242
M. Rueping, E. Sugiono
The enantioselective Brønsted acid catalyzed activation of a pure carbonyl compound using a chiral BINOL-phosphate had not previously
been described. Hence, we decided to develop such a reaction, a so
far unprecedented Brønsted acid catalyzed enantioselective Nazarov cyclization (Rueping et al. 2007c).
The Nazarov reaction belongs to the group of electrocyclic reactions and is one of the most versatile methods for the synthesis of five
membered rings which are the key structural element of numerous natural products (for reviews on the Nazarov cyclization, see: Habermas
et al. 1994; Denmark 1991; Frontier and Collison 2005; Pellissier 2005;
Tius 2005). Generally, the Nazarov cyclization can be catalyzed by
Brønsted acids or Lewis acids. However, only a few asymmetric variations have been described, most of which require the use of large
amounts of chiral metal complexes [metal-catalyzed enantioselective
Nazarov reactions (Liang et al. 2003; Aggarwal and Belfield 2003);
asymmetric Nazarov reactions through enantioselective protonations
(Liang and Trauner 2004)].
Within the above context and building on our previous results
(Rueping et al. 2005a,b, 2006a–e, 2007a; Rueping and Azap 2006), we
decided to examine a metal free, BINOL-phosphate catalyzed Nazarov
reaction. This would not only be the first example of a Brønsted acid
catalyzed, enantioselective, electrocyclic reaction but would additionally provide a simple and direct route to optically pure cyclopentenones.
Based on our earlier work, we assumed that the catalytic protonation
of a divinylketone 31 by the BINOL-phosphate 5 would result in the
formation of a cyclopentadienyl cation-phosphate anion adduct B. Subsequent conrotatory 4π-electrocyclization would lead to oxyallyl cation
C which, via the elimination of a proton, will form enolate D. Successive protonation of this enolate should then result in the formation of cyclopentenone 32 and the regenerated Brønsted acid catalyst 5 (Fig. 12).
At the outset of our experimental work we began by examining a suitable Brønsted acid catalyst for the enantioselective electrocyclization of
dienone 31. While the use of BINOL-phosphates resulted in the products 32 in good yields, better dia- and enantioselectivities were obtained
with the corresponding N-triflyl phosphoramides 33, which even at 0 °C
gave complete conversion after 10 min. With the optimized conditions
in hand, we applied various dienones to the Brønsted acid catalyzed
M. Rueping, E. Sugiono
The enantioselective Brønsted acid catalyzed activation of a pure carbonyl compound using a chiral BINOL-phosphate had not previously
been described. Hence, we decided to develop such a reaction, a so
far unprecedented Brønsted acid catalyzed enantioselective Nazarov cyclization (Rueping et al. 2007c).
The Nazarov reaction belongs to the group of electrocyclic reactions and is one of the most versatile methods for the synthesis of five
membered rings which are the key structural element of numerous natural products (for reviews on the Nazarov cyclization, see: Habermas
et al. 1994; Denmark 1991; Frontier and Collison 2005; Pellissier 2005;
Tius 2005). Generally, the Nazarov cyclization can be catalyzed by
Brønsted acids or Lewis acids. However, only a few asymmetric variations have been described, most of which require the use of large
amounts of chiral metal complexes [metal-catalyzed enantioselective
Nazarov reactions (Liang et al. 2003; Aggarwal and Belfield 2003);
asymmetric Nazarov reactions through enantioselective protonations
(Liang and Trauner 2004)].
Within the above context and building on our previous results
(Rueping et al. 2005a,b, 2006a–e, 2007a; Rueping and Azap 2006), we
decided to examine a metal free, BINOL-phosphate catalyzed Nazarov
reaction. This would not only be the first example of a Brønsted acid
catalyzed, enantioselective, electrocyclic reaction but would additionally provide a simple and direct route to optically pure cyclopentenones.
Based on our earlier work, we assumed that the catalytic protonation
of a divinylketone 31 by the BINOL-phosphate 5 would result in the
formation of a cyclopentadienyl cation-phosphate anion adduct B. Subsequent conrotatory 4π-electrocyclization would lead to oxyallyl cation
C which, via the elimination of a proton, will form enolate D. Successive protonation of this enolate should then result in the formation of cyclopentenone 32 and the regenerated Brønsted acid catalyst 5 (Fig. 12).
At the outset of our experimental work we began by examining a suitable Brønsted acid catalyst for the enantioselective electrocyclization of
dienone 31. While the use of BINOL-phosphates resulted in the products 32 in good yields, better dia- and enantioselectivities were obtained
with the corresponding N-triflyl phosphoramides 33, which even at 0 °C
gave complete conversion after 10 min. With the optimized conditions
in hand, we applied various dienones to the Brønsted acid catalyzed