Chemoselective allylic alcohols

High chemoselectivity is observed in this ruthenium-catalyzed isomerization of allylic alcohols. Simple primary and secondary alcohols and isolated double bonds are not affected by these catalysts. Furthermore, free hydroxy group is essential for this catalysis. The reaction of l-acetoxycyclododec-2-ene-4-ol furnished 4-acetoxycyclododecanone in high yield (Scheme 14).37... 

A ruthenium(n)-indenyl complex, which is an efficient catalyst for the isomerization of allylic alcohols, is also an effective catalyst for the isomerization of propargylic alcohols to both a,/3-enals and a,/ -enones (Scheme 57).96 In this reaction, the addition of 20—40 mol% InClj is highly effective. The reaction exhibits extraordinary chemoselectivity and a variety of functional groups are unaffected, which allows a highly efficient synthesis of dienals (R1 =Me2C = CH, R2 = H). 

Ruthenium catalysts have also been used in this context.200,201 In particular, the cationic ruthenium complex, CpRu(CH3CN)3PF6, in conjunction with carboxylic acid ligand 3, has been used to achieve the remarkably chemoselective allylation of a variety of alcohols via dehydrative condensation with allyl alcohol (Equation (50)).202 It is worth noting that this transformation proceeds with 0.05 mol% catalyst loading and does not require the use of excess allyl alcohol. 

Bianchini and coworkers [126] found a difference in the chemoselectivity between the metals Fe, Ru, and Os in the complexes [M(H2)H(P(CH2CH2PPh2)3)]-BPh4 in the hydrogenation of benzylideneacetone by transfer from iso-propanol. The Fe and Ru catalysts reduced the 0=0 bond to give the allyl alcohol, with Ru more active than iron (TOF 79 IT1 at 60°C for Ru versus 13 IT1 at 80°C for Fe), while the Os catalyst first reduced the 0=0 bond but then catalyzed isomerization of the allyl alcohol to give the saturated ketone (TOF 55 IT1 at 80°C). The difference in reactivity was attributed to the weak binding of the alkene of the allyl alcohol to Fe and Ru relative to Os in these complexes. A variety of selec-tivities was noted for other unsaturated ketones, whereas unsaturated aldehydes were not hydrogenated. 

This was the first example of catalytic chemoselective reduction of a,/ -unsatu-rated ketones to allylic alcohols by hydrogen transfer and, unusually, did not require the use of a basic co-catalyst. 

A more recent approach to the epoxidation of allylic alcohols makes use of a vanadium polyoxometallate, together with a sterically demanding chiral tartrate (or TADDOL) -derived hydroperoxide, to give a highly chemoselective, regiose-lective and enantioselective outcome (Figure 11.2). ... 

The sulfone moiety was reductively removed and the TBS ether was cleaved chemoselectively in the presence of a TPS ether to afford a primary alcohol (Scheme 13). The alcohol was transformed into the corresponding bromide that served as alkylating agent for the deprotonated ethyl 2-(di-ethylphosphono)propionate. Bromination and phosphonate alkylation were performed in a one-pot procedure [33]. The TPS protecting group was removed and the alcohol was then oxidized to afford the aldehyde 68 [42]. An intramolecular HWE reaction under Masamune-Roush conditions provided a macrocycle as a mixture of double bond isomers [43]. The ElZ isomers were separated after the reduction of the a, -unsaturated ester to the allylic alcohol 84. Deprotection of the tertiary alcohol and protection of the prima-... 

The RLi homochiral ligand complexes are seldom used for the base-promoted isomerization of oxiranes into allylic alcohols because their poor chemoselectivity lead to complex mixtures of products. As examples, the treatment of cyclohexene oxide by a 1 1 i-BuLi/(—)-sparteine mixture in ether at low temperature provides a mixture of three different products arising respectively from -deprotonation (75), a-deprotonation (76) and nucleophilic addition (77) (Scheme 32) . When exposed to similar conditions, the disubstituted cyclooctene oxide 78 affords a nearly 1 1 mixture of a- and -deprotonation products (79 and 80) with moderate ee (Scheme 32, entry 1). Further studies have demonstrated that the a//3 ratio depends strongly on the type of ligand used (Scheme 32, entry 1 vs. entry 2) . ... 

Considering the excellent chemoselectivity observed in the allylic oxidation of dehydroepiandrosterone (Scheme 16), it was interesting to evaluate the selective allylic alcohol oxidation in the presence of a secondary saturated hydroxyl group using the BiCls/f-BuOOH system. This study was performed using androst-... 

The level of syn induction increases as the size of the E-substituent increases as well as the size of the allylic substituent. An interesting application of these reaction conditions was reported in the synthesis of an advanced intermediate in halicholactone synthesis (equation 60). It is important to note that the reaction proceeded not only with excellent diastereocontrol, but also with complete chemoselectivity in favor of the allylic alcohol double bond. However, the participation of the trimethylsilylethoxymethyl (SEM)... 

Chemoselective reduction of conjugated enones to allylic alcohols via hydrogen transfer from propan-2-ol over metal oxides is investigated in vapour phase conditions. The unique ability of Mgo to reduce exclusively carbonyl group is observed. However, because of the high basicity of MgO side reactions are present. It is shown that by doping the Mgo catalyst with HC1 a significant decrease of its basicity occurs and consequently side reactions are minimized. 

Chemoselective catalytic reduction of a,/3 unsaturated ketones to allylic alcohols is a challenging problem since, but a few exceptions [1-3], this reaction generally proceeds with formation of saturated ketones or saturated alcohols [4]. This reduction indeed is best carried out with stoicheiometric hydrides [4] but even in this case overreduction products are often obtained [5]. Recently, we reported in a preliminary communication [6] the unprecedented observation that a,/3 unsaturated ketones are reduced to the corresponding allylic alcohols by hydrogen transfer from propan-2-ol over MgO as catalyst according to the following scheme ... 

As shown in Scheme 3.19, two competing pathways are possible with regard to allylic oxidation. The alkene 1 can either undergo abstraction of an allylic hydrogen and subsequent formation of the allylic alcohol 2 and the enone 3 (path A), respectively, or alternatively epoxidation of the C=C double bond occurs to give derivative 4 (path B). In order to develop a suitable catalytic system for path A, it is of utmost importance to achieve high chemoselectivity in addition to high catalytic... 

Porphyrin complexes, however, are prone to oxidative decomposition and therefore synthetic applications are hampered by rapid catalyst deactivation. This problem can be overcome by attaching electron-withdrawing groups to the periphery of the porphyrin system. Another problem is the poor chemoselectivity. In many cases, addition to the C=C double bond and formation of the epoxide are much faster than the corresponding hydrogen abstraction, which leads to the allylic alcohols. This is... 

Although allyl-arenes are prone to olefin isomerization, several successful reactions have been performed, for example in the chemoselective oxygenation of 22 to aryl-acetone 23 (Table 2) [38]. Allyl alcohols sometimes react sluggishly, but examples with high ketone selectivity are known, for example the oxidation of tertiary alcohol 24 to a-hydroxyketone 25 [39]. 

The chemoselectivity of the dioxirane oxyfunctionalization usually follows the reactivity sequence heteroatom (lone-pair electrons) oxidation > JT-bond epoxida-tion > C-H insertion, as expected of an electrophilic oxidant. Because of this chemoselectivity order, heteroatoms in a substrate will be selectively oxidized in the presence of C-H bonds and even C-C double bonds. In allylic alcohols, however, C-H oxidation of the allylic C-H bond to a,/ -unsaturated ketones may compete efficaciously with epoxidation, especially when steric factors hinder the dioxirane attack on the Jt bond. To circumvent the preferred heteroatom oxidation and thereby alter the chemoselectivity order in favor of the C-H insertion, tedious protection methodology must be used. For example, amines may be protected in the form of amides [46], ammonium salts [50], or BF3 complexes [51] however, much work must still be expended on the development of effective procedures which avoid the oxidation of heteroatoms and C-C multiple bonds. 

Chemoselective oxidation of the allylic alcohol in triol 865 with manganese dioxide followed by in situ cyclization and oxidation of the resulting 5,6-dihydropyran-2-ol provides the 5,6-dihydropyran-2-one subunit 866 of bryostatin (Equation 349) <20000L2189>. 

Eliminations of epoxides lead to allyl alcohols. For this reaction to take place, the strongly basic bulky lithium dialkylamides LDA (lithium diisopropylamide), LTMP (lithium tetramethylpiperidide) or LiHMDS (lithium hexamethyldisilazide) shown in Figure 4.18 are used. As for the amidine bases shown in Figure 4.17, the hulkiness of these amides guarantees that they are nonnucleophilic. They react, for example, with epoxides in chemoselective E2 reactions even when the epoxide contains a primary C atom that easily reacts with nucleophiles (see, e.g., Figure 4.18). 

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