ESSP 311 Organic Chemistry I
Ronald W. Rinehart, Ph.D.

Chapter 14 Organometallic Compounds

Reactions of aldehydes and ketones with Grignard reagents
by Paul R. Young, University of Illinois at Chicago
and  Preparation of alcohols by reaction of Grignard reagents with carbonyl compounds
Organometallic compounds by William Reusch at the University of Michigan
The Grignard  Reaction by Otto Meth-Cohn at the University of Sunderland
a few pics might not show, but the bulk is there
Organometallic Chemistry Carey Ch 14. from McGraw-Hill
Nucleophilic addition to C=O
from McGraw-Hill
Structure and Synthesis of Alcohols: Grignard Reagent QuickTime movies  from Prentice-Hall, Inc.
Grignard reagents by Steve Wathen at Siena Heights University
PowerPoint slides for Carey Chapter 14 from Columbia University
14.1 to 14.5: Organometallic Compounds
14.6 to 14.10: Synthesis of Alcohols Using Grignard Reagents
14.11 to 14.15:  Alkane Synthesis Using Organocopper Reagents

Chapter 14:  Organometallic Compounds 

I.  Carbon-Metal Compounds.
            A.  Carbanions
                        1.  Carbanions are organic ions in which a carbon atom carries a negative charge.
                        2.  Carbon-Metal bonds are carbanions (or at least have enough ionic character to be considered as such).
                                    a)  R-Na, R-K:  ionic C-Metal bonds.
D EN > 1.6
                                    b)  R-Li, R-Mg:  substantial ionic character. 
D EN 1.3 1.5
                        3.  The important fact is that the C-M bond results in the carbon becoming negative in character. 

This is the reverse of the C-X dipole [where C has positive character ]
                                    ►  This is important: C:
will be attracted to other C's with + character, most notably C=O         
                                                i)  Formation of new C-C bonds is extremely important in organic synthesis.
                                                ii)  organometallic compounds allow us to create C-C bonds in organic synthesis.
            B.  Nomenclature.
                        1.  Organometallic compounds are named as substituted derivatives of metals:



methylmagnesium bromide

            C.  Preparation of Organolithium Compounds
                        1.  Overall reaction:       RX  +  2Li 
  RLi  +  LiX
                        2.  Water cannot be present since an acid/base reaction occurs.
                                    a)  RLi  +  H2
  RH  +  LiOH
                                    b)  Solvents used include pentane, hexane, and diethyl ether.
                                    c)  Other solvents with O-H, N-H, and S-H cannot be used: also acidic enough to react with RLi.
                        3.  Reactivity of X:     I > Br > Cl > F   ;  RBr  most often used [compromise between $ and reactivity].
                        4.  R groups can vary greatly:  alkyl, aryl [no OH, NH, SH in substituents], vinylic, allylic, benzylic

                        RX = 1o RX,  2o RX, 3o RX, FX <aka Ph-X, ArX>, CH2=CH-X,  CH2=CHCH2X ,  FCH2X <PhCH2X>

                        5.  Mechanism: proceeds via radical anion intermediate


                        6.  Complete the following equations:




            D.  Preparation of Grignard Reagents.
                        1.  Overall Reaction:     RX  +  Mg   ( in ether) 

                        2.  Mechanism:                                                                .

                             Step 1.           RX  +  Mg   [RX]  +  Mg+ 
                             Step 2.           [RX]     R  +   X 
                             Step 3.      R  +  Mg+  +  X      RMgX

                                    a)  Note the similarity of the above mechanism to that of the preparation of RLi compounds:
                                                except in this case one Mg atom donates both e
[rather than two Li atoms each donating one e]
                        3.  Ethers are used as solvents, since solvents with O-H, N-H, or S-H react with the Grignard Reagent. 
                                    a)  Both RMgX and RLi are strong bases:

                                          RLi  +  R'OH    RH  +  R'OLi+  

                                                2RMgX +  2R'OH    RH  +  Mg(OR')2  +  MgX2 

                        4.  R groups can vary greatly:  alkyl, aryl [no OH, NH, SH in substituents], vinylic, allylic, benzylic

                        RX = 1o RX,  2o RX, 3o RX, FX <aka Ph-X, ArX>, CH2=CH-X,  CH2=CHCH2X ,  FCH2X <PhCH2X>
II.  Reactions of Organometallic Compounds.
            A.  Reactions of Grignard Reagents.


                        1.  With Formaldehyde:  product is 1o alcohol one C larger



                                    a)  Complete the equation (including workup):   CH3CH2MgBr + H2C=O 


                        2.  With Aldehydes R'CHO:  product is a 2o alcohol with R and R' on the  a-C.



                                    a)  Complete the equation (including workup):



                        3.  With Ketones R'COR":  product is a 3o alcohol


                                     a)  Complete the equation (including workup):



                        4.  With CO2 [dry ice]:  product is a carboxylic acid

                                     a)  Complete the equation (including workup):


                         5.  With Esters:  product is a 3o alcohol with 2 identical a-substituents.

                                     a)  Complete the equation (including workup):


                         6. With ethylene oxide [oxirane]:  product is a 1o alcohol 2C larger

                                     a)  Complete the equation (including workup):


                         7.  With Water, Alcohols, Amines, Thiols, Carboxylic Acids,: product is an alkane


                                    RMgX  +  H2     RH    +    MgOHX

                                     a)  Handy reaction if one needs to convert an alkyl halide into an alkane; otherwise it's a disaster!.
                                    b)  Complete the equation:



                               8.  Retrosynthetic Analysis.
                                    a)  Target Molecules from Precursors:  E. J. Corey, Harvard University.
                                    b)  Synthesize the following compounds from simpler starting materials (using Grignard Reagents):

             B.  Reactions of Organolithium Compounds
                        1.  Organolithium compounds react as Grignard Reagents react. They are also used as hyperstrong bases.

                         2.  Complete this equation:


             C.  Synthesis of Acetylenic Alcohols: two synthetic routes.
                        1.  With Acetylide Anions and Aldehydes/Ketones
                                    a)  Acetylenic alcohols are formed by reaction of acetylide anions with aldehydes and ketones.
                                    b)  Analogous to reactions of Grignard Reagents.           
                                    c)  Reaction:

                         2.  Alkynyl Grignard Reagents.
                                    a)  Preparation of the alkynyl Grignard reagent is an acid-base reaction. 

                                    R-C≡C-H  +  R'MgX    R-C≡C-MgX  +  R'H  

                                    b)  The alkynyl Grignard reagent then reacts as any other Grignard reagent.

                                     c)  Example.  Complete the following:


             D.  Alkane Synthesis with Organocopper Reagents.
                        1.  Lithium Dialkylcuprates are used to produce alkanes.
                        2.  Formation of the lithium dialkylcuprate:
                                    a)  Treat copper(I) halide with two equivalents of an alkyl lithium in THF or ether:

                                     b)  Mechanism: 

                                                Step 1:  R-Li  +  Cu-I   R-Cu  +  LiI

                                                Step 2:  R-Li  +  R-Cu   [R-Cu-R] Li+ 

                        3.  Lithium Dialkylcuprates react with alkyl halides to produce alkanes. 

                                    R2CuLi  +  R'X    R-R'  +  RCu  +  LiX 

                                    a)   The reaction works best with primary R'X and primary and phenyl dialkyl cuprates.
                                                i)  What problem might occur with 2o and 3o alkyl halides?
                                                            Answer:            ELIMINATION.
                                                ii)  R'X can also be vinyl halides and aryl halides (not consistent with nucleophilic attack.)
                        4.  Complete the following equations:                                                     

                                    a) (CH3CH2CH2)2CuLi  +  CH3CH2CH=CHBr                                   




                        5.  The alkyl groups in the dialkylcuprate ion can be phenyl groups or 1o alkyl groups but not 2o or 3o.
                                    a)  With 2o and 3o alkyl groups, steric hindrance seems to make R2CuLi less reactive toward R'X.

                                    b)  With 2o and 3o alkyls, R2CuLi also tends to be unstable -- decomposes before reacting with R'X            

                        6.  Examples:


                         7.  The reaction follows the trends seen for SN2 reactions.
                                    a)  Order of Reactivity of RX:   CH3X  >  1o  >  2o  >  3o 
                                    b)  Order of Reactivity of Halide:   I  >  Br  >  Cl  >  F

                        8.  Mechanism of this reaction is not well understood; seems to involve nucleophilic attack on R'X by the
                                    Cu atom of the dialkylcuprate; unstable intermediate then breaks apart into the observed products:
+  R'-X   [R2CuR'X]    R-R' + RCu + X 


                        9.  Synthesize the following compounds using lithium dialkylcuprates:

              E.  Organozinc Intermediates in Synthesis
                        1.  The reduction of alkyl halides by zinc can be used to form alkanes.
                                    a)  General overall reaction and mechanism: 

                                                 RX  +  Zn    RZnX ;  RZnX  + HX    RH  +  ZnX2 

                                    b)  Notice that an organozinc reagent (R-ZnX) is produced in this reaction.
                                                i)  R-ZnX is not as reactive towards carbonyl compounds as Grignard reagents (R-MgX).
                                    c)  Example.  Complete the reaction:



                               2.  Dehalogenation of vicinal dihalides to form alkenes:  Beta Elimination.
                                    a)  Overall reaction:


                                    b)  Mechanism:

                                     c)  This is beta-elimination since the leaving group is b to the a carbon bearing the ZnX group.
                                    d)  Examples:
                                                   CH3CHBrCHBrCH2CH3  + Zn/EtOH 


                         3.  Dehalogenation of 1,3-dihalides to form cyclopropanes:  Gamma Elimination.
                                    a)  This reaction only works to form 3-membered rings.
                                                i)  When the halogen atoms are more than 3 carbons apart yields of larger rings are poor.
                                    b)  The reaction is run in ethanol.
                                    c)  This is gamma-elimination since the leaving group is
g to the a carbon bearing the ZnX group.
                                    d)  Mechanism:

                                     e)  Complete the following reaction:       


                         4.  Simmons-Smith Reagent:  Preparation of Cyclopropane.
                                    a)  Cyclopropanes can also be synthesized using a zinc-copper couple (Zn surface-activated with Cu)
                                    b)  Zn(Cu) reacts with CH2I2 in ether to yield iodomethylzinc iodide, ICH2ZnI.
                                    c)  ICH2ZnI reacts with an alkene in ether to form a cyclopropane:

                                    d)  Mechanism:

                                     e)  The reaction is stereospecific due to syn-addition:
                                                groups which are cis in the alkene remain cis in the ring; 
                                                groups which are trans in the alkene remain trans in the ring.
                                    f)  Complete the following reactions:



                                    g)  ICH2I is a "carbenoid" since it resembles carbene (CH2:) chemically.
                                    h)  Yields often low; important since it offers a route to compounds otherwise difficult to make.
            F.  Carbenes and Carbenoids.
                        1.  Carbenes: neutral molecules containing a divalent carbon atom with no unpaired electrons.
                        2.  Carbenes are electrophilic.
                        3.  Extremely unstable but can be trapped in a frozen argon matrix.
                        4.  Dihalocarbenes produced when CHX3 treated with a strong base, e.g. potassium t-butoxide.
                                    i)  The base deprotonates HCX3 forming the trihalomethyl anion.
                                    ii)  This anion then splits apart [
a-elimination] into the dihalocarbene and halide ion.

                                      iii)  This is an alpha-elimination since both H+ and X are lost from the same atom.
                        5.  With alkenes, :CX2 undergoes cycloaddition to the C=C to produce 1,1-dihalocyclopropanes.
                                    a)  Addition is stereospecific:  syn addition is observed.
                        6.  Complete the following reactions.



               G.  Organic Derivatives of Mercury.  Oxymercuration-Demercuration of Alkenes.
                        1.  Recall the use of mercuric acetate in the production of alcohols via the Markovnikov hydration
                                    of alkenes (Chapter 6 notes.)
                        2.  Disposal of mercury wastes creates serious health problems.
                                    a)  Hg2+ converted to methylmercury, CH3Hg+, and dimethymercury, (CH3)2Hg, in the environment
                                                due to bacterial action.
                                    b)  These compounds collect in tissues of fish.  Ingested by humans, these compounds can cause
                                                serious health problems.
                                    c)  The California Department of Fish and Game, in their fishing regulations booklet, warns of
                                                contaminated fish in various waters of the state and how much fish can be safely consumed.

III.  Transition Metal Organometallic Compounds.
            A.  Many compounds consist of transition metals bonded to organic groups.

                        1.  Many of the organic groups are bonded to the transition metal through the pi system.
                                    a)  Ferrocene.  Two cyclopentadienide ions pi bonded to the ferrous ion in "sandwich" fashion.     

                                                    picture of cobaltocene is shown below


                                    b)  (Benzene)tricarbonylchromium.    Cr(CO)3C6H6 


                                                i)  Notice that it is benzene, not a phenyl group, bonded to Cr via benzene's pi system.

                                    c)  (Cyclobutadiene)tricarbonyliron.  Fe(CO)3C4H4 

                        2.  Several important industrial processes are catalyzed by transition metals and/or their complexes.
                        3.  The Monsanto Process:  an industrial             process which efficiently synthesizes acetic acid from carbon monoxide and methanol using a rhodium catalyst and an iodide promoter.
                                    a)  The reaction is believed to occur as follows:


                                    b)  The iodide is necesary  since methanol itself will not add to the rhodium catalyst.
                                    c)  The system is homogeneous, runs at one atmosphere of CO pressure and 175oC.
                                    d)  The reaction achieves 99% selectivity.
                                    e)  Acetic acid is easily separated from the reaction mixture since it has a relatively low boiling point.
                                                i)  This is an important factor since this results in a cost/energy efficient separation.
                                    f)  The Monsanto Process offers a great improvement over some earlier processes.
                                                i)  One system required H3PO4, PCO ~ 1000 psi, and temperatures of around 300oC.
                                                ii)  Both corrosion and poor selectivity were associated problems under these reaction conditions.
                                                iii)  A high energy cost was also necessary.

Many thanks to Rod Oka of MPC for generously sharing his "Lecture Companion" outline,
reproduced here in extensively modified form by permission, with web references and other goodies added by me.
Structures drawn with  CS ChemOffice ChemDraw and MDL IsisDraw.