Alcohols, allylic stereoselectivity

The magnesium ion-mediated nitrone cycloadditions of an a,y-disubstituted allyl alcohol are stereoselective, and show opposite regioselectivity to that observed when zinc-mediated reactions are examined (Scheme 11.48) (167). The exo-syn-isomer of the isoxazolidine-5-alcohol regioisomer and the exo-syn-isomer of the isoxazolidine-4-alcohol regioisomer are the exclusive cycloadducts in the magnesium- and zinc-mediated reactions, respectively. 

Selective reductions This complex borohydride is particularly useful for selective 1,2-reduction of acyclic a,/ -cnones and of conjugated cyclohexenones to allylic alcohols. However, the 1,2-selectivity is less marked with conjugated cyclopentenones. The reagent reduces unhindered cyclic ketones to the more stable (equatorial) alcohols with stereoselectivity greater than that of sodium borohydride. 

Epoxidation of / - or y-trimethylsilyloxy allylic alcohols. The stereoselectivity of cpoxidation of these allylic alcohols (followed by desilylation) can be controlled by substitution with a trimethylsilyl group. A /i-silyl substituted allylic alcohol is converted mainly into an erythro-epoxy alcohol, whereas a y-silyl substituent favors formation of a threo-epoxy alcohol. The stereoselectivity is usually the opposite to that obtained with m-chloroperbenzoic acid.1 Example ... 

In the oxidation of a diastereomeric mixture of carveol (syrr.anti = 42 58), the syn alcohol is stereoselectively oxidized and the anti alcohol is recovered in 98 % diastereomeric purity. This shows that the catalytic activity of (C6p5)2BOH is very sensitive to steric hindrance in the alcohols (Eq. 108). In oxidations of equimolar mixtures of geraniol and j8-citronellol, geranial is obtained in 96 % yield and most of the /8-citro-nellol is recovered imchanged (Eq. 109). The selective conversion of allylic alcohols in the presence of saturated alcohols is particularly noteworthy. 

The allylation of aldehydes with allylstannanes is effected with Lewis acids such as boron trifluoride etherate or titanium(IV) chloride (eq (104)) [99], in which diastereo-selectivity is dependent on the catalyst employed the most striking feature is that. n77-homoallyl alcohols are stereoselectively produced using boron trifluoride etherate. Although this allylation occurs without a catalyst, high reaction temperature must be used. 

Homoallylic alcohols. Allylic bromides are transformed into allyltin reagents that react with aromatic aldehydes with very high eryt/iro-selectivity. However, the stereoselectivity is only moderate in the reaction with aliphatic aldehydes. The intramolecular version is useful for the synthesis of cyclic alcohols. ... 

The [(Ti-allyl)PdCl]2-catalyzed reactions of allene-aldehydes or -ketones 153 with Me3SiSnBu3 led to the cyclic 2-vinylic alcohols 155 via the formation of an aldehyde- or ketone-containing 2-trimethysilyl-2-alkenyl tin intermediate 154 (Scheme 63) [38]. In the presence of an aryl iodide, Pd2(dba)3 could catalyze the coupling cyclization of allene-aldehydes or -ketones 153 with Bu3SnSnBu3 leading to the cyclic 2-(r-arylvinyl) cyclic alcohols 156 stereoselectively with the cis isomer being the major product (Scheme 64) [39]. 

Addition of y-disubstituted allylic phosphates to RCHO Both (E)- and (Z)-ally lie halides add to RCHO when catalyzed by CrCl2 to form nnri-homoallylic alcohols. Similar stereoselectivity obtains in additions of (E)- and (Z)-allylic phosphates. In this case addition of Lil and use of DMPU as solvent are usually required for satisfactory yields. In contrast, addition of y-disubstituted phosphates to aldehydes is both stereoselective and stereodivergent (equations I and II). 

Another option to gain access to T -allyliron complexes is the removal of a leaving group from substituted neutral (T] -alkene)iron complexes. This procedure starts from allylic alcohols, allylic ethers, or carboxylates, which are complexed with nonacarbonyldiiron and subsequently treated with tetrafluoroboric acid to aflbrd the cationic Ti -allyl(tetracarbonyI)iron complexes (Scheme 4-78). The reaction is stereoselective with respect to the geometry of the starting allyl alcohols. ( )-AlIyl alcohols give anti products, whereas syn complexes are formed from (Z)-allyl alcohols. The alkene complexes can also be generated in situ to afford the q -allyliron complexes after treatment with acid. ... 

Silyl ethers serve as preeursors of nucleophiles and liberate a nucleophilic alkoxide by desilylation with a chloride anion generated from CCI4 under the reaction conditions described before[124]. Rapid intramolecular stereoselective reaction of an alcohol with a vinyloxirane has been observed in dichloro-methane when an alkoxide is generated by desilylation of the silyl ether 340 with TBAF. The cis- and tru/u-pyranopyran systems 341 and 342 can be prepared selectively from the trans- and c/.y-epoxides 340, respectively. The reaction is applicable to the preparation of 1,2-diol systems[209]. The method is useful for the enantioselective synthesis of the AB ring fragment of gambier-toxin[210]. Similarly, tributyltin alkoxides as nucleophiles are used for the preparation of allyl alkyl ethers[211]. 

The Pd-catalyzed hydrogenolysis of vinyloxiranes with formate affords homoallyl alcohols, rather than allylic alcohols regioselectively. The reaction is stereospecific and proceeds by inversion of the stereochemistry of the C—O bond[394,395]. The stereochemistry of the products is controlled by the geometry of the alkene group in vinyloxiranes. The stereoselective formation of stereoisomers of the syn hydroxy group in 630 and the ami in 632 from the ( )-epoxide 629 and the (Z)-epoxide 631 respectively is an example. 

The stereoselective allylic rearrangement of the allylic alcohol 798 catalyzed by PdCl2(MeCN)2 and Ph3P under Mitsunobu inversion conditions is explained as proceeding via a rr-allylpalladium intermediate[496]. The smooth rearrangement of the allylic p-tolylsulfone 799 via a rr-allylpalladium intermediate is catalyzed by a Pd(0) catalyst[497]. 

Another useful modification of this reagent is the reaction of CF3CCI3 with zinc and DMF in the presence of AICI3 [60, 63] (equation 53). The alcohol product can be treated subsequently with DAST, thionyl chloride, or phosphorus chlorides to afford the allyl substitution product regio- and stereoselectively [66] (equation 54). 

Dipolar cydoadditions are one of the most useful synthetic methods to make stereochemically defined five-membered heterocydes. Although a variety of dia-stereoselective 1,3-dipolar cydoadditions have been well developed, enantioselec-tive versions are still limited [29]. Nitrones are important 1,3-dipoles that have been the target of catalyzed enantioselective reactions [66]. Three different approaches to catalyzed enantioselective reactions have been taken (1) activation of electron-defident alkenes by a chiral Lewis acid [23-26, 32-34, 67], (2) activation of nitrones in the reaction with ketene acetals [30, 31], and (3) coordination of both nitrones and allylic alcohols on a chiral catalyst [20]. Among these approaches, the dipole/HOMO-controlled reactions of electron-deficient alkenes are especially promising because a variety of combinations between chiral Lewis acids and electron-deficient alkenes have been well investigated in the study of catalyzed enantioselective Diels-Alder reactions. Enantioselectivities in catalyzed nitrone cydoadditions sometimes exceed 90% ee, but the efficiency of catalytic loading remains insufficient. 

Stereoselective preparation of CEi-allyl alcohols via radical elimination from ruin -y-phenylthio-fi-nkro alcohols has been reported. The requisiteruin -fi-nitro sulfides are prepared by protonadon of nitronates at low temperanire Isee Chapter 4, and subsequent treatment v/ith Bu-vSnH induces and eliminadon to givelE -alkenes selecdvely IseeEq. 7.112. Unfortunately, it is difficult to get the pure syu-fi-nitro sulfides. Treatment of a rruxnire of syu- and ruin -fi-nitrosulfides v/ith Bu- SnH results in formadon of a rruxnire of (Ey and lZ -alkenes. 

The emergence of the powerful Sharpless asymmetric epoxida-tion (SAE) reaction in the 1980s has stimulated major advances in both academic and industrial organic synthesis.14 Through the action of an enantiomerically pure titanium/tartrate complex, a myriad of achiral and chiral allylic alcohols can be epoxidized with exceptional stereoselectivities (see Chapter 19 for a more detailed discussion). Interest in the SAE as a tool for industrial organic synthesis grew substantially after Sharpless et al. discovered that the asymmetric epoxidation process can be conducted with catalytic amounts of the enantiomerically pure titanium/tartrate complex simply by adding molecular sieves to the epoxidation reaction mix-... 

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