The ZnCl2 catalyzed reaction of p-methoxybenzyl chloride with alkenes yields the 1:1 addition products 3, which are converted into the γ-lactones 4 via Ru(VIII) catalyzed oxidative degradation of the aromatic ring

Bäuml, Englbert

Mayr, Herbert

Pock, Rudolf

Tscheschlok, Kai

English

Universität München: Elektronischen Publikationen

Tetrahedron Letters,Vol.29,No.52,pp 6925-6926,1988 0040-4039/88 $3.00 + .OO 
Printed in Great Britain Pergamon Press plc 
SYNTHESIS OF -l-LACTONES FKt4 ALdDNES l+W_DYING p+ETH~ENZYL CHLCIRIDE AS +cH,-CO~ 
lzcwnrm 
Englbert B&ml, Kai Tscheschlok, Rudolf Pock, and Herbert Mayr* 
Institut fiir Chemie der Medizinischen Universitat zu Liibeck 
Ratzeburger Allee 160, D-2400 Liibeck 1, Federal Republic of Germany 
Abstract. The ZnCl, catalyzed reaction of p-methoxybenzyl chloride with alkenes yields 
the 1 :l addition products 3, which are converted into the Y-lactones 4 via Ru(VII1) 
catalyzed oxidative degradation of the aromatic ring. 
The transformation of alkenes into Y-lactones (eq.1) via addition reactions of free 
radicals has been described by several authors. Boldt performed the conversion (eq.1) by 
radical initiated addition of bromodicyanomethane towards alkenes and subsequent hydrolysis 
and decarboxylation.’ Analogously, Y-lactones were obtained from alkenes and a-bromo- 
carboxylic acids’ or the tin salts of a-iodo or a-bromoacetic acid.’ The oxidative addition 
of carboxylic acids to alkenes, which is achieved in basic medium with metal ions (e.g. 
Mn+++) as oxidants also involves a free radical addition step.5 We report now on an 
electrophilic addition pathway for the transformation (eq.l), which is especially suited 
for the synthesis of Y,Y-bisalkylated Y-lactones. 
0 
R1 R4 
(1) 
The ZnCl,*OEt, catalyzed’ reaction of p-methoxybenzyl chloride 1 with the alkenes 2a-f 
affords high yields of the 1:l addition products 3-f under conditions analogous to those 
reported for additions of other SHl active chlorides. ’ For the Ru(VIII)-catalyzed oxidations 
of the aromatic ring,’ solutions of the crude adducts 3 (10 mmol) in CH,Cl, (50 ml) were 
added dropwise to well stirred mixtures of RuCl, (0.8 mmol), CH,Cl, (50 ml) and 140 ml of 
a 2.16 M aqueous NaOCl solution. Satisfactory yields of the lactones 4 are obtained, 
if the rate of addition of 3 to the oxidants is slow enough to allow the intermediate 
regeneration of RuO, , which is recognizable by its gold-orange color. The use of acetonitrile 
as a cosolvent, which has been recommended for related oxidations,’ was found to diminish 
the yield of 4. As expected, the oxidation of the aromatic ring is greatly enhanced by 
the methoxy group, since the oxidation of 3P gave 26% of the lactone 4f (yield not opti- 
mized), which incorporates an intact phenyl group. 
6925 
6926 
CH2C1 
0 
R1 R4 
ZnCl,*OEt, 
1; + 
x 
R2 R3 
OCH, 
':;; * p: ,;;;y;; og2;+ 
OCH, 
1 2 3 4 
2, 3, 4 R' R2 R' R' 
% Y&d % Yield 
Ila 
13C-NMR (CDCl,) 
a H H CH, CH, a4 54 27.73 (q), 29.38 (t), 34.66 (t), 
84.63 (s), 176.74 (s) 
b H CH, CH, CH, a4 69 14.26 (q), 21.63 (q), 27.05 (q), 
36.74 (t), 39.87 cd), 86.98 b), 
175.86 (s) 
c CH, CH, CH, CH, 88 77 22.99 (q), 23.42 (q), 41.09 (s), 
43.88 (t), 88.57 (~1, 175.74 (9) 
d H H CH, n-C,H, 81 59 14.34 (91, 17.20 (t), 25.58 (q), 
29.19 (t), 32.95 (t), 43.21 (t), 
86.92 (s), 176.90 (s) 
e H H CH, CH,-C(CH,), 91 45 26.78 (q), 28.76 (t), 31.12 (s), 
31.23 (q), 36.04 (t), 53.44 (t), 
88.03 (s), 177.26 (s) 
f H 'H H C,H, 72 26 28.96 (t), 30.98 (t), al.24 cd), 
125.28 (d), 128.45 (d),l28.75 (d), 
139.39 (s), 176.93 (s) 
a) 'H NMR of 4a: ref."'; 4b, f: ref.'; 4~: ref."; 4d (CDCl,): 6 0.95 (t, J = 7.1 Hz, 3 
H), 1.35-1.70 (m (4 H) superimposed by s (3 H) at 1.341, 1.95-2.19 (m, 2 H), 1.56-2.66 (m, 
2 H); 4e (CDCl,): 6 1.04 (s, 9 H), 1.48 (.a, 3 H), 1.65 and 1.75 (A0 system with 3~ = 14.9 
HZ, 2 H), 1.80-2.14 (m, 2 H), 2.55-2.65 (m, 2 H). 
Preliminary experiments show that an analogous reaction sequence can be carried out with 
a-substituted benzyl chlorides. The scope of the novel lactone synthesis and of its intramole- 
cular variant is presently under investigation. 
Acknowledgement. We thank Ms. R. Lamners for exploratory experiments, the Deutsche Forschungs- 
gemeinschaft and the Fonds der Chemischen Industrie for financial support. 
References and Notes 
9) 
10) 
II) 
K. Tscheschlok, Diplomarbeit Fachhochschule Liibeck, 1988. 
P. Boldt, W. Thielecke, J. Etzemiiller, Chem. Ber. 102, 4157 (1969). 
T. Nakano, M. Kayama, H. Matsumoto, Y. Nagai, Chem. Lett. 1981, 415. 
G.A. Kraus, K. Landgrebe, Tetrahedron 41, 4039 (1985). 
E.I. Heiba, R.M. Dessau, P.G. Rodewald, J. Am. Chem. Sot. 96, 7977 (1974) 
H. Mayr, W. Striepe, J. Org. Chem. !?&I, 2995 (1985). 
H. Mayr, W. Striepe, J. Org. Chem. 48, 1159 (1983). 
Reviews: (a) D.G. Lee, M. van den Engh in "Oxidation in Organic Chemistry", Part B, 
W.S. Trahanovsky, Ed., Academic Press: New York, 1973, Chapt. IV.; (b) A.H. Haines, 
Methods for the Oxidation of Organic Compounds, Academic Press: London, 1985, pp. 192 
(a) P.H.J. Carlsen, T. Katsuki, V.S. Martin, K.B. Sharpless, J. Org. Chem. 46, 3936 
(1981). (b) H. Orita, T. Hayakawa, K. Takehira, Bull. Chem. Sot. Jpn. 59, 2637 (1986). 
J. Lehmann, M. Marquardt, Synthesis 1987, 1064. 
C. Metzger, D. Borrmann, R. Wegler, Chem. Ber. 100, 1817 (1967). 
(Received in Germany 3 October 1988) 


Synthesis of γ-lactones from alkenes employing p-methoxybenzyl chloride as +CH2---CO−2 equivalent

Open Access LMU ( Ludwig-Maximilians-Univ. München)

Tetrahedron Letters,Vol.29,No.52,pp 6925-6926,1988 0040-4039/88 $3.00 + .OO Printed in Great Britain Pergamon Press plc SYNTHESIS OF -l-LACTONES FKt4 ALdDNES l+W_DYING p+ETH~ENZYL CHLCIRIDE AS +cH,-CO~ lzcwnrm Englbert B&ml, Kai Tscheschlok, Rudolf Pock, and Herbert Mayr* Institut fiir Chemie der Medizinischen Universitat zu Liibeck Ratzeburger Allee 160, D-2400 Liibeck 1, Federal Republic of Germany Abstract. The ZnCl, catalyzed reaction of p-methoxybenzyl chloride with alkenes yields the 1 :l addition products 3, which are converted into the Y-lactones 4 via Ru(VII1) catalyzed oxidative degradation of the aromatic ring. The transformation of alkenes into Y-lactones (eq.1) via addition reactions of free radicals has been described by several authors. Boldt performed the conversion (eq.1) by radical initiated addition of bromodicyanomethane towards alkenes and subsequent hydrolysis and decarboxylation.’ Analogously, Y-lactones were obtained from alkenes and a-bromo- carboxylic acids’ or the tin salts of a-iodo or a-bromoacetic acid.’ The oxidative addition of carboxylic acids to alkenes, which is achieved in basic medium with metal ions (e.g. Mn+++) as oxidants also involves a free radical addition step.5 We report now on an electrophilic addition pathway for the transformation (eq.l), which is especially suited for the synthesis of Y,Y-bisalkylated Y-lactones. 0 R1 R4 (1) The ZnCl,*OEt, catalyzed’ reaction of p-methoxybenzyl chloride 1 with the alkenes 2a-f affords high yields of the 1:l addition products 3-f under conditions analogous to those reported for additions of other SHl active chlorides. ’ For the Ru(VIII)-catalyzed oxidations of the aromatic ring,’ solutions of the crude adducts 3 (10 mmol) in CH,Cl, (50 ml) were added dropwise to well stirred mixtures of RuCl, (0.8 mmol), CH,Cl, (50 ml) and 140 ml of a 2.16 M aqueous NaOCl solution. Satisfactory yields of the lactones 4 are obtained, if the rate of addition of 3 to the oxidants is slow enough to allow the intermediate regeneration of RuO, , which is recognizable by its gold-orange color. The use of acetonitrile as a cosolvent, which has been recommended for related oxidations,’ was found to diminish the yield of 4. As expected, the oxidation of the aromatic ring is greatly enhanced by the methoxy group, since the oxidation of 3P gave 26% of the lactone 4f (yield not opti- mized), which incorporates an intact phenyl group. 6925 6926 CH2C1 0 R1 R4 ZnCl,*OEt, 1; + x R2 R3 OCH, ':;; * p: ,;;;y;; og2;+ OCH, 1 2 3 4 2, 3, 4 R' R2 R' R' % Y&d % Yield Ila 13C-NMR (CDCl,) a H H CH, CH, a4 54 27.73 (q), 29.38 (t), 34.66 (t), 84.63 (s), 176.74 (s) b H CH, CH, CH, a4 69 14.26 (q), 21.63 (q), 27.05 (q), 36.74 (t), 39.87 cd), 86.98 b), 175.86 (s) c CH, CH, CH, CH, 88 77 22.99 (q), 23.42 (q), 41.09 (s), 43.88 (t), 88.57 (~1, 175.74 (9) d H H CH, n-C,H, 81 59 14.34 (91, 17.20 (t), 25.58 (q), 29.19 (t), 32.95 (t), 43.21 (t), 86.92 (s), 176.90 (s) e H H CH, CH,-C(CH,), 91 45 26.78 (q), 28.76 (t), 31.12 (s), 31.23 (q), 36.04 (t), 53.44 (t), 88.03 (s), 177.26 (s) f H 'H H C,H, 72 26 28.96 (t), 30.98 (t), al.24 cd), 125.28 (d), 128.45 (d),l28.75 (d), 139.39 (s), 176.93 (s) a) 'H NMR of 4a: ref."'; 4b, f: ref.'; 4~: ref."; 4d (CDCl,): 6 0.95 (t, J = 7.1 Hz, 3 H), 1.35-1.70 (m (4 H) superimposed by s (3 H) at 1.341, 1.95-2.19 (m, 2 H), 1.56-2.66 (m, 2 H); 4e (CDCl,): 6 1.04 (s, 9 H), 1.48 (.a, 3 H), 1.65 and 1.75 (A0 system with 3~ = 14.9 HZ, 2 H), 1.80-2.14 (m, 2 H), 2.55-2.65 (m, 2 H). Preliminary experiments show that an analogous reaction sequence can be carried out with a-substituted benzyl chlorides. The scope of the novel lactone synthesis and of its intramole- cular variant is presently under investigation. Acknowledgement. We thank Ms. R. Lamners for exploratory experiments, the Deutsche Forschungs- gemeinschaft and the Fonds der Chemischen Industrie for financial support. References and Notes 9) 10) II) K. Tscheschlok, Diplomarbeit Fachhochschule Liibeck, 1988. P. Boldt, W. Thielecke, J. Etzemiiller, Chem. Ber. 102, 4157 (1969). T. Nakano, M. Kayama, H. Matsumoto, Y. Nagai, Chem. Lett. 1981, 415. G.A. Kraus, K. Landgrebe, Tetrahedron 41, 4039 (1985). E.I. Heiba, R.M. Dessau, P.G. Rodewald, J. Am. Chem. Sot. 96, 7977 (1974) H. Mayr, W. Striepe, J. Org. Chem. !?&I, 2995 (1985). H. Mayr, W. Striepe, J. Org. Chem. 48, 1159 (1983). Reviews: (a) D.G. Lee, M. van den Engh in "Oxidation in Organic Chemistry", Part B, W.S. Trahanovsky, Ed., Academic Press: New York, 1973, Chapt. IV.; (b) A.H. Haines, Methods for the Oxidation of Organic Compounds, Academic Press: London, 1985, pp. 192 (a) P.H.J. Carlsen, T. Katsuki, V.S. Martin, K.B. Sharpless, J. Org. Chem. 46, 3936 (1981). (b) H. Orita, T. Hayakawa, K. Takehira, Bull. Chem. Sot. Jpn. 59, 2637 (1986). J. Lehmann, M. Marquardt, Synthesis 1987, 1064. C. Metzger, D. Borrmann, R. Wegler, Chem. Ber. 100, 1817 (1967). (Received in Germany 3 October 1988) 

9) 10) II) K. Tscheschlok, Diplomarbeit Fachhochschule Liibeck,

van den Engh in &quot;Oxidation in Organic Chemistry&quot;, Part

https://epub.ub.uni-muenchen.de/3799/1/086.pdf

Synthesis of γ-lactones from alkenes employing p-methoxybenzyl chloride as +CH2---CO−2 equivalent

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