Aldehydes alkynylation catalyzed

Table 1.6 Asymmetric Diels-Alder reactions of alkynyl aldehydes catalyzed by 8 [lOc]...

Optically active alkynyl alcohols can, however, be conveniently prepared by the addition of dialkylzinc reagents of alkynyl aldehydes catalyzed by the chiral ligand (S)-l-methyl-a,a-diphenyl-2-pyrrolidine methanol33-34. 

An indium chloride-catalyzed coupling of alkynes to aldehydes was also possible in giving a, (J>-unsaturatcd carbonyl compounds in water in low yields (Eq. 8.88).223 (Alkynylation is discussed in Chapter 4 on alkynes.)... 

Knochel demonstrated the effectiveness of soluble potassium or cesium alkoxides such as KO Bu or CsO Bu as well as KH in iV-methylpyrrolidinone (NMP) for promoting the 5-endo-dig cyclizations of 2-alkynylanilines to 2-substituted indoles in solution or the solid-phase <00AG(E)2488>. Alternatively, Cacchi coupled a palladium-catalyzed cyclization of o-alkynyltrifluoroacetanilides with the addition of benzyl bromide or ethyl iodoacetate to afford 2-substituted-3-benzyl or 3-indolylcarboxylate esters, respectively <00SL394>. Yamamoto reported a new palladium catalyzed indole synthesis in which 2-(l-alkynyl)-Ar-alkylideneanilines 117 give 2-substituted-3-(l-alkenyl)indoles 118 directly from the imine by the in situ coupling of an aldehyde with the alkynylaniline <00JA5662>. 

In addition, iodine snccessfnlly catalyzed the electrophilic snbstitntion reaction of indoles with aldehydes and ketones to bis(indonyl)methanes [225], the deprotection of aromatic acetates [226], esterifications [227], transesterifications [227], the chemoselective thioacetalization of carbon functions [228], the addition of mercaptans to a,P-nnsatnrated carboxylic acids [229], the imino-Diels-Alder reaction [230], the synthesis of iV-Boc protected amines [231], the preparation of alkynyl sngars from D-glycals [232], the preparation of methyl bisnlfate [233], and the synthesis of P-acetamido ketones from aromatic aldehydes, enolizable ketones or ketoesters and acetonitrile [234],... 

Alkynylation of aldehydes.3 The reaction of alkynylmetals with chiral aldehydes shows no or slight diastereoselectivity, but in the presence of TiCl4, alkyn-yltributyltin reagents react with the steroid aldehyde 1 with about 9 1 diastereoselectivity. TiCl4-catalyzed reaction of 1 with allyltrimethylsilane or allyltributyltin also shows similar and comparable diastereoselectivity. 

Interestingly, the first catalytic version of such nucleophilic additions of alkynyl silvers to aldehydes has been described." Indeed, silver chloride in the presence of tricyclohexylphosphine and mild bases such as ethyldiisopropylamine catalyzed the addition of terminal alkynes to aldehydes in good to high yields (Table 10.5). The reaction proved to be almost insensitive to electronic effects however, alkyla-cetylenes were less reactive than arylacetylenes. The solvent had a dramatic effect on the reaction course. Control experiments with preformed phenylethynylsilver showed that both phosphine and water activated the silver acetylide. 

Unlike previous alkyne-aldehyde additions [23], the generation of an alkynyl carbanion is unlikely owing to the large pK, difference between the terminal acetylene and the solvent water [24]. A mechanism was proposed involving the simultaneous activation of the C-H bond of alkyne by the ruthenium catalyst and the aldehyde carbonyl by the indium ion. The ruthenium intermediate then underwent Grignard-type addition followed by an in situ hydrolysis in water to give the desired carbonyl addition product and regenerated the ruthenium and indium catalysts to catalyze further reactions (Fig. 3). 

Lanthanide Lewis acids catalyze many of the reactions catalyzed by other Lewis acids, for example, the Mukaiyama-aldol reaction [14], Diels-Alder reactions [15], epoxide opening by TMSCN and thiols [14,10], and the cyanosilylation of aldehydes and ketones [17]. For most of these reactions, however, lanthanide Lewis acids have no advantages over other Lewis acids. The enantioselective hetero Diels-Alder reactions reported by Danishefsky et al. exploited one of the characteristic properties of lanthanides—mild Lewis acidity. This mildness enables the use of substrates unstable to common Lewis acids, for example Danishefsky s diene. It was recently reported by Shull and Koreeda that Eu(fod)3 catalyzed the allylic 1,3-transposition of methoxyace-tates (Table 7) [18]. This rearrangement did not proceed with acetates or benzoates, and seemed selective to a-alkoxyacetates. This suggested that the methoxy group could act as an additional coordination site for the Eu catalyst, and that this stabilized the complex of the Eu catalyst and the ester. The reaction proceeded even when the substrate contained an alkynyl group (entry 7), or when proximal alkenyl carbons of the allylic acetate were fully substituted (entries 10, 11 and 13). In these cases, the Pd(II) catalyzed allylic 1,3-transposition of allylic acetates was not efficient. 

The enantioselective alkynylation of ketones catalyzed by Zn(salen) complexes has been reported [24]. Polymeric salen ligand 30 was prepared with a polycondensation reaction and subsequently used as a polymeric chiral ligand of Zn. The polymeric Zn(salen) complex (prepared by 30) was then used as a catalyst of asymmetric addihon of phenylacetylene to aldehyde in the presence of 2 equivalents of Et/Zri. Subsequent asymmetric alkynylahon of 31 gave 33 in 96% yield and 72% ee (Scheme 3.9) [25]. 

Propargylic alcohols When catalyzed by Me2AlCl, the addition of alkynyl-stannanes to aldehydes is subject to chelation control by a (3-alkoxy or siloxy group in the substrate. 

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