Homoallylic substituents

The stereochemical outcome was in agreement with the formation of a chelated allyl alkenylzinc compound that underwent a metalla-Claisen rearrangement with delivery of the allyl moiety anti to the homoallylic substituent. Although the stereocenter was more remote from the alkenylmetal, excellent induction was still observed152,153. 

For alkenylmetals bearing two stereocenters at both the allylic and homoallylic positions, two situations have to be distinguished depending on their relative influence (matched or mismatched) with respect to the stereochemical outcome of the allylzincation. Not surprisingly, in the matched case, as illustrated for substrate 232, the diastereoselectivity was excellent and 233 was obtained as a single diastereomer. The allyl moiety was delivered anti to both the allylic and homoallylic substituents in the chelated allyl alkenylzinc species (equation 113). 

This transition state model also accounted well for the observed diastereoselectivities when the allyl and homoallyl substituents were both part of a six-membered ring153. 

Ether was a better solvent in cases where the propargylic position was unsubstituted (methylene group) since, in THF, a competitive [1,2] -Wittig rearrangement took place and led to diminished yields. When applied to the secondary homoallylic propargyl ethers 388, the zinc-ene-allene cyclization afforded the c -2,3,5-trisubstituted tetrahydrofurans 389 with moderate to satisfactory levels of diastereoselectivity, which could be rationalized by the preferential pseudo-equatorial positioning of the homoallylic substituent in the cyclic... 

Table 11 Relative Asymmetric Induction by Homoallylic Substituent (Equation 44)129...

High stereoselectivity has been observed in the cyclizations to y-lactams of thioimidate systems with a homoallylic substituent (equation lll).217W,7c The selectivity is considered to arise from A1 2 strain favoring a quasiaxial orientation of the homoallylic substituent in (17 see above). In comparison, the cyclizations to y-lactams shown in Table 29 were not stereoselective.233... 

When 1,4-dimethylcyclohexene is hydrogenated on Pt and Rh, ds-l,4-dimethylcyclo-hexane is formed in slight excess (Table 7). These data, again, are consistent with the involvement of 7r-adsorbed species with an almost equal degree of hindrance in the alternate adsorption modes. The homoallylic substituent, consequently, does not exert any strong influence on stereochemistry. The trans compound, however, is the main product on Pd (Table 7) indicating a favored trans adsorption mode (18). 

Vinyl nitrene intermediates may also be trapped intramolecularly by alkenes situated further from the azirine nucleus. A variety of products can result from these reactions, depending on the substituents present on the alkene. Scheme 16 illustrates the diverse processes that may operate <76JOC180, 78JOC2029). 2-Propargylic 2//-azirines also cyclize to provide pyridine derivatives (78JOC2029), while homoallylic substituents at C(2) allow cyclization to form pyridine and biphenyl derivatives (75CC789,77JA1871). 

The observed stereochemical induction and the retention of olefin configuration during the rearrangement are consistent with a mechanistic scheme in which pinacol cyclization of the ( )-oxonium intermediate 32 (X = O) occurs through a chairlike conformation in which the homoallylic substituent R2 adopts an equatorial orientation subsequent [1,2] migration via the chairlike conformation 33 results in the formation of stereochemically defined heterocyclic products. 

A homoallylic substituent (e.g., carbonate) imparts diastereoselectivity on the conjugate addition due to its interaction with the reagent. ... 

Scheme 10.17 Effect of homoallylic substituents on CM en route to prostaglandins.

The 4-hydroxy-1-alkene (homoallylic alcohol) 81 is oxidized to the hetni-acetal 82 of the aldehyde by the participation of the OH group when there is a substituent at C3. In the absence of the substituent, a ketone is obtained. The hemiacetal is converted into butyrolactone 83[117], When Pd nitro complex is used as a catalyst in /-BuOH under oxygen, acetals are obtained from homoallylic alcohols even in the absence of a substituent at C-3[l 18], /-Allylamine is oxidized to the acetal 84 of the aldehyde selectively by participation of the amino group[l 19],... 

Employing protocol V with the methanesulfonamide catalyst 122, a 93 7 er can be obtained in the cyclopropanation of cinnamyl alcohol. This high selectivity translates well into a number of allylic alcohols (Table 3.12) [82]. Di- and tri-substi-tuted alkenes perform well under the conditions of protocol V. However, introduction of substituents on the 2 position leads to a considerable decrease in rate and selectivity (Table 3.12, entry 5). The major failing of this method is its inability to perform selective cyclopropanations of other hydroxyl-containing molecules, most notably homoallylic alcohols. 

Hydroxy-l-alkenyl diisopropylcarbamates 2 (X = OCb), in this respect, occupy a medium position since they are stable in strongly acidic and basic protic solvents. For deblocking vinyl carbamates, the presence of catalytic amounts of mercuric or palladium(II) salts is required. Due to this stability, several reactions of homoallylic alcohols, proceeding with high diastereo-selectivity, e g., epoxidation, are applicable in order to introduce further hetero-substituents. 

Treatment of allyl bromides with the complex obtained from tin(II) chloride and the disodium salt of diethyl 2,3-dihydroxybutanedioate gives an intermediate which reacts with aldehydes to provide homoallylic alcohols with 50-65% ee. Lower enantiomeric excesses were obtained with bulky aldehydes and for allylstannanes with y-substituents. Pentacoordinated allyltin complexes may be involved97. 

Analyze the data below concerning the effect of allylic and homoallylic benzyloxy substituents on the regio- and stereoselectivity of hydroboration-oxidation. Propose a TS that is consistent with the results. 

The present homoallylation with isoprene under Ni-Et3B catalysis shows marginal success for the reaction with aliphatic aldehydes. Results are summarized in Table 6. Primary alkyl aldehydes (bearing no a-substituents) and sterically less-hindered secondary alkyl aldehydes undergo the homoallylation successfully to provide the expected products in good yields with excellent stereoselectivity (runs 1-5). The results in runs 3-5 indicate that the present reaction shows almost no diastereofacial selectivity with respect to the a-stereo centers of secondary alkyl aldehydes. Sterically demanding aldehydes, such as cyclohexanecarbaldehye and pivalaldehyde, provide the... 

The synthesis of optically active compounds by the diastereoselective reaction of allyltitanium reagents with chiral electrophiles has also been reported. The reaction of allyltitanium reagents with chiral imines proceeds with excellent diastereoselectivity, as shown in Eq. 9.28, thus providing a new method for synthesizing optically active homoallylic amines with or without a P-substituent [51,52],... 

Efforts have been made to apply r 3-allyltitanium chemistry to the asymmetric synthesis of homoallylic alcohols and carboxylic acids. The synthesis and reactions of chiral r 3 -allyl-titanocenes with planar chirality, or containing Cp ligands with chiral substituents, have been reported [6c,15,30—32]. The enantiofacial selectivity in the allyltitanation reactions has been examined for the complexes 12 [15], 13 [30], 14 [31], 15, 16, and 17 [32] depicted in Figure 13.2. 

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