-OF Cuhonymnencac ation is Q usefid method of ing vinylic ethers that may be aifh tp obtain otherwise. Similar to ommercuration, this reaction can be done in acidic conditions wlo Hg" present. This reaction, however, enerabtyy gives poor yields & number of unidanted side products g Exampbes: Ph-C=C-Ph feat Pe PICO -cec- = . = CHSOH H% och; =H% Ph cis trans Reaction has a poor sterenspecificity & often gives a mixture of cis & trans Products voith stight preference towacds a more thermodynamicatiy stable product, OY P HcecH + Yc-CHs HO onc, wi ester HO’ worn", ‘CHS, Coing? acetate) Owtkorymercieration may be used in sypdnesis of cydtic ethers 2 3 =o Hg" Coat) a a Best resutts are obtained for — 5 x (o-membered. rings & gwe NS resuets in ourer teases pes heat Ashiasis Tyg Sov Code’ ATIEEHydroboration- Oxidation of” ALkynes" R H R H e Baa THE 1,0. enol R-CaC-H cm C = Scat intermediate Hydroboration 4 eH, SH/ HOH not isotated) THF or ether is a typical Oxidation - Solvent used with meet Relo-enot wea Anti-Markounikor joselectivity means that the carbonyl product with the © on, less substituted carbon when applicable. RL ZA otaehi ae ary Cfinat product) Mechanism: Step 4: Reaction with the borane Ph-C=C-H Ph. UH H 2 H Etectophivie oe pt Stecbor BH, H & B add simuttas (syn addition) giving a On intermediate with both H & & on the same side Note: reaction can proceed to add the second of BHs along with other C=C bonds attaching to the borane intermediate. In other words, the mech, we usualy see in He textbook is an oversimplification. ‘Step 2: Oxidation of the borane intermediate om He pka.CH,O)= 183 Ho Oks Sy Hebe 6.8 Ho —— HO’ pka CH,O2)= 44.4 ~ sbonger acid peroxide ruacleophige, Ph. H y Ph. H i Ph. H N ic Oxidative Scace Muceeps Nee SE cae H Bh. Attack, H eH Rearrangement 7 Oy o — Oe oo SA Hoo oe Hor tH H “7 Hydrotysis of enok intermediate the intermediates Cnot isotated) enotate ) intermediate Ph. UH Ph_ UH Nese CE =n. +805] H7 OH | Hetransfee boric HOH acid, Ashiasis Tyg Sov Code’ ATIEEStep 3: Keto-enoe tautomerization (basic cond) ae rs Sie Ph LH _Htransfie [Ph oN yn Yee Cc, Ss C=C Sec H oe, ee H ‘O 8x SU ASH KET is an equi im that generally, | H-transfér ‘awers the C=O product due to its higher thermoayn stabil igher ecmodynamic st ty Poo on H7T No Cfinat product) H Examples: on on te - OH °C Canti-Markounikoo) ° 7 ll een 1. BHy THE Om heto-enot @.8: 2. H2O2 [NaOH e a oy tautomerization enck ‘intermediate 4 BANS 1 BHa THE s keto-enct Aerie 2. H202 [NaOH oe fauatomerization OF Flermediate Q -ntemat oars | show no vohat | About internal alkynes ? err oni wn bypica reactions. However, cat. dration , Oyjmercuration , or hydrobor when nes Uoith bt | eubhtsents are used , She Steric hindrance in the transition state starts to play a Gruciat role. Common "butky’ boranes H \ i & ar 8 A Ov disiamyloorane borane Q-berabicyclo[S.3 A]nonane Tein eH) eee @-B8N) 42% O° BBN Q- BEN keto-enot. al 3 CH —————— CH,-C-CH, OO 2. 4,0, /NoOH Oe taudomertzation. Deve z S sterically compare to hindeced C opts the OH oe! 2 Code: ATIEE Askari Tyagi Sov Nor FosmesHovo_do bulky boranes work ? Tre tats te aieetect sterics of te transition state . Bulky groups are further from each other guy & more stable transition ce" ‘State of the initial addition roON H ye Bucky g axe dose te each a) other giving a high amount of ce steric intertictions Creputsion) : moking this transition state less BrH stable “Chigher in Energy) => &ss yy While reaction doesnt give YA AQ complete regioselectivity, the selectivi becomes more pronounced os the difference in the bubkiness of the grou) on C=C increases. Examples: Lo bablig rane 4. Sia, BH HF 9° nos Pec THIS A + KR ° u traces ess steric maipr product i ce C50 on tess Nenarance, ‘ hindered side ) compare to 4. Bra THE 9° ae 2. H,02 164 ~rA * -8Sh ~4s% © a viebually no selectivity towards one isomer or another one Ashiasis Tyg Sov Code’ ATIEEOzonoeysis of Aveynes he Os H,0 e g R-cac rR i é é Cy RAO Mydodysis ROH HOT Carboxytic acid Carboxytic acids ride intermediate products not isolated) —> Jr\) > > 2 me AGS bie SG of / Se Note: this ts one of the few proposed mechanisms | “This reaction also occasionally "6 wad ives vicinal diketone, Pk 4 q HO \o-€ duct. The actuol mechanism How 4“ hydroeysis ° is Stel the matter of debates. Examples: Note: terminal abeynes produce COz instead of the firmic acid thot is Oxidized by Ox upon formation & therefore cannot be actually ioclated. 90 { Os ro i PhCH, CH,-CECH PRCHZCH,-C__C-H_ > PhCH, CH, -C. 1 HO g, Oo OH hydride, Qn intermediate + Re femic HOW ot ° va (CO, + H,0 <———— C. HO” “OH carbonic acid Cunstable intermediate) Ashiasis Tyg Sov Code’ ATIEEHatogenation of OLeynes _ oe ; x x double R-cSC-R De Nec > R-C-C-R jenation COly on CHeCly x R (eq) Xx prod typical solvents stereospecific Mechanism: oneeeee> Step 1: Single Addition Pro-CRC-CHs ___,. { Ph-C= Coc, PN as a ; Nucleophitic ce, te Rechophilic One oer oe B Osttock. &r Hagonum ton nki-adaition intermediate Ctrans product) Os double bonds are generatty more reactive in the reactions of electophitic addition, the addition of the Second equivalent of X, is typical & often unaveidable Step 2: Second addition Br Hs fe Hs & Os double ca > pc -C— ——__> _ p-c-C- ‘i NI, BERR OG age ET Regen ¢ Fs Ottack OB Oxtack Br Be Peau ' 2 Be Examples: Be Bear -as 82 5 Ny _ 82 NN Ch, gk VK CRC, my When mixed jens react with terminal akkynes, reaction shows regioselectivity, giving the Markovnitoo product elechdphite Cleophile Pre ygnceee _ I-d St Ph-C=C-H C=C further additions, however, show peor } d H regioselectivity & affera a. mixture oF more sub C isomeric tebrahatides. Cwhere the nucleophive adds per Markounikev rule) Ashiasis Tyg Sov Code’ ATIEErigdrongholegpnation. of wee oe ee ee teat ve R-cac- ry wo Ng R-C-C- 4 hi intermediate ae Mechanism: ‘on ‘S an an mes Etechopatie, POTS EH NiGeopratic a Ne Be: Ottace Gee Otack we hatonium ion. H-bransfer intermediate ° ar HQe HO2 9H bo Teenie Wear oS Pr“* cH, Pr* Nch,&r Ph S & Hees Reaction is STEREOSPECIFIC =" Pnti-Addition giving tans hatehydrin 8 intermediate. REGIOSELECTIVE =? gives Markcunikoo product C=O on the more ‘su. C) for terminal atkynes. Examples: a ~~ = AAAS, jist my if “oN ou &e Be beto-~ence, J \e/ —S > — = H,0 f toukomerzation “I HO 8 intermediate. Be, ba a. f0~enok, > wee Retomench SN H,0 taubomerization aaa d ° ® Both C's are 2, * on . sO nO joselectivity I I is Observed give a —_ Yr YY” mixture of cOnstifutional Be Br isomers Ashiasis Tyg Sov Code’ ATIEEx, R YX nbi= Addition somes R-Cc=c-R tA Nc= ce Mackoonikou R © R Multiple additions are possible Mechanism: HO-cHs, x e H Br — Nudeophitic “87 c=: Ottack. Pho Be | H-bransfec White Uris reackon gives a convenient way of HCO. 4 tne ayn tan woe multiple me ucts Lowering the tar oe motecue Ph &r wield. om pre 8 Examples: br = SARA AN S\N Gacion ~ \e Oskoushatogenation can be a neat way to make cyctic vinylic ethers Br, HO-CH,CH,CH, CHC 2 HO- CH CH,CH,CHY C= a H Etecbophitic a Attack. | Gre Tntramotecatar Nucleophitic ~“ Be H She t ONA poet Hee Re be cyctic vingpic Br Hetransfer HCE TC her product HACSy SCHe WH This cyctization typicably fawors the formation of S- & lo-membered. rings Ashiasis Tyg Sov Code’ ATIEEHydrohatogenation of! CWkynes e x HX = H-X Noa’ H=X | nal dihabide R-c=c-R cel -¢-¢-R eer ae 7 Sp 2 R yoy product of the anti- addition H double addition Ma.kounikeo product Mechanism: Step’: First Equivatent Addition e H Uinytic carbocation mS Ph-C=C-H Pa- C=O Matkoonitos rele ‘rms per SV . Stechophiie eo), 4 H7@e Osbock Be Nucleophitic Ottack Kinetic studies & observed. Be Reaction has an anti-addition stereospecificity of the ca’ y S stereospecificity givin trans addition acbiolly suggest Ph’ H product. that the reaction proceeds via. a termotecutar transitim state withoud formation of a carbocation at all: ©. ey & s Hq ° Ph-C=c-H ——> pore +o Hebe Pr 4 G Step 2: Addition of the Second Equivatent of H-Br 5 Be ‘BF 4 ene ey dati ee ped tiy pr’ 9 Sy Etecbepniic: 61 1 Hie Otte a H resonancely y Be stabilized “carbocation Nucleophitic Otack. This reaction iS Favors the Macon’ bei eminod diholide product Ph-C-C-H eminal dihalide product 4p the resonance Be H stabilization of the carbocation : . Ashiasis Tyg Sov Code’ ATIEEExamples: H HOM He - ~~ ee ee oe be ws % Be ae ey Be Be HBr i H-Br 4 pen EE AL ee ew be 2 eg, BK “Br The second equivatent of H-Be akways adds Internal alkynes + * regicselectively te give Show No cegioselectity be Be Br the geminat dinalide in the fist dation 9) AGA DSA step \ H HOH However! When an internal atkyne has & group capable of resonance stabilization of ‘the intermediate carbocation , we cbsewe o significant Markooniiioo Tegioselectioity H-Be nd a While reaction tends to give double addition, it is ste i to isckate the 8 ur @ single additm & ect it to A reactim with another reagent po ng 8 Be & ad hetero-dihavide [\ = ae QQ Ht OK product EkyN Be 84'%b yield. i acts as a catalyst Important: white this reaction may hawe a carbocationic character to it, we Never observe any carbocationic rearrangements! xX e+ & Br NOT observed Ashiasis Tyg Sov Code’ ATIEEFree-Radical Hydrohatogenation of _OReynes =c- H-e =c- : R-CEC-H carnal R= H No stereospecificity [selectivity Ceoth jemers F head Ho Be . ‘ « organic peroxide Ounki-Markoonikov Regicselectivity. Mechanism: Initiation —— so athouy radical Ch A eawnge s—bromine radical goes uve Bo! (afer BOK Bx se propagation ap more stable radical forms Termination (Recombination of ang two radicals) eg Bre BD ——™ 8r- Br Examples: Br rr. Hee AN RRA = peroxides Be H-Br = Se = mon Y-cH=cee Ashiasis Tyg Sov Code’ ATIEE