Stereoconvergent [1,2]- and [1,4]-Wittig rearrangements of 2-silyl-6-aryl-5,6-dihydropyrans: a tale of steric vs electronic regiocontrol of divergent pathways

Abstract

The regiodivergent ring contraction of diastereomeric 2-silyl-5,6-dihydro-6-aryl-(2H)-pyrans via [1,2]- and [1,4]-Wittig rearrangements to the corresponding α-silylcyclopentenols or (α-cyclopropyl)acylsilanes favor the [1,4]-pathway by ortho and para directing groups in the aromatic appendage and/or by sterically demanding silyl groups. The [1,2]-pathway is dominant with meta directing or electron-poor aromatic moieties. Exclusive [1,2]-Wittig rearrangements are observed when olefin substituents proximal to the silyl are present. cis and trans diastereomers exhibit different reactivities, but converge to a single [1,2]- or [1,4]-Wittig product with high diastereoselectivity and yield.

Scheme 1. Possible Wittig Rearrangement Pathways of an Allylic Ether

Scheme 2. Wittig Rearrangements of Dihydropyrans

Scheme 3. Synthesis of Precursors S1 and S2

Scheme 4. Synthesis of Dienes S3 and Silyl Cyclic Ethers 1 and 2

Values in parentheses refer to the yield of a mixture of diastereomers 1 and 2 prepared from the corresponding mixture of syn/anti precursors S3. See the Experimental Section for diastereomeric ratios.

Scheme 5. Alternative Synthesis of Dienes S3

Scheme 6. [1,2]- and [1,4]-Wittig Rearrangements of Model 2-Silyldihydropyrans 1a and 2a under Optimized Conditions

Figure 1

Hammett plots of log(k_X/k₀) vs σ and σ⁺.

Scheme 7. Isomerization of the [1,4]-Enolate to the [1,2]-Alkoxide (and Vice Versa) Was Not Observed

Scheme 8. Diradical Anion Species Leading to Alkoxide Products by Intramolecular Recombination ([1,2]-Product)

Scheme 9. Conformational Analysis for the trans (1) and cis (2) Diastereomers Relevant for the Deprotonation Step

Scheme 10. Effect of Increasing Steric Demand at the ortho Position of the Aromatic Ring

Figure 2

Crystal structure of [1,2]-Wittig product 4s.

Scheme 11. Rearrangements of Heteroaromatic Substrates

Scheme 12. Stereochemical Course of the [1,4]- and [1,2]-Wittig Rearrangements of (−)-1a and (+)-2a

Scheme 13. Deuterium Trapping Experiments and Proposed Origin of Stereoconvergence

Scheme 14. Determination of the Absolute Stereochemistry of Compound (−)-3a

Scheme 15. Determination of the Absolute Stereochemistry of Compound (+)-4a

Scheme 16. Competitive ortho Metalation vs Allylic Deprotonation of Compound 2d

Scheme 17. Competitive ortho Metalation vs Allylic Deprotonation of 2h

Scheme 18. Competitive Thiophene Metalation vs Allylic Deprotonation of 2aa

Scheme 19. Competitive Furan Metallation vs Allylic Deprotonation of 2bb