3281
Addition of a Functionalized Isoprene Unit to an Allyl Alcohol. and Related Topics I. The Synthesis of ,8-Sinensa11~2 Alan F. Thomas
Contribution from the Research Laboratories. Firmenich & Cie, Geneoa, Switzerland. Received January 11, 1969 Abstract: Full details of the synthesis of p-sinensal(l6) in one step from 2-methyl-6-methyleneocta-2,7-dienol (12) and l-ethoxy-2-methylbuta-l,3-diene (10)are given. The reaction is a general one for allyl alcohols, and its stereo-
chemistry has been examined using 2-methylbut-2-enol(19), nerol (26), and geraniol (27). The cis alcohol (nerol) leads to a rrans-double bond in the product to the extent of about 70%, the trans alcohol leading mainly to a cis product, The double “Claisen-Cope” type rearrangement involved occurs to only a minor extent when 1-ethoxybuta-l,3-diene (9) is used, the intermediate formed after the first rearrangement of the enol ether being stabilized by hydrogen rearrangement to give an a,&unsaturated aldehyde which cannot react further.
I
n preliminary communications, it was shown that an allyl alcohol will undergo trans etherification with a diene ether, the vinyl ether thus obtained undergoing a double rearrangement under mild conditions to yield an unsaturated aldehyde with the chain of the original allyl alcohol extended by the number of carbon atoms in the R group plus four, as in Scheme L1v3 The imScheme I
R
I
+
‘C=CCH-OH
/
I
EtOCH=CCH=CH:
-
I
sesses the carbon skeleton of the intermediate after the first rearrangement only. Results and Discussion Preparation of Diene Ethers. The method used to prepare both diene ethers 9 and 10 was the well-known one starting from acetaldehyde diethylacetal and reported to proceed by the mecha1-ethoxypropene (l)b nism shown in Scheme II.6 It has now been found Scheme I1
/OCZHS +BF3 CHICH
\
+
c ~ H ~ ~ ~ B F ~
+CHaCHOCzHj
OCzHj CH3
CH3
C H ~ H Z G J L--J CH=CHOC2Hj
1
+
CHI
\CHLHc~OCzHI /
C2HjO 2
1
JC*HL6BF8
CH3 CH3 /OCZH5 ‘CHLHCH
/
\
CzHjO
OCzHj
3
H
portance of this reaction arises from the fact that when R = CH3, a means is available to add an isoprene unit functionalized at the end, thereby making it possible t o synthesize a number of natural products by a very simple route, examples of which it is hoped to present in future publications. Such a reaction was recognized as a possibility by Julia, Julia, and Linarbs4 in 1962, but under their conditions they did not detect any of the chain-extended product, and as will be described below, when R = H, as in their example, the main product in any case pos(1) Preliminary communication: A . F. Thomas, Chem. Commun., 947 (1967). (2) The nomenclature of the sinensals has recently been changed in order to relate them to a- and 8-farnesene; see R. Teranishi, A. F. Thomas, P. Schudel, and G. Buchi, ibid., 928 (1968). (3) A. F. Thomas, Chimiu, 594 (1967). (4) S. Julia, M. Julia, and H. Linares, Bull. SOC.Chim. France, 1960 ( 1962).
that when the reaction is carried out with cis-1, 80% of the product consisted of one stereoisomer (presumably threo-3), but that the trans-ether led to 8 6 x of a different (erythro) product (3), signifying that the electrophilic attack of the carbonium ion on 1 must be subject to stereochemical control by the olefin. The principal by-products of this reaction were the expected ones,5 namely the acetals (4a and 4b) resulting from attack of 2 on 1, together with products arising from loss of ethanol from 4, i.e., a mixture of threoand erythro-acetals (5)’ ( 5 ) A review of this reaction has been published by L. S . Povarov, Rum. Chem. Rec., 639 (1965). (6) R. J. Hoglin and D. H. Hirsh, J . Am. Chem. Soc., 71, 3468 (1949). (7) The acetal mixture (5) was not resolvable, but the corresponding aldehydes (6) were readily separable by glpc, and converted to the alcohols (7). The ir spectra of these suggested the presence of an intramolecular hydrogen bond, stronger in one isomer than in the other. The stronger hydrogen bonds are generally formed by the threo isomer,8,9 which in this case corresponded to the first peak eluted from a Carbowax glpc column, and to which the configuration 7b is accordingly attributed, 10 The principal difference in the nmr spectra was that the chemical shift of the methyl group on the saturated carbon atom was at higher
Thomas J Synthesis of P-Sinesal
OCzHj CHICHCHzCH I /OCB5
A __f
\
i
8
4a, 4b, etc. (mixture of isomers)
H
- CzHjOH
‘ 7 3
catalyst
OC2Hj
,OCzHs
7 3 3
H-
I
\
CH?=CH
+
CHICH=CCHCHCH OCzHj 5
1
LiAlHa
CHICH=CCHCHCHO
__f
7a
+ 7b8
OCzH5
6
The pyrolysis of acetals has been studied many times, using ammonium dihydrogen phosphate, l 1 p-toluenesulfonic acid in quinoline,12 and many other cata1ysts,l3 but the stereochemistry of the products has been little discussed. l 4 We have examined the effect of certain catalysts on the pyrolysis of propionaldehyde diethylacetal, and found that the quinoline-toluenesulfonic acid catalyst gave nearly equal amounts of cis- and trans-ethers (1) when fresh, the proportion of cis-ether rising with time. On a column of silica gel at 280°, we found 65x cis-ether and 35% trans. Extending these studies to the pyrolysis of 1,1,3-triethoxybutane (8), we found the ammonium hydrogen phosphate catalyst t o produce almost exclusively truns-ethoxybutadiene (9b),lj while the quinoline-toluenesulfonic acid catalyst gave a mixture (2: 1) of trans (9b) to cis (gal. We were particularly desirous of having both cisand trans-I-ethoxy-2-methylbutadienes(loa and lob) in order to examine the stereochemistry of the double rearrangement described in the introductory section and it seemed likely that the quinoline-toluenesulfonic field in the first isomer eluted; this isomer was therefore again given the configuration which, when the hydrogen bond was present, resulted in a conformation having this methyl further from the oxygen on the neigh-
CHj
7a 7b boring carbon (i.e., 7b, not 7a). (8) L. P. Kuhn and R. A . Wires, J . Am. Chem. Soc., 86, 2161 (1964). (9) A . B. Foster, A . H. Haines, and M. Stacey, Tetrahedron, 16, 177 (1961). (10) See also B. Fremaux, M. Davidson, M. Hellin, and F. Coussemant, Bull. SOC.Chim. France, 4243 (1967). ( 1 1 ) I. N. Nazarov, S . M. Makin, and B . Kruptsov, Dok/. Akad. Nauk SSSR,117,823 (1957). (12) B. M . Mikhailov and L . S . Povarov, Zh. Obsch. Khim., 29, 2079 (1959). (13) W. Flaig, “Chemical Test No. 093,” (PB 52020), Reichsamt Wirtschaftsausbau, 1942, p 1073; Chem. Abstr., 6189 (1947). (14) W. Kirmse and M. Buschhoff, Chem. Ber., 100, 1491 (1967), give spectral characteristics of the methyl ethers corresponding to 1, making cis and tram isomers easily distinguishable. (15) cis- and rrans-diene ethers are readily distinguishable by the chemical shift of the vinyl C-3 hydrogen quadruplet, which is at higher field in trans-ethers (6.58 ppm in 9a, 6.13 ppm in 9b) or the C-1 hydrogen doublet ( J = 6 cps in 9a, 12.5 cps in 9b) which is at higher field in the cis-ethers (5.85 ppm in 9a, 6.47 ppm in 9b). See also ref 16.
Journal of the American Chemical Society
i
91.12
\
/H
/c=c\
OCgHj f CHz=CH
June 4 , 1969
/OCZHE
/c=c\H
9a
OCzHs
CH3 CH3
I
H
\
9b
acid method would give the larger amount of cis isomer (loa). In fact none of this isomer was ever detected using any of the catalysts (in contrast to a recent brief report 16), and, moreover, there was no difference in the composition of the products obtained from the threoor erythro-triethoxy compounds (3). The principal impurity identified was 1,3-diethoxy-2-methyl-l-butene (11) (the relevant spectra leading to the attribution of a structure are described in the Experimental Section). CHI
\
CHz=CH
CH3
\
/H
/c=c\
OCZHj
CHz=CH
1Oa
/OCZH5
,c=c\H 10b
OC2Hj
I
CHaCHC=CHOC,H; CH3
11
A few other minor impurities were present, including 2-methyl-2-butenal and its diethylacetal, but although a mass spectrum was taken of almost every other peak visible in the gas chromatogram, only one compound of molecular weight 112 was observed, namely lob. The Synthesis of P-Sinensal (16)’’ In the preliminary communication, the preparation and stereochemistry of the alcohol component 12 were amply described, and these have since been confirmed by Buchi and Wiiest. l 8 Vinyl ether exchange of allyl alcohols has already been reported to yield the aldehyde resulting from a Claisen-type rearrangement, *O i.e., stage 1 of the rearrangement we are now discussing, and in our case, the aldehyde in question can exist in principle in two conformations, 13 with the large group, R, equatorial and the hydrogen axial, or 14, with R axial and hydrogen equatorial. We suggested’ that the large groups would be expected to prefer a pseudoequatorial orientation in a chair-like intermediate, and evidence that this is indeed the case has been given by Viola, et af.,21and by Vitorelli, et It is thus clear that the sinensal obtained from this reaction should have the double bond at C-6 in the trans configuration (15 or 16 in Scheme 111). Unfortunately we have little evidence so far about the configuration of the diene (16) G . J. Martin and J.-P. Guesnard, Bull. SOC. Chrm. France, 2150 (19 66).
(17) Two other syntheses of p-sinensal have been described.18 19 (18) G. Buchi and H. Wuest, Helc. Chim. Acto, 50, 2440 (1967). We are very grateful t o these authors for a sample of their p-sinensal. (19) E. Bertele and P. Schudel, Ibid., 50, 2445 (1967). (20) (a) R. Paul, G. Roy, M. Fluchaire, and G . Collardeau, Bull. SOC. Chim. France, 121 (1950); (b) S. F. Reed, J . Org. Chem., 30, 1663 (1965). (21) A . Viola, E. J. Iorio, IC=CHO), 4.39 (1 H, q, J = 6.5 Hz, -(O)CH7 Hz, CH~CJYZO-),1.40 (
