J. Org. Chem. 1985,50, 3849-3859
3849
DABCO-Catalyzed Coupling of Aldehydes with Activated Double Bonds. 4.' Stereoselective Synthesis of Trisubstituted Olefins and Terpenoid Building Blocks via 2 4 Hydroxyalkyl)-2-propenoicEsters H. Martin R. Hoffmann* and Jurgen Rabe Department of Organic Chemistry, University of Hannouer, Schneiderberg 1 B, 0 - 3 0 0 0 Hannouer, Federal Republic of Germany Received D e c e m b e r 17, 1984
A variety of 2-(hydroxyalkyl)-2-propenoicesters 16a-g has been prepared in high yield by DABCO-catalyzed coupling of aldehydes 14a-g with methyl acrylate. The product esters 16a-g are useful building blocks in syntheses which undergo regioselective and 2-selective S N ~reactions ' with N-bromosuccinimide/dimethyl sulfide and N-chlorosuccinimide/dimethylsulfide to furnish (2)-2-(bromomethyl)-2-alkenoicesters 17a-g and (2)-2(chloromethyl)-2-alkenoic esters 18b,c,d,respectively. Similarly, the derived allylic acetates 21g,h and also allylic bromide 17g react with lithium triethylhydridoborate via mechanism SN2' to give (E)-2-methyl-2-alkenoicesters 22g,h and, respectively, 2-methylenealkanoic esters 20g. Methyl (2)-6,6-(ethylenedioxy)-2-methy1-2-heptenoate (22h) has been prepared as an intermediate en route to the norsesquiterpenoid ketone 23. The allylic bromides l7d,e,f also furnish (2)-6-methyl-5-[(trimethylsilyl)methyl]-4-heptene-l,6-diol (19a), (2)-2-methyl-3-[(trimethylsilyl)methyl]-3-octene-2,7-diol (19e).and (2)-7-methyl-6-[ (trimethylsilyl)methyl]-5-octene-1,2,7-triol(19f), which are terpenoid building blocks.
In recent years numerous methods have been developed for preparing a-functionalized acrylic esters 1 in response to a number of synthetic challenges, e.g., the naturally occurring a-methylene-y-butyrolactones.2 Among the precursors 2-13 of 1, many are masked acrylic esters of the
Scheme I. dZ Acrylic Ester Equivalents &02R
R
AC02Me 1
d2 variety as shown in Scheme I. However, with more complex target molecules there are drawbacks in generating carbanionic intermediates under strongly basic conditions. Other precursors of 1 contain activating groups that must be removed subsequently. In context with a number of ongoing synthetic efforts, we required a simple and efficient route to terpenoid building blocks such as 19c (see Scheme 11). Compound 19c is an acid-sensitive, trisubstituted olefin with Z configuration. The three substituents attached to the olefinic carbons contain different functionalities and also introduce some steric crowding. The other terminus of 19c contains a further functionality, i.e., C1. From previous experience we knew that 19c could be prepared from 15c with an excess of methy1lithi~m.l~~ Thus the synthetic problem (1)Part 3 Hoffmann, H. M. R.; Rabe, J. Helv. Chim. Acta 1984,67, 413. (2)Review: Hoffmann, H. M. R.; Rabe, J. Angew. Chem., Znt. Ed. Engl. 1985, 24, 94. (3)Marino, J. P.; Linderman, R. J. J. Org. Chem. 1981, 46, 3696. (4)Marino, J. P.;Farina, J. S. J. Org. Chem. 1976,41, 3213. Marino, J. P.; Floyd, D. M. Tetrahedron Lett. 1979,675. See also: Goldberg, 0.; Dreiding, A. S. Helu. Chim. Acta 1976, 59,1904. (5)Petragnani, N.; Ferraz, H. M. C. Synthesis 1978, 476. (6)Semmelhack, M.F.; Tomesch, J. C.; Czarny, M.; Boettger, S. J. Org. Chem. 1978,43, 1259. (7) Fleming, I.; Goldhill, J. J. Chem. Soc., Perkin Trans. I 1980, 1493. (8)Nishiyama, H.; Yokoyama, H.; Narimatsu, S.; Itoh, K. Tetrahedron Lett. 1982, 23, 1267. (9)Raucher, S.;Hwang, K. J.; Macdonald, J. E. Tetrahedron Lett. 1979,33, 3057. (10)Corbet, J. P.; Benezra, C. Tetrahedron Lett. 1979, 41, 4003. (11)Patterson, J. W.;McMurry, J. E. J. Chem. SOC.D 1971, 488. (12)Yu, L.C.; Helquist, P. J. Org. Chem. 1981, 46, 4536. (13) Seebach, D.; Henning, R.; Mukhopadhyay, T. Chem. Ber. 1982, 115. 1705. (14) Baraldi, P. G.; Guameri, M.; Pollini, G. P.; Simoni, D.; Barco, A.; Benetti, S. J. Chem. SOC.,Perkin Trans. I 1984, 2501. (15) (a) Hoffmann, H. M. R.; Henning, R. Helu. Chim. Acta 1983,66, 828. (b) Henning, R.; Hoffmann, H. M. R. Tetrahedron Lett. 1982,23, 2305.
89
6?
C3,3-s hi f tl
1
-COZEt O2N
(Eto)2 Y O p R
Me2NNLi'0
\
U O M e
10"
C3.2-shift1 9*
1 112
Scheme I1 / M e 3
k 14c
4
0
I OR
SiMe3
SiMe3
CI
r a c r s s MrLl
OR
15c
CI
4 OH
19c
amounted to preparing a range of functionalized acrylic esters 15 stereoselectively. We here describe two routes to 15 and 19, namely, (i) the Horner-Wittig reaction using aldehydes 14a,b,c and (ii) the a-functionalization of acrylic esters with aldehydes 14a-g followed by brominative allylic rearrangement and silylation. The second approach has
0022-3263/85/1950-3849$01.50/00 1985 American Chemical Society
J . Org. Chem., Vol. 50, No. 20, 1985
3R;O
Hoffmann and Rabe
Scheme III. Horner-Wittig Route to Functionalized Acrylic Esters 15a,b and Conversion into 19a
Table I. 2-(Hydroxyalkyl)-2-propenoicEsters 16 via DABCO-Catalyzed Coupling of Aldehydes 14 with Methyl Acrylate
0
0
R-CHO
14
DABCO ( c a 9 a I y 8 i I
t 0 Me
room t o m p
16 14 and 16
R
reacn time, daw
vield, %
a
7
95
b
7
87
C
7
60
15a
15b
MoLi, -5O.C IXi%
0 I
19a
/I
d
87
e
8
92
f
7
89
g
7
h
10
85 63
19b LiAlHq
7 9 Y. a The aldehyde was added to 0 "C to the Horner reagent prepared by (i) (EtO),P(O)CH,CO,Et + NaH in 1,2-dimethoxyethane;(ii) Me,SiCH,I, 7 0 'C, 4 h ; (iii) NaH, 0 "C room temperature, then 0 "C (and (iv) addition of 1 4 a or 14b, 0 "C room temperature, 16 h). --f
-+
-
proved to be simpler and could be applied to other syntheses. Horner-Wittig Reaction.16 This reaction was carried out several times in one pot as follows (see Scheme 111). (i) Ethyl(diethoxyphosphiny1)acetate [(EtO),P(O)CH2C02Et]was deprotonated with sodium hydride, (ii) the resulting anion was alkylated with (iodomethy1)trimethylsilane (Me3SiCH21),a reasonably good SN2 alkylating agent, (iii) the resulting phosphono ester was deprotonated again with sodium hydride, and (iv) aldehydes 14a,b were olefinated with the phosphonate anion. Aldehyde 14a gave (2)-olefin 15a in 32% yield and a minor amount of (E)-olefin (ZE= 4:1), which was detected by 'H NMR and removed by chromatography. The final conversion of 15a into 19a proceeded in 60% yield, which compares with a more favorable yield of 90% for converting 15c into 1 9 ~ ' ~ ~ As a test for the resistance of the benzyloxy group in 14a to the basic conditions of the Homer-Wittig reaction, we studied the 2,4,6-trimethylbenzoyl derivative 14b. As expected the transformation of 14b into the desired (Z)-arrylic ester 15b was feasible (35% yield), but the E-co ,rigurated olefin was again formed (Z:E 3:1), i.e., the X:orner-Wittig reaction in its simple form is not steretuntrolled.16 In this instance, 15b and its E isomer could not be easily separated by column chromatography, because the difference in polarity was less. Addition of n thyllithium to 15b and its E isomer at -50 "C gave 19b ir.
