Cyclization of dialdehydes

For the cyclization of dialdehydes, however, its utility seems limited. Being a nitromethane addition product, it can readily undergo retro-nitromethane addition with alkali to give formaldehyde and nitromethane. Thus, it is not surprising that reaction of glutaraldehyde with 2-nitroethanol under the usual conditions (i.e. 1 molar equivalent of sodium hydroxide in aqueous ethanol) should yield 2-nitrocyclohexane-1,3-diol 5), a nitromethane cyclization product With catal5dic amounts of sodium hydroxide (pH 8—9), however, 1-hydroxymethyl-l-nitro-cyclohexane-2-6-diol (80) can be isolated in yields of 24—29%... 

A. C. Richardson and H. O. L. Fischer, Cyclizations of dialdehydes with nitromethane, Part V. Preparation of some 3-amino-l,6-anhydro-3-deoxy-P-D-hexoses and the elucidation of their structures, Proc. Chem. Soc. (1960) 341-342. 

Aldol-type cyclization of dialdehydes with nitroalkanes is a valuatde syndietic loute to amino sugars, amino cyclitols and nucleosides of amino sugars. Recently, die cyclization of die di- and tetra- de-hydes derived from sucrose (15) with nitroalkanes has appeared. It is notewordiy that the oxidadve cleavage of sucrose with LTA affords the dialdehyde selectively (Scheme 8). ... 

Piperidine acetate also catalyzes the intramolecular cyclization of dialdehydes. Examples cyclization of (1) to (2) by Woodward et al conversion of (3) into... 

Similar behavior is seen in the cyclization of dialdehyde (104), an intermediate in the dimerization of 2-ethyI-2-hexenaI the resulting mixture of aldol products contains 99% of isomer (105 equation 136).23 -b... 

The synthesis of rhynchophyllol by van Tamelen et a/P illustrates a biogenetic-type approach to oxindole alkaloids. A key feature of this synthesis is generation of the desired tetracyclic structure by an intramolecular Mannich cyclization of dialdehyde (B) produced by oxidative cleavage of the substituted cyclopentanediol (A). 

This procedure is representative of a new general method for the preparation of noncyclic acyloins by thiazol ium-catalyzed dimerization of aldehydes in the presence of weak bases (Table I). The advantages of this method over the classical reductive coupling of esters or the modern variation in which the intermediate enediolate is trapped by silylation, are the simplicity of the procedure, the inexpensive materials used, and the purity of the products obtained. For volatile aldehydes such as acetaldehyde and propionaldehyde the reaction Is conducted without solvent in a small, heated autoclave. With the exception of furoin the preparation of benzoins from aromatic aldehydes is best carried out with a different thiazolium catalyst bearing an N-methyl or N-ethyl substituent, instead of the N-benzyl group. Benzoins have usually been prepared by cyanide-catalyzed condensation of aromatic and heterocyclic aldehydes.Unsymnetrical acyloins may be obtained by thiazol1um-catalyzed cross-condensation of two different aldehydes. -1 The thiazolium ion-catalyzed cyclization of 1,5-dialdehydes to cyclic acyloins has been reported. 

The carbon skeleton of helminthosporal can be accounted for from three isoprene units (XVI), but they cannot be formed by cyclization of a farnesol precursor, as the three units are not joined head to tail. There is the possibility that the aldehyde carbons were joined in the early stages of biosynthesis to form helminthosporane (XVII, XX) as an intermediate, followed by later oxidation to yield the dialdehydes. As a test of this hypothesis the actively growing fungus was fed mevalonic acid labeled with carbon-14 in the 2-position (mevalonic acid being a precursor of isoprene units) (2). Thus, three units of radioactivity should be incorporated, one being the... 

Base-catalyzed nitromethane cyclization of the dialdehyde generated by periodate oxidation of 1,2-O-cyclohexylidene-myo-inositol affords the nitrodiol with 1,4/2,3,5-configuration. This is converted into the a-mannosidase inhibitor, mannostatin A (Eq. 3.60).98... 

The first total synthesis of D/E-trans annellated yohimbines, e.g., ( )-yohim-bine (74) and ( )-pseudoyohimbine (88), was published in preliminary form by van Tamelen and co-workers (218) in 1958, while full details (219) appeared only in 1969. Key building block 393, prepared from butadiene and p-quinone, was condensed with tryptamine, yielding unsaturated amide 394, which was subsequently transformed to dialdehyde derivative 396. Cyclization of the latter resulted in pseudoyohimbane 397. Final substitution of ring E was achieved via pyrolysis, oxidation, and esterification steps. As a result of the reaction sequence, ( )-pseudoyohimbine was obtained, from which ( )-yohimbine could be prepared via C-3 epimerization. 

Three new centers of dissymmetry are formed on cyclization of a dialdehyde with nitroethane, hence — depending on the type of substitution of the dialdehyde — three, six or eight diastereomeric methyl-nitro-diols (2, R = CHs) can be expected a priori. In view of the analogy of this reaction to the dialdehyde-nitromethane-cyclization, which is endowed with a marked stereoselectivity, the thermodynamically more stable isomers should arise in considerable preponderance. The steric effects determining the orientation of the hydroxyl groups can reasonably be assumed to be the same, thus an e,c-arrangement (4) or (5) is to be expected for the major products. 

On the basis of these rationalizations, compounds of configuration 4 are to be expected as major products of this reaction. The experimental results on the nitroethane cyclization of seven 1,5-dialdehydes, presented below, are in good agreement with these predictive considerations. 

An unusual observation was made on nitroethane cyclization of the dialdehydes (37 a) and (37 b), obtainable from a- and p-methyl D-gluco-pyranoside (36), respectively, by periodate oxidation. In distinct contrast to the course of the nitromethane cycUzations of these and a range of other sugar dialdehydes D, the products that result, i.e. (43), have undergone epimerization at C-5 as compared to (39). thus raising the number of isomers to be expected to 16. 

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). 

The cyclization of glutaric dialdehyde or its 3-methyl homolog with hydrogen selenide in the presence of HC1 was found to be useful for the generation of simple 4//-selenopyrans 8 and 60.7,90... 

The situation is complex. In another study we examined the cyclization of compound 54 catalyzed by cyclodextrin bis-imidazoles [140]. This dialdehyde can perform the intramolecular aldol reaction using the enol of either aldehyde to add to the other aldehyde, forming either 55 or 56. In solution with simple buffer catalysis both compounds are formed almost randomly, but with the A,B isomer 46 of the bis-imidazole cyclodextrin there was a 97 % preference for product 56. This is consistent with the previous findings that the catalyst promotes enolization near the bound phenyl ring, but in this case the cyclization is most selective with the A,B isomer 46, not the A,D that we saw previously. Again the enolization is reversible, and the selectivity reflects the addition of an enol to an aldehyde group. The predominant product is a mixture of two stereoisomers, 56A and 56B. Both were formed, and were racemic despite the chirality of the cyclodextrin ring. 

The synthesis of prostaglandin PGB1 as described by Morin et al. (Eli Lily Research Labs.), starts with 7-(2-methoxyphenyl)heptanoic acid 142 which is converted into 143 through Birch reduction, esterification and acetalization. Ozone cleavage of 143 and cyclization of the resulting dialdehyde affords cyclopentene carbaldehyde 144 which was subjected to ( )-selective Wittig olefination with... 

The synthesis of the benzo[l, 2-b 4,5-6 ]difuran (56) is a variation of a common approach involving base-catalyzed cyclizations <87CA(106)176085>. Other variations formed 2-nitrobenzodifurans by cyclization of o-nitromethoxy aldehydes <87CA(107)211476>. The acidity of the 5-methyl protons in the bismethylthio dialdehyde (57a) allowed base-catalyzed cyclization to the benzo[2,l-6 3,4-6 ]dithiophene (58) <91BSB1>. 

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