Alkynyl aldehydes and

More recently, the scope of the Ni catalysed alkyne carbozincation has been extended to the cases of co-alkynyl aldehydes and even mixtures of aldehydes and alkynes.65 These reactions are generally accompanied by alkylation with organozincs (Scheme 11.20). 

Heterocyclization of alkynyl aldehydes and imines proceeds through two different mechanistic pathways (Scheme 95, routes a and b). A Lewis acidic transition metal is coordinated by a heteroatom of C=Y, the nucleophilic addition of Nu- to the electron-deficient... 

Scheme 7.22 Stereoselective prolinol Ik catalysed cross-aldol reactions employing alkynyl aldehydes and formaldehyde.

Phenyl trimethylsilylethyne (Chapter 20) undergoes a fluoride-ion-catalysed addition to aldehydes and ketones. This provides a remarkably mild, relatively non-basic method for the generation of an alkynyl anion or its equivalent. 

Thus far, the [5 + 2 + 1]-reaction works efficiently with alkynyl esters, amides, aldehydes, and ketones or an alkynyl-substituted allene44 as the two-carbon component (Scheme 58). Just as in the case of the [5 + 21-cycloaddition of VCPs and allenynes, the [5 + 2 + l]-reaction is selective for the allene over the alkyne subunit (Equation (35)). 

Comins et al. <20010L469> achieved the synthesis of the same allopumiliotoxin 267A 215 by a stereoselective alkynylation of the appropriately substituted 4-MeO-pyridine 226. The C-6 side chain is introduced by an aldol condensation between an aldehyde and indolizidinone 227 (Equation 17). 

In the hydroboration of terminal alkenes, carrying a ketone or aldehyde group, with a variety of borane reagents, dicyclohexylborane has been identified as the most efficient reagent. Analogous hydroboration of alkynyl ketones and alkynyl aldehydes with dicyclohexylborane yields the corresponding olefinic carbonyl compounds after protonation, or dicarbonyl compounds after oxidation. ... 

Although the CuBr/QUINAP system is an effective chiral catalyst in alkynylation of imines or iminiums, one drawback is that enantiopure QUINAP is quite expensive. An analog of QUINAP, PINAP (Figure 5.2), was readily synthesized and found as a very effective chiral ligand in the direct addition of alkynes to iminiums generated from aldehydes and secondary amines in situ (Scheme 5.8). ... 

Scheme 5.6. Asymmetric alkynylation of iminiums generated from aldehydes and amines.

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],... 

Alkynyl derivatives of 9-BBN act as mild sources of nucleophilic acetylenic groups. Reaction occurs with both aldehydes and ketones, but the rate is at least 100... 

Alcaide et al. (68,69) recently published their smdies of the intramolecular 1,3-dipolar cycloaddition reactions of alkynyl-p-lactams in which they found that the desired cycloaddition was in competition with a reverse-Cope elimination. The reaction of alkynyl aldehydes 37a-c with Al-methylhydroxylamine afforded a mixture of products depending on the reaction conditions and the chain length separating the alkyne and the lactam (Scheme 1.8). Thus, up to three separate... 

Acetylenic precursors employed in the syntheses of sugars may be divided into three groups (a) aldehydes (usually in the form of acetals), (b) alkyl alkynyl ethers, and (c) alkynols or alkynediols. Some of them are commercially available (for example, 2-butyne-l,4-diol), and others are prepared by Grignard-type reactions between 1-alkynylmag-nesium halides or lithium alkynes and suitable aldehydes, ketones, or epoxides. In this way, the synthesis of substrates having the desired number of carbon atoms, as well as the necessary functional groups, can be achieved. The next step consists in partial saturation of the triple bond to afford the desired cis- or trans-alkene. ct.s-Alkene systems... 

Besides electrophilic addition, terminal alkynes also perform acid-base type reaction due to acidic nature of the terminal hydrogen. The formation of acetylides and alkynides (alkynyl Grignard reagent and aUcylnyllithium) are important reactions of terminal alkynes (see Section 4.5.3). Acetylides and alkynides undergo nucleophilic addition with aldehydes and ketones to produce alcohols (see Section 5.3.2). 

Enantioselective addition of alkynyl groups to aldehydes and ketones afford enantioen-riched alkynyl alcohols62. Early approaches to the catalytic enantioselective addition of dialkynylzincs and alkynylalkylzincs to aldehydes employed catalytic amounts of chiral amino alcohol63 and amino pyridine64. Stoichiometric enantioselective addition of alkynylzinc halide is reported using the lithium alkoxide of IV-methylephedrine65. 

Aldehydes and ketones have also been prepared by nucleophilic cleavage of resin-bound O-alkyl hydroxamic acids (Weinreb amides [744]) with lithium aluminum hydride [745] or Grignard reagents (Entries 1 and 2, Table 3.41). Similarly, support-bound thiol esters can be cleaved with Grignard reagents to yield ketones [272], or with reducing agents to yield aldehydes (Entry 3, Table 3.41). Polystyrene-bound sele-nol esters (RCO-Se-Pol) react with alkynyl cuprates to yield alkynyl ketones [746]. 

Recently Carreira reported the first catalytic and highly enantioselective alkynylation. Thus, in the presence of a catalytic amount of Zn(II) salt and N-methylephedrine (21), the reaction of aldehydes and terminal acetylenes proceeds to give various chiral propargyl alcohols with high ee (Scheme 8) [30]. A... 

Isotellurazoles 4 were obtained in low yields (3-11%) by the one-pot reaction of alkynyl ketones with hydroxylamino-O-sulfonic acid and K2Te in aqueous solution containing sodium acetate (83S824 87H1587). A plausible mechanism of the reaction includes formation of the oxime derivative and subsequent nucleophilic addition of telluride anion to the triple bond followed by cyclization to 4. The reaction is accompanied by the formation of telluro bis(alkenyl ketones) 5 in yields approximately equal to those of 4. When alkynyl aldehydes are used instead of ketones, the single reaction products are the tellurobis(alkenyl nitriles) 6 (83S824). 

Aldehydes and ketones (RxCOR2) undergo an unusual tandem alkynylation and franx-hydrosilylation with alkynylsilanes (e.g. Ph-C=C-SiHR2) to give oxasilacy-clopentenes (54).210 A mild alkoxide initiator is required. 

Aldehydes and ketones have been alkynylated using indium(III) and Hunig s base (PrjNEt) as catalysts.213 IR and NMR evidence support a dual-activation role for indium it is a Lewis acid for the hard electrophile (carbonyl compound), and has sufficient n -coordination ability for a soft nucleophile such as a terminal alkyne. For the latter substrate, the amine then assists proton abstraction. 

The intramolecular nitrone-alkene cycloaddition reaction of monocyclic 2-azetidinone-tethered alkenyl(alkynyl) aldehydes 211, 214, and 216 with Ar-aIkylhydroxylamincs has been developed as an efficient route to prepare carbacepham derivatives 212, 215, and 217, respectively (Scheme 40). Bridged cycloadducts 212 were further transformed into l-amino-3-hydroxy carbacephams 213 by treatment with Zn in aqueous acetic acid at 75 °C. The aziridine carbaldehyde 217 may arise from thermal sigmatropic rearrangement. However, formation of compound 215 should be explained as the result of a formal reverse-Cope elimination reaction of the intermediate ct-hydroxy-hydroxylamine C1999TL5391, 2000TL1647, 2005EJ01680>. 

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