D. J. Lapinsky, S. C. Bergmeier / Tetrahedron Letters 42 (2001) 8583–8586
8585
TBSO
f, g
c
a, b
RO
TsN
H
NTs
20
NHTs
19
H
18
SiMe3
TsN
H
21
d
e
f, g
No product observed
CO2Me
CHO
TsN
TsN
TsN
H
H
H
22
23
24
Scheme 3. (a) AllylMgCl (300 mol%), CuCN (50 mol%), Et2O:THF (1:1.5), −78 to 0°C, 45 h, R=Si(Me2)tBu, 75%. (b) nBu4NF
(110 mol%), THF, 0°C, 1 h, R=H, 88%. (c) Ph3P (110 mol%), DEAD (110 mol%), THF, 0°C to rt, 4 h, 93%. (d) DIBAL-H (160
mol%), CH2Cl2, −78°C, 3 h. (e) Ph3PCH2 (250 mol%), THF, −20°C, 1 h, 29% (two steps). (f) 9-BBN (120 mol%), THF, rt, 4 h.
(g) 5 (110 mol%), 3 M aq. K3PO4 (210 mol%), PdCl2(dppf)·CH2Cl2 (5 mol%), DMF, rt, 18 h, 21 (65%).
In an effort to extend this synthesis we prepared olefins
20 and 24. Olefin 20 was readily prepared from the
serine derived aziridine 18.6a Reaction of 18 with allyl-
magnesium chloride/CuCN followed by removal of the
silyl protecting group and Mitsunobu ring closure pro-
vided aziridine 2011 in excellent overall yield. Standard
cross-coupling conditions using bromoallylsilane 5 pro-
vided substituted aziridine 21 in 65% yield.9,10 We next
turned our attention to olefin 24. The known aziridine
ester 226a,12 can be reduced to aldehyde 23 by reaction
with DIBAL-H. Wittig reaction of the aldehyde pro-
duces the vinyl aziridine 2413 in 29% yield over two
steps. Unfortunately, hydroboration of 24, followed by
Suzuki coupling conditions did not provide any of the
desired product. We have examined a number of varia-
tions of the Suzuki cross-coupling protocol and all were
unsuccessful. No aziridine containing products were
obtained, and we believe that the aziridinyl borane
formed upon hydroboration of 24 is unstable.
3. An intramolecular Heck reaction has been used in the
presence of an aziridine ring, see: Schkeryantz, J. M.;
Danishefsky, S. J. J. Am. Chem. Soc. 1995, 117, 4722–
4723.
4. Pearson, W. H.; Liam, B. W.; Bergmeier, S. C. In Com-
prehensive Heterocyclic Chemistry II; Padwa, A., Ed.;
Pergamon: Oxford, 1996; Vol. 1, pp. 1–60.
5. See Baeg, J.-O.; Bensimon, C.; Alper, H. J. Am. Chem.
Soc. 1995, 117, 4700–4701 and references cited therein.
6. (a) Bergmeier, S. C.; Seth, P. P. J. Org. Chem. 1997, 62,
2671–2674; (b) Bergmeier, S. C.; Fundy, S. L.; Seth, P. P.
Tetrahedron 1999, 55, 8025–8038.
7. While the desired organolithium reagent (2) has been
prepared via a reductive lithiation of a phenylsulfide (see
Manteca, I.; Ardeo, A.; Osante, I.; Lete, E.; Etxarri, B.;
Arrasate, S.; Sotomayor, N. Tetrahedron 1998, 54,
12361–12378), we were hoping to carry out a metal
halogen exchange between the corresponding iodide and
t-BuLi. The synthesis of the alcohol needed for prepara-
tion of the iodide has been reported (see Ahmed-
Schafield, A.; Mariano, P. S. J. Org. Chem. 1985, 50,
5667–5677). However, we were unable to convert this
alcohol to the iodide using a number of different
methods.
In conclusion, we have shown that the Suzuki coupling
reaction of olefinic aziridines proceeds quite well. This
reaction should be useful for the preparation of a
variety of substituted aziridines.
8. (a) Varray, S.; Gauzy, C.; Lamaty, F.; Lazaro, R.; Mar-
tinex, J. J. Org. Chem. 2000, 65, 6787–6790; (b) Voigt-
mann, U.; Blechert, S. Synthesis 2000, 893–898; (c)
Witulski, B.; Gossmann, M. Chem. Commun. 1999, 1879–
1880; (d) Bolton, G. L.; Hodges, J. C.; Rubin, J. R.
Tetrahedron 1997, 53, 6611–6634.
Acknowledgements
We would like to thank the National Science Founda-
tion (CHE-9816208) for support of this work.
1
9. All new products showed satisfactory H, 13C NMR and
HRMS.
10. Typical procedure for the Suzuki cross-coupling reaction:
The desired aziridinyl alkene (9 or 20, 1.1 mmol) was
dissolved in dry THF (3.7 mL) and cooled to 0°C. A
solution of 9-BBN (2.5 mL of a 0.5 M solution in THF)
was added and the reaction was warmed to room temper-
ature and stirred until no alkene remained (TLC, 20%
EtOAc:hexanes, ca. 4 h). Distilled DMF (1.8 mL) was
added followed by careful addition (H2 evolution) of
degassed aq. K3PO4 (3 M, 210 mol%). This was followed
by a rapid addition of R-X (110 mol%, X=Br or I) and
PdCl2(dppf)·CH2Cl2 (5 mol%). The reaction was stirred
overnight at room temperature. The solvent was removed
in vacuo and the remaining DMF residue was partitioned
References
1. (a) Suzuki, A. J. Organomet. Chem. 1999, 576, 147–168;
(b) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457–
2483.
2. Recently the Suzuki cross-coupling reaction has been
used to prepare a-amino acids and derivatives. (a) Camp-
bell, A. D.; Raynham, T. M.; Taylor, R. J. K. Tetra-
hedron Lett. 1999, 40, 5263–5266; (b) Sabat, M.; Johnson,
C. R. Org. Lett. 2000, 2, 1089–1092; (c) Collier, P. N.;
Campbell, A. D.; Patel, I.; Taylor, R. J. K. Tetrahedron
Lett. 2000, 41, 7115–7119.