very strong bases very strong nucleophiles

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1 hapter 14: rganometallic ompounds - eagents with carbon-metal bonds 14.1: rganometallic Nomenclature (please read) 3 -Li Butyllithium Mg vinylmagnesium bromide ( 3 ) u - Li Dimethylcopper lithium 14.: arbon-metal Bonds in rganometallic ompounds X MgX!! - X! -! MgX _ Alkyl halides: electrophiles arbanions: nucleophile react with electrophile 30 Alkyl halides will react with some metals (M 0 ) in or TF to form organometallic reagents 14.3: Preparation of rganolithium ompounds rganolithium ompounds -X Li (0) -Li LiX diethyl! -! Li _ very strong bases very strong nucleophiles organolithium reagents are most commonly used as very strong bases and in reactions with carbonyl compounds M (0) -X -M - M

2 14.4: Preparation of rganomagnesium ompounds: Grignard eagents Mg (0) -X -MgX (Grignard reagent) TF -X can be an alkyl, vinyl, or aryl halide (chloride, bromide, or iodide) Solvent: diethyl (Et ) or tetrahydrofuran (TF) 3 3 diethyl (Et ) tetrahydrofuran (TF) Alcoholic solvents and water are incompatible with Grignard reagents and organolithium reagents. eactivity of the alkyl halide: -I > - > -l >> -F alkyl halides > vinyl or aryl halides 304 The solvent or alkyl halides can not contain functional groups that are electrophilic or acidic. These are incompatible with the formation of the organomagnesium or organolithium reagent. Grignard reagents will deprotonate alcohols Mg 0 Mg Mg 3 ther incompatible groups: -, -, -S, N, N (amides) eactive functional groups: aldehydes, ketones, esters, amides, halides, -N, -S, nitriles 305

3 14.5: rganolithium and rganomagnesium ompounds as ønsted Bases - Grignard reagents (M = MgX) and organolithium reagents (M = Li) are very strong bases. -M - M- pka pka ( 3 ) 3-71 N Water ydrocarbons are very weak acids; their conjugate bases are very strong bases. 306 Lithium and magnesium acetylides TF Li Li terminal acetylene (pk a ~ 6) butyllithium lithium acetylide pk a > 60 TF 3 - -Mg Mg ethylmagnesium bromide magnesium acetylide 14.6: Synthesis of Alcohols Using Grignard eagents Grignard reagents react with aldehydes, ketones, and esters to afford alcohols! -! : MgX MgX

4 Grignard reagents react with... formaldehyde ( =) to give primary alcohols Mg 0, Mg 1) = ) 3 aldehydes to give secondary alcohols Mg Mg 0, 1) ketones to give tertiary alcohols esters to give tertiary alcohols ) 3 Mg 0, 1) Mg ) Mg 0, 3 -Mg 1) ) : Preparation of Tertiary Alcohols From Esters and Grignard eagents - mechanism: 3 3 -Mg 1) TF ) then eaction of Grignard reagents with (Lab, hapter 19.11) Mg(0) Mg == _

5 14.7: Synthesis of Alcohols Using rganolithium eagents rganolithium reagents react with aldehydes, ketones, and esters in the same way that Grignard reagents do. -Li Li : Synthesis of Acetylenic Alcohols NaN Na N 3 pka~ 36 pk a ~ 6 3 ( ) -Li Li 3 ( ) 3 pka > Mg Mg 3 3 pka > ecall from hapter _ Na - - acetylide anion 1 alkyl halide TF S N 1 Na new - bond formed Acetylide anions react with ketones and aldehydes to form a - bond; the product is an acetylenic (propargyl) alcohols 1 _ TF Mg 3 then acetylenic alcohol 311 5

6 14.9: etrosynthetic Analysis - the process of planning a synthesis by reasoning backward from the the target molecule to a starting compound using known and reliable reactions. it is a problem solving technique for transforming the structure of a synthetic target molecule (TM) to a sequence of progressively simpler structures along the pathway which ultimately leads to simple or commercially available starting materials for a chemical synthesis. The transformation of a molecule to a synthetic precursor is accomplished by: Disconnection: the reverse operation to a synthetic reaction; the hypothetical cleavage of a bond back to precursors of the target molecule. Functional Group Interconversion (FGI): the process of converting one functional group into another by substitution, addition, elimination, reduction, or oxidation 31 Each precursor is then the target molecule for further retrosynthetic analysis. The process is repeated until suitable starting materials are derived. Target molecule Precursors 1 Precursors Starting materials Prepare (Z)--hexene from acetylene Z--hexene -Phenyl--propanol

7 14.11: Alkane Synthesis Using rganocopper eagents 3 Li ui 3 _ u Li 3 LiI Gilman's reagent (dimethylcuprate, dimethylcopper lithium) uli = - strong nucleophiles Nucleophilic substitution reactions with alkyl halides and sulfonates (alkylation) 3 ( ) 8 -I ( 3 ) uli 3 ( ) u LiI S N reaction of cuprates is best with primary and secondary alkyl halides; tertiary alkyl halides undergo E elimination. 314 Vinyl and aryl (but not acetylenic) cuprates 4 Li (0), Li ui uli 4 Li (0), Li ui uli uli Ts TF uli I TF 315 7

8 eaction of cuprates with aryl and vinyl halides I ( 3 ) uli double bond geometry 3 is preserved ( 3 ) uli : arbenes and arbenoids arbene: highly reactive intermediate, 6-electron species. The carbon is sp hybridized; it possesses a vacant hybridized p-orbital and an sp orbital with a non-bonding pair of electrons 316 Generation and eaction of Dihalocarbenes: l 3 K l : Kl dichlorocarbene arbenes react with alkenes to give cyclopropanes. cis-alkene l 3, K l l cis-cyclopropane trans-alkene 3, K The cyclopropanation reaction takes place in a single step. There is N intermediate. As such, the geometry of the alkene is preserved in the product. Groups that are trans on the alkene will end up trans on the cyclopropane product. Groups that are cis on the alkene will end up cis on the cyclopropane product. trans-cyclopropane 317 8

9 14.1: An rganozinc eagent for yclopropane Synthesis Simmons-Smith eaction I Zn(u) I, Zn(u) I- -Zn-I = : I, Zn(u) cis-alkene cis-cyclopropane carbene The geometry of the alkene is preserved in the cyclopropanation reaction. I, Zn(u) trans-alkene trans-cyclopropane : Transition-Metal rganometallic ompounds (please read) 14.15: omogeneous atalytic ydrogenation (please read), Pd/ - The catalyst is insoluble in the reaction media: heterogeneous catalysis, interfacial reaction, (Ph 3 P) 3 hl - The catalyst is soluble in the reaction media: homogeneous catalysis : lefin Metathesis (please read) 14.17: Ziegler-Natta atalysis of Alkene Polymerization (please read) 319 9

pk a Values for Selected Compounds

pk a Values for Selected Compounds Appendix A pk a Values for Selected ompounds ompound pk a ompound pk a I 10 Br 9 2 S 4 9 + 3 3 7.3 3 S 3 7 Br 4.0 4.2 3 4.3 2 N l 7 [( 3 ) 2 ] + 3.8 [ 3 2 ] + 2.5 3 + 1.7 3 S 3 1.2 + 3 N2 0.0 F 3 0.2 l