Enyne acetates

The 1,5-substitution of l-chloro-2-en-4-ynes with Grignard reagents has been described by Dulcere and co-workers [41] but lacks generality with regard to the nucleophile (see Section 2.3). In contrast, the regioselective reaction of enyne acetates 47 with various lithium cuprates proceeds smoothly in diethyl ether, furnishing exclusively vinylallenes 48 with variable substituent patterns (Scheme 2.17) [42],... 

Although the resulting vinylallenes 48 were usually obtained as mixtures of the E and Z isomers, complete stereoselection with regard to the vinylic double bond was achieved in some cases. In addition to enyne acetates, the corresponding oxiranes (e.g. 49) also participate in the 1,5-substitution (Scheme 2.18) and are transformed into synthetically interesting hydroxy-substituted vinylallenes (e.g. 50) [42], Moreover, these transformations can also be conducted under copper catalysis by simultaneous addition of the organolithium compound and the substrate to catalytic amounts of the cuprate (see Section 3.2.3). 

Initial attempts to perform the 1,5-substitution enantioselectively with chiral enyne acetates proceeded disappointingly. For example, treatment of the enantio-merically pure substrate 51 with the cyano-Gilman cuprate tBu2CuLi LiCN at -90 °C provided vinylallene 52 as a 1 3 mixture of E and Z isomers with 20 and 74% ee, respectively (Scheme 2.19) [28], As previously described for the corresponding Sn2 substitution of propargylic electrophiles, this unsatisfactory stereoselection may be attributed to a racemization of the allene by the cuprate or other organome-... 

Due to the distance between the stereogenic center and the place of the nucleophilic attack, the enantioselective 1,5-substitution of chiral enyne acetates constitutes one of the rare cases of remote stereocontrol in organocopper chemistry. Moreover, the method is not limited to substrate 51, but can also be applied to the synthesis of enantiomerically enriched or pure vinylallenes 53-57 with variable substituent patterns (Scheme 2.20) [28]. 

Scheme 2.20 Enantiomerically enriched or pure vinylallenes formed by 1,5-substitution of chiral enyne acetates in the presence of tri-n-butylphosphine (53-56) or triethyl phosphite (57).

Highly enantioselective 1,5-substitution reactions of enyne acetates are also possible under carefully controlled conditions (Eq. 4.31) [46]. For example, treatment of enantiomerically pure substrate 70 with the cyano-Gilman reagent tBu2CuLi-LiCN at —90 °C provided vinylallene 71 as a 1 3 mixture of E and 2 isomers with 20% and 74% ee, respectively. This mediocre selectivity might be attributable to race-mization of the allene by the cuprate or other reactive copper species formed in the reaction mixture. The use of phosphines as additives, however, can effectively prevent such racemizations (which probably occur by one-electron transfer steps) [47]. Indeed, vinylallene 71 was obtained with an ee of 92% for the E isomer and of 93% for the 2 isomer if the substitution was performed at —80 °C in the presence of 4 eq. of nBusP. Use of this method enabled various substituted vinylallenes (which are interesting substrates for subsequent Diels-Alder reactions Sect. 4.2.2) to be prepared with >90% ee. 

The introduction of a double bond between the triple bond and the leaving group of a propargyl electrophile leads to enyne electrophiles (e.g., 198) which would give access to vinylallenes 199 if the attack of the nucleophile takes place at the triple bond in an Sn2" (l,5)-substitution reaction (Scheme 48). Besides the regioselectivity, two types of stereoselectivity have to be considered in this transformation, that is, the configuration of the olefinic double bond of the vinylallene and the (relative or absolute) configuration of the allenic chirality axis. In the event, the reaction of enyne acetates 198 with various lithium cuprates proceeds... 

On the other hand, R2CuLi reacts with 1 mainly by direct displacement of the acetate group (equation II). (CH3)2CuLi reacts with the enyne acetate 2 to give mainly a coupled product 3 (equation III). 

A highly efficient synthesis of a wide range of 2,5-disubstituted furans from enyne acetates was described. The reactions were conducted by using Lewis acid and palladium catalysts, and provided symmetrical and unsym-metrical products in good-to-excellent yields, with broad substrate scope, including with a variety of aromatic and aliphatic substituents at the 2- and 5-positions of the furan (14SL2341). 

Conjugated enynes were the major products obtained from palladium-catalysed reaction of vinyl bromides such as (32) with acetylenes (Scheme 53). Again the yields of simple enyne acetates are variable, with starting material and other products such as dienynes being isolated. The reaction demonstrates that when a substrate has a choice of undergoing either vinylic coupling or substitution (via a -allyl complex) the former process appears to be favoured. 

A mixture of 0.12 mol of KO-tert.-C jHg, 0.12 mol of HO-tert.-C Hg and 75 ml of dry DMSO was warmed in a one-necked, round-bottomed flask at about 50°C until all solid material had dissolved. After cooling to room temperature the solution obtained was transferred intothe dropping funnel. In the flask were placed 50 ml of dry DMSO and 0.10 mol of the enyne acetal (note 1). The solution of the base was added dropwise over a period of 30 min, while keeping the temperature of the reaction mixture between 28 and 32°C. After an additional 20 min, 200 ml of ice--water were added to the dark solution and the product was extracted five times with a 1 1 mixture of diethyl ether and redistilled pentane (note 2). The combined organic solutions were washed twice with a concentrated solution of ammonium Chloride, then dried over magnesium sulfate. The residue remaining after removing... 

The scope of regio- and stereo-selective synthesis of vinylallenes by 1,5-(>S )-substitution of enyne acetates and oxiranes with organocuprates has been explored the products are usually obtained as mixtures of E- and Z-isomers (Scheme 12), ° Optimum conditions for stereoselective alkynylation of trans-2,3-epoxy sulfides at C(2), with double inversion of configuration, on reaction with alkynylaluminiums (Scheme 13) have been sought. 

Cariou, K., Mainetti, E., Fensterbank, L., Malacria, M. (2004). Tandem PtC12 catalyzed-thermal [3,3] rearrangements of enyne acetates. Tetrahedron, 60,9745-9755. 

The oxidation of cyano-Gilman cuprates has enabled the synthesis of new cyclophanes. Moreover, while BuhCuLi-LiCN has been reported to effect vinylallene formation by the 1,5-substitution of enyne acetates, it has been revealed that the application of Bu"3P to the reaction system considerably enhances the enantioselectivity of the synthesis. " Recent kinetic isotope studies into the chlorotrimethylsilane-mediated addition of lithiocuprates to cyclo-hexenone have suggested that reaction proceeds via an intermediate rr-com-plex. ... 

The intramolecular cyclization of alkynals promoted by Brpnsted acids in tandem with a Nazarov cyclization has been reported to construct hydroazulenone skeletons from enyne acetals (Scheme 167). °... 

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