Stereoselective synthesis of oxygenated trisubstituted olefins using N-ylides [2,3]rearrangement

Article abstract of DOI:10.1055/s-1998-1745

[2,3]Sigmatropic rearrangement of N-(ethoxycarbonyl)-methyl-β-methallylammonium ylide with an oxygen functionality at the β-position or γ-position forms trisubstituted trans-olefins with high stereoselectivity. On the other hand, the rearrangement of salts having a tiglyl ester moiety instead of a carbethoxy group affords cis-olefins. The present method was applied to the synthesis of plaunotol.

Full text of DOI:10.1055/s-1998-1745

June 1998
SYNLETT
685
Stereoselective Synthesis of Oxygenated Trisubstituted Olefins Using N-Ylides
[2,3]Rearrangement
Kiyoshi Honda,* Daisuke Igarashi, Masatoshi Asami, Seiichi Inoue*
Department of Synthetic Chemistry, Faculty of Engineering, Yokohama National University, Tokiwadai, Hodogayaku, Yokohama 240, Japan
Fax +81-45-339-3970; E-mail: inoue@syn.synchem.bsk.ynu.ac.jp
Received 12 March 1998
Abstract: [2,3]Sigmatropic rearrangement of N-(ethoxycarbonyl)-
methyl-β-methallylammonium ylide with an oxygen functionality at the
β−position or γ'-position forms trisubstituted trans-olefins with high
stereoselectivity. On the other hand, the rearrangement of salts having a
tiglyl ester moiety instead of a carbethoxy group affords cis-olefins. The
present method was applied to the synthesis of plaunotol.
Reported herein is highly Z- and E-stereoselective [2,3]sigmatropic
rearrangement which provides trisubstituted allylic alcohol derivatives
9, 10 and 11 from ammonium salts 6, 7 and 8 oxygenated at the β- or γ'-
position.
We have reported stereoselective or stereocontrolled synthesis of
trisubstituted olefins using an N-ylide [2,3]sigmatropic rearrangement
1
of β-methallylammonium salts.
Recently, stereocontrolled elongation of a functionalized isoprene unit
on the E or Z terminal methyl of terpenoids was achieved by the N-ylide
rearrangement of the common N-tiglyl-β-methallyldimethylammonium
2
salts under the selected reaction conditions.
First, we examined the rearrangement of salt 7a oxygenated at the γ'-
position as shown in Table 1. Treatment of 7a with potassium tert-
butoxide in a mixture of THF-DMPU resulted in a 78 : 22 mixture of
10aE and the corresponding (Z)-isomer in a 43% combined yield and
treatment with lithium ethoxide in ethanol gave 10aE predominantly
(91% E) in a 41% combined yield. Determination of Z/E was
established by NMR and NOE analysis. This strong E-selective
character (cis relationship between long carbon chains around the
carbon-carbon double bond) is similar to that of the rearrangement of
salt 3 which shows highly cis-selectivity.
Treatment of 1 with potassium tert-butoxide in a mixture of THF-
HMPA resulted in a 71 : 29 mixture of 2E and 2Z in a 69% combined
yield. On the contrary, the stereoselectivity of the [2,3]sigmatropic
rearrangement was reversed under the following reaction conditions:
treatment of 1 with lithium ethoxide in ethanol resulted in a 13 : 87
mixture of 2E and 2Z in a 65% combined yield. Notably, isolation of
each rearrangement product was easily achieved by column
chromatography on silica gel.
Interestingly, treatment of 3 either with potassium tert-butoxide in THF-
HMPA or with alkali metal ethoxide in ethanol resulted in the formation
of an N-ylide 4, which underwent [2,3]sigmatropic rearrangement to
give exclusively diene 5Z which was composed of a newly formed Z and
3
tiglyl-origin E olefinic moiety. It should be noted that the high Z-
selective character of this system is in sharp contrast to our previous
2
system as shown in Scheme 1.
aCombined yield. bNMR analysis. cEach sterochemistry of the isolated
stereosisomers was analyzed by 1H and 13C NMR (CDCl3) spectroscopy
We next examined the rearrangement of 6b as shown in Table 2. All
reactions were highly E-selective (run 1~4) as well as the rearrangement
of the corresponding salts having no oxygen functionality at the β-
2b
position. And higher basicity increased the E-selectivity of the
rearrangement (run 3).
Scheme 1
Next, we examined the rearrangement of the corresponding salts with
carbonitrile as an electron-withdrawing group. Interestingly, no
stereoselectivity was obtained except for the case of R = H which is
strongly E-selective (run 4~6) as shown in Table 3.
Therefore, we suggested that this dramatical inversion of
stereoselectivity came from presence or absence of an oxygen
functionality in the β-position.
Finally, we examined the rearrangement of salt 8b oxygenated at the γ'-
position. The stereoselectivity of this rearrangement was the same as
that of salt 6b, which leads to a highly trans relationship between long
This observation prompted us to investigate the reactions of some
oxygenated ammonium salts with bases.

686
LETTERS
SYNLETT
mentioned stable ylides. Thus another envelope conformation can be
postulated as a plausible transition state leading to the cis olefin. The
conformational preference of I over II may result from vicinal repulsion
1
2
between R CH and the vinyl R CH group, which has been used for
2
2
5
the ylide [2,3] processes.
Scheme 2
6
The present method was applied with the synthesis of plaunotol as
shown in Scheme 3.
Scheme 3
Treatment of 7b with potassium tert-butoxide in THF at –70 °C afforded
(Z)-ester 10b exclusively in 96% yield.
carbon chains around the carbon-carbon double bond under two basic
rearrangement conditions as shown in Table 4.
A reductive removal of the dimethylamino group was achieved by
quaternization of 10b, followed by treatment of sodium amalgam in a
buffer solution. The subsequent reduction of ester was carried out with
lithium aluminum hydride to give the corresponding alcohol. p-
Tolylsulfone 12 was then obtained in 83% yield by the conventional
method from alcohol via the corresponding tosylate and iodide.
Tolylsulfone 12 was converted with n-BuLi into carbanion, which
reacted with methylheptenone and quenched with acetic anhydride to
give C product 13, which was subjected to Na/Hg and Na/NH
[2,3]Sigmatropic rearrangement of salts 6b, 8b and 6c (R = H) having
an electron-withdrawing group directly on the ylide carbon may have
4
the usual concerted transition state of a doubly suprafacial mode
1
2
exerting no vicinal repulsion between R CH and the vinyl R CH
2
2
group, which leads to a trans olefin as shown in Scheme 2. On the other
hand, the [2,3]sigmatropic rearrangement of salts 3 and 7a seems to
have an earlier (i.e., reactant-like) transition state than that of the above-
20
3
reduction succesively to furnish the desired plaunotol.

June 1998
SYNLETT
687
In summary, [2,3]sigmatropic rearrangement of β- or γ'-oxygenated N-
(ethoxycarbonyl)methyl-β-methallylammonium ylides form trisub-
stituted trans-olefins with high stereoselectivity. On the other hand, the
rearrangement of salts having a tiglyl ester moiety instead of a
carbethoxy group affords cis-olefins. These reactions will find
application to the synthesis of functionalized terpenoid and other natural
products having defined olefin stereochemistry.
(3) Honda, K.; Yoshii, I.; Inoue, S. Chem. Lett., 1996, 671.
(4) Yamamoto, Y.; Oda, J.; Inouye, Y. J. Org. Chem., 1976, 41, 303;
Inoue, S.; Iwase, N.; Miyamoto, O.; Sato, K. Chem. Lett., 1986,
2035.
(5) Trost, B. M.; Mervin, L. S. Jr., Sulfer Ylides; Blomquist, A. T.;
Wasserman, H. H., Eds.; Academic Press: New York, 1979, 108−
127
(6) For synthesis of plaunotol, see: Ogiso, A.; Kitazawa, E.;
Kurabayashi, M.; Sato, A.; Takahashi, S.; Noguchi, H.; Kuwano,
H.; Kobayashi, S.; Mishima, H. Chem. Pharm. Bull., 1978, 26,
3117 ; Sato, K.; Inoue, S.; Iwase, N.; Honda, K. Bull. Chem. Soc.
Jpn., 1990, 63, 1328 ; Inoue, S.; Honda, K.; Iwase, N.; Sato, K.
Bull. Chem. Soc. Jpn., 1990, 63, 1629.
References and Notes
(1) a) Honda, K.; Inoue, S.; Sato, K. J. Am. Chem. Soc., 1990, 112,
1999 ; b) Honda, K.; Inoue, S.; Sato, K. J. Org. Chem., 1992, 57,
428 ; c) Honda, K.; Inoue, S. Synlett, 1994, 739.
(2) Honda, K.; Tabuchi, M.; Inoue, S. Chem. Lett., 1996, 385.