Palladium catalyzed additions to allylic hydroxy phosphonates: Applications in the enantioselective synthesis of enterolactone and turmerone

Article abstract of DOI:10.1080/10426500212246

Reaction of nonracemic allylic hydroxy phosphonates, prepared by the asymmetric phosphonylation of unsaturated aldehydes, with methyl chloroformate in pyridine yields the corresponding carbonates. The carbonates are excellent substrates for the palladium-

Full text of DOI:10.1080/10426500212246

This article was downloaded by: [Monash University Library]
On: 26 November 2014, At: 08:15
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House,
37-41 Mortimer Street, London W1T 3JH, UK
Phosphorus, Sulfur, and Silicon and the Related
Elements
Publication details, including instructions for authors and subscription information:
http://www.tandfonline.com/loi/gpss20
Palladium Catalyzed Additions to Allylic Hydroxy
Phosphonates: Applications in the Enantioselective
Synthesis of Enterolactone and Turmerone
a
a
a
Bradley J. Rowe , Jeffrey Scholten & Christopher D. Spilling
a
Department of Chemistry , University of Missouri-St. Louis , 8001 Natural Bridge Road, St.
Louis, Missouri, 63121, USA
Published online: 27 Oct 2010.
To cite this article: Bradley J. Rowe , Jeffrey Scholten & Christopher D. Spilling (2002) Palladium Catalyzed Additions to
Allylic Hydroxy Phosphonates: Applications in the Enantioselective Synthesis of Enterolactone and Turmerone, Phosphorus,
Sulfur, and Silicon and the Related Elements, 177:6-7, 1881-1884, DOI: 10.1080/10426500212246
To link to this article: http://dx.doi.org/10.1080/10426500212246
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained
in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no
representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the
Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and
are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and
should be independently verified with primary sources of information. Taylor and Francis shall not be liable for
any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever
or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of
the Content.
This article may be used for research, teaching, and private study purposes. Any substantial or systematic
reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any
form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http://
www.tandfonline.com/page/terms-and-conditions

Phosphorus, Sulfur and Silicon, 2002, Vol. 177:1881–1884
Copyright �C 2002 Taylor & Francis
1
042-6507/02 $12.00 + .00
DOI: 10.1080/10426500290093216
PALLADIUM CATALYZED ADDITIONS TO ALLYLIC
HYDROXY PHOSPHONATES: APPLICATIONS
IN THE ENANTIOSELECTIVE SYNTHESIS
OF ENTEROLACTONE AND TURMERONE
Bradley J. Rowe, Jeffrey Scholten, and Christopher D. Spilling
Department of Chemistry, University of Missouri-St. Louis, 8001
Natural Bridge Road, St. Louis, Missouri 63121, USA
(Received July 29, 2001; accepted December 25, 2001)
Reaction of nonracemic allylic hydroxy phosphonates, prepared by the
asymmetric phosphonylation of unsaturated aldehydes, with methyl
chloroformate in pyridine yields the corresponding carbonates. The car-
bonates are excellent substrates for the palladium-catalyzed addition
of nucleophiles. Addition of the nucleophile is highly regioselective, re-
sulting in � -substituted vinyl phosphonates. The reaction of the al-
lylic carbonates with aryl stannanes and malonates has been inves-
tigated. Progress in the application of these reactions to the synthesis
of turmerone and enterolactone is reported.
Keywords: Allylic carbonates; aryl stannanes; malonates; palladium;
phosphonates
INTRODUCTION
The last 10 years have witnessed a rapid advance in methods for the
enantioselective synthesis of hydroxy phosphonates, giving access to
1
compounds with high enantiomeric purity. It has been recognized that
allylic hydroxy phosphonates are useful intermediates in the synthe-
2,3
sis of many � substituted phosphonates. In particular, allylic hydroxy
We are grateful to the Donors of the Petroleum Research Fund administered by the
American Chemical Society (34428-AC1) for financial support of this project and the
UMSL Graduate School for fellowship for BJR. We are also grateful to the NSF, the US
DOE and the University of Missouri Research Board for grants to purchase the NMR spec-
trometers (CHE-9318696, CHE-9974801, DE-FG02-92-CH10499) and mass spectrometer
(
CHE-9708640) used in this work.
Address correspondence to Christopher D. Spilling, Department of Chemistry, Uni-
versity of Missouri-St. Louis, 8001 Natural Bridge Road, St. Louis, Missouri 63121, USA.
E-mail: cspill@jinx.umsl.edu
1
881

1
882
B. J. Rowe et al.
phosphonates display some of the rich chemistry associated with allylic
alcohols. However, the steric and electronic influence of the phospho-
rus moiety may enhance the stereochemical and regiochemical outcome
of the reactions. This effect is amply demonstrated in the palladium-
catalyzed addition of nucleophiles to the corresponding acetate and
carbonate derivatives. The acetate and carbonate derivatives of al-
lylic hydroxy phosphonates 1 undergo palladium-catalyzed addition of
various nucleophiles to give substituted vinyl phosphonates 3 in high
yield (Scheme 1). The nucleophile often adds exclusively to the 3 posi-
tion, with migration of the double bond into “conjugation” with phos-
2
phoryl group. Our earlier success with the palladium catalyzed addi-
tion of amines to nonracemic allylic hydroxy phosphonate derivatives3b
prompted the exploration of reactions with other nucleophiles, namely
aryl stannanes and malonates.
SCHEME 1
RESULTS AND DISCUSSION
The (R) hydroxy phosphonate 1a was prepared (Scheme 2) by a titanium
4
alkoxide-catalyzed phosphonylation of crotonaldehyde in 65% e.e. The
alcohol was converted to the carbonate by reaction with methyl chloro-
formate in pyridine (80%). Reaction of the carbonate with p-tolyl trib-
�
utylstannane in N-methyl pyrrolidinone (NMP) at 60 C in the presence
of palladium (0) trifurylphosphine complex (formed in situ) gave the
E-vinyl phosphonate 4E (57%) and the Z-vinyl phosphonate 4Z (9%).
The use of trifurylphosphine was critical in this reaction.5 Triph-
enylphosphine and triphenylarsine resulted in slow reactions and led
to complex mixtures, predominating materials in which resulted from
reduction of the allylic carbonate. The H-H and P-H coupling of the
1
vinyl protons in the H NMR spectra easily distinguish the E and Z
isomers 4. In particular, H-1 of the Z-vinyl phosphonate 4Z exhibits a
trans P-H coupling constant of 53 Hz, whereas the in E-vinyl phospho-
nate 4E, H-1 shows a cis P-H coupling constant of 22 Hz. The mixture
of E- and Z-vinyl phosphonates 4 (85:15) were subjected to hydrobora-
tion to give exclusively the �-hydroxy phosphonate as 1.5:1 mixture of
6
diastereoisomers (80%). Treatment of the hydroxy phosphonate with

Palladium Catalyzed Additions to Allylic Hydroxy Phosphonates
1883
sodium bicarbonate in refluxing methanol/water solution gave the (R)
aldehyde 5 {78%, [�]D � 15.2 (c1, CHCl3), 38% e.e.}. The stereochemi-
cal assignment was made by comparison with (S)-(+)-3-(p-tolyl)butanal
7
{
[�]D + 39.6 (c1, CHCl3)} synthesized by Dulio et al. The observed alde-
hyde stereochemistry (R) is consistent with the expected mechanism
which involves inversion of configuration during �-allyl formation and
retention during transmetallation and reductive elimination (i.e., over-
all retention). The erosion in the enantiomeric excess is probably due to
formation of the E-vinyl phosphonate, which will have the opposite con-
figuration at C3 (S) as the Z-vinyl phosphonate (R). Dulio also reported
the conversion of the (S)-aldehyde 5 into ar-turmerone 6 by reaction
with 2-methyl-2-propenyl Grignard, followed by MnO2 oxidation of the
resulting alcohol.
SCHEME 2
Hydroxy phosphonate 1b was prepared (Scheme 3) by a titanium
4
alkoxide-catalyzed phosphonylation of cinnamaldehyde (88% e.e. after
recrystallization) as a model substrate for enterolactone 7.
SCHEME 3

1
884
B. J. Rowe et al.
The alcohol was converted to the carbonate by reaction with methyl
chloroformate in pyridine (78%). Reaction of the carbonate with mal-
onate 8 in refluxing THF in the presence of palladium (0) tetrakis-
(
triphenylphosphine) complex gave the E-vinyl phosphonate 9 (45%
yield, >80% e.e. by HPLC). It is anticipated, based on results with the
parent malonate, that ozonolysis of 9 and reduction of the ozonide with
NaBH4 will yield the lactone 10. Decarboxylation of 10 will provide an
analog of enterolactone.
REFERENCES
[
1] D. F. Wiemer, Tetrahedron, 53, 16609 (1997).
[
2] For examples see: (a) J. Zhu and X. Lu, Tetrahedron Lett., 28, 1897 (1987); (b) J. Zhu
and X. Lu, J. Chem. Soc., Chem. Commun., 1318 (1987); (c) E. Ohler and S. Kanzler,
Synthesis, 539 (1995); (d) E. Ohler and S. Kanzler, Liebigs Ann., 1437 (1997);
(e) M. Attolini, M. Maffei, B. Principato, and G. Peiffer, Synlett, 384 (1997).
[
3] (a) H. Shabany and C. D. Spilling, Tetrahedron Lett., 39, 1465 (1998); (b) M. A. De
la Cruz, H. Shabany, and C. D. Spilling, Phosphorus, Sulfur and Silicon, 146, 181
¨
1999); (c) D. Cooper and S. Trippett, J. Chem. Soc. Perkin 1, 2127 (1981); (d) E. Ohler
(
and S. Kotzinger, Synthesis, 497 (1993).
[
4] (a) M. D. Groaning, B. J. Rowe, and C. D. Spilling, Tetrahedron Lett., 39, 5485 (1998);
(
b) B. J. Rowe and C. D. Spilling, Tetrahedron Asymm., 12, 1701 (2001).
5] V. Farina, S. R. Baker, D. Benigni, and Jr., C. Sapino, Tetrahedron Lett., 29, 5739
1988).
[
(
[
[
6] G. Agnel and E. Negishi, J. Am. Chem. Soc., 113, 7424 (1991).
7] C. Fuganti, S. Serra, and A. Dulio, J. Chem. Soc., Perkin Trans. 1, 279 (1999).