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. 2007 Oct 25;9(22):4459-62.
doi: 10.1021/ol701768n. Epub 2007 Oct 2.

A stereoselective intramolecular halo-etherification of chiral enamides in the synthesis of halogenated cyclic ethers

Changhong Ko  1 , Richard P Hsung, Ziyad F Al-Rashid, John B Feltenberger, Ting Lu, Jin-Haek Yang, Yonggang Wei, Craig A Zificsak
Affiliations

A stereoselective intramolecular halo-etherification of chiral enamides in the synthesis of halogenated cyclic ethers

Changhong Ko et al. Org Lett. .

Abstract

A stereoselective halo-etherification of chiral enamides is described here. This work provides an approach to halogen containing cyclic ethers and reveals further mechanistic insights to the chemistry of chiral enamides.

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Figures

Figure 1
Figure 1
Effect of the chiral auxiliary on stereoselectivity. All are isolated yields. Conditions: At −78 °C in toluene or CH2Cl2, added a respective halogen source: Br2 [0.5 M in CH2Cl2] and NCS/TBAC; stirred from −78 °C to rt for 0.5–2 h, except it is 24–48 h for the chlorination with NCS/TBAC.
Figure 2
Figure 2
Halo-oxacycles of different ring sizes. All are isolated yields.
Figure 3
Figure 3
Nucleophilicity and the nature of iminium ion pairs in C.
Scheme 1
Scheme 1
An Arrested Bromination–Elimination of Enamides
Scheme 2
Scheme 2
Observation of a Desilylative Bromo-Etherification
Scheme 3
Scheme 3
A Sequential N-Alkenylation and Bromo-Etherification
Scheme 4
Scheme 4
A Proposed Stereochemical Model
Scheme 5
Scheme 5
Bromination of a Z-Enamide
See this image and copyright information in PMC

References

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    1. For reviews, see: Rappoport Z. The Chemistry of Enamines in The Chemistry of Functional Groups. New York: John Wiley and Sons; 1994. Whitesell JK, Whitesell MA. Synthesis. 1983:517. Hickmott PW. Tetrahedron. 1982;38:1975. Hickmott PW. Tetrahedron. 1982;38:3363.

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