Reactions asymmetric propargylation

In 1963, an asymmetric synthesis of chloroallenes was reported by the SNi reaction of propargyl alcohols with thionyl chloride [34]. Since then, rearrangement of pro-pargylic precursors has been one of the most useful methodologies for the synthesis of allenes [35]. Treatment of 84, obtained by asymmetric reduction with LiAlH4-Dar-von alcohol complex, with thionyl bromide gave 86 as the major product via 85 (Scheme 4.21) [36],... 

The catalytic asymmetric propargylation [108] and allenylation [109] of achiral aldehydes has been performed with high levels of enantioselection. The asymmetric propargylation promoted by the chiral Lewis acid derived from bind and Ti(0/-FT)4 are representative. Between 50 and 100 mol% of titanium is required for these reactions to go to completion (Scheme 10-70). The reaction of benzalde-hyde with allenyltributylstannane 170 and the chiral promoter produced the homo-propargylic alcohol 171 in >99% ee and 48% yield (7% of the undesired allenyl alcohol was also obtained). 

Yu and coworkers reported that use of PrSBEt2 as an additive accelerates the chiral Zr-catalyzed asymmetric allylation reaction and suppresses the concomitant Meerwein-Ponndorf-Verley reduction. The presence of the additive is thought to dissociate the product from the reaction complex and to regenerate the chiral catalyst [28]. This method was further extended to asymmetric propargylation with allenyltributylstannane by the same group [19]. In contrast, Taghavini and Umani-Ronchi and their group have shown that an enantioselective allylation of... 

Allylic geminal dicarboxylates 285 are prepared by Pd-catalyzed reaction of propargyl acetate 284 with AcOH [104], Two products 287 and 288 are obtained from gem-allylic compounds 286, and 288 is an allylic ester and undergoes the second allylation. Several applications to asymmetric syntheses have been reported [48]. Reaction of 289 with dimethyl methylmalonate afforded 290 with 95% ee. 

Catalytic asymmetric propargylation has been reviewed (131 references). Aldehydes have been propargylated in up to 99% yield and 92% ee by allenyl-zinc reagents, generated in situ from the action of diethylzinc on iodoallene (or 3-iodopropyne), with a bulky diarylprolinol catalyst. The reaction is conveniently carried out in DCM at low temperature and avoids the use of tin reagents. ... 

In 1988, an ASI workshop on Selectivities in Lewis acid promoted reactions was held in Greece, during which I proposed the mechanism of our asymmetric propargylation reaction using chiral allenyl boronic ester [13]. In an enantioface differentiation process, the chiral nucleophile was added to the carbonyl group of aldehydes, thus allowing the preparation of chiral propargylic alcohols [14]. Based... 

In addition, propargylic alcohols can generate stabiUzed carbocations under metal- and organocatalysis conditions. Thus, when used with enohzable aldehydes under these reactions, asymmetric access to the corresponding alkylated propar-gyhc compounds is given [50]. 

The 1,3-dipoles consist of elements from main groups IV, V, and VI. The parent 1,3-dipoles consist of elements from the second row and the central atom of the dipole is limited to N or O [10]. Thus, a limited number of structures can be formed by permutations of N, C, and O. If higher row elements are excluded twelve allyl anion type and six propargyl/allenyl anion type 1,3-dipoles can be obtained. However, metal-catalyzed asymmetric 1,3-dipolar cycloaddition reactions have only been explored for the five types of dipole shown in Scheme 6.2. 

In mosl allylation reactions, only a catalytic amount of CuCN-2LiCl is required [41]. Use of die chiral ferrocenylamine 104 as a catalyst makes enables asymmetric allylation of diorganozinc reagents to be effected witli allylic chlorides iScbeme 2.3G) [78]. Related electropb des such as propargylic bromides [79] and unsaturated epoxides [80] also undergo Su2 -substitution reactions iScbeme 2.37). 

Equation (81)), while the other two C=C double bonds in the structure are intact. Under the same reaction conditions, the racemic carvone is also resolved kinetically with a KR/KS ratio of 33 1. Asymmetric hydrogenation of a,/Tacetylenic ketones to chiral propargylic alcohols is still unavailable. 

Various transition metal complexes, in particular of late transition metals, were reported to be effective catalysts for such double bond isomerization. Because organic synthesis is the focus of this volume, this section will cover the transition metal-catalyzed isomerization of alkenes, which has the significant synthetic and industrial utilities. This chapter will also include the synthetic application, asymmetric reactions,4-6 and isomerization of alkynes, in particular, that of propargylic alcohols. 

All of the reactions discussed above are cyclic carbometallation reactions of metallacycles. Very recently, an interesting Cr-catalyzed carboalumination of propargyl derivatives producing allenes via a carbometallation-elimina-tion sequence has been studied. This reaction provides an asymmetric synthesis of chiral allenes (Scheme 57). 

Carreira and co-workers developed a highly efficient enantioselective addition of terminal alkynes to aldehydes giving propargyl alcohols by the mediation of zinc tri-flate and N-methylephedrine [17]. This reaction serves as a convenient and powerful synthetic route to a wide variety of enantioenriched allenes via propargyl alcohols. Dieter and Yu applied this alkynylation to the asymmetric synthesis of allenes (Scheme 4.12) [18]. Reaction of phenylacetylene with isobutyraldehyde afforded the propargyl alcohol in 80% yield with 99% ee, which was mesylated to 49 in quantitative yield. Reaction of 49 with the cyanocuprate 50 afforded the desired allene 51 with 83% ee. 

Intramolecular [4+2]-cycloaddition reactions, which involve base-induced isomerization of a propargyl ether to an allenyl ether, have been extensively studied. Treatment of 157 with a base caused an intramolecular Diels-Alder reaction of the intermediate allenyl ether to give tricyclic compounds 158 [131]. An asymmetric synthesis of benzofuran lactone 159 was achieved by an analogous procedure [132],... 

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