Trans stereoselectivity in the reaction of cyclic phosphonium salts with aromatic aldehydes

Article abstract of DOI:10.1055/s-1998-1702

The Wittig olefination of substituted aromatic aldehydes with ylides from phosphorinanium salts [RCH₂P(Ph)(CH₂)₅]⁺Br^- in which the phosphorus atom is incorporated into a six-membered ring, is E-selective.

Full text of DOI:10.1055/s-1998-1702

May 1998
SYNLETT
497
Trans Stereoselectivity in the Reaction of Cyclic Phosphonium Salts with Aromatic Aldehydes
Nicholas J. Lawrence* and Hayrettin Beynek
Department of Chemistry, UMIST, PO Box 88, Manchester, M60 1QD, UK; Email : Nick.Lawrence@umist.ac.uk
Received 18 February 1998
Abstract : The Wittig olefination of substituted aromatic aldehydes
under these conditions α-deprotonation was unfavoured and perhaps not
going to be a complication in the Wittig reaction. In addition, similar
reactions of both 4 and 5 mediated by n-butyllithium or potassium
bis(trimethylsilyl)amide (KHMDS) all failed to produce the
corresponding tetramethylated derivative. The triethoxysilane–
titanium(IV) isopropoxide reducing system,4 developed in our
laboratories, was used to convert the phosphine oxide 5 to 1-
phenylphosphorinane, which was quaternised in the same pot by the
addition of the appropriate alkylbromide to give the salts 2a-e.5
+
–
with ylides from phosphorinanium salts [RCH P(Ph)(CH ) ] Br in
2
2 5
which the phosphorus atom is incorporated into a six-membered ring, is
E-selective.
The reaction of an alkyltriphenylphosphorane with an aldehyde usually
generates an alkene with a high degree of cis-stereoselectivity. This is
particularly true for the reaction of an alkyltriphenylphosphorane with
an alkyl substituted aldehyde under lithium salt-free conditions in a non-
1
The effect of the base used in the Wittig reaction of the ylide derived
from a phenylphosphorinanium salt was first investigated using the
benzyl substituted salt 2a (scheme 2, table 1). Deprotonation of this
phosphorinanium salt with n-butyllithium and addition of benzaldehyde
produced stilbene with moderate trans-selectivity (E:Z 67:33) and in
good yield (91%). When KHMDS was used as the base the selectivity
was significantly higher (E:Z 97:3, 99% yield). For comparison, we
performed the corresponding reactions with benzyltriphenylphosph-
onium bromide (7a) and the selectivity was (E:Z) 38:62 (97%) for n-
butyllithium and (E:Z) 36:64 (93%) for KHMDS. In all cases, the
trans:cis ratio of the alkenes was determined from the crude reaction
protic polar solvent, as detailed by Schlosser et al. There are few
examples of the reaction of phosphorus ylides with aldehydes to give
predominantly the trans-alkene. Inspired by the publication of Vedjes
2
and Peterson in which the trans-selective Wittig reaction of the ylide 1
with a variety of aldehydes was reported (Eqn. 1) we undertook a study
of the Wittig reactions of a series of phosphorinanium salts 2.
1
mixture by H nmr spectroscopy.
We were attracted to the use of phosphorinanium salts, since the parent
phosphine, 1-phenylphosphorinane, is readily prepared. Tetraphenyl-
diphosphine 3 was prepared in 90% yield by the reaction of chloro-
diphenylphosphine with one equivalent of lithium metal (ca. 1% sodium
content) in THF (scheme 1). Subsequent reaction of the diphosphine 3
3
with 1,5-dibromopentane, according to the method of Märkl, gave 1,1-
diphenylphosphorinanium bromide 4 in 84% yield. Hydrolysis of 4 by
treatment with sodium hydroxide (10 M) gave the phosphine oxide 5
(
99%). It was clear that a potential problem with the use of
phosphorinanium salts would be competitive deprotonation of the
protons attached to the C-2 and C-6 atoms of the ring. As a
precautionary measure we first attempted to make 2,2,6,6-tetramethyl-
Scheme 2
1
,1-diphenylphosphorinanium bromide by reaction of the phosphonium
salt 4 with an excess of sodium hydride and iodomethane in DMF.
However, in our hands this reaction was unsuccessful, indicating that
Having established that the use of KHMDS gives good E-selectivity in
the reaction of 2a and benzaldehyde the reactions of the other cyclic
phosphonium salts (2b-e) with KHMDS, benzaldehyde and 3,4,5-
trimethoxybenzaldehyde were investigated. In all cases, the reactions
provided good yields of the alkenes and with high trans-selectivity
(
table 2).
Again for comparison, we carried out the reaction of the
triphenylphosphonium salts (7b-e) with benzaldehyde and 3,4,5-
trimethoxybenzaldehyde under the same conditions used in the Wittig
reactions of 2a-e, and isolated the alkenes with the expected cis-
selectivity (table 3). The selectivities we found in these reactions is
6
essentially the same as that observed by others; under lithium-free
conditions high Z-selectivity is observed for most ylides except for that
derived from the benzyl substituted salt 7a.
Scheme 1

4
98
LETTERS
SYNLETT
selectivity in the Wittig reaction, are currently under investigation. The
ease of preparation of phosphonium salts 2, make this new Wittig
procedure a potentially attractive olefination reaction.
Standard procedure: The base [nBuLi or potassium bis(trimethyl-
silyl)amide (Aldrich)(1 mmol)] was added to the phosphorinanium salt
3
or phosphonium salt (1 mmol) and base in dry THF (10 cm ) under a
nitrogen atmosphere at 0 °C. The mixture was stirred at 0 °C for 2 h and
cooled to -78 °C and aldehyde (1 mmol) added. The resulting mixture
was stirred at -78 °C for 2 h and then allowed to warm to ambient
3
temperature over 4 h. Water (1 cm ) was added and the solution was
3
then extracted with chloroform (3 × 10 cm ). The organic extracts were
dried (magnesium sulfate), filtered and evaporated under reduced
pressure. The residue was purified by chromatography (SiO , hexane) to
2
give a mixture of (E)- and (Z)-alkene. The E:Z ratio was measured by
1
H NMR spectroscopy of the crude reaction mixture.
Acknowledgements : We thank the Turkish Government for a
scholarship (H.B.).
References and Notes
1
Schlosser, M.; Schaub, B.; de Oliveira-Neto, J.; Jeganathan, S.
Chimia, 1986, 40, 244-245.
2
3
4
Vedejs, E.; Peterson, M. J. J. Org. Chem., 1993, 58, 1985-1986.
Märkl, G. Angew. Chem. Int. Ed. Engl., 1963, 2, 620.
Coumbe, T.; Lawrence, N. J.; Muhammad, F. Tetrahedron Lett.,
1
994, 35, 625-628.
5
6
All compounds were fully characterised and gave the expected
spectral and analytical data.
Johnson, A. W.; Kyllingstad, V. L. J. Org. Chem., 1966, 31, 334-
336; Bergelson, L. D.; Barsukov, L. I.; Shemyakin, M. M.
Tetrahedron, 1967, 23, 2709-2720; Allen, D. W.; Ward, H.
Tetrahedron Lett., 1979, 2707-2710; McEwen, W. E.; Cooney, J.
V. J. Org. Chem., 1983, 48, 983-987; Ward, Jr., W. J.; McEwen,
W. E. J. Org. Chem., 1990, 55, 493-500; Yamataka, H.;
Nagareda, K.; Ando, K.; Hanafusa, T. J. Org. Chem., 1992, 57,
2865-2869;
The reactions of 2a-e clearly show significantly greater trans-selectivity
than their triphenylphosphonium counterparts. The trans-selectivity is
7
consistent with the findings of others which illustrate that ylides
derived from polyalkylphosphines generally favour the formation of
(
E)-alkenes in Wittig reactions. The Wittig reaction of 2a-e with
aldehydes possessing protons adjacent to the carbonyl group failed. It
seems that the ylides are significantly basic, and de-protonation of the
aldehyde occurs to the exclusion of nucleophilic attack upon the
carbonyl group. We are currently investigating the effects of additives to
prevent this process.
7
Bissing, D. E. J. Org. Chem., 1965, 30, 1296-1298; Schlosser,
M.; Schaub, B. J. Am. Chem. Soc., 1982, 104, 5821-5823;
Maryanoff, B. E.; Reitz, A. B.; Mutter, M. S.; Inners, R. R.;
Almond, H. R.; Whittle, R. R.; Olofson, R. A. J. Am. Chem.
Soc., 1986, 108, 7664-7678; Vedejs, E.; Marth, C. F.; Ruggeri,
R. J. Am. Chem. Soc., 1988, 110, 3940-3948; Vedejs, E.; Marth,
C. F. J. Am. Chem. Soc., 1988, 110, 3948-3958.
Clearly an important feature in the design of an E-selective Wittig
reagent containing more than one alkyl substituent is the control of
desired ylide formation. In the case of phosphorinanium salts 2a-e, the
exocyclic ylide is formed preferentially; the reasons for this, and their E-