J. Org. Chem. 1982,47, 1904-1909
1904
80963-52-6;triphenyl(3-butenyl)stannane,29972-16-5; trimethyl(5hexenyl)stannane, 73017-74-0; trimethyl(cyclopenty1methyl)stannane, 73017-75-1;triphenyl(cyclopentylmethyl)stannane,76001-27-9; triphenyl(5-hexenyl)stannane,73017-73-9;trimethyl(5-hexeny1)germane, 80963-53-7; triphenyl(5-hexenyl)germane, 76001-24-6; trimethyl(6-hepten-2-yl)stannane, 76879-52-2;ck-trimethyl(2-methylcyclopentylmethyl)stannane,76879-57-7;trans-trimethyl(2-methylcyclopentylmethyl)stannane,76879-58-8; dimethylphenyl(6-hepten2-yl)stannane, 76879-53-3; cis-dimethylphenyl(2-methylcyclopentylmethyl)stannane, 76879-59-9; trans-dimethylphenyl(2methylcyclopentylmethyl)stannnane,76879-60-2; methyldiphenyl( 6 - h e p t e n - 2 - y l ) s t e , 76879-54-4;cis-methyldiphenyl(2-methylcyclopentylmethyl)stannane,76879-61-3; trans-methyldiphenyl(2menylcyclopentylmethyl)s~ane,76879-62-4;triphenyl(6-hepten2-yl)stannane,76879-555; triphenyl(6-hepten-2-yl)germane,7687956-6; cis-triphenyl(2-methylcyclopentylmethyl)germane,76900-25-9; trans-triphenyl(2-methylcyclopentylmethyl)germane,76900-26-0; trimethyl(6-hepten-2-yl)germane,76879-49-7; trimethyl(5(Z)-hep-
ten-a-yl)germane,76879-50-0;trimethyl(5(E)-hepten-2-yl)germane, 76879-51-1; cis-trimethyl(2-methylcyclopentylmethyl)germane, 76879-63-5; trans-trimethyl(2-methylcyclopentylmethyl)germane, 76879-64-6; 2-deuterio-6-heptene, 80963-54-8; cis-1-(deuteromethyl)-2-methylcyclopentane,80963-55-9; trans-1-(deuteriomethyl)-2-methylcyclopentane,80963-56-0;ntrimethyktanny1)lithium, 17946-71-3; (dimethylphenystannyl)lithium,76879-67-9; (methyldiphenylstannyl)lithium,4167-85-5; (triphenylstannyl)lithium, 4167-90-2;(trimethylgermyl)lithium, 18489-76-4;(triphenylgermy1)lithium, 3839-32-5. Supplementary Material Available: Tables of the observed and calculated '% NMR chemical shifts (and 'SC-"%n couplings) for the products of the reactions between substituted cyclohexyl bromides with MeSzPhzMLi (M = Sn, Ge) and also for the corresponding reactions with 6-bromo-1-exene and 6-bromo-lheptene (Tables VI and VII) (7 pages). Ordering information is given on any current masthead page.
Oxidatively Assisted Nucleophilic Substitution/Elimination of Alkyl Iodides in Alcoholic Media. A Further Study Robert I. Davidson and Paul J. Kropp* Department of Chemistry, University of North Carolina, Chapel Hill, North Carolina 27514 Received April 28, 1981 Oxidation of a series of alkyl halides with alcoholic 3-chloroperoxybenzoicacid afforded the resulh outlined in Charta 1-111 and Tables 1-111. The reaction was found to be a powerful and convenient method for effecting nucleophilic substitution in a variety of systems, including the highly inert 1- and 7-bicyclo[2.2.l]heptylsystems. Qualitatively, the number of molar equivalents of oxidant required varied inversely with the expected ease of substitution for a given system. A mechanism is suggested whereby the iodide is oxidized stepwise to a species RIO, in which n is an integer sufficiently large that the system in question will undergo nucleophilic substitution or elimination. Reaction in the presence of added chloride or bromide ion usually resulted in a facilitation of reaction rate and a decrease in the number of molar equivalents of oxidant required; the principal product under these conditions was usually the corresponding chloride or bromide. Treatment of alkyl iodides with peroxy acids has been the subject of several recent papers.'" In nonnucleophilic media simple alkyl iodides are converted principally to the corresponding alcohols, while elimination is t h e predominant pathway for more complex However, when simple alkyl iodides are oxidized in solvents such as methanol or acetic acid, nucleophilic substitution occurs in~tead.'?~?~ Iodoso intermediates (RIO) have been proposed to account for this beha~ior.~"W e now report the results of a detailed, systematic study of the oxidation of alkyl iodides with 3-chloroperoxybenzoic acid in alcoholic media which show that this reaction affords an exceptionally mild but powerful, efficient, and selective method for effecting nucleophilic substitution of many systems. Some additional insight into the mechanism of the reaction was also obtained.
Chart I
3
4
Results The alkyl iodides selected for study, along with t h e products resulting from their oxidation with 3-chloroperoxybenzoic acid, are shown in Charts 1-111. The results from oxidation in methanolic solution are summarized in Table I. Most of the alkyl iodides afforded methyl ether substitution products upon oxidation. (+)-(S)-2-Iodo(1)Ogata, Y.; Aoki, K. J. Org. Chem. 1969,34,3974-3980. (2) Bsely, N. R. A.; Sutherland, J. K. J. Chem. SOC.,Chem. Commun. 1977, 321-322. (3) Reich, H. 3.; Pede, S. L. J. Am. Chem. SOC.1978,100,4888-4889. (4) Cambie, R. C.; Chambers, D.; Lindsay, B. G.; Rutledge, P. S.; Woodgate, P. D. J. Chem. SOC.,Perkin Tram. 1 1980,822-827. (6) Macdonnld. T. L.: Narasimhan, N.: Burka, L.T. J.Am. Chem. Soc. 1980; 102, 7760-7765.
0022-3263/82/1947-1904$01.25/0
octane (17) which was 76% optically pure6 afforded (-)(R)-ether 18 (Y = OCH3) which was 25% optically pure7 (33% n e t inversion). One system, 3,3-dimethyl-l-iodopropane (25) underwent accompanying rearrangement, and three systems (14,19, and 29) apparently underwent initial 0 1982 American Chemical Society
J. Org. Chem., Vol. 47, No. 10, 1982 1905
Nucleophilic Substitution/Elimination of Alkyl Iodides Table I. Oxidation of Alkyl Iodides with Methanolic 3-Chloroperoxybenzoic Acid a yield,b % sufficient molar equiv 2 molar [O]for of [0]reequiv comquired for iodide product of [0Icpletiond completion 74 99 2(Y= 3 OCH,) 3 94 98 3 4(Y= OCH,) 3 66 97 5 6 7 84 8(Y= OCH,) 16 8(Y= OH) 9 lO(Y= 10 e 67 OCH,) 10 (Y = e 16 OH) 11 7 1 2 (Y = e 66 OCH,) 13 (Y = e 15 OCH,) 14 121 15 23 16 17g 18 (Y = 3 53 60 OCH,) 19 4 4 20 5 44 e 21 34 95 22 21 3 48 78 22 23 3 57 69 24 (Y = OCH,) 25 4 26 54 65 27 4 28 ( Y = 60 97 OCH,) 29 4 30 L921 i 37 f 65j.k 31 4 32 a Conducted as described in the Experimental Section by using 0 . 0 5 M methanolic solutions of iodide. Determined by gas chromatographic analysis relative to an internal hydrocarbon standard except where noted. Analysis of aliquots removed from the reaction mixture after treatment with 2 molar equiv of [0 for 3 h as described in the Experimental Section. Analysis of the reaction mixture after treatment with additional 1 molar equiv portions of [ 01 every 3 h until the iodide was consumed as described in the Experimental Section. e None detectable. f Additional products present as an insep-2.7". No arable mixture. g [ c ( ] * ~ Dt 4 3 . 1 " . detectable amounts of 29 or 30. j Yield of isolated product. Product collected after 1 2 h of oxidation. 1
h O C H 3
-
p
o
c OCH3 H 3
I OCH3 15
14 (4--
chart I1 +
QyOCli3
CH30 OCH3
16
-v
I
Y
18
17
19
20
21
22
-1-
-
21
y
22
Y
OCH3
OCH3
24
23
Scheme I 13
14
22Y o
29%
15
16
d 19
[(u]',~
elimination or fragmentation to afford alkene intermediates (33-35) which reacted further under the oxidation conditions. As shown in Scheme I, independent treatment of each of the suspected alkene intermediates 33-35 under the reaction conditions afforded a mixture of products similar to that obtained from the corresponding iodide. With a fixed amount of oxidant (2 molar equiv) the various iodides went to varying degrees of completion, and differing molar equivalent amounts of oxidant were required for complete oxidation. Interestingly, the 1-and 7-iodobicyclo[2.2.l]heptanes 9 and 11 underwent no detectable reaction until more than 2 molar equiv of oxidant had been added. In contrast with its alkyl analogues, iodobenzene (31) afforded none of the substitution produd, instead, the iodoxy derivative 32 precipitated from solution. The results of a detailed study of the oxidation of 1iodooctane (1) in various alcoholic solvents in the presence or absence of various added salts are summarized in Table 11. Nucleophilic displacement also occurred in isopropyl and tert-butyl alcohols but with reduced efficiency relative
*
CO I... ..-. -.
29
?==4 35
I
12/LO1 CH30H
I
7 1" i o
30
OCH3
1906 J. Org. Chem., Vol. 47, No. 10, 1982
Davidson and Kropp
Table 11. Oxidation of 1-Iodooctane(1) with 3-Chloroperoxybenzoic Acida yield,b 7%
solvent (ROH) CH,OH CH,OH (CH,),CHOH (CH,),COH CH,OH CH,OH CH,OH CH,OH CH,OH CH,OH CH,OH CH,OH CH,OH CH,OH CH,OH CH,OH (CH,),CHOH (CH,),COH
salt
molar equiv time, of [O] h 2 3 6 3 2 3 2 3 2 3 2 3 3 2 0 3 2
3
2 2
3 3 3 3 3 3
2 2 2 2 2 2 2
MX
2
molar equiv
1
Y=OR
25
74 99 50 12c 22 7 10
1
Li C1 LiCl LiCl LiCl Li Br NaCl KC1 Li F LiClO, NaCN KCN (C,H,)"c LiCl Li C1
3
3 3
1
5 10 10 5 5
5 5 5 5 5 5 5
5
49 34 42 21 18 98 4 14 13 43 26 100 100 87 19 23
d
14 24 44 57 73 d d
10 3 18
Y=X
35 72 72 d 82 62 43 d d d d d
78 59
Oxidations were conducted as described in the Experimental Section by using 0.05 M solutions of iodide 1. Determined by gas chromatographic analysis relative to an internal hydrocarbon standard on aliauots removed from the oxidation 2 ( Y = OH) formed in k3% yield. mixture and quenched as described in the Experimental Section. None detectable. Chart I11
A I 'I 25
-.
\-jGCH3
/
26
I -SITI
27
28
A I
I
1
29
A -0 kd
102
32
31
to methanol. In the latter solvent the principal product was 1-octanol (2, Y = OH), with only a small amount of the tert-butyl ether 2 [Y = OC(CH,),] being formed. In the presence of various chloride salts the corresponding chloride 2 (Y = C1) was formed in competition with the nucleophilic substitution product 2 (Y = OR). Analogous behavior was exhibited in methanolic lithium bromide; however, other salts either quenched oxidation or had a minimal effect. The resdta from oxidation of a number of iodides in the presence of lithium chloride are summarized in Table 111. As with 1-iodooctane (I),a mixture of the corresponding methyl ether and chloride substitution products was obtained, but the relative amounts varied from system to system. (+)-(8)-2-1odoodane(17)which was 76% optically pure6 afforded (-)-(R)-2-chloroocte (18, Y = C1) which was 62% optically pure* (82% inversion) and (-)-(R)-ether 18 (Y = OCHJ which was 34% optically pure' (45% in(6)
