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. 2006 May 24;128(20):6745-54.
doi: 10.1021/ja060812g.

Sequential Ru-Pd catalysis: a two-catalyst one-pot protocol for the synthesis of N- and O-heterocycles

Barry M Trost  1 , Michelle R Machacek, Brian D Faulk
Affiliations

Sequential Ru-Pd catalysis: a two-catalyst one-pot protocol for the synthesis of N- and O-heterocycles

Barry M Trost et al. J Am Chem Soc. .

Abstract

An atom economic, selective, and highly practical two-metal one-pot synthesis of heterocycles has been developed that efficiently affords enantio- and diastereopure N- and O-heterocyclic products. Furthermore, use of a chiral catalyst in the two-metal procedure allows formation of all possible diastereomers, even those that are traditionally difficult to access via cyclization routes due to thermodynamics. Interestingly, the nature of the enantiodiscriminating event differs between the use of amine versus alcohol nucleophiles. The method also affords heterocyclic products that are synthetically useful intermediates. Through the Z-vinylsilane a variety of stereodefined trisubstituted olefin products can be accessed including several all-carbon motifs. Finally, the utility of these heterocyclic products in total synthesis is demonstrated through concise syntheses of a kainoid intermediate, a constituent of oil of rose, and the ring B portion of bryostatin, a potent chemotherapeutic.

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Figures

Scheme 1
Scheme 1
Tandem Coupling Cyclization
Scheme 2
Scheme 2
The Regioisomer Solution
Scheme 3
Scheme 3
Catalyst Compatibility
Scheme 4
Scheme 4
Sulfonamides - Ionization is Enantiodetermining
Scheme 5
Scheme 5
Oxygen Nucleophiles - Nucleophilic Addition as Enantiodetermining
Scheme 6
Scheme 6
Synthesis of 4-oxyproline derivative
Scheme 7
Scheme 7
Completion of Rose Oil Oxide
Scheme 8
Scheme 8
Representative Further Synthetic Transformations
Scheme 9
Scheme 9
Bryostatin 1 and 2
Scheme 10
Scheme 10
Synthesis of Ring B
See this image and copyright information in PMC

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