Acyclic diastereoselection allylations

Kinetic resolution (enantiomer differentiation) of cycloalkenyl diazoacetates has been achieved (for example, according to Eq. 3) [34]. In these cases one enantiomer of the racemic reactant matches with the catalyst configuration to produce the intramolecular cyclopropanation product in high enantiomeric excess, whereas the mismatched enantiomer preferentially undergoes hydride abstraction from the allylic position [35] to yield the corresponding cycloalkenone. With acyclic secondary allylic diazoacetates the hydride abstraction pathway is relatively unimportant, and diastereoselection becomes the means for enantiomer differentiation [31]. 

The reaction of the acyclic bis(allyl)titanium complexes 16 with the imino esters 23a-c in the presence of Ti(OiPr)4 and ClTijOiPrjs at low temperatures proceeded with >98% regioselectivity and >98% diastereoselectivity and gave the corresponding T-syn-configured unsaturated a-amino acid derivatives E-24 in good yields (Scheme 1.3.11) [21, 22]. 

Hydrogen bonding is a possible reason also for the diastereoselectivity of the [2+2] photocycloaddition of benzophenone also in case of acyclic chiral allylic alcohols 142 (Sch. 49). These substrates afforded only one regioisomer of the diastereomeric threo, erythro oxetanes 143 and preferentially the threo isomer [144]. The diastereoselectivity was remarkably reduced in the presence of a protic solvent (methanol as a competitive intermolecular hydrogen bonding substrate) and totally disappeared in case of the silylated substrate [145]. 

Chirahty transmission can also be induced in thio-Claisen reactions by a chiral center adjacent to the allyl vinyl sulfide core. The group of Metz-ner examined the diastereoselectivity of the rearrangement of acyclic S-allyl ketene dithioacetals bearing a chiral center adjacent to carbon 6. hi these substrates, the sigmatropic shift proceeded smoothly and with modest syn anti diastereoselectivity [74]. In contrast, higher selectivities are foimd for thio-Claisen precursors bearing a chiral center adjacent to carbon 1 mainly due to steric effects and allylic strain [75]. In 1991, the group of Beslin examined the effect of a hydroxyl substituted chiral center attached to C-1 of Z and E S-allyl ketene dithioacetals [76,77] (Scheme 7). Under the reaction conditions, these... 

Allylic alcohols undergo cyclopropanation faster than unfunctionalized alkenes, " and excellent diastereoselectivities have been observed in reactions of the Furukawa reagent with acyclic chiral allylic alcohols. ... 

Similarly, reactions of the modified Simmons-Smith reagent with acyclic (Z)-allylic alcohols are highly diastereoselective (Table 3) while those of the corresponding -isomers are rather unselcctive40. 

Synthetic highlight Diastereoselective production of rac-menthol from its aromatic precursor is achieved by site-selective isopropylation and diastereoselective hydrogenation to the all-trans racemate. Enantioselective allylic amine-enamine-imine rearrangement of an acyclic diene-allylic amine, catalyzed by an Rh(I)-(—)-BINAP complex, affords (—)-menthol the process has been scaled-up to production of 1,000 tons/year. 

The Kishi synthesis ot monensin teatures allylic conformational analysis to predict stereochemistry of hydroboratlon-oxidations in acyclic systems. The Still synthesis features acyclic diastereoselection in carbonyl addition reactions (chelation control and Felkin-Ahn control). 

To explore synthetic methods for optically active compounds, we next turned our attention to systematic studies on diastereoselectivity in this tandem process, using acyclic secondary allyl alcohols (Z)-12 and (E)-12. Treatment of nitrone lb with alcohol (Z)-12 in the presence of a catalytic amount of TiCLt and MS4A led to smooth transesterification and intramolecular cycloaddition even at room temperature, affording 13b accompanied by a small amount of 14b (Table 6.4, entry 1). The bulkier nitrone Ic also reacted with (Z)-12 under the same conditions, giving 13c and 14c in an excellent combined yield with high diastereofacial selectivity (entry 2). It was also found that reactions of chiral nitrones Im and In with (Z)-12 proceeded smoothly to give 13m and 13n as the major cycloadducts in excellent yields with high diastereofacial selectivity, which was independent of the chirality of nitrones Im and In (entries 3 and 4). 

The reaction of aryldiazoacetates with cyclohexene is a good example of the influence of steric effects on the chemistry of the donor/acceptor-substituted rhodium carbenoids. The Rh2(reaction with cyclohexene resulted in the formation of a mixture of the cyclopropane and the G-H insertion products. The enantios-electivity of the C-H insertion was high but the diastereoselectivity was very low (Equation (31)). 0 In contrast, the introduction of a silyl group on the cyclohexene, as in 15, totally blocked the cyclopropanation, and, furthermore, added sufficient size differentiation between the two substituents at the methylene site to make the reaction to form 16 proceed with high diastereoselectivity (Equation (32)).90 The allylic C-H insertion is applicable to a wide array of cyclic and acyclic substrates, and even systems capable of achieving high levels of kinetic resolution are known.90... 

Over the past two decades, chiral allyl- and crotyl-boron reagents have proved to be extremely valuable in the context of acyclic stereoselection. The development of superior allyl-boron reagents, which can give enantio- and diastereoselectivities approaching 100%, has become both challenging and desirable.68... 

Cyclopropanation.1 The carbenoid obtained from the reaction of CH2I2 with Sm or Sm/Hg in THF effects cyclopropanation of ally lie alcohols, but not of isolated double bonds. The reaction of both cyclic and acyclic allylic alcohols proceeds in generally high yield and often with marked diastereoselectivity. 

The asymmetric allylic C-H activation of cyclic and acyclic silyl enol ethers furnishes 1,5-dicarbonyl compounds and represents a surrogate of the Michael reaction [136]. When sufficient size discrimination is possible the C-H insertion is highly diastereoselective, as in the case of acyclic silyl enol ether 193 (Eq. 22). Reaction of aryldia-zoacetate 192 with 193 catalyzed by Rh2(S-DOSP)4 gives the C-H insertion product 194 (>90% de) in 84% enantiomeric excess. A second example is the reaction of the silyl enol ether 195 with 192 to form 196, a product that could not be formed from the usual Michael addition because the necessary enone would be in its tautomeric naphthol form (Eq. 23). 

In the epoxidation of acyclic allylic alcohols (Scheme 6), the diastereoselectivity depends significantly on the substitution pattern of the substrate. The control of the threo selectivity is subject to the hydroxyl-group directivity, in which conformational preference on account of the steric interactions and the hydrogen bonding between the dioxirane oxygen atoms and the hydroxy functionality of the allylic substrate steer the favored 7r-facial... 

One of the classical ways to perform diastereoselective 1,3-dipolar cycloaddition is by the addition of a 1,3-dipole to an allyl alcohol derivative (65, 107-120). Very recently, a short review article was devoted to this area (13). Among the most commonly applied acyclic allyl alcohol derivatives are alkenes 73-75 (Scheme 12.25). These alkenes have been used in reactions with nitrones. 

Benzamido allylic acetates 242 and 243 undergo palladium-catalyzed cychza-tion to oxazolines. Excellent yields and very high diastereoselectivity is observed for the conversion of several acyclic primary and secondary benzamido aUyhc acetates to tran -5-vinyl substituted oxazolines 244. The diastereoselectivity of the reaction is determined by the the steric interactions between the R group and the hydrogen of the 7i-allylpalladium complex in the transition state, trans-Oxazolines are obtained since transition state A is favored over transition state B (Scheme 8.66). 

The diastereoselective cyclopropanation of acyclic allylic alcohols is a very useful synthetic transformation. It was recognized early on by Pereyre and coworkers that the cyclopropanation of Z-substituted chiral allylic alcohol was highly syn selective (equation 58) °. It was later shown that most zinc carbenoids react with these substrates with high syn stereocontrol. 

The level of diastereoselection in the cyclopropanation of chiral acyclic E-aUylic alcohols is highly dependent upon the choice of the reagent, the stoichiometry and the solvent. Charette has shown that, with simple ii-substituted chiral allylic alcohols, the use of an excess of the Furukawa reagent in dichloromethane provided the highest syn stereocontrol (equation 59). ... 

The double stereodifferentiation is also found in the reactions of acyclic nucleophiles (Scheme 8E.42). Whereas the alkylation of W-imino(methylphosphonates) affords the simple allylated product in poor enantioselectivity (11% ee) using ligand 38a, excellent enantioselec-tivity and good diastereoselectivity can be obtained from the alkylation with the 1,3-diphenyl-allyl system [188],... 

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