Inside alkoxy effect

The oxygen atom has also been used to generate other functionalities, such as the aldehyde moiety in Kibayashi s syntheses of (—)-coniine (197) and its enantiomer (Scheme 1.43) (253). Here, reaction of tetrahydropyridine N-oxide 93 with a silylated chiral allyl ether dipolarophile 198 delivered the adduct 199 with the desired bridgehead stereochemistry via the inside alkoxy effect . Desilylation and hydrogenolytic N—O bond rupture with palladium(II) chloride provided the diol 200... 

However, a computational study124 shows that the Kishi model controls the stereoselectivity for (Z)-alkenes. Note also that in the Diels-Alder reactions of hexachloropentadiene with chiral alkenes, the inside alkoxy effect is attributed to electrostatic repulsion of the oxy group in the125 outside position with the chlorine atom of hexachloropentadiene in the 1-position. 

In contrast to the dihydroxylations, the hydroboration of allylic alcohols takes place without an inside alkoxy effect in the sense 5.132 with the oxygen atom treated as the medium-sized group. It is probably significant that the inside alkoxy effect is most noticeable with reagents which are relatively electrophilic in nature, and not with boranes, which are only mildly electrophilic. 

The inside alkoxy effect is useful for predicting the stereoselectivity of nitrile oxide cycloaddition reactions with chiral lylic ethers. The hypothesis states that allylic ethers adopt the inside position and alkyl substituents prefer the sterically less-crowded anti conformation in transition states for these electrophilic cycloadditions . The terms inside and outside are defined in (17) for a hypothetical nitrile oxide cycloaddition transition state. Both ab initio (Gaussian 80 with 3-2IG basis set) and molecular mechanics calculations agree, each predicting the lowest-energy transition state to be the one described, i.e. (18 H outside) just above it lies one where the alkyl group is anti, OR outside and H inside (19 ). As illustrated, the former leads to a product wherein OR and the nitrile oxide oxygen are anti, the latter to one with them syn (Scheme 19). 

Houk KN, Moses SR, Wu Y-D, Rondan NG, Jager V, Schohe R, Fronczek FR (1984) Stereoselective nitrile oxide cycloadditions to chiral allyl ethers and alcohols. The inside alkoxy effect. J Am Chem Soc 106 3880-3882... 

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