GEORGIA INSTITUTE OF TECHNOLOGY
OFFICE OF CONTRACT ADMINISTRATION
SPONSORED PROJECT INITIATION
Date:
June 2, 1978
Project Title:
Onganometatlic ChemistAy o6 the Main. GAoup Etements: Mechanisms,
StoteOcheinisVuj and TAansition Metal Cataboi6
Project No:
G-33-636
Project Director:
Vt. E.C. A4hby
Sponsor:
Nationat Science Foundation, Was hington, D. C . 20550
Xn--,
Agreement Period:
From
6/1/78
y peilkod
u.
-
49'67
1-PM-74L—.
No. 0E78-00757
Type Agreement: Gnarly
Amount:
1
Until
* inete,6 6n
3D
$42,000 NSF Funds (G-33-636)
12,415 OTT ContAibution (G 33 325)
$54,415 Total
-
Reports Required:
-
AnnuaeSumnruujRepaAts; Finat Technicat Repo/a
Sponsor Contact Person (s):
Technical Matters
Contractual Matters
Ohm OCA)
Kenneth G. flaricach
Ma. Many Fnancea O'Connett
Grants Specialist Area 4
Chemicat Dynaricz PAppyLam
Nationae Science Foundation
1800 G St/met, N.W.
Wadhington, D.C. 20550
Phone (202) 632-4272
Defense Priority Rating:
n/a
Assigned to:
Chem:i4txy
-
National. Science Foundation
1800 G Stuet, N.W.
Washington, D.C. 20550
Phone (202) 632-2858
(School/Laboratory)
COPIES TO:
Project Director
Library, Technical Reports Section
Division Chief (EES)
EES Information Office
School/Laboratory Director
EES Reports & Procedures
Deen/Director—EES
Project File (OCA)
Accounting Off ice
Project Code (GTRI)
Procurement Office
Other
Security Coordinator (OCA)
von: Coordinator (OCA)
CA-3 (3/76)
OFFICE OF CONTRACT ADMINISTRATION
GEORGIA INSTITUTE OF TECHNOLOGY
SPONSORED PROJECT TERMINATION SHEET
Date 7/14/82
Project Title:organannetallic Chemistry of the Main Group Elements:
Mechanisms, Stereochemistry and Transition Metal Catalysis
Project No: G-33-636
Project Director: Dr. E.C. Ashby
Sponsor: National Science Foundation
Effective Termination Date: 11/30/81
Clearance of Accounting Charges:
2/28/82
Grant/CoclseuAinRmag:
n
Final Invoice and Closing Documents
❑
Final Fiscal Report
Final Report of Inventions
Govt. Property Inventory & Related Certificate
❑
Classified Material Certificate
Other
Assigned to:
COPIES TO:
Research Security Services
Administrative Coordinator
Research Property Management
'ReptirtriZi5R11Thnor (OCA)
Accounting
Legal Services (OCA)
Procurement/EES Supply Services
Library
EES Public Relations (2)
Computer Input
Project File
Other
BRIEF ANNUAL TECHNICAL REPORT
(1)
This past year has been dedicated to working on several problems.
The first problem involves the use of probes in the detection of radical
intermediates in the reaction of Grignard reagents with ketones. The
reaction below e.g, shows that even primary Grignard reagents react
with aromatic ketones by electron transfer.
H 0
--2-4 Ph 2 COH + Ph 2 SOH
N),/N MgC1 + Ph 2 C=0
(88%)
(12%)
This result was obtained sometime ago, but had to be verified by
a new graduate student. More recently we have used this probe and other
probes to establish the electron transfer nature of LiA1H
4
in its reaction
with alkyl halides and ketones.
LiA1H
"\,
T HF
--->
4
(10%)
+ LiA1H
THE
4
(90%)
These latter results are remarkable and represent a most important finding.
We are presently exploiting these results as rapidly as possible.
The second problem is concerned with the determination of the composition of the Normant Reagent.
RMgX + CuX
RCu • MgX 2
RCu • MgX2
+
RA C
/
R
= C/H
\
Cu • MgX
2
The Normant Reagent has been represented by the empirical formula RCu • MgX 2 .
By variable temperature nmr studies, we have determined that RCu • MgX 2 is
not formed, but rather a series of copper magnesium alkyls which do not
contain halogen. The active species in the Normant Reagent responsible for
addition to alkynes is Cu 2MgR4 which adds to alkynes activated by MgX 2 via
a 7-complex.
The third project is concerned with reactions of Grignard reagents
with CO to form acyl Grignards (R? - MgX). This .study is complete and will
be reported in detail shortly. The reaction of acid haldies with magnesium
is also being studied as a route to acyl Grignard reagents. Reasonable
success so far has been achieved.
R -
F-
+
-100°
Mg
(activated) THE
0
R8 - MgX
substrate
0
R -
8
And last a study has been carried out concerning the reaction of RMgH
compounds with ketones. In most cases exclusive reduction takes place
with a high degree of stereoselectivity. A study is also nearly complete
-substrate
concerning the hydrometallation of olefins by RMgH, R 2Mg and RMgX
compounds.
V
R - Mg - H + 2RC = CH 2
_SE2 TiC1 2_,
(RCH CH ) Mg
2 2 2
APPENDIX VI
,..
NATIONAL SCIENCE FOUNDATION
WaAhington, D.C. 20550
- - "ir-'., • Ls t--
FINAL .PROJECT REPORT
FoRNI ost k
PLEASE READ INSTRUCTIONS Off' REVERSE 8F.FORF COMPLETING
PART I—PROJECT IDENTIFICATION INFORMATION
2. NSF' Program
1. Institution and Address
3. NSF Award Number
Chemical Dynamics
Georgia Institute of Technology
Atlanta, Georgia 30332
CUE 78-00757
5. Cumulative Award Amount
4. Award Penod
6/1/78
From
To
5/31/81
8126,000
.
6. Project Title
Organometallic Chemistry of the Main Group Elements.
chemistry and Transition Metal Catalysis
Mechanisms, Stereo-
PART II—SUMMARY OF COMPLETED PROJECT (FOR PUBLIC USE)
Our research sponsored by NSF over the past three years has been concerned with
three major areas: (1) the mechanism of Grignard compound addition to ketones; (2) the
development of new reagents to be used for various synthetic transformations and (3) the
evaluation of single electron transfer as an important mechanistic pathway in organic
reactions. Our efforts over the past three years have resulted in 35 publications.
IrVe have essentially completed our work concerning the mechanism of Grignard compound addition to ketones although it seems clear that with the specific methodology we
have developed, we should later on extend these studies to include aldehydes, esters
Rs5A1 compounds. We have also e sentially comandnitrilesaswellasRU,R 2 Znandpleted our studies involving reactions with new reagents. The new reagents: LiA1H 4 transition metal halide, higher lithium alkylcuprates, RMgH compounds, ROMgH compounds,
MaH 2 -CuI, mgH -Cp TiC1
2 2
2' RMgOR and RMgNR 2 compounds have been tested in various reactions and found to be very valuable reagents for certain transformations. Our evaluation of reactions of MI, MR, NOR, NENIR 2 compounds as electron transfer reagents toward
a variety of organic substrates (e.g., alkyl halides, ketones, etc) has provided results beyond our expectations. This work will be continued in the immediate future.
s
• .
•
PART III—TECHNICAL INFORMATION (FOR PROGRAM MANAGEMENT USES)
I.
NONE
ITEM (Check appropriate blocks)
ATTACHED
a. Abstracts of Theses
X
b. Publication Citations
c. Data on Scientific Collaborators
X
d. Information on Inventions
e. Technical Description of Project and Results
L Other (specify)
\\'•4
Check (V)
Approx. Date
'.\
3. Prirtrin,11,,o:riritnriProiect
Director Signature
4. Date
5/3/S2
E.C. Ashby
,. ,
orm 9
TO BE FURNISHED
SEPARATELY TO PROGRAM
,...
•'
2. Principal Investigator/Project Director Name (Typed)
PREVIOUSLY
FORNiSHED
•.
. _,
of .
(5-78) Superseacs All FreviOUS Editions
24
PUBLICATIONS (1978 through mid 1981)
The following publications are as a result of work supported by NSF.
1.
E.C. Ashby and T.L. Wiesmann, "Organometallic Reaction Mechanisms. XV.
Factors Influencing the Nature of Grignard Reactions with Ketones," J.
Amer. Chem. Soc., 100, 189, (1978).
2.
E.C. Ashby and T.L. Wiesmann, "Organometallic Reaction Mechanisms. XV:r : .
The Use of 2,2,6,6-Tetramethy1-4-Hepten-3-One as a Probe for the Detection of Single Electron Transfer in Grignard Reactions with Ketones,"
J. Amer. Chem. Soc., 100, 31, 01, (1978).
3.
E.C. Ashby and J.J. Lin, "Transition Metal Catalyzed Reactions of Lithium Aluminum Hydride with Alkyl- and Aryl Halides," J. Org. Chem. 43,
1263, (1978).
,
4.
E.C. Ashby, J.J. Lin and A.B. Goel, "Reactions of Magnesium Hydrides. II.
Stereoselective Reduction of Cyclic and Bicyclic Ketones by Hydridomagnesuim-Alkoxides," . J. Org. Chem., 43, 1560, (1978).
5.
E.C. Ashby, J.J. Lin and A.B. Goel, "Reactions of Magnesium Hydrides. 1
Reduction of Organic Functional Compounds by Magnesium Hydride and
2,6-Diisopropylphenoxymagnesium Hydride," J. Org. Chem., 43, 1557, (1978).
6.
E.C. Ashby, J.J. LIn and A.B. Goel, "Reactions of Magnesium Hydrides. III.
Stereoselective Reduction of Cyclic and Bicyclic Ketones by Dialkylaminomagnesium Hydrides," J. Org. Chem., 43, 1564, (1978).
7.
E.C. Ashby and J.J. Lin, "Reactions of Lithium Aluminum Hydride Transition
Metal Halides with Alkenes and Alkenes," J. Org. Chem., 43, 2567, (1978).
8.
E.C. Ashby and A.B. Goel, "Preparation and Characterization of Dialkyl(aryl)aminomagnesium Hydrides," Inorg. Chem., 17, 1862, (1973).
9.
E.C. Ashby and A.B. Goel, "Preparation and Characterization of LiMgH,,
LiMg 2H5 , LiMgRH 2 , and LiMg 2H3R2 Compounds," Inorg. Chem., 17, 322, (1978).
10.
E.C. Ashby, J.J. Lin and A.B. Goel, "A Convenient Method for the Stereoselective Reduction of Alkynes to Alkenes by the New Reagents MgH 2 -CuI
and MgH 2 -Cu0But,"7. Org. Chem.; 43, 757, (1978).
11.
E.C. Ashby and T. Smith, "The Hydrometallation of Alkenes and Alkynes with
Magnesium Hydride," Chem. Comm., 30, (1978).
12.
E.C. Ashby and G.F.Willard, "Stereoselective Alkylation of Cyclic Ketones
by Dialkyiamino- and Alkoxy (methyl) Magnesium Compounds," J. Org. Chem.,
43, (1978).
13.
E.C. Ashby and G.F. Willard, "A New, Convenient and Stereospecific Method
for the Conversion of Secondary Amines to Primary Amines and Olefins.
Thermal Decomposition of Magnesium, Zinc and Aluminum Amides," J. Org ..
Chem.,.43, 4750, (1978).
PUBLICATIONS (Con't)
14.
E.C. Ashby, A.B. Goel and S. Goel, "Preparation and Characterization of
Magnesium Tetrahydridozincate, MgZnH 4 ," Incrg. Chem., 18, 1433, (1979).
15.
E.C. Ashby, G.F. Willard and A.B. Goel,
Method for the Dehydration of Alcohols.
Magnesium, Zinc and Aluminum Alkoxides.
Chem., 44, 1221, (1979).
16.
E.C. Ashby and A.B. Goel, "Preparation and Characterizaiton of Alkoxy
(Aroxy) Magnesium Hydrides," Inorg. Chem., 18, 1306, (1979).
17.
E.C. Ashby and S.A. Noding, "Hydrometallation III. Hydroalumination of
Alkenes and Dienes Catalyzed by Transition Metal Halides," J. Org. Chem.,
44, 4364, (1979).
13.
E.C. Ashby and S.A. Noding, "Concerning the Effects of Added Salts on
the Stereoselectivity and Rate of Organometallic Compound Addition to Ketones," J. Org. Chem., 44, 4371, (1979).
19.
E.C. Ashby and S.A. Noding, "Alkvlation of Enones and Ketones Using Substituted Alkyl- and Arylaluminum Compounds," J. Org. Chem.,'44, 4792, (1979).
20.
E.C. Ashby, "Stereochemistry and Regioselectivity of Complex Metal Hydride
Reduction," Third Hydride Symposium, 5-33, (1979).
21.
E.G. Ashby and S.A. Noding, "Hydrometallation IV. Hydroalumination of
Alkynes by HAl(NR2 ) 2 Compounds Catalyzed by Cp 2TiCl 2 ," J. Organometal. Chem.,
117, (1979).
22.
E.C. Ashby, "A Detailed Description of the Mechanism of Reaciton of Grignard
Reagents with Ketones", Pure and Applied Chemistry, 52, 545, (1930).
Convenient and Sterespecific
The Thermal Decomposition of
A Mechanistic Study," J. Org.
23. .E.C. Ashby, S.A. Noding and A.B. Goel, "Reactions of Magnesium Hydride IV.
Stereoselective Reduction of Cyclic and Bicyclic Ketones by Lithium Alkoxymagnesium Hydrides," J. Org. Chum., 45, 1023, (1980).
24.
E.C. Ashby and S.A. Noding, "Hydrometallation V. Hydroalumination of Alkenes and Alkynes with Complex Metal Hydrides of Aluminum in the Presence
of Cp 2TiC1 2 ," J. Org. Chem., 45, 1035, (1980).
25.
E.C. Ashby and S.A. Noding, "Hydrometallation VI. Evaluation of Lithium
Hydride as a Reducing Agent and Hydrometallation Agent," J. Org. Chem.,
45, 1041, (1980).
26.
E.C., L. Fernolt, A. Haaland, R. Seip and R.S. Smith, "The Molecular
Structure of Monomeric Bis(neopentyl) Magnesium by Gas Phase Electron
Diffraction," Acta. Chemica. Scandinavica A., 34, 213, (1980).
27.
E.C. Ashby, A.B. Goel and R.N. DePriest, "Evidence for Electron Transfer
Mechanisms in the Reduction of Ketones by Main Group Metal Hydrides,"
J. Amer. Chem. Soc., 102, 7779, (1980).
28.
E.C. Ashby, J. Bowers and R.N. DePriest, "The First Reported Evidence of
Single Electron Transfer in the 1,2-Addition of Primary Grignard Reagents
to Ketones," Tetrahedron Lett., 21, 3541, (1980).
PUBLICATIONS (Con't)
29.
E.C. Ashby, R.N. DePriest and A.B. Goel, "Electron Transfer in the Reduction of Primary Halides by Metal Hydrides," Tetrahedron Lett. 22 , 1763,
(1981).
30.
E.C. Ashby and A.B. Goel, "Evidence for Singele Electron Transfer in the
Reduction of Alcolhols with Lithium Aluminum Hydride," Tetrahedron Lett.,
22, 1879, (1981).
31.
E.C. Ashby, A.B. Goel, R.N. DePriest and H.S. Prasad, '", fetal Hydride Reduction via Single Electron Transfer. II. Evidence for an Electron Transfer Pathway in the Reactions of Single and Complex Metal Hydrides of the
Main Group Metals with Polynuclear Hydrocarbons", J. Amer. Chem. Soc.,
103, 973, (1981).
32, E.C. Ashby and A.B. Goel, "Reactions of Magnesium Hydride with Pyridine:
Formation of H_Mg 2NCSH6 ,4I\IgNC 5H6 and Mg(NC 5H6 ) 2 ," J. Organometal. Chem.,
204, 139, (1981).
-
33. E.C. Ashby and J. Bowers, "Organometallic Reaction Mechanisms. XVII. The
Nature of Alkyl Transfer in Reactions of Grignard Reagents with Ketones.
Evidence for Radical Intermediates in the Formation of 1,2-Addition Products Involving Tertiary and Primary Grignard Reagents," J. Amer. Chem.
Soc., 103, 2242, (1981).
E.C. Ashby, A.B. Goel and R.N. DePriest, 'Evidence for Single Electron
Transfer in the Reactions of Alkali Metal Amides and Alkoxides with Alkyl
Halides and Polynuclear Hydrocarbons," J. Org. Chem., 46, 2429, (1931).
35.
E.C. Ashby, R.S. Smith and A.B. Goel, "The Addition of the Nonnant Reagent
("CfylgBr" + CuBr) to Terminal Alkynes in THF. Concerning the Nature oC the
Reaction Species in Solutions," J. Organometal. Chem., 215, Cl-05, (19S1).
THESIS
1.
John P. Oliver
2.
Robert Scott Smith
STEREOSELECTIVE ALKYLATION AND REDUCTION REACTIONS INVOLVING
SELECTED CYCLIC KETONES: A STUDY IN THREE PARTS
A THESIS
Presented to
The Faculty of the Division of Graduate Studies
By
John Paul Oliver
In Partial Fulfillment
of the Requirements for the Degree
Doctor of Philosophy in Chemistry
Georgia Institute of Technology
July, 1979
xiv
SUMMARY
PART I. STEREOSELECTIVE ALKYLATION REACTIONS INVOLVING
METHYLMAGNESIUM ALKOXIDES
The stereoselective nature of several methylmagnesium alkoxides,
when reacting with a series of substituted cyclohexanones, was investigated. The bulky lioand attached to the magnesium enhanced the
stereoselectivity of these alkylating agents over
that
observed with the
usual Grignard reagents. Enolization was a competitive side reaction
involved in these alkylations.
PART
:I.
INVESTIGATIONS OF HALOMAGNESIUM ALKOXIDE
REDUCTION OF KETONES
Various halomagnesium alkoxides were prepared and investigated as
stereoselective reducing agents. With 4-t-butylcyclohexanone the thermodynamically more stable isomer was produced in high yield. Experiments
were carried out which indicated that the alcohol ratios obtained were
not an artifact of equilibration. These Meerwein-Pondorf-Verley type
reductions were carried out in various solvents under different conditions to obtain product ratios and optimum reaction conditions. The
almost exclusive mode of attack was from the axial side and appears to
be an inherent property of these reagents. Aldol condensation leading
to undesired by-product did not detract from the high stereoselectivity.
xv
Camphor and norcamphor were not reduced to any significant extent
by these reagents nor was 3,3,5-trimethylcyclohexanone. 2-Methylcyclohexanone also yielded poor stereochemical and stoichiometric results.
PART III. STEREOSELECTIVE REACTIONS OF COMPLEX METAL HYDRIDES
AND TRIALKYL ALUMINUM COMPOUNDS WITH KETONES
Stereoselective alkylation and reduction reactions were carried
out on the following diagnostic ketones: 2-methylcyclohexanone, 4-tbutylcyclohexanone, cis and
trans-2-methyl -4-t-butylcyclohexanone,
cis,cis and c .fs,trans-2,6-dimethy1-4-t-butylcyclohexanone. The ketones
were alkylated with Grignard reagents and with trimethylaluminum in both
1:1 and 3:1 ratio. Reductions of the ketones were carried out using
triisobutyl aluminum hydride, lithium aluminum hydride, chloromagnesium
aluminum hydride, magnesium aluminum hydride and aluminum hydride.
For the series of complex metal hydrides, reduction of anchored
and, therefore, conformationally stable 4-t-butylcyclohexanones yielded
relatively constant axial to equatorial alcohol ratios as the result of
torsional versus steric strain. The results are dictated by steric
factors in the substrate molecule. Complexation of the carbonyl with a
cation or other Lewis base caused a conformational change in the
unanchored 2-methylcyclohexanone as reflected in results dirfering from
the other diagnostic ketones.
Analysis of the data obtained from the alkylation reactions
indicated that the Grignard reagent is generally smaller than trimethylaluminum when the aluminum alkyl reacts in 1:1 ratio with ketone.
Analysis of the transition state energies for lithium aluminum hydride
xv i
reductions indicated that the Grignard is the more bulky species. When
used in excess the trimethylaluminum reaction results are explained on
the basis of the compression effect. Differences in transition state
energies were used to arrive at a semi-quantitative value of the
compression effect. Using 4-t-butylcyclohexancne as the parent ketone
relative values for excess destabilization energies were calculated for
the other diagnostic ketones. This excess destabilization energy
reflects itself in the compression strain energy which causes the
reversal of the axial to equatorial product ratio when trimethylaluminum
is used in 3:1 ratio with ketone.
•4-p4v7,4•4r.
ELECTROPHILIC CLEAVAGE OF MAIN GROUP ORGANOMETALLIC
COMPOUNDS BY CARBONYL ELECTROPHILES
A THESIS
Presented to
The Faculty of Division of Graduate Studies
By
R. Scott Smith
In Partial Fulfillment
of . the Requirements for the Degree
Doctor of Philosophy in the School of Chemistry
Georgia Institute of Technology
May 19 80
xii
SUNR,IARY
Part I. Electron Transfer Participation in the Reactions
of Grignard Reagents with Ketones
Competition experiments involving the reaction of a ketone with
two different Grignard reagents and a Grignard reagent with two different
ketones were carried out for a series of ketones and Grignard reagents.
The steric: and electronic properties of both the ketones and Grignard
reagents were varied in order to determine whether a polar or electron
transfer (ET) mechanism is in effect. For the biaryl ketones studied,
the results of the competition experiments are consistent only with an
ET mechanism. Conversely, acetone was found to react exclusively by a
polar. mechanism with all the Grignard reagents studied. We have concluded that the major factor determining whether or not ET occurs in these
reactions is the stability of the ketyl intermediate. In this regard,
acetophenone was found to be on the borderline for ketyl stability necessary for ET to occur. Steric hinderance, especially due to branching
at the f3-carbon of the Grignard reagent was found to influence the rate
determining step involving alkylations by the ET mechanism. A mechanistic
scheme is presented that defines different rate determining steps for ET
reactions of primary and secondary or tertiary alkyl Grignard reagents.
In addition, the method and results should be applicable to identifying
ET steps in the electrophilic cleavage of other alkyl metal compounds.
Part II. The Nature of the Transition State in the
Reaction of Trialkylaluminum Compounds
With Ketones
Because of the stereochemical significance of the reaction of
trialkylaluminum compounds with substituted cyclohexanones in 2:1 ratio
in benzene, an attempt was made to more clearly define the nature of the
transition state involved in this reaction. In this connection,
molecular weight and NMR studies were carried out in hydrocarbon solvents
(CH ) Al-Ph C=0 and (CH ) A1C1-Ph C=0
on the systems-(CH ) A1-0(C H )
2 5 2'
3 3
2
3 2
2
3 3
in an attempt to observe an intermediate that would reflect the transition state structure. In addition, Et AICH A1Et (I) was allowed to reac:
2
2
2
with 4-tert-butylcyclohexanone in hydrocarbon solvent at different molar
ratios as a mechanistic probe that would constrain two aluminum atoms to
a bridging configuration in the transition state. The results support
the importance of a bridging alkyl group described in the formation of
a six centered transition state for the reaction of two equivalents of a
trialkylaluminum compound with a ketone in hydrocarbon solvent. The
results also argue against any significant contribution from a transition
state described by two moles of trialkylaluminum compound complexed to
the carbonyl oxygen atom.
As a precondition for the use of (I) as a mechanistic probe (I)
was prepared in benzene and the solution composition deteLmined. The
addition of one molar equivalent of diethyl ether to this mixture formed
a substitution labile etherate, Et A1CH A1Et • OEt 2.
2
2
2
Low temperature
1H nmr data indicates that the ether oxygen is simultaneously coordinated
•
xiv
to both aluminum atoms. In addition to (I), Me 2A1CH 2A1Me 2 (II) was
synthesized in diethyl ether solvent, but could not be synthesized in
hydrocarbon solvent. Attempts to synthesize (II) from C1 A1CH A1C1 and
2
2
2
dimethylzinc in toluene led to the formation CIZnCH ZnCl.
2
Part III. Concerning the Preparation of Acyl
Grignard Reagents
An attempt was made to prepare an acyl Grignard reagent by two
different methods. The first method involved the carbonylation of
hindered aryl Grignard reagents. While this method did not produce a
stable acyl Grignard reagent, the presence of unreacted aryl Grignard
reagent was identified as the major contributing factor to its instability. The results are best rationalized by an electron transfer from
aryl Grignard reagent to the intermediate acyl Grignard reagent. The
second method involved the reaction of an acid halide with magnesium
metal, a reaction which has not been previously reported. While this
method holds promise for the formation of acyl Grignard reagents,
severe problems still need to be solved.