Ketones with allylic alcohols

It is possible to treat ketones with allyl alcohol and an acid catalyst to give y,5-unsaturated ketones directly, presumably by initial formation of the vinylic ethers, and then Claisen rearrangement.In an analogous procedure, the enolates (126) of allylic esters [formed by treatment of the esters with lithium isopropylcyclohex-... 

Scheme 39 Diastereoselective cathodic coupling of ketones with allylic alcohols yields 60-90%.

Cathodic heterocoupling of ketones with allylic alcohols takes place at a carbon fiber cathode with high regio- and diastereoselectivity to afford the corresponding... 

Tamaru reported that Pd-catalyzed a-allyladon of aldehydes to afford 168 can be carried out even with allyl alcohols in the presence of a stoichiometric amount of EtaB, NEt3, and LiCl. Although the mechanism is not clear, activation of allyl alcohol by Et3B occurs by coordination to generate 7r-allylpalladium. In addition, boron enolates are formed by the reaction of aldehydes with Et3B and Et3N, and attacked by r-allylpalladium [62]. Similarly allylation of malonates and ketones with allylic alcohols 169 and 169a were carried out [63],... 

Scheme 12.47 Pd-catalyzed a-allylation of ketones with allyl alcohols involving proline activation [109dj.

Generally, isolated olefinic bonds will not escape attack by these reagents. However, in certain cases where the rate of hydroxyl oxidation is relatively fast, as with allylic alcohols, an isolated double bond will survive. Thepresence of other nucleophilic centers in the molecule, such as primary and secondary amines, sulfides, enol ethers and activated aromatic systems, will generate undesirable side reactions, but aldehydes, esters, ethers, ketals and acetals are generally stable under neutral or basic conditions. Halogenation of the product ketone can become but is not always a problem when base is not included in the reaction mixture. The generated acid can promote formation of an enol which in turn may compete favorably with the alcohol for the oxidant. 

Reactions of the hydrido(hydroxo) complex 2 with several substrates were examined (Scheme 6-14) [6]. The reactions are fairly complicated and several different types of reachons are observed depending on the substrate. Methyl acrylate and small Lewis bases such as CO, P(OMe)3, BuNC coordinate to the five-coordinated complex 2 affording the corresponding six-coordinate complexes. In reactions with the unsaturated bonds in dimethylacetylenedicarboxylate, carbon dioxide, phenylisocyanate indications for the addition across the O-H bond but not across the Os-OH bond were obtained. In reactions with olefins such as methyl vinyl ketone or allyl alcohol, elimination of a water molecule was observed to afford a hydrido metalla-cyclic compound or a hydrido (ethyl) complex. No OH insertion product was obtained. 

Pb. Homoallylic alcohols can be obtained from allylation of aldehydes and ketones with allyl bromide promoted by metallic lead in aqueous media.176... 

The complex OsH(OH)(CO)(P Pr3)2 also reacts with methyl acrylate, methyl vinyl ketone, and allyl alcohol.91 Reaction with methyl acrylate leads to OsH(OH) (COXrf-CH2=CHC02MeXP Pr3)2 containing the olefin trans to the hydride ligand. In solution, this complex releases the olefin to generate the starting complex. The thermodynamic magnitudes involved in the equilibrium have been determined in toluene-t/a by 31P 1H NMR spectroscopy. The values reported are AH° = 17.0 0.5 kcal-mor1 and AS° = 54.0 1.2 cal-K 1-mol 1. In the presence of the methyl vinyl ketone complex OsH(OH)(CO)(P Pr3)2 affords 0sH CHCHC(0) Me (CO)(P Pr3)2 and water, whereas in the presence of allyl alcohol the loss of... 

A combination of a Heck reaction with an aldol condensation is observed on treatment of aromatic aldehydes or ketones as 6/1-151 with allylic alcohols as 6/1-152, as described by Dyker and coworkers [83]. The Pd-catalyzed reaction led to 6/1-154 via 6/1-153, in 55% yield (Scheme 6/1.40). 

The intermolecular Heck reaction of halopyridines provides an alternative route to functionalized pyridines, circumventing the functional group compatibility problems encountered in other methods. 3-Bromopyridine has often been used as a substrate for the Heck reaction [124-126]. For example, ketone 155 was obtained from the Heck reaction of 3-bromo-2-methoxy-5-chloropyridine (153) with allylic alcohol 154 [125]. The mechanism for such a synthetically useful coupling warrants additional comments oxidative addition of 3-bromopyridine 153 to Pd(0) proceeds as usual to give the palladium intermediate 156. Subsequent insertion of allylic alcohol 154 to 156 gives intermediate 157. Reductive elimination of 157 gives enol 158, which then isomerizes to afford ketone 155 as the ultimate product This tactic is frequently used in the synthesis of ketones from allylic alcohols. 

Both 2-bromothiophene and 3-bromothiophene have been coupled with allyl alcohols to make thienylated a, 3-unsaturated ketones [124], Iodothiophenes were more reactive than the corresponding bromides, whereas the chlorothiophenes were unreactive. As expected, 2-bromothiophene was two to three times more reactive than 3-bromothiophene. In addition to the expected Heck adduct 149, the reaction of 2-bromothiophene 148 with l-methylprop-2-en-l-ol also resulted in the regiosmer 150. 

The Barhier-type reaction of aldehydes and ketones with allyl halides (485) in the presence of Sml2, leading to homoallyl alcohols (486), has received recent interest as a one-step alternative to the Grignard reaction. However, the reactions require the use of stoichiometric amounts of the reducing Sm(III) species. Recently, the electroreductive Barhier-type allylation of carbonyl compounds in an SmH-mediated reaction has been developed [569]. The electrolysis of (485) is carried out in a DMF-SmCl3-(Mg/Ni) system in an undivided cell to give the adduct (486) in 50 85% yields (Scheme 168) [569]. Electrosynthesis of y-butyrolactones has been achieved by the reductive coupling of ethyl 3-chloropropionate with carbonyl compounds in the presence of a catalytic amount of SmCfi [570]. 

The formation of 3-aryl-substituted aldehydes and 3-aryl-substituted ketones by the reaction of arylpalladium salts with allylic alcohols is a general reaction.2 Illustrations of the preparation of two aldehydes and two ketones are given in Table I. 

From a-substituted allylic alcohols, the formation of p,y-unsaturated ketones is favored, whereas conjugated enones are obtained from simple ally alcohol [46]. This transformation of terminal alkynes via coupling with allylic alcohol and formation of a C—C bond with atom economy has been applied to the synthesis and modification of natural compounds such as rosefuran and steroids [48, 49]. 

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 ... 

A broad variety of special aldehydes and ketones are easily accessible by Heck-type reactions with allylic alcohols and their homologs [3]. The potential for the synthesis of carbocydic structures is illustrated by the macrocyde 11 [4] which obviously is the product of a fourfold Heck reaction (Scheme 3). A domino process consisting of a double Heck reaction followed by an intramolecular Aldol condensation leads to the annulated ring system 15 [5]. 

The reduction of a, 3-unsaturated ketones to allylic alcohols can be easily done using lithium aluminium hydride under carefully controlled conditions (Following fig.). With sodium borohydride, some reduction of the alkene also occurs. 

The selective intramolecular nucleophilic addition of a hydroxy group at Cyof a ruthenium allenylidene generated by activation of propargylic alcohol by RuCl(Cp)(PPh3)2/NH4PF6 provides a ruthenium vinylidene species, which reacts with allylic alcohols as previously described in the section Formation of Unsaturated Ketones (Eq. 11, Scheme 18) [79]. This unprecedented tandem reaction makes possible the construction of tetrahydrofuran derivatives in good yields and has been used as a key step in the synthesis of (-)calyculin A [80]. 

Cydization of acetylenic Ketones to allyl alcohols by one electron reduction with U/NH3. al electiocheniically (Shono) or by Smla (Molander)... 

The pyrolysis of allyl vinyl ethers derived by acid- or mercuric ion-catalyzed ether exchange of ethyl vinyl ether or substituted vinyl ethers with allylic alcohols produces the corresponding y, 8-unsaturated aldehydes or ketones, respectively. 

With allyl alcohols, terminal alkynes react with C-C linking to give the corresponding ketones (eq. (24)). This method makes possible a range of new possibilities for synthesis [51]. 

Despite these two experiments, convincing evidence exists that the syn-intramolecular route occurs for hydroxypalladation. Reports by Henry and Francis54 described experiments designed to probe both the kinetics and the stereochemistry of the Wacker process. Scheme 9.6 illustrates the two stereochemical outcomes possible starting with allylic alcohol 27, designed so that oxidation to form the ketone is not possible. When Cl concentrations were low and comparable to Wacker conditions, 28 formed, a compound that indicated syn intramolecular attack by a coordinated OH ligand had occurred. At higher CP concentrations, similar to those used by Backvall, compound 29, a product that must result from anti intermolecular attack by H20, was produced instead. 

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