New Developments in EnantioselectiveBrønsted Acid Catalysis
245
sponding cyclopentenones in good yields and with excellent enantioselectivities (86%–98% ee). The Nazarov reaction introduced represents
the first BINOL-phosphate catalyzed enantio-selective carbonyl activation. Compared to the metal catalyzed reaction, special features of our
new Brønsted acid catalyzed electrocyclization are the lower catalyst
loadings (2 mol%), higher enantioselectivities, access to all possible
stereoisomers, as well as the mild conditions and fast reaction times.
In summary, in the first 3 years of our research we have made important contributions to the field of organocatalysis. In this highly competitive and fast moving topical area of organic chemistry we have set
important milestones by, for example, developing the first metal-free,
highly enantioselective Brønsted catalyzed biomimetic transferhydrogenations, cascade reductions, Strecker reactions, azaenamine additions,
direct Mannich reactions, pyridine reductions, as well as domino Mannich-Michael additions. The enantioselectivities observed for such
transformations are impressive with most exceeding 90% enantiomeric
excess. In addition to these novel chiral ion pair catalyzed transformations, we were the first to realize that chiral Brønsted acids can activate carbonyl groups which resulted in the development of the first
organocatalytic electrocyclic reactions. This is not only the first example of such a method but more significantly, it opens the door for many
further enantioselective carbonyl transformations.
References
Achari B, Mandal SB, Dutta PK, Chowdhury C (2004) Synlett 2004:2449
Aggarwal VK, Belfield AJ (2003) Catalytic asymmetric Nazarov reactions promoted by chiral Lewis acid complexes. Org Lett 5:5075–5078
Akiyama T, Itoh J, Fuchibe K (2006c) Adv Synth Catal 348:999
Akiyama T, Itoh J, Yokota K, Fuchibe K (2004) Enantioselective Mannich-type
reaction catalyzed by a chiral Brønsted acid. Angew Chem Int Ed Engl
43:1566–1568
Akiyama T, Morita H, Itoh J, Fuchibe K (2005a) Chiral Brønsted acid catalyzed
enantioselective hydrophosphonylation of imines: asymmetric synthesis of
alpha-amino phosphonates. Org Lett 7:2583–2585
Akiyama T, Morita H, Fuchibe K (2006b) Chiral Brønsted acid-catalyzed inverse electron-demand aza Diels–Alder reaction. J Am Chem Soc 128:
13070–13071
245
sponding cyclopentenones in good yields and with excellent enantioselectivities (86%–98% ee). The Nazarov reaction introduced represents
the first BINOL-phosphate catalyzed enantio-selective carbonyl activation. Compared to the metal catalyzed reaction, special features of our
new Brønsted acid catalyzed electrocyclization are the lower catalyst
loadings (2 mol%), higher enantioselectivities, access to all possible
stereoisomers, as well as the mild conditions and fast reaction times.
In summary, in the first 3 years of our research we have made important contributions to the field of organocatalysis. In this highly competitive and fast moving topical area of organic chemistry we have set
important milestones by, for example, developing the first metal-free,
highly enantioselective Brønsted catalyzed biomimetic transferhydrogenations, cascade reductions, Strecker reactions, azaenamine additions,
direct Mannich reactions, pyridine reductions, as well as domino Mannich-Michael additions. The enantioselectivities observed for such
transformations are impressive with most exceeding 90% enantiomeric
excess. In addition to these novel chiral ion pair catalyzed transformations, we were the first to realize that chiral Brønsted acids can activate carbonyl groups which resulted in the development of the first
organocatalytic electrocyclic reactions. This is not only the first example of such a method but more significantly, it opens the door for many
further enantioselective carbonyl transformations.
References
Achari B, Mandal SB, Dutta PK, Chowdhury C (2004) Synlett 2004:2449
Aggarwal VK, Belfield AJ (2003) Catalytic asymmetric Nazarov reactions promoted by chiral Lewis acid complexes. Org Lett 5:5075–5078
Akiyama T, Itoh J, Fuchibe K (2006c) Adv Synth Catal 348:999
Akiyama T, Itoh J, Yokota K, Fuchibe K (2004) Enantioselective Mannich-type
reaction catalyzed by a chiral Brønsted acid. Angew Chem Int Ed Engl
43:1566–1568
Akiyama T, Morita H, Itoh J, Fuchibe K (2005a) Chiral Brønsted acid catalyzed
enantioselective hydrophosphonylation of imines: asymmetric synthesis of
alpha-amino phosphonates. Org Lett 7:2583–2585
Akiyama T, Morita H, Fuchibe K (2006b) Chiral Brønsted acid-catalyzed inverse electron-demand aza Diels–Alder reaction. J Am Chem Soc 128:
13070–13071