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Bond cleavage, fragment modification and reassembly in enantioselective three-component reactions.

Zhang D, Zhou J, Xia F, Kang Z, Hu W - Nat Commun (2015)

Bottom Line: The stereoselective reaction went through a unique process that involves cleavage of a C-N bond, modification of the resulting amino fragment and selective reassembly of the modified fragment.This innovative multi-component process represents a highly efficient way to build structurally diversified polyfunctional molecules in an atom and step economic fashion.A keto-iminium is proposed as a key intermediate and a chiral palladium/phosphate complex is proposed as an active catalyst.

View Article: PubMed Central - PubMed

Affiliation: Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, and Department of Chemistry, East China Normal University, Shanghai 200062, China.

ABSTRACT
Chemical bond cleavage and reconstruction are common processes in traditional rearrangement reactions. In contrast, the process that involves bond cleavage, fragment modification and then reconstruction of the modified fragment provides an efficient way to build structurally diversified molecules. Here, we report a palladium(II)/chiral phosphoric acid catalysed three-component reaction of aryldiazoacetates, enamines and imines to afford α-amino-δ-oxo pentanoic acid derivatives in good yields with excellent diastereoselectivities and high enantioselectivities. The stereoselective reaction went through a unique process that involves cleavage of a C-N bond, modification of the resulting amino fragment and selective reassembly of the modified fragment. This innovative multi-component process represents a highly efficient way to build structurally diversified polyfunctional molecules in an atom and step economic fashion. A keto-iminium is proposed as a key intermediate and a chiral palladium/phosphate complex is proposed as an active catalyst.

No MeSH data available.


Discovery of the novel process.(a) Prior works for the enantioselective trapping of zwitterionic intermediates. (b) Hypothetical pathway for the enamine-participated multi-component reaction. (c) Actual process: bond cleavage, fragment modification and reassembly.
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f2: Discovery of the novel process.(a) Prior works for the enantioselective trapping of zwitterionic intermediates. (b) Hypothetical pathway for the enamine-participated multi-component reaction. (c) Actual process: bond cleavage, fragment modification and reassembly.

Mentions: We have recently reported an efficient trapping process in which zwitterionic intermediates were trapped by electrophiles to produce polyfunctional molecules in a single synthetic step1112. In the reported reactions, for example, indoles and pyrroles containing a cyclic enamine as a key structural motif were successfully employed as substrates (Fig. 2a). In continuation with this study, we envisioned that using an acyclic enamine should undergo a similar transformation to afford a zwitterionic intermediate trapping product (Fig. 2b)13. Thus, the three-component reaction of methyl phenyldiazoacetate, an acyclic enamine and an imine was conducted. However, the proposed process did not occur as expected, but we discovered a novel process that involves cleavage of a C–N bond, modification of the resulting amino fragment by forming an ammonium ylide and regio- and stereoselective reassembly of the modified fragment back to another iminium fragment to produce a chiral α-amino-δ-oxo pentanoic acid derivative (Fig. 2c). In this three-component reaction, one bond cleavage and three bonds formation take place in one step to produce a new molecule bearing two stereogenic centres including one quaternary carbon centre in excellent diastereoselectivity and high enantioselectivity. This unique process provides an easy access for highly efficient construction of chiral α-amino-δ-oxo pentanoic acid derivatives14151617 from simple substrates under mild reaction conditions.


Bond cleavage, fragment modification and reassembly in enantioselective three-component reactions.

Zhang D, Zhou J, Xia F, Kang Z, Hu W - Nat Commun (2015)

Discovery of the novel process.(a) Prior works for the enantioselective trapping of zwitterionic intermediates. (b) Hypothetical pathway for the enamine-participated multi-component reaction. (c) Actual process: bond cleavage, fragment modification and reassembly.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4309444&req=5

f2: Discovery of the novel process.(a) Prior works for the enantioselective trapping of zwitterionic intermediates. (b) Hypothetical pathway for the enamine-participated multi-component reaction. (c) Actual process: bond cleavage, fragment modification and reassembly.
Mentions: We have recently reported an efficient trapping process in which zwitterionic intermediates were trapped by electrophiles to produce polyfunctional molecules in a single synthetic step1112. In the reported reactions, for example, indoles and pyrroles containing a cyclic enamine as a key structural motif were successfully employed as substrates (Fig. 2a). In continuation with this study, we envisioned that using an acyclic enamine should undergo a similar transformation to afford a zwitterionic intermediate trapping product (Fig. 2b)13. Thus, the three-component reaction of methyl phenyldiazoacetate, an acyclic enamine and an imine was conducted. However, the proposed process did not occur as expected, but we discovered a novel process that involves cleavage of a C–N bond, modification of the resulting amino fragment by forming an ammonium ylide and regio- and stereoselective reassembly of the modified fragment back to another iminium fragment to produce a chiral α-amino-δ-oxo pentanoic acid derivative (Fig. 2c). In this three-component reaction, one bond cleavage and three bonds formation take place in one step to produce a new molecule bearing two stereogenic centres including one quaternary carbon centre in excellent diastereoselectivity and high enantioselectivity. This unique process provides an easy access for highly efficient construction of chiral α-amino-δ-oxo pentanoic acid derivatives14151617 from simple substrates under mild reaction conditions.

Bottom Line: The stereoselective reaction went through a unique process that involves cleavage of a C-N bond, modification of the resulting amino fragment and selective reassembly of the modified fragment.This innovative multi-component process represents a highly efficient way to build structurally diversified polyfunctional molecules in an atom and step economic fashion.A keto-iminium is proposed as a key intermediate and a chiral palladium/phosphate complex is proposed as an active catalyst.

View Article: PubMed Central - PubMed

Affiliation: Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, and Department of Chemistry, East China Normal University, Shanghai 200062, China.

ABSTRACT
Chemical bond cleavage and reconstruction are common processes in traditional rearrangement reactions. In contrast, the process that involves bond cleavage, fragment modification and then reconstruction of the modified fragment provides an efficient way to build structurally diversified molecules. Here, we report a palladium(II)/chiral phosphoric acid catalysed three-component reaction of aryldiazoacetates, enamines and imines to afford α-amino-δ-oxo pentanoic acid derivatives in good yields with excellent diastereoselectivities and high enantioselectivities. The stereoselective reaction went through a unique process that involves cleavage of a C-N bond, modification of the resulting amino fragment and selective reassembly of the modified fragment. This innovative multi-component process represents a highly efficient way to build structurally diversified polyfunctional molecules in an atom and step economic fashion. A keto-iminium is proposed as a key intermediate and a chiral palladium/phosphate complex is proposed as an active catalyst.

No MeSH data available.