Abstract:A new method for the preparation of 3-isochromanone derivatives is reported. The method consists of the ethoxycarbonylation of o-acylbenzyllithiums with ethyl chloroformate and the subsequent NaBH4 reduction of the resulting o-acylphenylacetic acid derivatives.
“…Next, to demonstrate the synthetic utility of the synthesized product, first, compound 5a was treated with NaBH 4 in methanol followed by acid workup to obtain 1-methylisochroman-3-one ( 9a ) in 74% yield (Scheme ). Remarkably, compound 9a contains the bicyclic core of cytosporone C . Similarly, reduction of 5u and 5v affords 1–7,8,9,9 a -tetrahydrobenzo[de]chromen-2(3 H )-one ( 9u ) and phenylisochroman-3-one ( 9v ), respectively, in high yields.…”
An expeditious Ir(III)-catalyzed
carboxymethylation of aryl ketone
with diazotized Meldrum’s acid has been developed in aqueous
medium. Flavanone and chromanone were also found to be facile substrates
with the developed catalytic system. Mechanistic studies revealed
the active catalytic species and the role of water in the reaction
process as hydroxy and proton sources. Employing the developed method,
total synthesis of cytosporone A was achieved in two steps and that
of cytosporones B–C was achieved in three steps starting from
resorcinol.
“…Next, to demonstrate the synthetic utility of the synthesized product, first, compound 5a was treated with NaBH 4 in methanol followed by acid workup to obtain 1-methylisochroman-3-one ( 9a ) in 74% yield (Scheme ). Remarkably, compound 9a contains the bicyclic core of cytosporone C . Similarly, reduction of 5u and 5v affords 1–7,8,9,9 a -tetrahydrobenzo[de]chromen-2(3 H )-one ( 9u ) and phenylisochroman-3-one ( 9v ), respectively, in high yields.…”
An expeditious Ir(III)-catalyzed
carboxymethylation of aryl ketone
with diazotized Meldrum’s acid has been developed in aqueous
medium. Flavanone and chromanone were also found to be facile substrates
with the developed catalytic system. Mechanistic studies revealed
the active catalytic species and the role of water in the reaction
process as hydroxy and proton sources. Employing the developed method,
total synthesis of cytosporone A was achieved in two steps and that
of cytosporones B–C was achieved in three steps starting from
resorcinol.
“…In contrast, the reaction of the carbonate where both the functional groups are separated by four carbons proceeded via path b providing the alkenyltitanium compound having an ester group presumably due to lower stability of the seven-membered lactone ring compared to five- or six-membered ones (entry 8). The carbonates having an aromatic ring as a tether between the triple bond and carbonate group react similarly, thus providing an easy access to 3-isochromanone derivatives (entries 9 and 10). 2 …”
Treatment of acetylenic or olefinic carbonates and esters with a
low-valent titanium reagent diisopropoxy(η2-propene)titanium (1), readily
generated by the reaction of Ti(O-i-Pr)4 or
ClTi(O-i-Pr)3 with 2i-PrMgX,
resulted
in an intramolecular nucleophilic acyl substitution (INAS) reaction to
afford organotitanium compounds having a
carbonyl functional group, in good to excellent yields. Thus, the
treatment of alkyl alkynyl carbonates 2 or
alkyl
alkenyl carbonates 4 with 1 gave organotitanium
compounds having a lactone and/or ester group. Similarly,
alkyl
alkynoates 10 or alkynyl esters 14 of carboxylic
acids reacted with 1 to give organotitanium compounds having
a
cyclic or acyclic ketone group, respectively. Thus, the reaction
provides, after hydrolysis, five- or six-membered
α-alkylidene lactones and/or α,β-unsaturated esters from
2, γ-butyrolactone derivatives from 4, five- or
six-membered
α-alkylidene cyclic ketones from 10, and acyclic
α,β-unsaturated ketones 15 from 14. In
all cases, the yields are
excellent and the generation of the organotitanium compounds was
confirmed by deuterolysis. The organotitaniums
6 and 11c reacted smoothly with iodine to afford
2-(iodomethyl)-4-butanolide (9) and
α-[iodo(trimethylsilyl)methylidene]cyclopentanone, respectively. The organotitanium
compounds obtained here also reacted with aldehydes
to give the corresponding adducts, thus opening up a new access to
substituted α,β-butenolides from 2, to
γ-butyrolactones from 4, and to the corresponding
tetrasubstituted furan from 10 and
14.
“…Synthesis of Isochroman-3-ones. As an application of the reductive electrophilic substitution of phthalans, we have investigated their ring expansion to substituted 1,4-dihydro-3 H -2-benzopyran-3-ones (substituted isochroman-3-ones), which are useful intermediates in the synthesis of biologically active heterocyclic compounds. , …”
The behavior of phthalan (1a) was investigated under
conditions of electron transfer from alkali
metals in aprotic solvents. Reaction with lithium in the presence
of a catalytic amount of
naphthalene in THF led to the reductive cleavage of an arylmethyl
carbon−oxygen bond, with
formation of a stable dilithium compound. Trapping of this
intermediate with several electrophiles
(alkyl halides, carbonyl derivatives, CO2) was successful.
The extension of this procedure to several
substituted phthalans (1b
−
i) was
investigated, and the regiochemistry as well as the
synthetic
usefulness of these reactions are discussed.
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