Stereoelectronic Control of the Diastereoselectivity in the Photooxygenation (Schenck Ene Reaction) of an Electron-Poor Allylic Alcohol and Its Ethers

Full text of DOI:10.1021/jo971963s

226
J . Org. Chem. 1998, 63, 226-227
Sch em e 1. P h otooxygen a tion of th e Allylic Alcoh ol
Der iva tives (4S)-1 a n d Su bsequ en t Tr a n sfor m a tion of
Ster eoelectr on ic Con tr ol of th e
Dia ster eoselectivity in th e P h otooxygen a tion
(Sch en ck En e Rea ction ) of a n Electr on -P oor
Allylic Alcoh ol a n d Its Eth er s
th e Hyd r op er oxid es 2 to th e La cton es 3
Waldemar Adam,* J u¨rgen Renze, and Thomas Wirth
Institut fu¨r Organische Chemie, Universita¨t Wu¨rzburg,
Am Hubland, D-97074 Wu¨rzburg, Germany
Received October 27, 1997
The diastereoselectivity of the Schenck ene reaction
(singlet oxygen) has been recently intensively investigated,
in which the chiral alkene substrates are conformationally
fixed through 1,3-allylic strain (A1,3).1 While electron-poor
(X ) CO2Me) and electron-rich olefins (X ) Me) with alkyl
The synthesis of the known allylic substrates 1a -c
followed the literature procedures,8 and the unknown silyl
ether 1d was prepared from the allylic alcohol 1a by
standard silylation procedures.9 In the photooxygenations
of the substrates 1 the corresponding hydroperoxides 2 are
formed quantitatively (Scheme 1, Table 1). The threo
diastereoselectivities increase with the size of the R sub-
t
or aryl substituents (Y ) Ph, Bu) at the stereogenic center
afford with singlet oxygen preferentially the erythro dia-
stereomeric hydroperoxides (eq 1),2 electron-rich (X ) Me,
stituent in the order H ≈ CH2Ph < SiMe2 Bu < Si(iPr)3
t
(entries 1 and 3-5). In contrast to the photooxygenation of
electron-rich allylic alcohols,3 the nature of the solvent exerts
no significant influence on the diastereoselectivity (entries
1 and 2).
The conformational assignment of the hydroperoxides
2a ,c,d was achieved by means of chemical correlation
(Scheme 1). After reduction by triphenylphosphine and
subsequent acid-catalyzed cyclization, the known lactones
3 were obtained.3d
SnBu3; Y ) OH, OR, OSiR3) allylic alcohols and their ether
derivatives react threo-selectively.3 The highest threo control
is observed for the free allylic alcohols in nonpolar solvents.
The latter threo diastereoselectivity was rationalized in
terms of irreversible formation of a perepoxide-like inter-
mediate (exciplex), stabilized through intramolecular hy-
drogen bonding with the allylic hydroxy functionality in the
singlet-oxygen complex.1,4
Since for the ene reaction of singlet oxygen with electron-
rich versus electron-poor olefins distinct rate-determining
steps have been proposed,1,5 which also has been rationalized
theoretically,6 it was of interest to probe the consequences
of such electronic differences on the π-facial selectivity in
chiral allylic alcohols. For this purpose, we chose the chiral,
electron-poor allylic alcohol 1a and its ether derivatives
1b-d to assess the importance of intramolecular hydrogen
bonding in the singlet oxygen ene reaction of such low-
reactive, acyclic substrates, conformationally fixed by means
of A1,3 strain. Our present results reveal that a novel
stereoelectronic effect (Houk model7) rather than intramo-
lecular hydrogen bonding or steric congestion determine the
diastereoselectivity in these photooxygenations.
The stereochemical results in Table 1 exhibit clearly that
the ene reaction of singlet oxygen with these chiral, electron-
poor allylic alcohols 1a -d proceeds in all cases threo-
selectively, regardless of whether the hydroxy functionality
is free or masked by alkyl or silyl groups. In contrast, the
corresponding olefin with a phenyl substituent (Y ) C6H5,
X ) CO2Me) at the allylic stereogenic center reacts erythro-
selectively.2c Steric effects alone cannot adequately rational-
ize these conflictive stereochemical results; instead, we
propose that Houk’s stereoelectronic effect is responsible.7
The transition state A (Figure 1) of the rate-determining
hydrogen-atom transfer is favored for 1a -d , in which singlet
oxygen abstracts the allylic hydrogen on the π face opposite
to the methyl group, while the oxygen functionality resides
preferentially in the outside position to minimize A1,3 strain;
consequently, the threo product is preferred for these
substrates. The transition state B, which should apply for
purely sterically controlled photooxygenations of olefins (Ph
instead of OR) and affords predominantly the erythro
diastereomer,2c is for the allylic alcohol derivatives 1a -d
unfavorable, because in this conformation the σ*(CO)/π
interaction removes electron density from the already
electron-deficient activated complex.7 Furthermore, the
higher threo diastereoselectivity with increasing size of the
OR substituent at the allylic site may be accounted for by
the fact that transition state C, which leads to the erythro
product, becomes depreciated with increasing A1,3 strain.
The unusual lack of a solvent effect on the diastereose-
lectivity in the photooxygenation of the free alcohol 1a (Table
* To whom correspondence should be addressed. Fax: +49/931/8884756.
E-mail: adam@chemie.uni-wuerzburg.de.
(1) Review: Adam, W.; Prein, M. Angew. Chem., Int. Ed. Engl. 1996,
35, 477-494.
(2) (a) Kropf, H.; Reichwaldt, R. J . Chem. Res. 1987, 412-413. (b) Adam,
W.; Bru¨nker, H.-G.; Kumar, A. S.; Peters, E.-M.; Peters, K.; Schneider, U.;
von Schnering, H. G. J . Am. Chem. Soc. 1996, 118, 1899-1905. (c) Adam,
W.; Nestler, B. Liebigs. Ann. Chem. 1990, 1051-1053.
(3) (a) Adam, W.; Nestler, B. J . Am. Chem. Soc. 1992, 114, 6549-6550.
(b) Adam, W.; Nestler, B. J . Am. Chem. Soc. 1993, 115, 5041-5049. (c)
Adam, W.; Nestler, B. Tetrahedron Lett. 1993, 34, 611-614. (d) Adam, W.;
Klug, P. Synthesis 1994, 567-572.
(4) Stratakis, M.; Orfanopoulos, M.; Foote, C. S. Tetrahedron Lett. 1996,
37, 7159-7162.
(5) (a) Stratakis, M.; Orfanopoulos, M.; Chen, J . S.; Foote, C. S.
Tetrahedron. Lett. 1996, 37, 4105-4108. (b) Elemes, Y.; Foote, C. S. J . Am.
Chem. Soc. 1992, 114, 6044-6050.
(6) Yoshioka, Y.; Yamada, S.; Kawakami, T.; Nishino, M.; Yamaguchi,
K.; Saito, I. Bull. Chem. Soc. J pn. 1996, 69, 2683-2699.
(7) (a) Houk, K. N.; Moses, S. R.; Wu, Y.-D.; Rondan, N. G.; J a¨ger, V.;
Schohe, R.; Fronczek, F. R. J . Am. Chem. Soc. 1984, 106, 3880-3882. (b)
Houk, K. N.; Duh, H.-Y.; Wu, Y.-D.; Moses, S. R. J . Am. Chem. Soc. 1986,
108, 2754-2755.
(8) (a) Chambers, M. S.; Thomas, E. J .; Williams, D. A. J . Chem. Soc.,
Chem. Commun. 1987, 1228-1230. (b) Bernardi, A.; Cardani, S.; Scolastico,
C.; Villa, R. Tetrahedron 1988, 44, 491-502.
(9) Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis;
J ohn Wiley & Sons: New York, 1991; p 74.
S0022-3263(97)01963-4 CCC: $15.00 © 1998 American Chemical Society
Published on Web 01/01/1998

Communications
J . Org. Chem., Vol. 63, No. 2, 1998 227
Ta ble 1. Dia ster eoselectivities in th e P h otooxygen a tion of th e Ch ir a l, Electr on -P oor Allylic Alcoh ol 1 a n d Its Eth er
Der iva tives 1b-d
diastereoselectivitya
time
(h)
convn
(%)a,b
R
solvent
T (°C)
(3S,4S)-2
:
(3R,4S)-2
1a
1a
1b
1c
1d
H
H
CCl4
-5
-7
-10
-5
0
60
54
164
160
120
g95
61
85
g95
g95
84
86
83
93
g95
16
14
17
7
CD3ODc
CCl4
CH2Ph
t
SiMe2 Bu
CCl4
CCl4
Si(iPr)3
e5
a
b
Determined by 1H-NMR analysis directly of the crude product mixture; error (5% of the stated values. The hydroperoxides 2 were
formed quantitatively. c Methylene blue as sensitizer, all others tetraphenylporphine (TPP).
Sch em e 2. High ly Efficien t a n d Th r eo-Selective
Syn th esis of En a n tiom er ica lly P u r e Ma h u ba la cton es
6
F igu r e 1. Transition-state geometries A-C for the rate-deter-
mining hydrogen abstraction in the singlet oxygen ene reaction
of chiral, electron-poor allylic alcohols.
The photooxygenation [with tetrapentafluorophenylpor-
phine (TPFPP) as sensitizer11] of the optically active allylic
alcohol 4 [prepared through the Wittig-Horner reaction of
1, entries 1 and 2) speaks against a strongly polarized
transition state stabilized by hydrogen bonding, unlike the
situation previously documented for the electron-rich allylic
alcohols.3 This confirms that for electron-poor olefins the
perepoxide-structured exciplex intermediate is formed re-
versibly and not in the rate-determining step (cf. Figure 4b
in ref 1). The enhanced reactivity for the free alcohol 1a
compared to the ethers 1b-c (Table 1) originates most likely
from steric effects, since the π systems of the bulky ethers
1b-d are less accessible for the attacking singlet oxygen
compared to the free alcohol 1a .
t
optically active BuMe2Si-protected lactaldehyde, followed
by desilylation] led to a 74:26 E/Z mixture of the allylic
hydroperoxides 5; reduction by triphenylphosphine and
subsequent acid-catalyzed cyclization afforded the desired
lactones 6 (E:Z ) 75:25) in 60% overall yield. This sequence
constitutes to date the most efficient and convenient syn-
thesis of these natural products in optically pure form.10
Ackn owledgm en t. Generous financial support is grate-
fully appreciated by the Deutsche Forschungsgemeinschaft
(Schwerpunktprogramm Peroxidchemie) and the Fonds der
Chemischen Industrie (doctoral fellowship to T.W. during
1996-1998). J .R. was a research participant in Spring
1996.
Our present results demonstrate for the first time that
the threo diastereoselectivity in the singlet oxygen ene
reaction of electron-poor allylic alcohol derivatives may be
controlled effectively by means of bulky silyl substituents
at the allylic oxygen functionality. The steering effect comes
about through the synergistic interplay between conforma-
tional (A1,3) and stereoelectronic [σ*(CO)/π interactions]
factors rather than solely steric influence. This novel threo-
diastereoselective control applies also to the free alcohol 1a ,
rather than intramolecular hydrogen bonding of the allylic
hydroxy group with singlet oxygen, as in the case of electron-
rich derivatives.3
Su p p or tin g In for m a tion Ava ila ble: Experimental details
(22 pages).
J O971963S
(10) For a previous synthesis of dihydromahubanolides see: Wood, W.
W.; Watson, G. M. J . Chem. Soc., Perkin Trans. 1 1990, 3201-3202.
(11) In view of the long irradiation times and elevated reaction temper-
ature, TPFPP was used since this sensitizer is more resistant toward
autoxidation compared to TPP. Quast, H.; Dietz, T.; Witzel, A. Liebigs Ann.
1995, 1495-1501.
The synthetic value of this for photooxygenations unprec-
edented stereoelectronic effect is illustrated by the prepara-
tion of the enantiomerically pure dihydromahubanolide B
[(Z)-6] and isodihydromahubanolide B [(E)-6] in Scheme 2.10