Topic 14 AlkaliOrganometallics
Transcript of Topic 14 AlkaliOrganometallics
Topic 14: Alkali Organometallics
Read:F. A. Carey & R. J. Sundberg Advanced Organic Chemistry, Part A: Structure and Mechanisms. 5th Ed. Ch. 6M. Schlosser, Ed. Organometallics in Synthesis: A Manual Wiley, 1994. "Chapter 1. Organoalkali Reagents"
Professor David L. Van VrankenChemistry 201: Organic Reaction Mechanisms I
LiX
X OR2
E+
Misconception
■ Avoid ionizing R-M bonds; just use the bond as the base/nucleophile.
■ Electronegativity determines ionic character & basicity
R-MgBr R-Li R-Na R-K R-Cs< < < <
Li Na K Rb CsMg > > > >>
1.3 0.98 0.93 0.82 0.82 0.79
R-M Covalent character:
Electronegativity:
H >
2.2
(Ionic character) Basicity:
R MgBr R Li R Na R K R Cs
■ Consider these two resonance forms:
R3C M R3C M+
..
covalent ionic
-
H3C Li H3C Li+
..-
O
like this not this
They want 8 valence electrons! Here’s what H3CLi does in hexane.
■ COMPLETE FICTION: Li, Na, K, Mg, Ca, etc. want no electrons
CH3Li
H3C Li H3C Li
CLiH H
H+
- C Li
CLiH H
H+
-H
HH
+
-H3C Li Lewis structure
Formal charges: Li2-, C2+
3 bonds to each Li6 bonds to each C
CLi CH3
Li
LiC Li
C
HHH
HH H
HHH
+2
+2
+2
+2
-2
-2
-2
Aggregation of Alkali Organometallics
■ Metal alkoxides also aggregate
■ Alkyllithiums aggegrate to form tetramers, hexamers, etc. to help lithium satisfy the octet. Sterics often prevents Li from achieving an octet. Bulkier alkyl groups lead to less aggregation. Using dative bond representations reduces the complexity of these structures.
CLi CH3
Li
LiC Li
C
HHH
HH H
HHH
Lewis structure
CLi CH3
Li
LiC Li
C
HHH
HH H
HHH
+2
+2
+2
+2
-2
-2
-2
dative bonds
OKO
K
KOK
O
+2
+2
+2
+2
-2
-2
-2
t-Bu
t-But-Bu
t-Bu
t-BuOK
OLi=
■ You don’t have to draw these aggregrates; but never be afraid to form additional bonds to alkali metals.
crystal structures of (MeLi)n
Dos and Don’ts for Drawing Mechanisms with Organoalkali Species in Chem 201
■ Draw arrow-pushing mechanisms that avoid ionizing anions and cationic metals
H3C MgBr H3C+MgBr..
-
H3C MgBr MgBr
O
H3CO-
+
Don't do this:
Do this:
O
t-BuO K t-BuO+K..
-Don't do this:
RH
t-BuO KDon't do this:
RH
t-BuO HR:-
+K
t-BuO KDo this:
RH
.. t-BuOH
K+ R:- t-BuO
H
K+ -R
t-BuO HK R
I'll accept.. t-BuO K
RH
.. t-BuOH
K+ R:- t-BuO H
K Rt-BuO
HR:-
+K
Metal Hydrides
■ Example: metal hydride basicity
■ Basicity (vs nucleophilicity) increases from RMg to RK.
Grovenstein, E. JACS 1959, 4842
(Arrow pushers: pretend M—H is a monomer)
Na-H K-H
Dyck, W.; Jex, H. J. of Physics C 1981, 14, 4193
■ Na—H = cubic lattice
more negative charge= more basic
Na–H
O
R
H–OR Na–OR
OM
H2C Ph H H
H H
KH
Li-HMH
NaH+ +
krel1
1,0001,000,000
+ +
M H
Ph-MO
PhH
H H
OM
CH3 Ph
OM
CH2 PhPh
0977514604670
Ph M
π∗ σ∗M
Ph MgBrPh LiPh NaPh K
Synthesis of Organometallics
■ Rates depend on R-X: RI > RBr > RCl
■ Kronos behaviour (children swallowed by creator)
■ Always make R–Li from R––Cl but not R –– I. Here’s why…
Formation of R-Na requires special conditions:(finely dispersed Na, high speed stirrer, vortical fluid motion, special glass, -10 °C)
Why don’t we make n-BuNa?
σ*C——I
σ*C—Br
σ*C-Cl
Step 1 =e- into σ* orb
Why rel. order?
E
■ We don’t have arrow pushing representations for electron transfers, nor good Lewis representations for the radical anion intermediates.
NaCl + +
e-R Cl
•–
2Na NaCl
Na+
R•-NaCl
MNa+
σC-Cl
σ*C-Cl
EMOR Cl•– =
ClE2 +
Wurtz coupling
n-BuM
SN2
n-BuX n-BuLi
X
ClBrI
Et2Ot1/2
40 h30 min< 5 min
t1/2
>100 h40 h3 h
in C6H6...
+ E2 + SN2
Preparation of Alkyllithiums by Reductive Lithiation
■ Reductive lithiation of thiophenyl ethers. Li + naphthalene = LiNp, but it is a pain to remove one equivalent of naphthalene after the reaction is over. Dimethylaminonaphthylamine is readily removed with an acid wash.
Cohen, T. J. Am. Chem. Soc. 1984, 106, 1130.
O SPh
NMe2
.. .-
-78 °C O Li
Li+
"LDMAN"
SPh SPhR
SPh
rate of reductive lithiation:
many, manyres. structs.
S .. -. .
Li+
Li+e-
Li+e-
radical
■ LiNp efficiently adds an electron to the pi* antibonding orbital of PhS groups. Rates of reductive lithiation correlate with the ease of radical formation.
Preparation of Alkyllithiums by Exchange Reactions
Rates depend on R-X: RI > RBr > RCl
Sn: MacDonald, T. J. Am. Chem. Soc. 1988, 110, 842.I: Farnham, W. B. J. Am. Chem. Soc, 1986, 108, 2449.
■ Sn-Li exchange proceeds with retention at carbon Reich, H J. Am. Chem. Soc. 1992, 114, 6577-9.
Kanda, T J. Phys. Org. Chem. 1996, 9, 29.
Mechanism = stann"ate"
With R-I, instantaneous at -80 °C
Mechanisms: Newcomb, M. TL, 1989, 26, 1183R-I, low temp - iodate; R-Br, high temp = e- transfer
■ Metal/halogen exchange
■ Sn-Li exchange (same with lithium-iodide exchange)
+ X—Phn-Bu—Li + Li—Phn-Bu—X
Rates: I >> Me3Sn > Me3Sn
-70 °C
80 : 1
R
MeO
SnMe3n-BuLi
Et2OR
MeO
SnMe
MeMeBu
Li+
R
MeO
Li Bu—SnMe3–
stann-ate
Metal-Halogen Exchange Driven by Thermodynamics
■ Metal-halogen exchange is faster than SN2 (at low temp.)
Applequist, D.E.; O'Brien, D. F. “Equilibria in Halogen-Lithium Interconversions” J. Am. Chem. Soc., 1963, 85, 743-748.
R Li Ph I+ R I Ph Li+
Li
Li
Li
Li
0.004
Keq
1
10
7,500
Compound
Li 10,000,000
-70 °C
R Li R'I
R'IR- Li+
R Li R' I
way faster than SN2
R I Li R'
Li >10,000,000
n-BuLi ~
s-BuLi ~
Formation of Organometallics by Metalation
■ Recall:
■ Alkynes can be directly metalated ...also with BuLi
■ Direct metalation (deprotonation) of benzene is too slow to be useful
■ Recall: deprotonation of alkyne C-H is relatively fast
Shiner, V. J.; Humphrey, J. S., Jr. J. Am. Chem. Soc. 1967, 89, 622.See also… Sonogashira couplings
H3C CH2Li H2C CHLi HC CLi R2NLi> >> <
109 1017 1012Basicity:
pKa' 50 41 24 36
+ +Lislow!
Li H
Et-MgBr Et-HR C C H + R C C MgBr +fast
H
Cl
H
OEtNaOEt
EtOH
CC -
Cl
CC
EtO -
....
CC
Ph
Ph
(w/ t-BuOK)
Directed Ortho Metalation
■ Chelation of R-Li speeds up metalation and stabilizes Ar-Li
■ Relative directing power; (you keep the chelate in the aryllithium)
V. Snieckus“Directed ortho metalation. Tertiary amide and O-carbamate directors in synthetic strategies for polysubstituted aromatics”Chem. Rev. 1990, 90, 879.
OH OHMe?
O
NEt2
O
THF -78 °C,1 h
O
NEt2
O
HLiH
O
NEt2
OLi
+ C4H10
‡
OCONEt2Me
n-BuLi
CH3I
NaOH
+-
+-
O
NEt2
OLi
S O
Li
t-Bu O
Li
NO
> > Li
N
Li
LiO NMe
O OMeLi
Metalation of Strained Rings
■ Lithium amide bases convert epoxides to allylic alcohols. The base removes the proton syn to the epoxide.
Cope, A. C.; Lee, H.-H.; Petree, H. E. JACS 1958, 80, 2849.Hodgson, D.M.; Bray, C.D.; Humphreys, P.G. Synlett 2006,1.
■ Very aggressive bases deprotonate epoxides and generate lithium carbenoids.
■ Epoxides undergo two competing reactions with bases
Thummel, R.P.; Rickborn, B. J. Am. Chem. Soc., 1970, 92, 2064
LiNR2OHLiNR2..
OOLi
OR-LiH
OLi
O -carbenoid
Li+
O
H
H
Li NEt2
OLiOLiH
70%16%
H
H
filled σC-Li
empty p
Li
it's anelectrophile
it's anucleophile
Aggregation of R-Li
■ Ether solvents coordinate to alkali metals. n-BuLi forms a tetramer in THF + some dimer
■ Li enolates = 99% dimer in THF, but reacts via monomer.
■ C=O Addition: Me—Li / n-Bu—Li add as dimer! Arrow Pushers: Pretend RM is monomer
StreitwieserJOC 1995, 4688
Kaufmann, E.; Schleyer, P. v. R.; Houk, K. N.; Wu, Y. D. JACS 1985, 107, 5560.Nakamura, M.; Nakamura, E.; Koga, N; Morokuma, K. JACS 1993, 115, 110167.
But never forget aggregation
IMPORTANT RULE:
CLi
CLi
O
OTHF
CLi
LiC
LiC
CLi O
C = n-Bu
.
Li wants octet MgPh
Br
OEt2OEt2
MgPh
Br
OEt2
OEt2+–....
wrong!
dative bonds to metalsdon't draw chargesdon't use for arrow pushing
Li = Li•THF
i-Pr2N–LiO
ArH
O
Ar
PhTHF, -78 °C 25 °C
OLi
Ar
" "
LiO
LiO
Ar
Ar
~1%
99%
25 °C
Bn-Br
SLOW
LiOC R
LiR+ -
OC
+
R LiR
Li-
O M
R+M = Li, MgBr O
R
M
Organocuprates
■ Cuprates, R2CuLi are ARE nucleophilic.They do all the things you wished RLi could do: substn with R-X, opening epoxides, 1,4-addn., etc.Require exquisite technique and involve complex mechanisms.
■ Cuprates favor SN2'
■ Organocopper, R-Cu is not very nucleophilic or basic
■ Cross-coupling
The true structures are complex
2 MeLi + "Me2CuLi" + LiICu-I
HB
HH
H-
HAl
HH
H-
HSiEt
EtEt-
ORCuMe
Me-
cuprate borate aluminate silicate
1. nucleophilic C2. low charge on C other "-ate" complexes
not soft
actually, aggregated
" "
i.e., SOFT
Li+LiI
(Me2CuLi = Gilman reagent)
Br Ph
Et2O0 °C, 5 h
Ph2CuLi
X
Me
Bu
X = Cl, OAc
Bu2CuLi
CuCu
CuCu
SMe2Me2S =
PhCu • 1/2Me2S
LiCu
LiCu
OEt2Et2O =
Ph2CuLi•Et2O
X-ray struct.
1,4 - Addition by Organocuprates
■ TMS-Cl accelerates 1,4 addn.
Nakamura, E.-I.; Kuwajima, I. JACS 1984, 3368
■ Cuprates add 1,4- to α,β-unsaturated aldehydes. All other organometallics would add to C=O.
■ 1,4-Addition
Canisius, J.; Gerold, A.; Krause, N. Angew. Chem. Int. Ed. 1999, 38, 1644.
O
MeLiO
O
Me
CuMe-
MeLi
Me2CuLi
Li+Cu–R
OLi
CuR
R
OLi
R
O
CuR
Li
R
OBu2CuLi
•LiI
O
Me
SiMe3
Me -70 °C< 1 sec no rxn at -70 °C
w/o TMSClBu
99%added last
+ Me3SiCl silyl enol ether
H
O
H
O
Me
SiMe3
Me
+ Me3SiCl
Bu
R2CuLi