4316 J. Org. Chem., Vol. 43, No. 22, 1978
House et al.
Perhydroindan Derivatives. 19. Opening of a Cyclopropyl Ketone That Is Part of a n Indanone System' Herbert 0. House,* William C. McDaniel, Ronald F. Sieloff, and Don Vanderveer School of Chemistry, Georgia Institute of Technology, Atlanta, Georgia 30332 Received May 15, 1978 Reaction of the relatively rigid cyclopropyl ketone 19 with MezCuLi gives significantly more ring-opened product 30 than is found in an analogous reaction with the less rigid cyclopropyl ketone 8. However, both the direction of ring opening and the effect of added donor solvents on the reaction 19 30 indicate that this reaction does not involve an initial electron transfer step. Reduction of the ketone with Li and t-BuOH in liquid NH3 (a process that does involve initial electron transfer) results in the formation of products 41-43. These products are thought to result from rearrangement of the initial anion radical 20 to the anion radical 21b followed by further transformations to yield the products. +
A number of fl-cyclopropyl enones 1 (Scheme I) react normally with MezCuLi and other cuprate reagents to form the conjugate adducts 2. However, when special structural features hold the cyclopropyl bond a (structure 1) approximately perpendicular to the plane of the enone system, then an alternative reaction path involving formation of a ring-opened product 3 becomes either a significant competing reaction or the dominant reaction.2 This ring-opening reaction 1 3 appears to predominate only in those cases where rearrangement of the intermediate enone anion radical 4 to the ringopened radical 5 is relatively fast (half-life of 4 is s or less); a geometry with bond a (structure 1) perpendicular to the -+
Scheme I (1) Me,CuLi,
~ C H C H = = C R
CH,CH,
1
I
0-
,CH?CH=CHCOR
CH,
4
3
i
CH i
% '
(1) Me,CuLi,
f{
PhCO, .5.
$ $ '
I
9
PhCOCH,CR
(2) H,O
I
H W R ) 6, R = 7, R =
CHzCH
R'= H R'= CH,
10
8 , R = H ; R' = P h ( E l e d = -1.82 V )
11
12
OH P h C O T R 13, R = H or alkyl 14,R = CO-PI1
-
enone system is of course favorable to this anion radical rearrangement 4 5. In a related study of the reaction of MenCuLi with the aryl cyclopropyl ketones 6-8 (all of which have reduction potentials in the range -1.8 to -2.1 V vs. SCE),7the major product was invariably the 1,2-adduct 9 with only minor amounts (0.6-3.5%) of ring-opened products 10. Electrochemical reduction3 of the ketones 6 and 7 in an aprotic medium formed relatively stable anion radicais (half-lives 4-5 s). A much less stable anion radical 11 (half-life 0.005 s) was formed from the ketone 8 with a phenyl substituent that could stabilize the rearranged anion radical 12. In keeping with these relative anion radical stabilities, both reduction of various cyclopropyl ketones 13 with Li or Na in NHs4 and electrochemical reduction of ketone 6 in aqueous EtOH5 formed products (15, 16, and the corresponding pinacol) with the cyclopropyl ring intact. In contrast, the cyclopropyl ring was opened in the electrochemical reduction of ketone 8 to form ketone 185and in the reduction of ketones 8 and 14 with Na in NHJto form hydrocarbons 17.4" However, the structures of the ring-opened products 10 (attack a t the less substituted cyclopropane carbon atom) formed in the cuprate reactions all corresponded to the result expected from an S Nattack ~ by the cuprate reagent rather than rebonding to a rearranged radical anion (eg., 12) derived from the cyclopropyl ketone (eg., 8). To explore further the question of whether any cuprate-aryl cyclopropyl ketone reaction might involve, a t least in part, an initial electron transfer step to form an anion radical (eg., l l ) , we wished to examine the cuprate reaction with a cyclopropyl ketone whose anion radical underwent rearrangement faster than the ketyl 11. For this purpose we elected to study the fused cyclopropyl ketone 19 (Scheme 11) since this molecule is held in a rigid conformation with one cyclopropyl bond (bond a in structure 19) approximately perpendicular to the plane of the carbonyl group. Our selection of this substrate was also influenced by the possibility of an efficient conversion of ketone 19 via the intermediates 20 and 21a to indanone derivatives of interest in other synthetic work.6 Known procedures; were used to convert the styrenes 22 and 23 to the esters 24 and 25 (mixtures of stereoisomers) and the acids 26 and 27 (mixtures of stereoisomers). Reaction of the acid 26 (a mixture of stereoisomers) with polyphosphoric acid7d or, preferably, with SOC12 to form 28 followed by reaction with A1C138produced the desired ketone 19. In a t least the latter procedure, where the ketone 19 was obtained in 61% yield, trans cis epimerization is believedab to occur during the cyclization of the acid chloride 28. Our efforts to effect the same cyclization with the methoxy acid 27 led to complex mixtures even when we employed reaction conditions that are satisfactory6"for the formation of the methoxyindanone 49 from the corresponding acid chlo-
I TR PhCH2V-
Ph-ICH,),-Ph 1 7 , II = 4 or 5
R
PhCH
15
16
PhCO(CH21,Ph 18
0022-326317811943-4316$01.00/0 0 1978 American Chemical Society
-
J. Org. Chem., Vol. 43, No. 22, 1978 4317
Perhydroindan Derivatives
Scheme I11
Scheme I1
19 ( 3 - ? 0 k recovery)
+ H
(1)Me,CuLi.
22, R = H 23, R = C H , O
CH,CH,
Et,O.
CH,
0 19
OH
0 30 (13-18% yield)
29 ( 3 9 4 0 % yield)
t
t
24, R = H 25, R = CH,O PhCH=CHCO.Et 34
SOCI,
-
PhCH-
I
PhCHCH,CO.R
( 2 ) H,O
35, R = Et 36, R = H
PhCOCH!CH,CH, 37
26, R = H 27, R = CH,O
I
CHCOCI
polyphosphonc acid. 70-80 'C
CH-CH,
(1) Et,CuLi, Et,O. -30 to 0 'C
(1) Me,". CH,O, HCI. H,O (2) M e 1
PhCOCHCH.S*Me I-
I CH.CH
KOBu-t +
PhCOC=CH,
t.BuOH. 2 7 'C
I
CH.CH 39
38
+
NaOH. MeOH. 0-l0'C
PhCOCHCH.OCH,
I CH.CH
H?SO,. 25-70 3c
24-80 'C
0
40
0-
021b
21a
0
CHI
620
s 48, R = H (E& = -2.03 V ) 49, R = C H 3 0 (E,,d = -2.01 V )
31
020
ride. In view of our subsequently described results obtained with the indanone 19, other possible synthetic routes to the 6-methoxy derivative of indanone 19 were not investigated. The reduction potentials of the cyclopropyl ketone 19 (Ered = -2.03 V vs. SCE) and the analogous indanone 48 (Ered = -2.03 Q vs. SCE) were the same and were in a range where one-electron reduction by Me2CuLi to form the ketyl20 was r e a ~ o n a b l eAs . ~ we had hoped, the anion radical 20 was less stable than its open chain analogue 11 and had a half-life (0.001 s) sufficiently short enough that a significant amount of rearrangement could occur during a cuprate reaction. In fact, reaction of the ketone 19 (Scheme 111) with ethereal MezCuLi produced a mixture of the 1,2-adduct 29 (75-82% of the product) and a substantial amount of the ring-opened product 30 (18-25% of the product). Only the 1,2-adduct 29 was isolated from the reaction of the cyclopropyl ketone 19 with MeLi. Consequently, in the cuprate reaction the proportion of ring-opened product 30 (or 10;R = H, R' = Ph) was enhanced at least 20-fold by changing the substrate from the flexible ketone 8 to the rigid system 19. One could imagine that any one of the three cyclopropane C-C bonds in ketone 19 might be cleaved during the cuprate reaction so that any or all of the ketone products 30-33 might be formed. To insure that our ring-opened product was in fact the ketone 30, we obtained authentic samples of the ketones
32
33
30-33 and demonstrated that our product 30 contained less than 5% (if any) of the isomeric ketones 31-33. Authentic samples of ketones 30 and 31 were prepared by the routes indicated in Scheme 111. The foregoing results might be interpreted as reaction of the ketone 19 with MezCuLi to form the ketyl20 followed by partial rearrangement to 21a and rebonding to form 29 and 30. However, such a conclusion would be warranted only if the ketyl20 actually rearranges to the anion radical 21a (favored by the geometry of the system) rather than some other anion radical such as 21b (which allows stabilization of the radical by the adjacent phenyl ring). A clear indication that this second possibility might be correct was provided by an earlier studylo of the reduction of ketone 19 with Li in an ",-Et20 mixture. The reported products were an unidentified solid (mp 160-185 "C), tetralin, and tetralone. We have repeated this reduction of ketone 19 (Scheme IV) employing a solution containing 2 equiv of Li and 1equiv of t-BuOH in an NHS-Et20 mixture. The products were tetralol (41), tetralone (42), and the dihydro dimer 43 (mp 188-189.9 "C). Authentic samples of the alternative reduction products, the known" alcohols 44 and 45, were prepared to demonstrate their absence among the reduction products. Consideration of the products (41-43) formed in this metal-NHa reduction leaves little doubt that the initially formed ketyl20 rearranges to form anion radical 21b and not 21a. Further reduction of anion radical 21b to the dianion 46 readily accounts for all of the isolated products 41-43. In view of this, we conclude that reaction of the ketone 19 with MezCuLi to form ketone 30 does not involve the intermediate ketyl20 since this latter intermediate should have rearranged to 21b and then formed ketone 32. Instead, the reaction with the cuprate to form ketone
House et al.
4318 J . Org. Chem., Vol. 43, No. 22, 1978 S c h e m e IV
I
45 (ca. 71% of p r o d u c t )
44 ( r a . 29% of p r o d u c t )
Li. t-BuOH
\
"3
~
(I), Et20
0
020
19
i
H
H
I
I
0-
0-
46 f-BuoH
21b
1 \
q -q\ OH
(1)addition to 19 ( 2 ) t-BuOH
0
H
4 2 ( 12-14%
41 (13-2 4% yield)
47
0 43 (15-23% yield)
c enoiate
J. H*O 30
30 must again be an example of an s N 2 ring opening (see structure 47) in which the geometry of the substrate is especially favorable for attack a t the cyclopropyl CH2 group to displace an enolate anion. In agreement with this conclusion, the yield of ketone 30 from reaction of Me2CuLi with ketone 19 was increased (see Table 111)by the addition of good donor solvents (DME or THF). In reactions of cuprates with ketones where an initial electron transfer step is involved, the presence of good donor solvents normally retards or inhibits the reaction.12 The structure of the dihydro dimer 43, determined by a single crystal X-ray diffraction study, is shown in Figure 1. The bond lengths and bond angles obtained from this structural determination are listed in Table I.
Experimental Section13 Preparation of t h e Acid Derivatives 24,26, a n d 28. A cold (0 "C) solution of 28.53 g (0.25 mol) of N2CHC02Et14 in 26.04 g (0.25 mol) of styrene (22) was added dropwise with stirring during 15 min to 13.02 g (0.125 mol) of styrene (22) that was maintained at 130-140 "C under
Figure 1. A perspective view of the molecular structure of the dihydro dimer 43.
an N2 atmosphere. The resulting mixture was stirred a t 130-135 "C for 24 h and then distilled to separate 4.89 g of forerun (mainly PhCH=CH2) followed by 36.93 g of the crude ester 24 as a pale yellow liquid: bp 80-90 "C (0.15 mm); n Z 51.5182. ~ Redistillation afforded 34.28 g (72%)of the ester 24 (a mixture of stereoisomers) as a colorless liquid: bp 80.5-82 "C (0.14 mm); nZ5D1.5182 [lit. bp 103-105 "C (0.5-0.7 mm),7an Z o D 1.5187d];IR (CC14) 1725 cm-l (ester C=O); UV (95% EtOH) intense end absorption with a series of weak maxima ( e 251-472) in the region 253-273 nm; NMR (CC14) 6 6.8-7.4 (5 H, m, aryl CH), 4.10 and 3.81 (2 H, overlapping quartets, J = 7 Hz, CHzO), and 0.7-2.7 (7 H, m, ethoxyl CH3 and cyclopropyl CH and C H d ; mass spectrum, mle (relative intensity) 190 (M+. 29), 145 (211, 144 (18), 117 (loo), 116 (23), 115 (50), and 91 (22). Saponification of 32.64 g (172 mmol) of the ester 24 with a refluxing solution of 10.35 g (259 mmol) of NaOH and 15 mL of H20 in 100 mL of EtOH for 24 h followed by the usual isolation procedure yielded the crude acid 26 (a mixture of stereoisomers) as a cream-colored solid, mp 68-73 "C (lit7c mp 55-63 "C). Recrystallization from H20 afforded a mixture of stereoisomeric acids 26 in 57% yield as colorless crystals, m p 62.5-101 "C [lit.78m p 93 (trans isomer) and 106-107 "C (cis isomer)]. This crude acid (8.11 g, 50 mmol) was dissolved in 17.85 g (150 mmol) of warm SOClz and then stirred at 25 "C for 24 h, concentrated, and distilled. The acid chloride 28 (a mixture of stereoisomers) was collected as 8.69 g (96%)of pale yellow liquid: bp 126-128 "C (24 mm) [lit. bp 10%110 (2.1 mm)7aand 130 "C (10 mmjic]; n Z 51.554a1.5551; ~ IR (CC14)1780 cm-' (C=O); NMR (CC14) 6 6.7-7.6 (5 H, m, aryl CH) and 1.2-3.0 (4 H, m, CH and CH2); mass spectrum, mle (relative intensity) 182 (M+,
