318-9 - Organic Organic Lecture Series CH 318 N LECTURE 9...

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Unformatted text preview: Organic Organic Lecture Series CH 318 N LECTURE 9 Textbook Assignment: Chapter 16 Homework (for credit): POW 4 posted Today’s Topics: Organometallic Reagents Notice & Announcements: Grading in Progress 1 Organic Lecture Series Drawing Mechanisms • Use double-barbed arrows to indicate the flow of pairs of e• Draw the arrow from higher e- density to lower e- density i.e. from the nucleophile to the electrophile • Removing e- density from an atom will create a formal + charge • Adding e- density to an atom will create a formal - charge • Proton transfer is fast (kinetics) and usually reversible 2 Organic Organic Lecture Series Organometallic Reagents 3 Organic Lecture Series Organometallic Organometallic Compound • Organometallic compound: a compound that contains a carbon-metal bond • The focus will be on organometallic compounds of Mg, Li, and Cu – these classes illustrate the usefulness of organometallics in modern synthetic organic chemistry – the use of organometallics can bring about transformations that cannot be accomplished in any other way 4 Organic Organic Lecture Series Grignard Reagents • Grignard reagent: an organomagnesium compound – prepared by addition of an alkyl, aryl, or alkenyl (vinylic) halide to Mg metal in diethyl ether or THF + Mg Br 1-Bromobutane ether MgBr Butylmagnesium bromide (an alkyl Grignard reagent) Br + Mg Bromobenzene ether MgBr Phenylmagnesium bromide (an aryl Grignard reagent) 5 Organic Lecture Series RMgX & RLi • Grignard reagents dissolve as coordination compounds solvated by ether – ethylmagnesium bromide, EtMgBr 6 Organic Organic Lecture Series RMgX & RLi • Organolithium reagents – prepared by reaction of an alkyl, aryl, or alkenyl halide with lithium metal Cl + 2 Li 1-Chlorobutane pentane Li Butyllithium + LiCl 7 Organic Lecture Series RMgX & RLi The carbon-metal bonds in RMgX and RLi are polar covalent C-M Bond C- Li C- M g C- Al C- Zn C- Sn C- Cu C- Hg Difference in Percent Ionic Electronegativity character* 2.5 - 1.0 = 1.5 2.5 - 1.2 = 1.3 2.5 - 1.5 = 1.0 2.5 - 1.6 = 0.9 2.5 - 1.8 = 0.7 2.5 - 1.9 = 0.6 2.5 - 1.9 = 0.6 60 52 40 36 28 24 24 EC - EM EC x 100 8 Increasing Ionic Character *Percent ionic character = Organic Organic Lecture Series • Reaction with proton donors: – RMgX and RLi are strong bases δδ+ δ+ δCH3 CH2 - MgBr + H-OH Stronger pK a 15.7 base Stronger acid CH3 CH2 -H + Mg 2 + + OH- + BrpK a 51 Weaker base Weaker aci d p Ke q = -35 – they react readily with these proton acids R2 N H pK a 38-40 1° an d 2° A min es RC CH p Ka 25 Termin al alkynes ROH p Ka 16-18 Alcoh ols HOH ArOH pK a 15.7 pKa 9-10 Water Phen ols RSH p Ka 8-9 Thiols RCOOH pK a 4-5 Carboxylic acids 9 This is often an undesired side reaction-to be avoided!! Organic Lecture Series Organometallic reagents have 2 general types of reactions: 1. As Strong bases (Bronsted-Lowry) 2. As nucleophilic reagents: C H 3C H 2C H 2 M gBr Regard the alkyl group as “R-” 10 Organic Organic Lecture Series RMgX & RLi • RMgX and RLi are valuable in synthesis as nucleophiles – the carbon bearing the halogen is transformed from an electrophile to a nucleophile carbon is an electrophile δ+ δC Br CH3 CH2 CH2 H H H H - carbon is a nucleophile Mg 2 + Br - C CH3 CH2 CH2 – their most valuable use is addition to the electrophilic carbon of C=O groups of aldehydes, ketones, carboxylic esters, and acid chlorides to form a new carbon-carbon bonds 11 O H 3C C H 3C H 2C H 2 M gBr A Simple Example: M gBr O H CH3 H 3C C H 3C H 2C H 2 a lk o x id e CH3 Organic Lecture Series OH OH H 3C C H 3C H 2C H 2 a lc o h o l 12 M g B rO H H 2O M g (O H ) 2 CH3 Reactions • Reaction with oxiranes (epoxides) Organic Organic Lecture Series – reaction of RMgX or RLi with an oxirane followed by protonation gives a primary alcohol with a carbon chain two carbons longer than the original chain MgBr + Butylmagnesiu m b romide O Ethylen e oxid e O MgBr+ A magnesiu m al k oxi de 1-Hexanol OH 13 Reactions • Reaction with oxiranes (epoxides) Organic Lecture Series – the major product corresponds to SN2 attack of RMgX or RLi on less hindered carbon of the epoxide MgBr + O PhenylMeth yloxirane magnesium (Propylene oxide) (racemic) b romide HCl O MgBr A magnes ium alkoxide + H2 O OH 1-Phenyl-2-propanol (racemic) 14 Organic Organic Lecture Series Gilman Reagents • Lithium diorganocopper reagents, known more commonly as Gilman reagents Gilman – prepared by treating an alkyl, aryl, or alkenyl lithium compound with Cu(I) iodide 2 CH3 CH2 CH2 CH2 Li + Butyllithium diethyl ether or THF Copper(I) iodide CuI + ( CH3 CH2 CH2 CH2 ) 2 Cu - L i Lithium dibutylcopper (a Gilman reagent) + LiI 15 Reactions Organic Lecture Series • Coupling within organohalogen compounds – form new carbon-carbon bonds by coupling with alkyl and alkenyl chlorides, bromides, and iodides – Example R'Br + R2 CuLiBr d iethyl eth er or TH F 1 . L i, pent ane 2 . CuI d ie th yl ethe r Br or THF R'- R + RCu + LiBr I 1-Iod od ecane 2 CuLi 2-Methyl-1-dodecen e 16 Reactions Organic Organic Lecture Series coupling with a vinylic halide is stereospecific: the configuration of the carbon-carbon double bond is retained I+ t rans- 1-Iodo-1-nonene 2 CuLi Lithiu m dib utylcopper d i e thy l e th e r or THF t ra ns -5-Tri de ce n e 17 Reactions • A variation on the preparation of a Gilman reagent is to use a Grignard reagent with a catalytic amount of a copper(I) salt CH3 (CH2 ) 7 (CH2 ) 7 CH2 Br + CH3 ( CH 2 ) 4 Mg Br Organic Lecture Series CC H H (Z )-1-Bromo-9-octadecene Cu THF + CH3 (CH2 ) 7 (CH2 ) 1 2 CH3 CC H H (Z )-9-Tricos ene (Muscalu re) 18 Organic Organic Lecture Series Carbenes & Carbenoids • Carbene, R2C: a neutral molecule in which a carbon atom is surrounded by only six valence electrons • Methylene, the simplest carbene – prepared by photolysis or thermolysis of diazomethane + H2 C N N: : hν H2 C : + : N N: Methylene (th e simp lest carben e) – methylene prepared in this manner is so nonselective that it is of little synthetic use 19 Organic Lecture Series Carbenes & Carbenoids Dichlorocarbene – prepared by treating chloroform with potassium tert-butoxide CHCl3 + (CH3 ) 3 CO K Trichlorometh ane Potas sium (Cloroform) t ert -b utoxid e + Cl2 C: + (CH3 ) 3 COH + K Cl D ichlorocarbe ne tert -Bu tyl alc oh ol + - 20 Organic Organic Lecture Series Dichlorocarbene reacts with alkenes to give dichlorocyclopropanes H Cl 2 C: Dichlorocarbene ( CH3 ) 3 CO - K + H + CCl2 H A dichlorocyclopropane Cl + cis- 3-Hexene HCCl 3 H Cl cis- 1,1-Dichloro2,3-diethylcyclopropane 21 Organic Lecture Series • Simmons-Smith reaction Simmons– a way to add methylene to an alkene to form a cyclopropane – generation of the Simmons-Smith reagent CH 2 I 2 Diiodomethane + Zn( Cu) Zinc-copper couple diethyl ether ICH 2 ZnI Iodomethylzinc iodide (Simmons-Smith reagent) – this organozinc compound reacts with a wide variety of alkenes to give cyclopropanes (prepared by: Zn dust; CuCl & heat) 22 Organic Organic Lecture Series Simmons-Smith reaction: the organozinc compound reacts with an alkene by a concerted mechanism* I CH2 I Zn ZnI 2 + H2C *concerted mechanism-one in which there is simultaneous bond breaking and bond formation. 23 Organic Lecture Series Uses of the Simmons-Smith reagent: Zn(Cu) + CH2 I2 Methylenecyclopentan e O Zn(Cu) + CH2 I2 2-Cyclohexenone diethyl ether + ZnI2 diethyl ether Spiro[4.2]h eptane O H CH2 + ZnI2 H Bicyclo[4.1.0]h eptan-2-one 24 Organic Organic Lecture Series Naltrexone opioid receptor antagonist used primarily in the management of alcohol dependence and opioid dependence. 25 25 ...
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