Allenyl vinyl ketones

The addition of allenyl ether-derived anions to Weinreb [4] or to morpholino amides [5] follows a slightly different pathway (Eq. 13.2). For example, the addition of lithioallene 6 to Weinreb amide 7 at -78 °C, followed by quenching the reaction with aqueous NaH2P04 and allowing the mixture to warm to room temperature leads to cyclopentenone 9 in 80% yield [6]. The presumed intermediate of this reaction, allenyl vinyl ketone 8, was not isolated, as it underwent cyclization to 9 spontaneously [7]. These are exceptionally mild conditions for a Nazarov reaction and are probably a reflection of the strain that is present in the allene function, and also the low barrier for approach of the sp and sp2 carbon atoms. What is also noteworthy is the marked kinetic preference for the formation of the Z-isomer of the exocyclic double bond in 9. Had the Nazarov cyclization of 8 been conducted with catalysis by strong acid, it is unlikely that the kinetic product would have been observed. 

The origin of this preference is illustrated by Eq. 13.3. When the allene is terminally substituted, as it is in 6, it is axially chiral. Consequently, there are two reaction pathways that the allenyl vinyl ketone (10 in Eq. 13.3) can follow. The major reaction pathway for 10 involves counterclockwise conrotation, leading to 11, whereas the... 

A very unusual Nazarov cyclization of propargyl vinyl ketones has been reported by Hashmi et al. (Eq. 13.16) [18]. Propargyl alcohol 50 was oxidized to ketone 51 with the Dess-Martin periodinane. Attempts to purify 51 by column chromatography on silica gel led to cyclopentenone 53 in 59% isolated yield. This suggests that the solid support catalyzed the isomerization of 51 to allenyl vinyl ketone 52, which was not isolated, but which underwent spontaneous cyclization to 53. This result is consistent with earlier observations of the great ease with which allenyl vinyl ketones undergo the Nazarov reaction (cf. 8, Eq. 13.2). 

Elegant work by Tius and co-workers has demonstrated that the transfer of asymmetry need not be from an sp hybridized carbon atom. Instead, they have reported examples of the controlled Nazarov cyclization of allenyl vinyl ketones. In one such example, in situ formation of 67 resulted in efficient formation of cyclopentenone 68 with > 95% chirality transfer. The excellent axial to point chirality transfer is a result of the large ter/-butyl substituent forcing counterclockwise rotation (as viewed by the reader). 

The presence of sp-hybridized P-carbons, in the form of allenes, minimizes steric hindrance, thereby increasing the s-transis-trans population and thus increasing reactivity [10]. Furthermore, the cydization alleviates allenic strain, which further increases reactivity. In 1999, Tins and coworkers [11] reported a Nazarov cydization of allenyl vinyl ketones (Scheme 3.8). The combination of substituted vinyllithium 27 with enantiomerically pure allene 28 produced dienone 29 in situ, which was converted into cyclopentenone 30 in 65% yield. The enantiomer ratio of the precursor allene (ee >95%) is transcribed without... 

Scheme 3.8 Cydization of allenyl vinyl ketones with complete transfer of chirality.

Scheme 3.13 Torquoselectivity in allenyl vinyl ketones during the Nazarov reaction.

Zard has studied the isomerization/Mislow-Evans rearrangement of vinyl sulfoxides such as 237, arising from enolate addition to alkynyl sulfoxides [Scheme 18.60). Isomerization of 237 to the allylic sulfoxide 238 enabled the [2,3]-sigmatropic rearrangement to a-hydroxy-a-vinyl ketone 239. In this case, diastereoselectivity was low in formation of the carbinol center within a steroid framework. Additions to allenyl sulfoxides provide a similar sequence, leading to 2-propenyl substitution at the tertiary alcohol center (not shown). 

We also studied the reaction of CpW(CO)2(l-allenyl-2-COOMe-allyl) 170 and methyl vinyl ketone which likewise gives two diastereomeric [2+2+2] cycloadditive structures 171a,b. The stereochemistries of the... 

The generality of a method for the conversion of aj3-unsaturated acids into a/S-unsaturated diazomethyl ketones has been demonstrated by the synthesis of the highly reactive ketones, vinyl diazomethyl ketone and allenyl diazomethyl ketone. ... 

The nucleophilic addition of alcohols [130, 204-207], phenols [130], carboxylates [208], ammonia [130, 209], primary and secondary amines [41, 130, 205, 210, 211] and thiols [211-213] was used very early to convert several acceptor-substituted allenes 155 to products of type 158 and 159 (Scheme 7.25, Nu = OR, OAr, 02CR, NH2, NHR, NRR and SR). While the addition of alcohols, phenols and thiols is generally carried out in the presence of an auxiliary base, the reaction of allenyl ketones to give vinyl ethers of type 159 (Nu = OMe) is successful also by irradiation in pure methanol [214], Using widely varying reaction conditions, the addition of hydrogen halides (Nu= Cl, Br, I) to the allenes 155 leads to reaction products of type 158 [130, 215-220], Therefore, this transformation was also classified as a nucleophilic addition. Finally, the nucleophiles hydride (such as lithium aluminum hydride-aluminum trichloride) [211] and azide [221] could also be added to allenic esters to yield products of type 159. 

The attack of the nucleophile on the acceptor-substituted allene usually happens at the central sp-hybridized carbon atom. This holds true also if no nucleophilic addition but a nucleophilic substitution in terms of an SN2 reaction such as 181 — 182 occurs (Scheme 7.30) [245]. The addition of ethanol to the allene 183 is an exception [157]. In this case, the allene not only bears an acceptor but shows also the substructure of a vinyl ether. A change in the regioselectivity of the addition of nucleophilic compounds NuH to allenic esters can be effected by temporary introduction of a triphenylphosphonium group [246]. For instance, the ester 185 yields the phos-phonium salt 186, which may be converted further to the ether 187. Evidently, the triphenylphosphonium group induces an electrophilic character at the terminal carbon atom of 186 and this is used to produce 187, which is formally an abnormal product of the addition of methanol to the allene 185. This method of umpolung is also applicable to nucleophilic addition reactions to allenyl ketones in a modified procedure [246, 247]. 

It is interesting that the reaction of triphenylphosphine with a 1,2-allenyl ketone leads to the formation of a vinyl phosphonium salt 449, which upon protection of the carbonyl group would accept nucleophilic attack followed by elimination in the presence of Et3N to afford y-nudeophile substituted- ,/j-unsaturated enones 451 [197]. 

The reaction of an allene with an aryl- or vinylpalladium(II) species is a widely used way of forming a Jt-allyl complex. Subsequent nucleophilic attack on this intermediate gives the product and palladium(O) (Scheme 17.1). Oxidative addition of palladium ) to an aryl or vinyl halide closes the catalytic cycle that does not involve an overall oxidation. a-Allenyl acids 27, however, react with palladium(II) instead of with palladium(O) to afford cr-vinylpalladium(II) intermediates 28 (Scheme 17.12). These cr-complexes than react with either an allenyl ketone [11] or with another alle-nyl acid [12] to form 4-(3 -furanyl)butenolides 30 or -dibutenolides 32, respectively. 

Diethylzinc catalyses allenylation of aldehydes and ketones by an allenyl boronate, via a site-selective B/Zn exchange a balance of allenyl and propargyl alcohols are produced. A mild enantioselective addition of vinylzinc reagents (derived from vinyl iodides and diethylzinc) has been reported, with wide tolerance of functional groups. 

Kirsch et al. reported that vinyl propargyl ethers 36 could be converted into the densely substituted furans 38 via the Au(I)-catalyzed cycloisomerization reaction (Scheme 8.17) [125] A variety of substituted furans 38 (Table 8.1) could be obtained under very mild reaction conditions at only 2 mol% catalyst loading. It is believed that this cascade process begins vith the Au(I)-catalyzed Claisen-type rearrangement of 36 leading to the formation of skipped allenyl ketone 37, vhich, upon the Au(I)-catalyzed 5-exo-dig-cyclization, provides furan 38. 

A recent report from Kirsch s group illustrated that vinyl propargyl ethers 36, as surrogates of skipped allenyl ketones 37, could be employed in a very efficient synthesis of densely substituted pyrroles 29S via the Ag/Au(I)-catalyzed... 

Silyl and geimyl functionalised vinyl cyclopropenes ring-open thermally to give allene and alkyne derivatives with the former dominating, a-trimethylsilyl a-allenyl ketones couple to give enediynes related to the neocarzinostatin chromophore and also result fnnn Y-(t-BuMe2Si)allenylborane and acetylenic aldehydes. Allenylsilanes couple with AdQ and... 

Species (30) derived from RCHO and CH2=C(Li)SEt are isomerized by acid to a-thiolated ketones.Oxidation to sulphoxide and elimination gives the unsaturated ketone. Allenyl analogues of the above reagent add to epoxides to give products which can undergo further useful synthetic modification. The Shapiro method for the generation of vinyl-lithiums from sulphonyl hydrazones has been applied to a new one-pot synthesis of a-methylene-y-lactones involving elimination and carboxylation of the trianionic intermediate (31). ... 

The elimination pathway of stereochemically defined / -halovinyl ketones has been investigated using triethylamine leading to the formation of allenyl ketones and propargyl ketones. A preferential a-vinyl enolization of ( )- -chlorovinyl ketones has been observed where a nonplanar s-cis conformation is proposed as a dominant conformation as opposed to a planar s-cis conformation of (Z)- -chlorovinyl ketones. The synthetic utility of the elimination reaction of j5-chlorovinyl ketones was further demonstrated for a one-pot synthesis of 2,5-disubstituted ftirans in the presence of 1 mol % CuCl (Scheme 2). 

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