Stereoselectivities and Regioselectivities of (4 + 3) Cycloadditions Between Allenamide-Derived Chiral Oxazolidinone-Stabilized Oxyallyls and Furans: Experiment and Theory

Abstract

A systematic investigation of the regioselectivities and stereoselectivities of (4+3) cycloadditions between unsymmetrical furans and a chiral oxazolidinone-substituted oxyallyl is presented. Cycloadditions were performed using an oxyallyl containing a (R)-4-phenyl-2-oxazolidinone auxiliary (2Ph), under either thermal or ZnCl2-catalyzed conditions. Reactions of 2Ph with 2-substituted furans gave syn cycloadducts selectively, while cycloadditions with 3-substituted furans gave selectively anti cycloadducts. The stereoselectivities were in favor of a single diastereoisomer (I) in all but one case (2-CO2R). Density functional theory calculations were performed to explain the selectivities. The results support a mechanism in which all cycloadducts are formed from the E isomer of the oxyallyl (in which the oxazolidinone C=O and oxyallyl oxygen are anti to each other) or the corresponding E ZnCl2 complex. The major diastereomer is derived from addition of the furan to the more crowded face of the oxyallyl. Crowded transition states are favored because they possess a stabilizing CH–π interaction between the furan and the Ph group.

Control of Regioselectivity and Stereoselectivity in (4 + 3) Cycloadditions of Chiral Oxyallyls with Unsymmetrically Disubstituted Furans

“…Confirmation of the structure of 9 was obtained following reduction/esterification, which afforded a rearranged derivative ( 12 ) whose X-ray structure was determined (Figure 1). 7 The regioselectivities observed for both 4 and 5 match those previously obtained 6b with the achiral oxyallyl 3a , which displayed syn selectivities of ≥95:5.…”

“…6 We performed density functional theory calculations to explore the selectivities. Transition states for ZnCl 2 -catalyzed cycloadditions of the oxyallyls 3b and 3c with furans 4–7 were computed at the B3LYP/6-31G(d) level (with LANL2DZ on Zn), as we have previously done in our studies of related oxyallyl (4+3) cycloadditions.…”

“…Surprisingly, reactions of 3b with most monosubstituted furans were found to favor the endo-I stereochemistry, which entails addition of the furan to the more crowded face of 3b . Density functional theory calculations 6 showed that the crowded transition state is favored because it contains a stabilizing edge-to-face aromatic interaction (CH–π) between furan and Ph. Of the monosubstituted furans studied, only those containing a 2-CO 2 R group did not follow this behavior.…”

Allenamides: A Powerful and Versatile Building Block in Organic Synthesis

“…Krenske, Houk, and Hsung 145 further studied both regio- and stereoselectivity of [4 + 3] cycloadditions of 2 or 3-monosubstituted furans with chiral allenamides 548 (Schemes 153). For brevity and clarity, only a few examples of C-3-substituted cases are shown here, while details can be referred back to the original publication.…”

A Highly Stereoselective Diels–Alder Cycloaddition of Enones with Chiral Cyclic 2-Amidodienes Derived from Allenamides

“…Single crystal X-ray structure of 22a provided unambiguous confirmation of the endo-I selectivity [left Figure 1]. 20,21 …”