T. Kunz, H.-U. ReiRig 891

Radical Additions in Aqueous Medium: Direct Synthesis of 5-Allyl-Substituted y-Lactones from Allylic Bromides/Zinc and Methyl y-Oxocarboxylates Thomas Kunz and Hans-Ulrich Reiflig*

Institut fur Organische Chemie der Technischen Hochschule Darmstadt, PetersenstraBe 22, D-6100 Darmstadt

Received March 28, 1989

Key Words: y-Lactones / Radical additions / Felkin-Anh model

Recently, Luche reported that aldehydes and ketones un- dergo smooth Barbier reaction with allylic halides and zinc in aqueous medium (sat. NH,Cl/tetrahydrofuran) to provide the corresponding homoallylic alcohols’). We found that in- troduction of easily available methyl y-oxocarboxylates 1 3,

into this procedure affords y-lactones 2 after treatment with acid in reasonable yields.

Scheme 1

11 Zn. //var

THF/ H20/ N H C 1

H+CO&4e R 2) H P +

yield trans: cis l a R = He 77% 52 : 48 2a l b R - i-Prop 55% 68 : 32 2b I C R - Ph 77% 77 : 23 2c

As shown in Scheme 1, the addition reaction is stereo- random for l a (R = Me), while with larger substituents (R = iPr, R = Ph) moderate selectivity in favor of the trans- y-lactones 2b and 2c is observed. The ratio of diastereomers is determined in the first addition step. This was demon- strated for 1 a which after neutral workup gives the corre- sponding y-hydroxycarboxylate as a 1 : 1 mixture of synlanti isomers ‘1.

The following mechanistic scheme has been suggested for this r ea~ t ion~ ,~ ) : formation of an allyl radical at the metal surface and its addition to the carbonyl group is succeeded by fast reduction of the intermediate alkoxy radical to give the corresponding homoallylic alcohol. Therefore, it is in- teresting to compare the stereoselectivities observed under these conditions involving a (nucleophilic) radical on the one

hand with those of Lewis acid promoted allyltrimethylsilane additions to the chiral aldehydes 1

Table 1 shows that translcis ratios obtained with Zn/H20 (column 1) are rather similar to those received under “cat- ionic” conditions with BF3 as Lewis acid (column 2). How- ever, chelate-controlled additions to l allow significantly higher stereoselectivities as shown in column 3 for TiC1,- promoted additions of allyltrimethylsilane. Of further inter- est is comparison of the synlanti ratios employing simpler chiral aldehydes not capable to form chelates. Thus, line 4 displays results reported for 2-phenylpr0panal*,~), where a slight decrease in selectivity can be noted by going from column 1 to 3.

on the other.

Tab. 1. Stereoselectivities of chiral aldehydes 1 a - 1 c and 2-phenylpropanal in allylic additions

aldehyde CHz=CHCHzBr CHZ =CHCHz SiMea Zn/HzO BF3/CHzClz TiClr /CHzClZ

trans/cis trans / cis trans/cis

la 52 : 48 52 : 48 63 : 37

- lb 68 : 32 15 : 25 9 2 : 8

- lc 17 : 23 70 : 30 93 : 7

PhCHMeCHOaJ 79 : 2lZJ 67 : 3 3 6 ) 61 : 396,

For this line the synlanti ratio is recorded.

Overall, the nucleophilic allyl radical (in proximity to the metal surface) shows similar stereoselectivities as organo- metallic nucleophiles under non-chelating conditions. The Felkin-Anh model7) may reasonably rationalize this behav- iour. A conformation with the aldehyde’s largest substituent

Liebigs Ann. Chem. 1989, 891 - 893 0 VCH Verlagsgesellschaft mbH, D-6940 Weinheim, 1989 0170-2042/89/0909-0891 $ 02.50/0

892 T. Kunz, H.-U. ReiDig

orthogonal to the carbonyl group and anti to the attacking species would lead to the observed major products.

As further substrate we tested prenyl bromide which re- acts at the more substituted carbon” with l a to afford y-lactone 2d (“iso-Eldanolide”*)) as a 1 : 1 mixture of trans/ cis isomers. No enhancement of stereoselectivity is observed as compared to the addition of the unsubstituted allyl rad- ical.

0 \ /

la 56 X 2d

Although mixtures of diastereomers are obtained with chiral substrates, the transformation of methyl y-oxocar- boxylates 1 into 5-allyl-substituted y-lactones 2 described in this paper might be of preparative interest due to the simple and inexpensive chemicals used as source of the allylic side chain.

Support of this work by the Deutsche Forschungsgemeinschaft, the Fonds der Chemischen Industrie, the Vereinigung von Freunden der Technischen Hochschule zu Darmstadt, and the Karl- Winnacker- Stiftung (Hoechst AG, Frankfurt) is gratefully acknowledged. Ex- perimental help by Brigitte Suchlund is very much appreciated.

Experimental For general informations see ref?). - Commercially available

zinc dust has been used for the transformations described. -

Methyl y-oxocarboxylates 1 a - 1 c are prepared analogously to the general procedure published in ref.3a). - All y-lactones are colorless liquids; the spectroscopic data for 2a-2d are compiled in Tables

5-Allyl-4,5-dihydro-4-metlzyl-2(3H)-furanone (2a): To a suspen- sion of 0.325 g (2.50 mmol) of l a and 0.196 g (3.00 mmol) of zinc dust in tetrahydrofuran/sat. NH,CI solution (0.5 m1/2.5 ml) is added 0.363 g (3.00 mmol) of allyl bromide. A strongly exothermic reaction occurs and the metal dissolves within 2 min. After 1 h, 2.5 ml of 50% H,S04 is added. The clear solution is stirred for 8 h at room temp., diluted with 5 ml of CH2CI2, and further extracted with this solvent. Drying (MgSO,), concentration, and kugelrohr distillation (70”C/0.01 Torr) provide 0.271 g (77%) of 2a”) (trans:cis = 52:48, purity z 95%). CsHlzOz (140.2) Found C 67.82 H 8.84

5-Allyl-4,5-dihydro-4-isopropyl-2(3H)~furanone (2 b): Analo- gously to the preceeding experiment, 0.316 g (2.00 mmol) of l b , 0.290 g (2.40 mmol) of allyl bromide, and 0.157 g (2.40 mmol) of zinc dust in THF/sat. NH4CI solution (0.4 m1/2 ml) afford 0.184 g (55%) of 2b (b.p. 7O0C/O.01 Torr) as a 68:32 truns:cis mixture.

C10H1602 (168.2) Found C 71.05 H 9.70

5-Allyl-4,5-dihydro-4-phenyl-2(3H),furanone (2c): Analogously to the synthesis of 2a, 0.384 g (2.00 mmol) of l c , 0.290 g (2.40 mmol) of allyl bromide, and 0.157 g (2.40 mmol) of zinc dust in THF/sat. NH4C1 solution (0.4 m1/2 ml) provide 0.309 g (77%) of 2c (b.p. 130”C/0.02 Torr) as a 77:23 trans:cis mixture.

CI3Hl4O2 (202.3) Calcd. C 77.20 H 6.98 Found C 77.20 H 6.98

5- (I,1-Dimethyl-2-propenyl)-4,5-dihydro-4-methyl-2(3H)-fura- none (2d): Analogously to the synthesis of 2a, 1.08 g (8.30 mmol) of l a , 1.43 g (9.96 mmol) of 3,3-dimethylallyl bromide, and 0.650 g

2-4.

Calcd. C 68.55 H 8.63

Calcd. C 71.39 H 9.59

Tab. 2. ‘H-NMR data (300 MHz, CDCl3, ppm) for y-lactones 2a-2d (6-H, 7-H, and 8-H are protons of the allyl substituent)a)

3-H 4-H 5-H(~is)~) 6-H 7-H 8-H 4-R 5-H(tran~)~ )

2.78 - 2.12 5.82 5.24 - 5.10 - 2a 2.78 - 2.12 4.51 4.10 (m) (dt, J = 8.2, (td, J = 6.9, (m) (mc) (in)

5.7 Hz) 5.1 Hz)

- 2b 2.60, 2.31 2.08 (mc) 4.59 4.34 2.55 - 2.23 5.80 5.22 - 5.09 (AB part, (ddd, J = 9, (9, J = 5.7 Hz) (m) (mc) (m) JAB = 18 Hz, 7, 6 Hz) JAX = 9.5 Hz, Jex = 7.0 Hz)~)

- 2c 2.94, 2.74 3.39 trans (AB part, (dt, J = 10.2,

JAB = 17 Hz, 8.5 Hz) JAX = 10.2 Hz, JBX = 8.5 Hz)

- 2c 2.98, 2.76 3.76 4.77 cis (AB part, (ddd, J = 8.7, (add, J = 8.7,

JA B = 17.5 Hz. 6.7, 4.7 Hz) 6.5, 5.0 Hz) JAX = 8.7 Hz, JBX = 4.7 Hz)

4.54 2.58 - 2.34 5.74 5.15 (ddd, J = 8.5, (m) (mc) (mc) 6.7, 4.6 Hz)

2.14 - 1.86 5.67 5.00 (in) (mc) (mc)

- 2d 2.76 - 2.56 2.76 - 2.56 4.15 3.86 1.16, 1.08 6.02 5.18 - 4.96

(2nd (m, mc) 10.8 HZ)

(dd, J = 17.4,

2.22 - 2.06 2.37 ( d , J = 5.0 Hz) ( d , J = 5.2 Hz) (2s)e) (dd , J = 17.6, (m)

5.79

11.2 Hz)

1.14=) ( d , J = 6.4 Hz) 1.05b) ( d , J = 7 . 0 Hz)

1.73d) (sept, J = 6.7 Hz) 0.94, 0.91 (2d. J = 6.7 Hz)

7.41 - 7.12 (m)

7.41 - 7.12 (m)

1.14 1.03 (Zd, J = 7 Hz)

a) The integrals provide the expected values. - bJ Signal of the cis isomer. - cJ Signal of the trans isomer. - dl Signal of the truns isomer; the corresponding signal of cis-2 b is hidden by multiplets. - Signals for 6-Me.

Liebigs Ann. Chem. 1989, 891 - 893

Radical Additions in Aqueous Medium 893

Tab. 3. I3C-NMR data (75.5 MHz, CDCI,, ppm) of y-lactones 2a-2d (numbering of the allyl side chain: C-6, C-7, C-8)

C-2 C-3 / C-6 C-4 C-5 C-7 C-8 R (S) ( 2 t ) (d) (d) (d) ( t )

trans-& 176.1 37.7, 36.7 34.9 86.0 132.4 118.4 17.3 (9) cis-& 176.4 37.2, 34.1 32.7 82.4 132.8 118.0 13.6 (q)

trans-@ 176.5 39.5, 31.7 45.2 82.7 132.4 116.8 30.5 ( d ) , 20.1, 19.0 (29) cis-@ 176.4 33.8, 32.1 46.3 82.0 133.2 116.2 27.5 ( d ) , 20.9 (q)

t r a n s - 2 175.3 37.4, 37 .1 46.1 85.6 132.1 118.8 138.8 (s). 129.0, 127.6, 127.1 (3-3) cis-& 176.4 35.6, 35.4 44.1 83.1 132.8 117.9 137.6 (s). 128.6, 127.7 ( 2 d I a )

t r a n s - z b ) 176.8 39.1, 39.4=) 34.0 93.7 142.4 114.4 25.8, 23.7, 23.0 (3q) c i s - H 176.5 37.0, 39 .QC) 30.0 89.2 140.0 112.8 22.4, 21.2, 15 .6 (3q)

One signal is hidden by other signals. - bJ Figures in this line are exchangable with those of the line below; assignment to cisltrans isomer is not possible. - ci Two singlets.

Tab. 4. IR data (C, cm-') of y-lactones 2a-2d ') Thomas Kunz, Dissertation, Technische Hochschule Darmstadt,

2i 2a) C. Petrier, J.-L. Luche, J. Org. Chem. 50 (1985) 910. - 2bi C. s o l v e n t =CH CH c=o c=c Petrier, C. Einhorn, J.-L. Luche, Tetrahedron Lett. 26 (1985)

1449. - C. Einhorn, J.-L. Luche, J. Organomet. Chem. 322 (1987) 177. - See also: H. Mattes, C. Benezra, Tetrahedron Lett.

1989.

2a CC14 3080 2970, 2920 1785 1640 26 (1985) 5697 -

- 26 f i l m 3080 2970, 2940, 2890 1775 1640

- 2C CHC13 3080 2940, 2860 1775 1640

- 26 f i l m 3040 2940, 2910, 2850 1765 1620

(9.96 mmol) of zinc dust in THFJsat. NH4C1 solution (1.7 m1/8.3 ml) give after careful distillation (b.p. 70"C/0.01 Torr) 0.778 g (56%) of 2d (trans:cis = 50:50). C,"HI6O2 (168.2) Calcd. C 71.39 H 9.59 Found C 71.31 H 9.64

CAS Registry Numbers

la:65038-34-8/1b: 71464-85-2/1c: 51232-29-4/trans-2a: 112423- 33-3 / cis-2a: 212423-36-6 1 trans-2b: 112423-34-4 1 cis-2b: 112423- 37-7 J trans-2c: 112423-35-5 / cis-2c: 112423-38-8 J trans-2d: 121013-30-7 / cis-2d: 121013-31-8 / allyl bromide: 106-95-6 / 3,3- dimethylallyl bromide: 870-63-3

1 - - - - I - - - ' . 3J TajE. Kunkel, I. Reichelt, H.-U. ReiSig, Liebigs Ann. Chem. 1984,

802. - I b ) Full experimental details for the synthesis of l a - l c : T. Kunz, A. Janowitz, H.-U. ReiBig, Synthesis, in the press.

4J J.-L. Luche, C. Allavena, C. Petrier, C. Dupuy, Tetrahedron Lett. 29 (1988) 5373.

5J T. Kunz, H.-U. ReiRig, Angew. Chem. 100 (1988) 297; Angew. Chem., Znt. Ed. Engl. 27 (1988) 268; manuscripts with full exper- imental details: Chem. Ber., in the press. The cisltrans assign- ments will be discussed in this paper.

ni C. H. Heathcock, S. Kiyooka, T. A. Blumenkopf, J. Org. Chem. 49 (1984) 4214.

') M. Cherest, H. Felkin, N. Prudent, Tetrahedron Lett. 1968, 2199. - N. T. Anh, Top. Curr. Chem. 88 (1980) 145. - K. N. Houk, Pure AppJ. Chem. 55 (1983) 277.

8i Eldanolide [4,5-Dihydro-4-methyI-5-prenyl-3(2H)-furanone] is the wing gland pheromone of the african sugar-cane borer Eldana saccharina; for synthesis and further references see: H. Frauenrath, T. Phillips, Liebigs Ann. Chem. 1985, 1951.

9J R. Zschiesche, H.-U. ReiBig, Liebigs Ann. Chem. 1988, 1165. loiY. Ueno, 0 . Moriyaa, K. Chino, M. Watanabe, M. Okawara,

J. Chem. SOC., Perkin Trans. 1 , 1986, 1351. W 8 9 l

Liebigs Ann. Chem. 1989, 891 -893