3-Chroman amine

The reduction can also be achieved by utilizing in situ generated BHj THF (from sodium borohydride and boron trifluoride etherate). The scope of this reaction includes the synthesis of novel 3-chroman-amine derivatives (60 equation 33). This stereoselective reaction proceeds via the hydroxylamine intermediate only c/s-2-aryl-3-amino derivatives are obtained. 

Intramolecular reactions of a phenolate were also reported (Scheme 9.33) [22a]. The preparation of a chromane derivative is described below, where the catalyst was activated with the base TBD. As in the case of intramolecular aminations, these cyclizations could be run at concentrations as high as 0.5-1 M. 

Nitro groups attached to the benzene ring of chromans or chromanones may be reduced catalytically to give the amines but 3-aminochromanones (698) are usually obtained from the oxime (697) of the chromanone by the Neber rearrangement. The free bases are rather unstable (69JMC277). 

A 2-amino group in chroman is more labile than its isomers and is hydrolyzed to the alcohol by acids for example both the amines (699) and (700) give the corresponding alcohols by treatment with nitrous acid and 50% hydrochloric acid, respectively. 6-Amino-chromans are of interest because of their chemical and biological resemblance to the tocopherols. The tocopheramines (701 R1, R2, R3 = H or Me) show antioxidant and other properties of the corresponding phenols and are no more toxic. They may be obtained by catalytic or chemical reduction of the nitrochromans (81HC(36)189). 

During a study of dihydrocoumarins (68JOC1202) it was observed that 4-(2-bromoethyl)-3,4-dihydrocoumarin (291) was converted into a 4-substituted chroman on reaction with an amine. Ring opening occurs through nucleophilic attack at C-2 and this is followed by an intramolecular nucleophilic substitution. In a similar manner, chroman-4-ylacetic acid results on reaction with potassium hydroxide in methanol. 

The synthesis of some 2,2-spiroannelated chroman-4-ones from o-hydroxyacetophenone and a cycloalkanone in the presence of a secondary amine has been described (78S886). The reaction has also been used to prepare a range of chromanones bearing non-identical or... 

Salicylaldehyde reacts with trimethylsilylketene dithioacetal in the presence of a Lewis acid to form the chroman 502, the product of a deoxygenative divinylation (Equation 208) <2001JOC3924>. This reaction can also be applied to salicylaldimines <2003JOC4947>. Treatment of 3,5-dibromosalicylaldehyde with methyl vinyl ketone (MVK) in the presence of DABCO leads to a chroman-4-ol as the major product <2002J(P1)1318>. A stereoselective one-pot synthesis of vy/z-fused chromans from salicylaldehydes, aromatic amines and cyclic enol ethers is carried out in the... 

Chroman, 4-( p-hydroxyphenyl)-2,2,4-trimethyl-X-ray studies, 3, 622 Chroman, 2-methoxy-synthesis, 3, 806 Chroman, 5-methoxy-synthesis, 3, 778 Chroman, 7-methoxy-synthesis, 3, 778 Chroman, 8-methoxy-acylation, 3, 732 Chroman, 2-methoxy-2-methyl-synthesis, 3, 780 Chroman, 2-methyl-synthesis, 3, 785 Chroman, 5-methyl-reactivity, 3, 732 Chroman, 6-nitro-synthesis, 3, 784 Chroman, 4-phenyl-synthesis, 3, 783 Chroman, thio-metabolism, 1, 241 Chroman, 5,6-thio-2-substituted metabolism, 1, 241 Chromanamines H NMR, 3, 580 Chroman-3-amines conformation, 3, 630 (S) -Chroman-2-carbaldehyde synthesis, 3, 779 Chromancarbaldehydes synthesis, 3, 782 Chroman-4-carbamic add synthesis, 3, 782 (R)-Chroman-2-carboxylic add methyl ester... 

A few other examples are listed in Scheme 49 intramolecular addition of amine giving a good synthesis of (/ )-(-P)-camegine, synthesis of chiral butenolides by carbonation of vinylic carbanions and conjugate additions of cuprates yielding chiral chromans. ... 

The large-scale pilot plant preparation of the chiral aminochroman antidepressant ebaizotan (also known as NAE-086) was developed by H.J. Federsel and co-workers. The structural features of the target included a disubstituted chroman skeleton, a stereocenter, as well as a non-symmetrical tertiary amine moiety at the C3 position and a secondary carboxamide group at C5. The backbone of the target molecule was constructed using the Perkin condensation of 2-hydroxy-6-methoxybenzaldehyde with hippuric acid under mild conditions. 

With much increased understanding of the reaction and its controlling factors, the next challenge to address was the search for a solvent that incorporated the good performance shown by DEA in creating the chroman product, but, at the same time, one that offered a considerably easier workup combined with a less-pronounced toxicity prohle (aromatic amines are notoriously toxic). When screening a variety of options, diphenyl ether was quickly identified as a suitable replacement. 

Another example of organocatalytic AFC alkylation reaction with p,y-unsaturated a-keto esters was reported by Wang and co-workers in 2012. In the presence of 10 mol% rosin-derived tertiary amine-thiourea 96, a variety of p,y-unsaturated a-keto esters reacted with 1-naphthol smoothly to afford the modified chromanes 97 in good yields (79-86%) with up to 96% ee (Scheme 6.39). Again, the hydrogen bonding between substrates and catalyst was proposed to be a key element for the enantioselective control. 

SoHman et al. reported the synthesis of 3-triphenylphosphoranylidene-chromanes 117 from Mannich bases 115 of the commercial moUusddde niclosamide and the ciunulated yhdes 2, 82 or 88 [73]. The reaction was carried out in boihng toluene and is thought to proceed by initial addition to give the acyl ylides 116, which then cycHze by the unusual expulsion of a secondary amine, i.e. by nudeophihc attack of the ylidic carbon atom at the benzyhc carbon atom. Intermediates 116 were not isolated. The moUusdddal activities of compounds 117 were found to be about tenfold lower than that of the parent niclosamide (Scheme 25). 

Azomethine ylides, derived from condensation of ethyl ( )-4-(2-formy-laryloxy)but-2-enoates with various secondary amines, undergo intramolecular [3 + 2] cycloaddition reactions to provide polycyclic amine-fused chromans. This one-pot reaction is mediated by the combined action of benzoic acid and molecular sieves (Scheme 32) (14OL5910). 

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