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

Info iconThis preview shows page 1. Sign up to view the full content.

View Full Document Right Arrow Icon
This is the end of the preview. Sign up to access the rest of the document.

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 ...
View Full Document

  • Spring '10
  • Diethyl ether, Grignard reaction, Organic Lecture Series, Bond C- Li C- M g C- Al C- Zn C- Sn C- Cu C- Hg Difference, Organic Organic Lecture

{[ snackBarMessage ]}

Ask a homework question - tutors are online