Alkyne allyl alcohols, rearrangements with

Trust s group has shown that another selective reaction involving C—O bond formation followed by rearrangement and C—C bond formation occurred when Cp-containing ruthenium complexes were used as catalytic precursors. With RuCl(Cp)(PPh3)2 in the presence of NH4PF6, an additive known to facilitate chloride abstraction from the metal center, the addition of allylic alcohols to terminal alkynes afforded unsaturated ketones [46, 47]. It has been shown that the key steps are the... 

Dehydrobromination of bromotrifluoropropene affords the more expensive trifluoropropyne [237], which was metallated in situ and trapped with an aldehyde in the TIT group s [238]synthesis of 2,6-dideoxy-6,6,6-trifluorosugars (Eq. 77). Allylic alcohols derived from adducts of this type have been transformed into trifluoromethyl lactones via [3,3] -Claisen rearrangements and subsequent iodolactonisation [239]. Relatively weak bases such as hydroxide anion can be used to perform the dehydrobromination and when the alkyne is generated in the presence of nucleophilic species, addition usually follows. Trifluoromethyl enol ethers were prepared (stereoselectively) in this way (Eq. 78) the key intermediate is presumably a transient vinyl carbanion which protonates before defluorination can occur [240]. Palladium(II)-catalysed alkenylation or aryla-tion then proceeds [241]. 

As a supporting evidence, it is well-known that the electron-rich 0 6-arene)Ru complex of terminal alkyne 428 rearranges easily by the treatment with NaPR, of the )/ -vinylidenc complex 429, which is a strongly electrophilic carbene complex. Attack of ROH on the carbene carbon generates the the alkoxycarbene complex 431 via 430 [166]. Formation of ketone 427 by attack of the allylic alcohol is understanable by this mechanism. Formation of Ru-vinylidene complex 429 from the terminal alkyne has been proposed as the intermediate 432 of the reaction of terminal alkyne, amine and CO2 to form the vinyl carbamate 433 [167,168]. 

It is well-known that RuCl(cyclopentadienyl)(PPh3)2 stoichiometrically activates terminal alkynes in the presence of a chloride abstractor to produce [Ru(cyclopen-tadienyl)(=C=CHR)][X] complexes. This reaction has been used with advantage to perform anti-Markovnikov addition of allylic alcohols to terminal alkynes followed by intramolecular rearrangement to produce unsaturated ketones according to Scheme 8 [18, 19]. 

Scheme 8. Ruthenium-catalyzed addition of allyl alcohol to terminal alkynes with skeleton rearrangement.

The principally practicable route to allyl vinyl ethers by alkenation of allyl formates, has not yet been exploited in this context. In another approach, the nucleophilic addition of allylic alcohols to alkynic esters, one observes the exclusive formation of franr-enol ethers 2 the stereochemical information is lost, however, after the rearrangement, due to enolization of the formed formylacetic acid derivatives. On the other hand the nucleophilic addition of allyl alcohols to acceptor-substituted allenes like allenic sul-fones or phosphonates offers a novel route with fascinating potential. " Such systems that are readily... 

Certain sulfoxides can be prepared by rearrangement of the sulfenate esters thus, allyl arenesulfenate esters (7), obtained by condensation of the sulfenyl chloride with allyl alcohol (8), spontaneously rearrange to the allyl sulfoxides (9) (Scheme 6). The rearrangement also occurs with alkynic alcohols for instance, trichloromethanesulfenyl chloride (10) reacts with propargyl alcohol (11) to form the allenic sulfoxide (12) (Scheme 7). 

In a formal synthesis of brefeldin A, treatment of the allyl propargyl ether 305 with the base n-BuLi promoted deprotonation a- to the alkyne, followed by rearrangement to give predominantly the homoallylic alcohol 306 (3.199). " Likewise, deprotonation and rearrangement of the macrocyclic substrate 307 promoted rearrangement to the homoallylic alcohol 308, used in a synthesis of the diterpene kallolide B (3.200). Regioselective deprotonation of the diallyl ether 309 and... 

In comparisvjn with the isomerization of alkynes, the base-catalysed r-ear,rangements of alkenes are less well known. Such reactions deserve further attention, however, as recent work demonstrates. Allylic alcohols, for example, rearrange to give aldehydes (25-74% yield) (Scheme 13). Of particular interest is the conversion of undec-10-en-1-ol to undecanal, albeit in low yield (3%). The intermediacy of a stabilized dianion (51) is plausible which is supported by the observations that, e.g. cyclo-hexen-3-ol failed to rearrange. 

Two new routes to allyl vinyl ethers, suitable substrates for Claisen rearrangement, are summarized in Scheme 41 and equation (22) one involves copper-catalysed solvolytic cleavage by an allylic alcohol of (E)-alkenylpentafluorosili-cates available from hydrosilylation of alkynes," and the other is based on the base-promoted reaction of dimethyl diazomethylphosphonate with aliphatic ketones in the presence of an allylic alcohol." Electrolytic synthesis of allylic ethers direct from alkenes has been discussed earlier in this Report (Scheme 11). ... 

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. 

The hydroalkoxylation of alkynes has recently attracted some marked interest. Several groups have developed alkyne alkoxylation/Claisen rearrangement tandem processes using allylic alcohols as nucleophiles and NHC-Au complexes as the catalysts. The group of Nolan developed, in 2013, the hydrophenoxylation of alkynes by using a cooperative NHC-Au catalysis pro-cess. The hydroalkoxylation of allenes could also be performed. This reaction was shown to proceed in a regioselective manner with the alcohol being introduced on the least hindered terminal carbon of the allene. ... 

Ariza et al. utilized the TST-RCM in conjunction with the Ireland-Claisen rearrangement to facilitate the total synthesis of (—)-phaseolinic acid (Scheme 8.3) [14]. The C2-symmetrical silaketal 6 was prepared in 58% overall yield using an adaptation of the protocol described by Evans and Murthy [13], which employed enantiomerically enriched propargylic alcohols to form the symmetrical bis-alkoxysilane rather than allylic alcohols. Selective reduction of the his-alkyne with Lindlar catalyst, followed by RCM with catalyst [Ru]-I, afforded the silaketal... 

Among many methods, the addition of alcohol to alkyne is a potential method of choice to prepare vinylethers [101]. However, even though the addition of methanol to electron-deficient alkynes such as acetylene dicarboxylates is easy, the intermo-lecular addition of alcohol to unactivated alkynes in the presence of metal catalysts is not straightforward. With ruthenium catalysts, the only reported examples concern the addition of allylic alcohols to terminal alkynes. Thus, in the presence of a catalytic amount of RuCl(tris(pyrazolyl)borate)(pyridine)2, allyl alcohol adds to phenylacetylene in refluxing toluene to produce a 1 1 mixture of allyl (3-styryl ether and 2-phenylpent-4-enal (resulting from Claisen rearrangement) in 72% overall yield. (Scheme 22) [86]. 

The cycloaddition of allenyl sulfoxide 135 and cydopentadiene occurred at room temperature, giving the single adduct 136. The initially formed allylic sulfoxide underwent a rapid [2,3]-sigmatropic rearrangement. Treatment of 136 with trimethyl phosphite furnished alcohol 137. It should be noted that the reaction of methyl 4-hydroxy-2-butynoate with cydopentadiene failed to give 137. Thus, the allene 135 is considered as a masked and more reactive alkyne equivalent. 

Protonolysis can also be effected with weaker acids in some cases this may be essential. For example, hydrozirconation of alkynic alcohols Me(CH2)nC=C(CH2)mOH with 2 equiv. of (6), followed by hydrolysis with 2% aqueous NH4CI, affords the corresponding cis-alkenol in high yield and selectivity, whereas use of aqueous HCl causes both cis-trans isomerization and allylic rearrangement. Protonolysis by weak acid may be slow enough for other reactions to compete TBHP can be used as an oxidant (see below). 

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