Aldehydes acetylenic

Acetylenic aldehydes and ketones or their chloroenone equivalents have been used (58GEP1040040), as have acetylenic esters such as DMAD (e.g. 76JOC1095, 73CPB2014). 

Dicarbomethoxyacetylene has also been added to the pyrrolidine enamine derivative of acetylacetone, demonstrating a new synthesis of phthalic esters (345). A 3-acylpyridine synthesis was achieved by the addition of an acetylenic aldehyde to the vinylogous amide derived from ammonia and dihydroresorcinol (346). 

Disubstituted isotellurazoles 1 (4-11%) and bis((3-acylvinyl)tellurides 3 (3-10%) were isolated in very low yields from the reaction mixture as the products of nucleophilic addition of telluride anion to the triple bond of the initial ethynyl ketones (83S824). This method cannot be applied to the synthesis of 3//-isotellurazoles. When a-acetylenic aldehydes were used instead of ethynyl ketones, bis((3-cyanovinyl)tellurides 4 obtained in 14-20% yields were the only products (83S824). 

One of the most important routes to isoxazole and isoxazoline rings involving the formation of the 1—5 and 2—3 bonds involves the condensation of hydroxylamine with a,/8-unsaturated carbonyl compounds. This method was previously widely used, but it is now of no preparative value, though it has been recently applied to determine the configuration of oximes. " The only new modification of this synthesis is the use of the acetals (27) of a,/8-acetylenic aldehydes for preparation of 5-substituted isoxazoles (28)... 

Another application of catalyst 8 is to the reaction of acetylenic aldehydes [10c] (Scheme 1.18, Table 1.6). Two acetylenic dienophiles have been reacted with cyclo-pentadiene or cyclohexadiene to give bicyclo[2.2.1]heptadiene or bicyclo[2.2.2]octa-diene derivatives in high optical purity. A theoretical study suggests that this reaction proceeds via an exo transition state. 

This catalyst was successfully applied to the Diels-Alder reaction of propargyl aldehydes as dienophUes [12] (Scheme 1.21, Table 1.8). Though 2-hutyn-l-al and 2-oc-tyn-l-al are unreactive dienophUes, silyl- and stannyl-suhstituted a,/ -acetylenic aldehydes react with cydopentadiene readily in the presence of 20 mol% of the catalyst at low temperature to give hicyclo[2.2.1]heptadiene derivatives in high optical purity these derivatives are synthetically useful chiral building blocks. 

Yamamoto et al. have developed a catalytic enantioselective carbo-Diels-Alder reaction of acetylenic aldehydes 7 with dienes catalyzed by chiral boron complexes (Fig. 8.10) [23]. This carbo-Diels-Alder reaction proceeds with up to 95% ee and high yield of 8 using the BLA catalyst. The reaction was also investigated from a theoretical point of view using ab-initio calculations at a RHF/6-31G basis set. 

Fig. 8.10 The catalytic enantioselective carbo-Diels-Alder reaction of acetylenic aldehydes 7 with cyclopentadiene 2 catalyzed by chiral...

Retrosynthetic cleavage of the indicated bond in 9 provides acetylenic aldehyde 23 as a potential precursor. It was anticipated that the action of a suitable base on 23 would result in the formation of an acetylide anion, a competent carbon nucleophile that could... 

A second consequence of the cyclic transition state of these reactions is that (Z)-alkenyl-stannanes are less reactive than their (E)-isomers and can in some cases be recovered unchanged from reactions in which mixtures of isomers are used109. a-Alkoxy-2-butenylstannanes fail to react with 0,/J-dialkylated a./J-unsaturated aldehydes, on heating, and give low syn/anli stereoselectivity with ,/i-acetylenic aldehydes, perhaps because of reduced steric effects110. 

FRAGMENTATION OF a,(J-EPOXYKETONES TO ACETYLENIC ALDEHYDES AND KETONES PREPARATION OF 2,3-EPOXYCYCLOHEXANONE AND ITS FRAGMENTATION TO 5-HEXYNAL... 

The N-aminoaziridine version7 of the a,/3-epoxyketone->alkynone fragmentation is a possible alternative in situations where the simple tosylhydrazone version6-9 fails. The tosylhydrazone method often gives good yields at low reaction temperatures, but it tends to be unsuccessful with the epoxides of enones that are not cyclic or are not fully substituted at the /5-carbon atom. For example, it has been reported9 that 2,3-epoxycyclohexanone docs not produce 5-hexynal by the tosylhydrazone route. The A-aminoaziridine method can also be recommended for the preparation of acetylenic aldehydes as well as ketones. 

Similar reactions have been carried out on acetylene. Aldehydes add to alkynes in the presence of a rhodium catalyst to give conjugated ketones. In a cyclic version of the addition of aldehydes, 4-pentenal was converted to cyclopen-tanone with a rhodium-complex catalyst. In the presence of a palladium catalyst, a tosylamide group added to an alkene unit to generate A-tosylpyrrolidine derivatives. ... 

Cyclic a,p-unsaturated ketones can be cleaved by treatment with base of their epoxy tosylhydrazone derivatives to give acetylenic ketones. The reaction can be applied to the formation of acetylenic aldehydes (R=H) by using the corresponding, 2,4-dinitrotosylhydrazone derivatives.Hydrazones (e.g., 47) prepared from... 

Scheme 12 Orbital phase environment in the EHels-Alder reactions of acetylenic aldehydes exo-selectivity...

Similar enantioselective Diels-Alder reactions between cyclopentadiene and a,p-acetylenic aldehydes catalyzed by a chiral snper Lewis acid were reported by Corey and Lee [58],... 

Secondary orbital interactions (SOI) (Fig. 2) [5] between the non-reacting centers have been proposed to determine selectivities. For example, cyclopentadiene undergoes a cycloaddition reaction with acrolein 1 at 25 °C to give a norbomene derivative (Fig. 2a) [6]. The endo adduct (74.4%) was preferred over the exo adduct (25.6%). This endo selectivity has been interpreted in terms of the in-phase relation between the HOMO of the diene at the 2-position and the LUMO at the carbonyl carbon in the case of the endo approach (Fig. 2c). An unfavorable SOI (Fig. 2d) has also been reported for the cycloaddition of cyclopentadiene and acetylenic aldehyde 2 and its derivatives (Fig. 2b) [7-9]. The exo-TS has been proposed to be favored over the endo- IS. 

By analogy, the acetylene aldehyde 500 gives, on addition of the chiral Li-enolate 501 [79-82], the chiral //-lactams 502 and 503 in 75% yield [80-82]. Similar (fhc-tam-forming reactions are discussed elsewhere [70, 83-88]. The ketone 504 affords, with the lithium salt of the silylated lithium amide 505, the Schiff base 506, in 74% yield (Scheme 5.27). The Schiff base 506 is also obtained in 25% yield by heating ketone 504 with (C6H5)3P=N-C6H4Me 507 in boiling toluene for 7 days... 

Scheme 12 Reductive cyclization of acetylenic aldehydes via Rh-catalyzed asymmetric hydrogenation...

An intermolecular version of a [4+2] cycloaddition-retrofragmentation of alkyne-oxazoles can be adapted to the synthesis of 2,3,4-trisubstituted furan in high regioselectivity if acetylenic aldehydes are used as starting materials. The product of this reaction is a pivotal intermediate for the synthesis of (-)-teubrevin G <00JA9324>. 

The inter- and intramolecular catalytic reductive couplings of alkynes and aldehydes recently have experienced rapid growth and are the topic of several recent reviews.5 h-8k 107 With respect to early transition metal catalysts, there exists a single example of the catalytic reductive cyclization of an acetylenic aldehyde, which involves the titanocene-catalyzed conversion of 77a to ethylidene cyclopentane 77b mediated by (EtO)3SiH.80 This process is restricted to terminally substituted alkyne partners (Scheme 53). 

The very first example of the catalytic reductive cyclization of an acetylenic aldehyde involves the use of a late transition metal catalyst. Exposure of alkynal 78a to a catalytic amount of Rh2Co2(CO)12 in the presence of Et3SiH induces highly stereoselective hydrosilylation-cyclization to provide the allylic alcohol 78b.1 8 This rhodium-based catalytic system is applicable to the cyclization of terminal alkynes to form five-membered rings, thus complementing the scope of the titanocene-catalyzed reaction (Scheme 54). 

For a review encompassing the intermolecular reductive coupling of acetylenic aldehydes, see Miller, K. M. Molinaro, C. Jamison, T. F. Tetrahedron Asymmetry 2003, 14, 3619-3625. 

Macrocyclization,3 A new route to cembranolides (3) involves intramolecular coupling of an alkoxyallyltin derivative (1) with an acetylenic aldehyde catalyzed by BF30(C2H5)2 (cf. 12, 513-514). Thus in the presence of BF3 etherate 1 cyclizes to 2 with syn-selectivity. The product is converted to the cembranolide 3 by hydrolysis of the enol ether and oxidation. 

In olefines, acetylenes, aldehydes, ketones, acids and esters, etc. if the proton is present in the positive region, it will be shielded and absorption occurs upfield. On the other hand if the proton is in the negative region, its absorption is downfield. 

The latter method can also be applied to aliphatic or ,/Tunsaturated ketones, to diketones and to aromatic or acetylenic aldehydes. Furthermore, it tolerates a variety of functional groups present in the substrate, as demonstrated by the efficient formation of allenes 174 and 175, which bear an additional nitro and ester group, respectively (Scheme 2.55) [89]. 

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