3708 348 (1974). (12) F. R . Dollish, '$4. G. Fateley, and F. F. Bentley, "Characteristic F " n Frequencies of Organic Compounds", WileY, New York, N.Y., 1974, P 23. (13) R. P. Lattimer, U. Mazur, and R. L. Kuczkowski, private CO"UniCatiOn,
(14) (15) (16) (17)
1976. R. J. Jensen and G. c. Pimentel, J. Phys. Chem., 71, 1803 (1967). F. Gozzo and G. Camaggi, Chim. lnd. (Milan),5 0 , 197 (1968). C. W. Gillies, J. Am. Chem. SOC., 97, 1276(1975). K. Griesbaum and P. Hofmann, J. Am. Chem. Soc., 98, 2877 (1976).
Vinylic Radicals Are Intermediates in the Oxidation of Vinylic Lithium Reagents to Lithium Enolates by Dioxygen, But Not by Lithium tert-Butyl Peroxide' Edward J. Panek,2a Larry R. Kaiser,2aand George M. Whitesides*zb Contribution from the Department of Chemistry, Tulane University, New Orleans, Louisiana 70118, and Massachusetts Institute of Technology, Cambridge, Massachusetts 021 39. Receiued October 26, 1976
Abstract: ( E ) - and (Z)-I-lithio-I-propene (1) and ( E ) - and (Z)-I-lithio-I-phenyl-1-butene (2) react with dioxygen at -78 OC and yield the corresponding lithium enolates with partial loss of stereochemistry around the double bond. Reactions of 1 and 2 with lithium rut-butyl peroxide yield enolates with retention of configuration. These stereochemical observations implicate free vinylic radicals in reactions of vinylic lithium reagents with dioxygen, and exclude them in reactions with lithium tertbutyl peroxide.
Transformation of an organolithium or -magnesium reagent to the corresponding alcoholate by reaction with dioxygen ordinarily occurs in two distinct steps:3
Results ( E ) - and (2)-1-lithiopropene ( ( E ) - and (Z)-l)were prepared by reaction of lithium metal with ( E ) - l-chloropropene and (Z)-1-bromopropene, respectively, in diethyl ether soluRM 0 2 ROOM (1) tion.1°s12 (2)-I-Lithio-I-phenyl-1-butene ((2)-2) was obtained by a lithium-halogen exchange reaction between n-butylROOM RM 2ROM (2) lithium and ( E ) -1-bromo-] -phenyl- 1-butene in hexane solution at 22 "C or T H F solution at -78 OC,I3 and (E)-1-lithio-IFormation of an intermediate organic peroxide by reaction phenyl- 1-butene ( ( E ) - 2 )by reaction of n-butyllithium with between the organometallic reagent and dioxygen has been proposed to require initial single-electron transfer to d i ~ x y g e n ; ~ (Z)-I-bromo-I-phenyl-1-butenein T H F solution a t -78 OC.I3 The diastereomers of 1 and 2 are configurationally stable this electron transfer may or may not generate a free radical, a t the temperatures used for the oxidation studies (-78 R., depending on the solvation or extent of aggregation of the 0C).10,12,13 The lithium enolates 3 and 4, generated by oxiorganometallic specie^.^ T h e mechanism(s) of conversion of dation of the lithium reagents 1 and 2, can be assayed for diorganic peroxides to alcoholates has not been carefully exastereomeric composition by acylation with acetic anhydride, amined, but a related reaction-that of di-tert-butyl peroxide and analysis by G L C of the resulting enol acetates 5 and 6.The with ethyllithium, yielding, inter alia, lithium tert-butoxide yields and isomeric composition of the enolate anions formed and ethyl tert-butyl ether-has free alkyl and alkoxy1 radical by oxidations of these reagents were determined by quenching intermediates6 the reaction mixtures with excess acetic anhydride, and anaHere we describe stereochemical evidence that indicates that lyzing the resulting enol acetates by G L C (Scheme I). Before vinylic radicals are intermediates in the oxidation of vinylic the compositions of these mixtures of enol acetates could be lithium reagents to lithium enolates by dioxygen, but not by used as the basis for conclusions concerning the stereochemlithium terr-butyl peroxide. E and 2 diastereomers of approistry of conversion of vinylic lithium reagents to lithium enopriately substituted vinylic lithium reagents, and of the derived lates, however, it was necessary to establish that (a) conversion lithium enolates, can be prepared with high stereoselectivity of lithium enolate to enol acetate proceeded in high yield and proved to be stereochemically stable under the conditions without isomerization, (b) the lithium enolates were stereorequired for these oxidations. Vinylic radicals undergo chemically stable under the oxidative conditions used to genrapid Z - E isomerization ( k , = 108-10io s-I for vinyl radical erate them from the vinylic lithium reagents, and (c) neither Thus, if free vinylic radicals are intermediates in diastereomer of the pairs of enolates was destroyed oxidatively oxidation of diastereomerically pure 2 or E vinylic lithium at a much faster rate than the other. reagents, the product lithium enolates will be formed as a Authentic lithium enolates were prepared by treating enol mixture of diastereomers.1° Conversely, if the products of reacetates with an excess of methyllithium. If stereochemically action are generated with retention (or inversion) of stereopure (>99%) ( 2 ) -or ( E ) - 5 or -6 was converted to lithium chemistry, vinylic radicals are not intermediates. enolate by this procedure, and then quenched with acetic anThese studies contribute to the body of mechanistic inforhydride, the original enol acetate was obtained in >90% yield, mation which will eventually rationalize the nucleophilic and with no detectable loss of stereochemistry. The yields and electron-transfer pathways followed in reactions of organostereochemistry of the enol acetates obtained by acylation with metallic compounds. They also provide a new method for the acetic anhydride thus accurately reflect the composition of the stereoselective generation of enolates, and may have applicalithium enolates from which they were derived. tions in synthesis."
+ +
+
-
Journal of the American Chemical Society
/
99:11 / M a y 25, 1977
3709 Scheme I. Interconversions Used in Testing the Stereochemical Course of Oxidation of Vinylic Lithium Reagents t o Lithium Enolates
100-,
t
(CHJ)&OOLi
- %""'
-0
R2
R2
(Ztl (E>2
I
(2)-3,-4 (CHIXCOOLi
R, R,
= =
R2
(Zh5-6
t
d [ (19-31 = - k [~( E ) 3]*Cdt -
(3)
Here a and C are unknown constants which are the same for (E)-3and ( 2 ) - 3 .If (Y = 1, a plot of -In (E/&) vs. -In (Z/Zo) should be linear, with slope k E / k Z . Figure 2 indicates that the relation is followed experimentally, and that kE/kz N 1.5. The significance of this number lies in the fact that it establishes that (E)-3 and ( 2 ) - 3present in the same solution are destroyed by autoxidation at similar rates. It is therefore unnecessary to try to correct the relative amounts of ( E ) -and (Z)-5,the enol acetates obtained from ( 2 ) and - (E)-3,for differential rates of autoxidation of these enolates before treatment with acetic anhydride, in order to estimate accurately the relative amounts
0.9
Figure 1. Addition of dioxbgen to a solution containing predominantly (€)-3 (0.1 N . EtzO. 22 "C) results in concomitant isomerization of E to Z enolate and destruction of the enolates. Enolates were analyzed by GLC following conversion to enol acetates with acetic anhydride.
CH,; R, = H 1, 3, 5 C,H,; R, = C,H, 2 , 4, 6
To test the isomeric stability of the lithium enolates to oxidation, isomerically pure samples of (E)-3and ( 2 ) - 3 in ether 8 At solution were exposed to dioxygen a t 22 and a t ~ 7 "C. both temperatures, enolates were destroyed by autoxidation. A t the higher temperature, loss of stereochemistry in the enolate occurred competitively with this autoxidation. Figure 1 shows the absolute yields of (E)-3and ( 2 ) - 3(estimated as enol acetates 5 ) following treatment with acetic anhydride of aliquots from a sample to which increasing volumes of dioxygen were added. The production of 2 isomer from E is evident in this plot. Similar conversions from (2)to (E)-3were observed in samples originally highly enriched in the former. At -78 "C, however, no evidence for isomerization of Z to E (or vice versa) during autoxidation was observed. Whatever the reaction responsible for the isomerization during oxidation, it is unimportant a t -78 "C. Oxidations of 1 could, accordingly, be conducted at this temperature with the assurance that the initially formed lithium enolates would not isomerize under the reaction conditions. The relative rates of autoxidation of the enolates derived from 1, ( E ) - 3 ,and ( 2 ) - 3were established by exposing mixtures of the two to dioxygen a t -78 "C, periodically withdrawing aliquots, and converting the remaining enolates to enol acetates and analyzing. The mechanism and the kinetic rate expression for the disappearance of enolate are not known. The simplest realistic assumption about this reaction is that autoxidation of both Z and E enolates is described by rate expressions that are of the same form (e.g., for (E)-3,eq 3).
0;6
O2 (mole/mole enolate)
2.X H,Li
Ac,O
03
?N
f
:::L/:,,I 0.2 0.0
0.0 0.2
0.4
0.6
0.8
1.0
1.2
-In ( E / L )
Figure 2. Analysis of competitive autoxidations of mixtures of ( € ) - I and (Z)-l according to eq 3 indicates that k E / k z 1.5. Open and filled circles are data from two independent experiments.
of the diastereomeric enolates generated by oxidations of propenyllithium (1). These studies establish that the diastereomeric composition of the enolates produced by oxidation of 1 can be determined by conversion to enol acetates with acetic anhydride and analysis by GLC, provided that the enolates are not exposed to oxygen at temperatures above -78 "C. Although we have not carried through analogous studies for the enolates 4 explicitly, we assume that the same conclusion applies to their determination; this assumption is justified qualitatively by the results that follow. Oxidation of Vinylic Lithium Reagents with Lithium and Sodium tert-Butyl Peroxides Occurs with Retention of Configuration, The lithium salt of terr-butyl hydroperoxide was prepared by slowly adding a solution of methyllithium in ether to a well-stirred solution of tert-butyl hydroperoxide in ether (or T H F ) cooled to -78 "C. The sodium salt was prepared by allowing tert-butyl hydroperoxide to react with a suspension of sodium hydride in T H F solution a t 0 O C . I 4 Analysis of the distribution of products obtained by permitting (E)- and (Z)-1 to react with lithium tert-butyl hydroperoxide in ether at -78 "C, and ( E ) - and ( 2 ) - 2 to react with lithium and sodium tert-butyl hydroperoxide in T H F a t -78 "C, establishes that conversion of the vinylic lithium reagent to lithium enolate occurs cleanly with retention of configuration around the double bond (Table I). Unreacted organolithium reagents present on quenching the reaction mixture with acetic anhydride appear as substituted methyl vinyl ketones. The major side products in the oxidation reactions are olefins. it is not known whether these materials are generated from proton
Panek, Kaiser, Whitesides
/
Oxidation of Vinylic Lithium Reagents
3710 Table I. Diastereomeric Compositions and Product Yields from Oxidations of Vinylic Lithium Reagents RCHCR'Li with 0 2 and Metal tert-Butyl Hydroperoxides (ROOM)
Products, yield, % % Eb
RLi"
Oxidant
RLi
RCH=CR'OAc
RCH=CR'OAc E
Z
RC H=C R'COCHi E
RCH=CHR' Z
E
1
ROOLi
2
ROONa If
95 4.1
96 3.7
80
21 [79]
13 25
83 [I71 74 [26] 83
96 2.4 8.3 43 16 15
100 100
02g
f
81
21
97 97 97 97 5.3 4.5 4.5
78
17
80
21 12 22
2" n n n
80 80
0
20 10
51 [49] 55 [45] 83 [I71 83 [I71 73 [27] 85 [I51
h h i i i
i. I i, I
18 18
0
78 76 15 14 11
3.0 1.5 4.5 29 29 66 61 40 56
4.4 63 32
17
9.1 34 28 24 14 13 15 IO
~~~
~~~~~~~
~
~
~~
IO0
33 40 5.0 16
8.8
5.7 3.0 5.0 5.0 5.3 3.3 7.0
RCH2COR' Total"
Z ~
8.8
e
39 45
e
2.0
37 e
13
(68)J,k (74)J,m
88
(eY
e
4.6 e e e
83
55 26 82 74 89 42
60 48 74
e
98 89 98
15 I2 e
e e e
19 29 2.6 3.7
84 38 99 97
1.6
5.9 8.3 9.0
I03
5.7
8.3 1.3 8.0 12
71
2.4
4.4
4.0 16
5. I
95 89
" [RLi] = 0. I O f 0.01 M, unless noted otherwise. The diastereomeric composition of the vinylic bromides was determined by G LC analysis of the vinylic bromides produced by reaction with 1,2-dibromoethane. The Z , E system of nomenclature is such that oxidation of ( 2 ) - 2 with retention of configuration generates ( E ) - 6 .The numbers in brackets in the column for enol acetates are simply 100 - % E , and are included to facilitate direct comparison with % E for RLi. ( E ) - and (Z)-pent-3-en-2-one were not distinguished under the GLC conditions used. Both methyl vinyl ketones and 1-bromopropene are derived from unreacted vinylic lithium reagents present in solution. Product balance, based on starting RLi. Not detected (
