Tetrahedron Letters,Vol.29,No.46,pp 5937-5938,1988 0040-4039/88 $3.00 + .oo
Printed in Great Britain Peraamon Press plc
REACTION OF DITHIO- SUBSTITUTED CINNAMYLLITHIUM WITH CARBONYL COMPOUNDS : A TEST OF THE HSAB PRINCIPLE
Jim- Min Fang*, Ming- Y i Chen and Wen- Jin Yang Department of Chemistry, National Taiwan University
Taipei, 10764, Taiwan, Republic of China
Abstract-- By mediation of BFs.EtsO, dithio-substituted cinnamyllithium 2 reacted predominantly at the o-site with carbonyl compounds. No selectivity was found when the reaction was
performed in the absence of BFs.Et20.
We have recently observed the dichotomous regiochemistry of aldehyde and ketone in addition reactions with a lithium anion 1 generated from 2-propenyl-1,3-dithiane. While aldehydes reacted exclusively at the r-site of 1, most ketones of modest size attacked the a-site of this unsymmetric allylic anion.1 On the other hand, Murphy and Wattanasin have shown that percentage of alkylation at the &site of the cinnamyl anion 2 increases as the hardness of electrophile RX (X = I, Br, Cl. and OTs) increases.2 We thus carried out the reaction of anion 2 with carbonyl compounds in order to see if the regioselectivity can be correlated with above mentioned results.
Cinnamyllithium 2 was generated from a THF solution of 2-styryl-1,3-dithiane with n-BuLi. On contrary to 1, anion 2 did not exhibit any regio- or stereoselectivity in reactions with various carbonyl compounds at -78 ‘C, except for the reaction with benzophenone (Table). The discrepancy of selectivitiesof anions 1 and 2 can be attributed to difference of electronic properties of r-substituents .3 On the other hand, treatment of the lithium anion 2 (in an ethereal solution) with one equivalent of boron trifluoride etherate prior to addition of carbonyl compounds afforded predominantly a-addition products, except for the reaction with isobutanal . The regioselectivity is consistent with the HSAB principle4 as well as in the trend of alkylations.2 Accordingly, the hardness of carbonyl compound would significantly
5 2
4 6
increase when it coordinates with BFs,5 and thus it preferred to attack the relatively hard a-site of 2. However, the possibility of anion 2 behaving as a cinnamylborona or as an “ate” complex7 was not excluded.
From the synthetic point of view, cinnamyl anion 2 serves as an equivalent of
a,p-unsaturated acyl anion.8 Thus, n-addition products 4 were hydrolyzed with HgCl2 to give 5937
5938
high yields of o’-hydroxy enones 6, which are structural subunits of many natural products9 and the precursors of cyclopentenones (via Nazarov cyclization)iu.
Table. Reactions of Unsymmetric Allylic Anion 2 with Carbonyl Compounds.’
electrophile 0: 7 (anti/syn) b in the absence of BFa total yield (X) a:~ (anti/syn) mediated by BFa total yield (1)
MeCHO MeCHn CHO ;; (;Fc H iCHD CH: =CHCHO MeCH=CBCHO PhCHO cyclopentanone cyclohexanone 2- butanone 3- pentanone 2- heptanone 4- heptanone benzophenone CHZ =CHCOMe 64~36 77~23 53:47 (68132) -0: 100 64 -1oo:o 66:34 (-lOO:O)c :: -0:100 (-loo:o)c 88 90
ii
98:2 93 100: <1 lOO:<l :x 100: <l 83 lOO:<l 786
a) Experimental procedure: ropwise n-BuLi (1.2 mmol, 1.6 M in K To 2-st ryl- 1,3-dithiane exane) at -40 OC. (1 mmol) in ether (10 mL) was added After stirrin f for 20 min, the solution was cooled to -78 “C, and 1 mmol of BFa.EtnO (in 1 mL of ether) was a ded dropwise, followed by addition of 1.2 mmol of appropriate carbonyl compound.min as revealed by the TLC analysis. di
The addition reaction completed in 20 compatible spectra (IR, MS, rH and 13 b All products had satisfactory MR). The ratio of products was determined by the HPLC elmental analyses and and iH NMR analyses and occasionally assisted with measurement of isolated weights of products. The structures of anti and syn isomers were rigorously determined by analyses of corresponding Spiro dithianes (via acid-catalyzed cyclization)ii
group is b6$ier than R’ group). HgClz ) 1
and/or r-lactones (via hydrolysis with c The anti products were obtained as their corresponding trans 7-lactones 5 (R
Acknowledgment: We thank the National Science Council (ROC) for financial support. References:
1. (a) Fang, J. M.; Hong, B. C.; Liao, L. F. J. Org. Chem. 1987, 52, 855. (b) Fang, J. M.; Hong, B. C. ibid. 1987, 52, 3162.
2. Murphy, W. S.; Wattanasin, S. J. J. Chem. Sot., Perk-in Trans 1 1980, 2678.
3. (a) Biellmann, J. F.; Ducep, J. B. Organic Reactions 1982, 27, 1. (b) Meyers, A. I.; Strickland, R. C. J. Org. Chem. 1972, 37, 2579. (c) Koksal, Y.; Raddatz, P.; Winterfeldt, E.
Liebigs Ann. Chem. 1984, 450.
4. Ho, T. L. Tetrahedron 1985, 41, 3.
5. Eis, M. J.; Wrobel, J. E.; Ganem, B. J. Am. Chem. Sot. 1984, 106, 3693.
6. (a) Yamamoto, Y.; Yatagai, K.; Maruyama, K. Chemistry belt. 1979, 385. (b) Naruta, Y.; Ushida, S.; Maruyama, K. ibid. 1979, 919
7. Yamaguchi, M.; Hirao, I. Tetrahedron Lett. 1983,
24,
391.8. (a) Seebach, D. Synthesis 1969, 17. (b) Seebach, D.; Maetzke, T.; Haynes, R. K.; Paddon-Row, M. N.; Wong, S. S. Helv. Chim. Acta. 1988, 71, 299 and references cited therein.
9. Davis, F. A .; Vishwakarma, L. C.; Billmers, J. M.; Finn, J. J. Org. Chem. 1984, 49, 3241. 10. Santelli-Rouvier, C.; Santelli, M. Synthesis 1983, 429.
11. Suzuki, K.; Tomooka, K.; Matsumoto, T.; 'Katayama, E.; Tsuchihashi, G. I.
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