C O M M U N I C A T I O N S
Table 1. Two-Step Formal [3+2] Cycloadditions
mixture of diastereomeric aldehydes 8 and 9 with a practically
identical ratio (2.81/1) was isolated in 85% overall yield (eq 2).
NOESY-1D experiments confirmed that the major product, 8, has
the aldehyde moiety cis to the vicinal ethyl group.
Several features of this two-step cycloaddition sequence are
noteworthy: it is operationally simple and no purification of
the TMS ether intermediate is necessary; the adduct possesses an
all-carbon quaternary center with readily functionalizable and
well differentiated aldehyde/ketone and enol ether substituents;
beside the excellent diastereoselectivity, it is regiospecific; syntheti-
cally useful spirobicyclic compounds (e.g., 6j and 6k) can be readily
prepared; moreover, with stereocontrol on the formation of the
intermediate allenyl carbinol silyl ether, the configuration of the
all-carbon quaternary center can be readily controlled and predicted
(e.g., entry 12, Table 1).
In summary, a highly diastereoselective, two-step formal [3+2]
cycloaddition between allenyl MOM ether and an enal/enone is
developed. An intramolecular 1,3-dipolar cycloaddition using allene
as 1,3-dipole precursor is proposed. Synthetically versatile cyclo-
pentanone enol ethers containing an all-carbon quaternary center
can be readily prepared with excellent stereocontrol.
Acknowledgment. This research was supported by the Uni-
versity of Nevada, Reno.
Supporting Information Available: Experimental procedures and
compound characterization data. This material is available free of charge
a The substrate concentration was 0.05 M. b No other diastereomer was
observed. c Isolated yield over two steps based on the enal/enone starting
material. d Value represents a 1:1 mixture of diastereomers. e Reaction run
using 5 mol % of catalyst 4.
References
the aldehyde moiety. Notably, 5e is a difficult substrate, and 6e
was formed in only 37% yield using wet CH2Cl2. Fortunately, using
AcOH as the proton source led to much improved reaction, and 6e
was isolated in 60% yield using 5 mol % of 4 (entry 5). Surprisingly,
cinnamaldehyde did not participate in this reaction.
(1) For selected reviews, see: (a) Yamago, S.; Nakamura, E. Org. React.
2002, 61, 1-217. (b) Chan, D. M. T. In ComprehensiVe Organic Synthesis,
1st ed.; Trost, B. M.; Fleming, I.; Eds.; Pergamon: Oxford, New York;
1991; Vol. 3, pp 271-314.
(2) For recent reviews on gold catalysis, see: (a) Stephen, A.; Hashmi, K.;
Hutchings, G. J. Angew. Chem., Int. Ed. 2006, 45, 7896-7936. (b) Zhang,
L.; Sun, J.; Kozmin, S. A. AdV. Synth. Catal. 2006, 348, 2271-2296. (c)
Widenhoefer, R. A.; Han, X. Eur. J. Org. Chem. 2006, 4555-4563. (d)
Ma, S.; Yu, S.; Gu, Z. Angew. Chem., Int. Ed. 2006, 45, 200-203. (e)
Marion, N.; Nolan, S. P. Angew. Chem., Int. Ed. 2007, 46, 2750-2752.
(3) (a) Nieto-Oberhuber, C.; Munoz, M. P.; Bunuel, E.; Nevado, C.; Cardenas,
D. J.; Echavarren, A. M. Angew. Chem., Int. Ed. 2004, 43, 2402-2406.
(b) Echavarren, A. M.; Nevado, C. Chem. Soc. ReV. 2004, 33, 431-436.
(c) Zhang, L.; Kozmin, S. A. J. Am. Chem. Soc. 2004, 126, 11806-11807.
(d) Gorin, D. J.; Davis, N. R.; Toste, F. D. J. Am. Chem. Soc. 2005, 127,
11260-11261.
We were delighted to find that this efficient reaction applied
well to enone substrates. In general, AcOH was the preferred
proton source, and the reactions proceeded well at 0 °C. For
example, without purification of intermediate TMS ethers, 1-ace-
tylcycloalkenes of different ring sizes underwent smooth reactions,
and the cis-fused bicyclic ketones were formed in excellent
yields (entries 6-8). Notably, phenyl enone 5i participated in this
two-step reaction as well, albeit in a low yield (entry 9). Remark-
ably, R-ylidenecycloalkanones such as 5j and 5k were
good substrates, leading to spiral adducts with complete diastereo-
selectivity in good to excellent yields (entries 10 and 11).
With bicyclic enone 5l (entry 12), tricyclic ketone 6l was isolated
pure in 83% yield. The excellent stereoselectivity is due to the
excellent diastereoselectivities in both the formation of the TMS
ether intermediate and the Au-catalyzed [3+2] cycloaddition.
The observed high diastereoselectivities can be readily explained
using the 1,3-dipolar cycloaddition mechanism proposed in Scheme
2 instead of alternative stepwise mechanisms involving carbon
cation formation in the enal/enone double bond.
(4) Silylallenes have been used as C3 units, see: Danheiser, R. L.; Carini, D.
J.; Basak, A. J. Am. Chem. Soc. 1981, 103, 1604-1606.
(5) For selected examples, see: (a) Morita, N.; Krause, N. Angew. Chem.,
Int. Ed. 2006, 45, 1897-1899. (b) Zhang, Z.; Liu, C.; Kinder, R. E.; Han,
X.; Qian, H.; Widenhoefer, R. A. J. Am. Chem. Soc. 2006, 128, 9066-
9073. (c) Nishina, N.; Yamamoto, Y. Angew. Chem., Int. Ed. 2006, 45,
3314-3317.
(6) For our original study, see Zhang, L. J. Am. Chem. Soc. 2005, 127, 16804-
16805. For our later works as well as others’ works, see ref 2e.
(7) Tius, M. A. Acc. Chem. Res. 2003, 36, 284-290.
(8) Hashmi, A. S. K.; Weyrauch, J. P.; Rudolph, M.; Kurpejovic, E. Angew.
Chem., Int. Ed. 2004, 43, 6545-6547.
(9) Extensive NMR studies including NOESY-1D experiments were used to
establish its structure.
(10) A stepwise mechanism was proposed in a related case, see: Buzas, A.;
Gagosz, F. J. Am. Chem. Soc. 2006, 128, 12614-12615.
(11) Generated by shaking CH2Cl2 with H2O followed by phase separation.
(12) The starting enal had a Z/E ratio of 2.3/1. The increase of Z/E ratio in 7
is likely due to the slightly different reactivities of the Z- and E-enal toward
R-lithiated allenyl MOM ether.
Further support for the proposed concerted, if not synch-
ronous, mechanism was obtained: a crude mixture of TMS ether
712 with a Z/E ratio of 2.79/1 was treated with catalyst 4, and a
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