was treated with (R)-(2)-2-phenylglycinol to give the corre-
sponding tetrahydrophthalimide (97%). Treatment of this with
Cl2SiPh2 in DMF followed by an excess of allyl alcohol gave
the SiPh2 tethered phthalimide 27 in 46% overall yield.
Irradiation gave a high yield of cycloaddition products (89%)
which, upon cleavage with Bu4NF (93%), afforded the
diastereoisomeric diols 28 and 29 in a ratio of 3:1. This clearly
demonstrates that the valinol unit is superior to phenylglycinol
in controlling diastereoselectivity during photocycloaddition.
Finally, treatment of the valinol derivative 14 with Cl2SiPh2
followed by treatment with an excess of prop-2-ynyl alcohol
gave the SiPh2 tethered alkynol variant 30 in moderate overall
yield (58%). Irradiation of 30 gave a 46% yield of the
corresponding cyclobutenes which, upon desilylation with
Bu4NF (81%), gave the diastereoisomeric diols 31 and 32 in a
ratio of 4:1. Although the ratio was not as good as in the allyl
alcohol case (24) this is, to the best of our knowledge, the first
example of this type of diastereoselective cyclobutene forma-
tion (Scheme 4).
In summary, l-(+)-valinol derived tetrahydrophthalimides
containing silicon tethered alkenol and alkynol units have been
shown to undergo efficient, diastereoselective intramolecular [2
+ 2] photocycloadditions. Present studies are concerned with
the assignment of the absolute configuration of the major
diastereoisomer from these cycloadditions in order gain some
information about the transition state, and hopefully increase
the diastereoselectivity by investigating different reaction
conditions. We are also investigating the efficient hydrolytic
removal of the valinol linker so that ultimately it can be used as
a true chiral auxiliary in the enantioselective, photochemical
synthesis of highly substituted cyclo-butanes and -butenes.
We would like to thank the Canakkale Onsekiz Mart
University, Turkey (S. G.) and the EPSRC (GR/K15985) (A. S.)
for financial support of this work.
to try and increase the diastereoselectivity of the cycloaddition
by changing the nature of the groups on silicon. Thus treatment
of 14 with Cl2SiPh2 in DMF followed by treatment with an
excess of allyl alcohol gave the SiPh2 tethered variant 24 in 60%
overall yield. Irradiation (60 min) of 24 gave an excellent yield
(82%) of the two cycloadducts 25 and 26 which, upon treatment
with Bu4NF, gave the diastereomeric diols 19 and 20 in 97%
yield and in a very pleasing ratio of 8:1. Again it was not
possible to assign which was the major diastereoisomer,
although it was the same as that obtained with the diisopropyl
tether (Scheme 3).
O
HO
HO
H
O
ii
i
1
N
N
O
H
HO
15
O
14
H
iii or iv
or v
O
O
O
O
X
X
X
H
O
O
O
H
H
N
vi
O
N
O
O
O
+
N
H
O
H
17 X = CO
18 X = CO
16 X = CO
22 X = SiPri2
25 X = SiPh2
23 X = SiPri2
26 X = SiPh2
21 X = SiPri2
24 X = SiPh2
vii or viii
HO
HO
H
O
H
O
+
N
N
O
O
HO
1:1 from 16
2:1 from 21
8:1 from 24
HO
H
20
19
H
Footnotes
* E-mail: k.booker-milburn@uea.ac.uk
Scheme 3 Reagents and conditions: i, l-(+)-valinol, toluene, heat, 95%; ii,
hn, allyl alcohol, MeCN, 6 h, 75%; iii, allyl chloroformate, pyridine, THF,
3 h, 0 °C, 61% for 16; iv, Cl2SiPri2, Et3N, CH2Cl2, then allyl alcohol (4
equiv.), 71% for 21; v, Cl2SiPh2 (2 equiv.), Et3N, DMF, then allyl alcohol
(4 equiv.), 60% for 24; vi, hn, MeCN, 60–90 min, 90% for 17/18, 74% for
22/23, 82% for 25/26; vii, KOH (1.2 equiv.), EtOH–H2O (1:1), 74% from
17/18; viii, Bu4NF, THF, 87% from 22/23, 97% from 25/26
† Glassware consisted of a standard, water cooled, pyrex immersion well
photochemical apparatus of 100 ml reaction volume. All reactions were
carried out in dry, degassed MeCN (100 ml) with concentrations of between
0.01–0.036 m in substrate. Irradiations were performed using a 125 W
medium-pressure mercury vapour lamp obtained from Osram HQL (MBF-
U) bulbs. All new compounds were fully characterised by IR, 1H NMR and
13C NMR spectroscopy, and either elemental analysis or HRMS.
‡ The diastereoisomeric ratio was readily ascertained by 1H NMR
spectroscopy from comparison of the integrals of the two pairs of
diastereotopic Me groups present in the various mixtures of 19 and 20.
Ph Ph
HO
H
Ph
Si
O
O
O
O
i, ii
iv
N
O
1
HO
N
Ph
H
H
References
O
27
Ph
28
1 B. S. Green, Y. Rabinsohn and M. Rejto¨, Carbohydr. Res., 1975, 45, 115;
B. S. Green, A. T. Hagler, Y. Rabinsohn and M. Rejto¨, Isr. J. Chem.,
1976/77, 15, 124; G. L. Lange, C. Decicco and M. Lee, Tetrahedron Lett.,
1987, 28, 2833; A. I. Meyers and S. A. Fleming, J. Am. Chem. Soc., 1986,
108, 306; H. Herzog, H. D. Koch, H. D. Scharf and J. Runsink,
Tetrahedron, 1986, 42, 3547; M. Demuth, A. Palomer, H. D. Sluma,
A. K. Dey, C. Kruger and Y. H. Tsay, Angew. Chem., Int. Ed. Engl., 1986,
25, 1117; M. Sato, K. Takayama, Y. Abe, T. Furuya, N. Inukai and
C. Kaneko, Chem. Pharm. Bull., 1990, 38, 336; D. Haag and
H. D. Scharf, J. Org. Chem., 1966, 61, 6127; M. T. Crimmins and
T. L. Reinhold, Org. React., 1993, 44, 297.
3:1
+
Ph
O
HO
H
Ph
Si
O
O
O
iii
iv
N
14
O
N
H
HO
O
H
30
29
HO
HO
O
2 S. A. Fleming and S. C. Ward, Tetrahedron Lett., 1992, 33, 1013;
C. L. Bradford, S. A. Fleming and S. C. Ward, Tetrahedron Lett., 1995,
36, 4189,
H
O
+
H
N
O
N
4:1
O
3 M. T. Crimmins and L. E. Guise, Tetrahedron Lett., 1994, 35, 1657.
4 S. Faure, S. Piva-Le Blanc, O. Piva and J.-P. Pete, Tetrahedron Lett.,
1997, 38, 1045.
HO
31
32
HO
5 K. I. Booker-Milburn, J. K. Cowell and L. J. Harris, Tetrahedron Lett.,
1994, 35, 3883; K. I. Booker-Milburn, F. Delgado Jime´nez and
A. Sharpe, Synlett, 1995, 735; K. I. Booker-Milburn, J. K. Cowell,
A. Sharpe and F. Delgado Jime´nez, Chem. Commun., 1996, 249.
Scheme 4 Reagents and conditions: i, (R)-(2)-2-phenylglycinol, toluene,
heat, 97%; ii, Cl2SiPh2 (2 equiv.), Et3N, MeCN, then allyl alcohol (4
equiv.), 46%; iii, Cl2SiPh2 (2 equiv.), Et3N, MeCN, then prop-2-yn-1-ol (4
equiv.), 58%; iv, hn, MeCN, 5–6 h, then Bu4NF, THF, 83% overall for
28/29 and 38% overall for 31/32
Received in Liverpool, UK, 8th April 1997; 7/02386C
1386
Chem. Commun., 1997