82
D. Enders, M.R.M. Hüttl, O. Niemeier
for a four-step procedure (35%–56%). In this process, five new C–C
bonds and seven or eight new stereocenters were generated with complete enantioselectivity (≥99% ee). Interestingly, the reactions of structures that consisted of three six-membered rings 77 gave only two diastereomers with a ratio of 10:1 to 15:1, whereas reactions of the more
strained structures 76 gave three diastereomers in ratios of 5:1:1 to
12:2:1. One of the diastereomers emanates from the triple cascade as
an epimer in the position α to the nitro group, the other diastereomer
is formed in the course of the IMDA reaction. The relative and absolute configuration of the complex structures was determined by X-ray
analysis of the compound 76 and also by NOE measurements based on
the known configuration of the intermediates. The relative and absolute
configuration of compounds 76 and 77 supports the mechanism that we
proposed earlier (Enders and Hüttl 2006), and also the selectivity for
trans-fused endo configuration of the intramolecular cycloaddition promoted by a Lewis acid (Enders et al. 2007b).
A comparison of the relevant transition states of the intramolecular Diels-Alder reaction can explain the observed configuration of the
products 76 and 77. In the case of 76 (n = 0), the diene moiety is more
likely to approach from underneath the enal face in an ‘endo manner’
(the Alder rule) because of a steric interaction with the phenyl group.
The other structures 77 that contain a longer side chain (n = 1) allow
the approach from both beneath and above the enal face, but NOE analyses of the isolated products 77 revealed that the diene approaches the
dienophile from the top. Thus, in both systems, the trans-fused endoconfiguration is preferred because of steric interactions with the phenyl
substituents and the nitro group (Enders et al. 2007b).
3
C–C-Bond Formations Employing
N-Heterocyclic Carbene Catalysis
3.1
Enzymes as Archetypes
In Nature, realms of complex biochemical reactions are catalyzed by
enzymes, many which lack metals in their active site. Among them, nucleophilic acylation reactions are catalyzed by transketolase enzymes
in the presence of coenzyme thiamine (78, vitamin B 1 ), a natural thia-
D. Enders, M.R.M. Hüttl, O. Niemeier
for a four-step procedure (35%–56%). In this process, five new C–C
bonds and seven or eight new stereocenters were generated with complete enantioselectivity (≥99% ee). Interestingly, the reactions of structures that consisted of three six-membered rings 77 gave only two diastereomers with a ratio of 10:1 to 15:1, whereas reactions of the more
strained structures 76 gave three diastereomers in ratios of 5:1:1 to
12:2:1. One of the diastereomers emanates from the triple cascade as
an epimer in the position α to the nitro group, the other diastereomer
is formed in the course of the IMDA reaction. The relative and absolute configuration of the complex structures was determined by X-ray
analysis of the compound 76 and also by NOE measurements based on
the known configuration of the intermediates. The relative and absolute
configuration of compounds 76 and 77 supports the mechanism that we
proposed earlier (Enders and Hüttl 2006), and also the selectivity for
trans-fused endo configuration of the intramolecular cycloaddition promoted by a Lewis acid (Enders et al. 2007b).
A comparison of the relevant transition states of the intramolecular Diels-Alder reaction can explain the observed configuration of the
products 76 and 77. In the case of 76 (n = 0), the diene moiety is more
likely to approach from underneath the enal face in an ‘endo manner’
(the Alder rule) because of a steric interaction with the phenyl group.
The other structures 77 that contain a longer side chain (n = 1) allow
the approach from both beneath and above the enal face, but NOE analyses of the isolated products 77 revealed that the diene approaches the
dienophile from the top. Thus, in both systems, the trans-fused endoconfiguration is preferred because of steric interactions with the phenyl
substituents and the nitro group (Enders et al. 2007b).
3
C–C-Bond Formations Employing
N-Heterocyclic Carbene Catalysis
3.1
Enzymes as Archetypes
In Nature, realms of complex biochemical reactions are catalyzed by
enzymes, many which lack metals in their active site. Among them, nucleophilic acylation reactions are catalyzed by transketolase enzymes
in the presence of coenzyme thiamine (78, vitamin B 1 ), a natural thia-