LETTER
Phosphine-Catalyzed [3+2] Annulation of Cyanoallenes
1695
asymmetric [3+2] annulations with the corresponding 3- reoconfigurations, therefore undesired complexity in the
substituted allenoates have been reported so far.12f Of the asymmetric induction cannot be excluded.
array of catalysts screened (Figure 1), phosphine catalysts
In conclusion, the use of cyanoallenes in phosphine-cata-
lyzed [3+2] annulations successfully provided the cyano-
like (R)-MeO-Biphep, (R,R)-Me-Duphos, (R)-Synphos
and Miller’s amino acid derived phosphine12f provided
substituted dihydropyrroles. The use of a 3,3-dimethyl-
very low yields and ee values. Other catalysts that provid-
substituted allene was demonstrated for the first time.
ed significant ee values and reasonable to good yields are
Some initial results in the asymmetric phosphine-cata-
listed in Table 3.
lyzed [3+2] annulations with cyanoallenes were also es-
tablished.
Table 3 Asymmetric [3+2] Annulation with Cyanoallenes 1 and 8
NC
SO2Ph
Supporting Information for this article is available online at
N
chiral
phosphine
Ph
R
N
+
R
•
CN
Ph
H
benzene, r.t.
SO2Ph
7a R = H
9a R = Me
1 R = H
8 R = Me
Acknowledgment
This research has been financially supported by the Netherlands
Organisation for Scientific Research (NWO).
Entry Cyanoallene Catalyst
Time Product ee
(h)
Yield
(%)a (%)b
1
2
3
4
5
6
7
8
9
1
1
1
1
8
8
8
8
8
(S)-NMDPP
(S),(S)-Chiraphos
(–)-DIOP
96
7a
7a
7a
7a
9a
9a
9a
9a
9a
+5 99
References and Notes
16
72
–10 77
+10 81
–10 54
+28 50
(1) Lovas, F. J.; Remijan, A. J.; Hollis, J. M.; Jewell, P. R.;
Snyder, L. E. Astrophys. J. 2006, 637, L37.
(2) (a) Brandsma, L. Best Synthetic Methods: Synthesis of
Acetylenes, Allenes and Cumulenes: Methods and
Techniques; Elsevier Academic Press: Boston / Amsterdam,
2004. (b) Brandsma, L.; Verkruijsse, H. D. Synthesis of
Acetylenes, Allenes and Cumulenes, a Laboratory Manual in
Studies in Organic Chemistry, Vol. 8; Elsevier: Amsterdam,
1981. (c) Kurtz, P.; Gold, H.; Disselnkötter, H. Justus
Liebigs Ann. Chem. 1959, 624, 1. (d) For a review on allene
syntheses, see: Brummond, K. M.; DeForrest, J. E. Synthesis
2007, 795.
(3) For a few selected examples on the use of 1, see:
(a) Danheiser, R. L.; Casebier, D. S.; Huboux, A. H. J. Org.
Chem. 1994, 59, 4844. (b) Loebach, J. L.; Bennet, D. M.;
Danheiser, R. L. J. Org. Chem. 1998, 63, 8380. (c) Pasto,
D. J.; L’Hermine, G. J. Org. Chem. 1990, 55, 685.
(4) For examples, see: (a) Ma, S. Chem. Rev. 2005, 105, 2829.
(b) Ma, S. Acc. Chem. Res. 2003, 36, 701.
DUANPhos
(S)-NMDPP
(S),(S)-Chiraphos
(–)-DIOP
168
24
16
0
78
16
+12 85
–60 18
+13 79
DUANPhos
catASium®D(R)
168
16
a Determined by chiral HPLC, OD column, n-heptane–i-PrOH
(90:10), the sign is given relative to each other.
b Isolated yield after column chromatography.
Interestingly, we found no account on the use of (S)-(+)-
neomenthyldiphenylphosphine [(S)-NMDPP] in phos-
phine-catalyzed annulations. For both cyanoallenes 1 and
8, this phosphine gave good to reasonable yields of the an-
nulation products 7a (99%) and 9a (50%), but with an ee
of only 5% for 7a and 28% for 9a (entries 1 and 5). Chira-
phos gave good yields for both products, but with low or
no ee (entries 2 and 6). In terms of yield, (–)-DIOP proved
to be the most reliable catalyst, though no ee values higher
than 12% were obtained (entries 3 and 7). For cyanoallene
(1), DUANPhos gave 7a in a yield of 54% with slight ex-
cess of the other enantiomer (entry 4). For both substrates
1 and 8, the sterically very hindered DUANPhos gave a
very slow conversion. After prolonged reaction times, 9a
was isolated in 18% yield. Being the highest so far, the ee
was determined to be 60%. Higher temperatures or a
change in solvent did not lead to improvements for this
specific case. catASium®D(R), bearing a tertiary nitrogen,
gave a good yield (79%) but the ee did not reach signifi-
cant values (entry 9). Most of the phosphines tested are
diphosphines with the phosphorus atoms in different ste-
(5) (a) Zhang, C.; Lu, X. J. Org. Chem. 1995, 60, 2906.
(b) Zhu, G.; Chen, Z.; Jiang, Q.; Xiao, D.; Cao, P.; Zhang, X.
J. Am. Chem. Soc. 1997, 119, 3836. (c) Xu, Z.; Lu, X.
J. Org. Chem. 1998, 63, 5031. (d) Zhu, X.-F.; Henry, C. E.;
Kwon, O. Tetrahedron 2005, 61, 6276. (e) Zhu, X.-F.; Lan,
J.; Kwon, O. J. Am. Chem. Soc. 2003, 125, 4716.
(f) Castellano, S.; Fiji, H. D. G.; Kinderman, S. S.;
Watanabe, M.; de Leon, P.; Tamanoi, F.; Kwon, O. J. Am.
Chem. Soc. 2007, 129, 5843. (g) Watanabe, M.; Fiji, H. D.
G.; Guo, L.; Chan, L.; Kinderman, S. S.; Slamon, D. J.;
Kwon, O.; Tamanoi, F. J. Biol. Chem. 2008, 283, 9571. For
more examples, see the following reviews: (h) Ye, L.-W.;
Zhou, J.; Tang, Y. Chem. Soc. Rev. 2008, 37, 1140.
(i) Cowen, B. J.; Miller, S. J. Chem. Soc. Rev. 2009, 38,
3102.
(6) Horner, L.; Jurgeleit, W.; Klüpfel, K. Justus Liebigs Ann.
Chem. 1955, 591, 108.
(7) Representative Experiment: To a stirred solution of imine
6 (4.08 mmol) in anhyd benzene (20 mL) at r.t. were added
triphenylphosphine (0.8 mmol, 20 mol%) and cyanoallene
(70% w/w solution in toluene, 4.9 mmol, 1.2 equiv). The
solution was stirred until the imine was consumed (ca. 16 h)
as judged by TLC (hexanes–EtOAc, 1:1). The solution was
concentrated and the crude oil was purified by column
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