Intermolecular reactions unsaturated alcohols

A regio- and stereospecific INOC reaction of unsymmetrical silaketals 114, synthesized in one pot from unsaturated alcohols, nitro ethanol, and dichloro-silanes, via the nitrile oxide 115 to isoxazolines 116 has been described (Scheme 14) [37a]. The intermolecular version of the cycloaddition, under similar conditions, proceeds with poor regio and stereoselectivity. 

Carbenoids derived from the metal catalysed decomposition of diazo compounds undergo various chemical transformations. Control of chemoselectivity by choice of the appropriate catalyst has significantly increased the synthetic viability of catalytic cyclopropanation reactions. Intermolecular reaction of unsaturated alcohols with carbenoids derived from catalytic decomposition of alkyl diazoesters has been reported by Noels and... 

The choice of mercury salt for this reaction appears to be less critical than intermolecular variants and many salts (X = Cl, OAc, NO3, SO4, CIO4, CF3CO2) have been successfully utilized. The electrophilicity of the salt can effect the regio- and stereo-chemistry of addition.434-438 The regioselectivity is also determined by the substitution pattern of the unsaturated alcohol. For cycloalkenes, steric factors, ring strain, and other reaction variables become important (equation 264). High regio- and stereo-selectivity are often encountered in these intramolecular processes. 

A transition metal catalyzed synthesis of ethers by carbene insertion into the O—bond has been reported. Not only saturated but also unsaturated alcohols can be utilized in this catalytic process. ° Intermolecular and intramolecular oxirane ring opening reactions by alkoxides and phenoxides also provide efficient and stereospecific preparations of acyclic and cyclic ethers. The procedures have been surveyed in detail. ... 

Asymmetric intermolecular Mizoroki—Heck reaction From phosphine/ phosphinite-nitrogen to phosphite-nitrogen hgands 12IJC572. Asymmetric palladium-catalyzed intramolecular Wacker-type cycliza-tions of unsaturated alcohols and amino alcohols to give O- and N-het-erocycles 13MOL6173. 

Hydroalkoxylation. The cycloisomerization of unactivated unsaturated alcohols has been achieved using Al(OTf)3 (eq Reaction with unsaturated oximes also led to 1,2-oxaza heterocycles with five-, six-, and seven-membered rings. This catalyst provided a straightforward route to cyclic ethers with a Markovnikov-type regioselectivity. Notably, these conditions were used for efficient synthesis of olfactory-active rose oxide derivatives. Mechanistic studies showed that Al(OTf)3 coordinates to the oxygen atom of the alcohol, leading to strong acidification of the hydroxyl proton. Intermolecular hydroalkoxylation with methanol has also been reported. ... 

Intermolecular addition of alcohols to catalytic ruthenium vinylidenes is far more difficult than the addition of water except when allylic alcohols are employed (Scheme 9) [92-96]. In this case, the reaction of an allylic alcohol with a terminal alkyne catalyzed by CpRuCl(PPh3)2 afforded a p,Y-unsaturated ketone. The initial ruthenium oxacarbene obtained by addition of the alcohol to the ruthenium vinylidene evolves through a Claisen rearrangement to a Jt-allyl ruthenium species. Reductive elimination then gives rise to the final unsaturated ketone. 

Intramolecular oxonium ylide formation is assumed to initialize the copper-catalyzed transformation of a, (3-epoxy diazomethyl ketones 341 to olefins 342 in the presence of an alcohol 333 . The reaction may be described as an intramolecular oxygen transfer from the epoxide ring to the carbenoid carbon atom, yielding a p,y-unsaturated a-ketoaldehyde which is then acetalized. A detailed reaction mechanism has been proposed. In some cases, the oxonium-ylide pathway gives rise to additional products when the reaction is catalyzed by copper powder. If, on the other hand, diazoketones of type 341 are heated in the presence of olefins (e.g. styrene, cyclohexene, cyclopen-tene, but not isopropenyl acetate or 2,3-dimethyl-2-butene) and palladium(II) acetate, intermolecular cyclopropanation rather than oxonium ylide derived chemistry takes place 334 ). 

A novel route was examined for the synthesis of the u,y9-unsaturated amide 59 vio the intermolecular couphng of four components an alkyne, a hydrosilane, an amine, and CO (Eq. 11). All of these components are assembled in an ordered manner with the assistance of a rhodium complex. The use of pyrrolidine as the nucleophile gave the optimum results, whereas alcohols were not reactive nucleophiles under similar reaction conditions [19 ej. 

Unlike many other type of radical addition reactions, the product is most often an alkyl-cobalt(III) species capable of further manipulation. These product Co—C bonds have been converted in good yields to carbon-oxygen (alcohol, acetate), carbon-nitrogen (oxime, amine), carbon-halogen, carbon-sulfur (sulfide, sulfinic acid) and carbon-selenium bonds (equations 179 and 180)354. Exceptions to this rule are the intermolecular additions to electron-deficient olefins, in which the putative organocobalt(III) species eliminates to form an a,/ -unsaturated carbonyl compound or styrene353 or is reduced (under electrochemical conditions) to the alkane (equation 181)355. 

Photocatalytic reductions may concern organic unsaturations (C=0, C=C, etc.), or inorganic CO2, or bicarbonate. Even carbon tetrachloride is very efficiently photo-reduced to chloroform by alcohols with mc.9o-tetra(2,6-dichlorophenyl)porphyrin [108]. Intermolecular hydrogen transfer is catalyzed by cobalt-phosphine complexes [109]. In this reaction photoirradiation generates the active hydride species CoH[PPh(OEt)2]3 for the reduction of ketones with secondary alcohols. The... 

Further efforts demonstrate that the reaction of triethyl phosphite occurs under quite mild conditions in a conjugate manner with a wide range of oc,p-unsaturated aldehydes provided that a proton source is present (Scheme 5.21). The use of protic solvents, such as alcohols or phenols, not only provides a source of proton for the anionic site of the zwitterionic adduct but also furnishes a nucleophile for the required dealkylation step. The simplest hypothesis consistent with all of these facts is that the protonation-valency expansion of the quasiphosphonium ion intennediate using a proton source proceeds at a rate greater than the intermolecular pathway to enol ether. ... 

Mechanistically related to the Mukaiyama aldol reaction, the carbonyl ene reaction is the reaction between an alkene bearing an allylic hydrogen and a carbonyl compound, to afford homoallylic alcohols. This reaction is potentially 100% atom efficient, and should be a valuable alternative to the addition of organometallic species to carbonyl substrates. However, the carbonyl ene reaction is of limited substrate scope and works generally well in an intermolecular manner only with activated substrates, typically 1,1-disubstituted alkenes and electron-deficient aldehydes (glyoxylate esters, fluoral, a,p-unsaturated aldehydes, etc.), in the presence of Lewis acids. The first use of chiral catalyst for asymmetric carbonyl ene was presented by Mikami et al. in 1989. ° By using a catalytic amount of titanium complexes prepared in situ from a 1 1 ratio of (rPrO)2titaniumX2 (X = Cl or Br) and optically pure BINOL, the homoallylic alcohols 70a,b were obtained in... 

---