Intramolecular dialdehydes

The 1,5- and 1,6-dialdehydes 22 and 24 undergo the annulative pinacol coupling to give the cyclic vzc-diols 23 and 25, respectively (Scheme 13) [29]. The vanadium-catalyzed intramolecular coupling reaction of 1,5-diketone 26 also proceeds with excellent selectivity (Scheme 14) although the intermolecular coupling of ketones such as acetophenone results in low diastereoselectivity under these conditions [21]. 

Hofmann degradation of the nonnatural protoberberine 454 afforded the 10-membered ring base 455 (65%) in addition to the styrene-type compound (13%) (Scheme 92). Dihydroxylation of the former with N-bromosuccinimide in the presence of a large excess of hydrochloric acid and subsequent oxidation of the product diol 456 with periodic acid afforded the dialdehyde 457. On irradiation in tert-butyl alcohol 457 provided ( )-cis-alpinigenine (445) along with ( )-alpinigenine (441) as a result of endo and exo intramolecular cycloaddition, respectively, of the intermediate photodienol (221,222). 

Suitable dialdehydes can also undergo intramolecular hydride transfer, as in the Cannizzaro reaction of ethan- 1,2-dial (55, glyoxal ) — hydroxyethanoate ( glycollate, 56) anion,... 

The slow, rate-limiting step is almost certainly the migration of phenyl that occurs in the initial eOH adduct (135). This is essentially the analogue for 1,2-diketones of the intramolecular Cannizzaro reaction on the 1,2-dialdehyde glyoxal, OHCCHO (p. 217). In the latter... 

One very fascinating domino reaction is the fivefold anionic/pericydic sequence developed by Heathcockand coworkers for the total synthesis of alkaloids of the Daphniphyllum family [351], of which one example was presented in the Introduction. Another example is the synthesis of secodaphniphylline (2-692) [352]. As depicted in Scheme 2.154, a twofold condensation of methylamine with the dialdehyde 2-686 led to the formation of the dihydropyridinium ion 2-687 which underwent an intramolecular hetero- Diels-Alder reaction to give the unsaturated iminium ion 2-688. This cydized, providing carbocation 2-689. Subsequent 1,5-hydride shift afforded the iminium ion 2-690 which, upon aqueous work-up, is hydrolyzed to give the final product 2-691 in a remarkable yield of about 75 %. In a similar way, dihydrosqualene dialdehyde was transformed into the corresponding polycyclic compound [353]. 

Microgels can not only be synthesized by polymerization but also by polycondensation or polyaddition [350]. In an early work on crosslinking of single linear macromolecules, it could be shown that if a crosslinking agent, such as terephthal dialdehyde, was added to a very dilute solution of a linear polymer such as polyvinyl alcohol, almost exclusively a intramolecular crosslinking of the individual macromolecules took place [351]. 

In order to gain more insight into this proposed mechanism, Montgomery and co-workers tried to isolate the intermediate metallacycle. This effort has also led to the development of a new [2 + 2 + 2]-reaction.226 It has been found that the presence of bipyridine (bpy) or tetramethylethylenediamine (TMEDA) makes the isolation of the desired metallacycles possible, and these metallacycles are characterized by X-ray analysis (Scheme 56).227 Besides important mechanistic implications for enyne isomerizations or intramolecular [4 + 2]-cycloadditions,228 the TMEDA-stabilized seven-membered nickel enolates 224 have been further trapped in aldol reactions, opening an access to complex polycyclic compounds and notably triquinanes. Thus, up to three rings can be generated in the intramolecular version of the reaction, for example, spirocycle 223 was obtained in 49% yield as a single diastereomer from dialdehyde 222 (Scheme 56).229... 

This route was also employed for the synthesis of macrocydic allenes 169 via intramolecular coupling of aromatic dialdehydes 168 [88]. Depending on the ring size, chemical yields of up to 90% of the desired products were achieved (Scheme 2.53). Furthermore, the introduction of additional oxygen atoms into the tether did not diminish the efficiency of the protocol and therefore allowed an access to allenic crown ethers of type 171. 

A different behavior is exhibited by naphthalene-1,8-dicarbocal-dehyde (73). No m-naphthane derivatives are obtained on reaction with nitromethane, nitroethane or other methylene components. The basic medium, required for aldol type additions, causes the dialdehyde to undergo Cannizzaro reaction to the naphthopyranon (74) via an intramolecular 1,5-hydride shift, which is sterically favoured by the peri-position of the two aldehyde functions 28). 

The proline-mediated intramolecular aldol condensation of dialdehyde substrates was also reported by List in 2003, affording enantioselective synthesis of cyclic p-hydroxy aldehydes via a 6-e ofexo-aldolization reaction (Scheme 11.7d). 

The preparation of lactones via intramolecular catalytic esterification can be carried out by the Tishchenko reaction of dialdehydes. Alkaline earth metal oxides have been shown to be active not only for the intermolecular Tishchenko reaction, but also for the intramolecular Tishchenko lactonization. Thus, these solid catalysts have been applied for the Tishchenko reaction of o-phthalaldehyde to phthalide 182) (Scheme 34). 

Thieno[3,2-/4,5-/ ]bis[l]benzothiophene has been prepared by an intramolecular cyclization reaction of dialdehydes utilizing Amberlyst 15 as the acid catalyst <2004JOC2197> (Equation 80). 

From prior attempts at FruA-catalyzed DHAP additions to glyoxal or glutaric dialdehyde no product had been isolated, probably because the dialdehydes can cause cross-linking of the protein and thereby irreversibly destroy its enzymatic activity. On the other hand, hydroxylated aldehydes were assumed to form stable intramolecular hemiacetals in aqueous solution, which may mask the reactivity of free dialdehydes. Using the branched-chain glutaric dialdehyde 38 as a potential precursor to carbon-linked disaccharide mimetics (Scheme 2.2.5.14), we... 

Wittig-Homer reaction with 1,4- and 1,5-dialdehydes.1 Reaction of these aldehydes with 1 equiv. of a Wittig-Horner phosphonate in an aqueous medium with K2C03 as base is accompanied by an intramolecular aldolization to provide five- or six-membered cycloalkenols. 

Dialdehyde 227 was prepared by intramolecular coupling of acetal 228 under Ullmann conditions (Scheme 66) <2005ICC1049>. 

Intramolecular aldo condensation.1 The opposite regioselectivity of this system (1) as compared to that of piperidinium acetate (1, 888-889) is also observed with dialdehydes of the general structure 2. 

The conversion of this dialdehyde to cyclopentene-l-carbaldehyde is an intramolecular aldol condensation and is achieved by treatment with potassium hydroxide. 

Intramolecular Aldol Reaction Starting from Dialdehydes... 

---