Reaction of 3-halogeno-2H-1-benzopyran-2-ones with organometallic compounds. Synthesis of 4-Alkyl-2H-1-benzopyran-2-ones. X-Ray molecular structure of 3-bromo-3,4-dihydro-4-isopropylcoumarin

Abstract

3-Halogeno-2H-I -benzopyran-2-ones react with magnesium, lithium, aluminium and copper derivatives to give 3,4-dihydrocoumarins and 3-(0-hydroxyphenyl) propenols as major products. The nature and the ratio of the products in the final mixture depend on the solvent and on the organometallic reagent. Grignard derivatives yield 1,4-monoalkylation compounds in tetrahydrofuran (TH F) or 1,2-dialkylation derivatives in toluene. In some cases the dehalogenation competes with the 1,2-alkylation process in the reactions with alkyllithiums. The presence of the halogen at C-3 increases the reductive ability of organoaluminiums. In general, the reaction with lithium dialkylcuprates leads to complex mixtures of products. The 4-alkyl-3-halogeno-3,4-dihydrocoumarins obtained undergo dehydrohalogenation easily, and lead to 4-alkylcoumarins in good yields. The tandem alkylation-dehydrohalogenation of 3-halogeno-2H-I -benzopyran-2-ones constitutes a versatile synthesis of 4-alkylcoumarins.The reaction of coumarins with organometallic compounds is a very well known synthetic method to 2H-1-benzopyrans. We have now studied the reactivity of 3-chloro-and 3-bromocoumarins towards magnesium, lithium, aluminium and copper derivatives in order to confirm the influence of the halogen on the behaviour of these substrates.The Grignard derivatives react with 3-chlorocoumarin 1, 3-bromocoumarin 2, and 3-bromo-4-methylcoumarin 3 leading to dihydrocoumarins, chromen-2-ols, and open-chain compounds as a consequence of 1,4-and/or 1,2-addition or reduction processes (Scheme 1). The rate of reaction is intermediate between that with the organolithiums and that with organoaluminiums, and the solvent plays an important role in determining the ratio of the products in the final mixture ( Table 1).As previously described for 3-phenyl-and 3-ethoxycarbonyl~o u m a r i n , ' -~ in our case the 1P-addition process was favoured when the reactions were carried out in ether solvents (THF or diethyl ether) and with increasingly bulky groups R; the resulting 4-alkyl-3-halogeno-3,4-dihydrocoumarins 4 and 5 were obtained as a mixture of cis (80-90%) and trans (20-10%) isomers.Indeed a double 1,2-addition was the major process for 3-bromo-4-methylcoumarin or when benzene or toluene was used as solvent.The ratio of products in the final mixture also depends on the nature of the magnesium derivative; thus, EtMgI and EtMgBr led to the same mixture, but MeMgI did not produce 1,4-addition, and Pr'MgBr gave reduction products (E)-2-bromo-1-(o-hydroxyphenyl)-4-methylpent-l -en-3-01 12d and (E)-2-chloro-l-(o-hydroxyphenyl)-4-methylpent-1 -en-3-01 1 Id in 5 s 60% yield.On the other hand, 3-chloro-and 3-bromo-coumarin behave in similar fashion towards organometallics. Only in the case of phenylmagnesium bromide did 3-bromocoumarin lead to phenyl2,3-dihydro-3-phenylbenzofuranyl ketone 7f, whereas 3-chlorocoumarin yielded 3-chloro-3,4-dihydro-2,4-diphenyl-2H-l-benzopyran-2-016f, but both products derive from a common hydroxy ketone (acyloin) intermediate 6' that in the hydrol...

Mg-Promoted Regio- and Stereoselective C-Acylation of Aromatic α,β-Unsaturated Carbonyl Compounds

“…Moreover, high stereoselectivity is another noteworthy feature of the present Mg-promoted coupling. Thus, similar treatment of 3-alkylated coumarins 5a − d with acid anhydrides 2 /TMSCl gave exclusively one stereoisomer 6a − d[A] (isomer ratios of 6a − d[A] / 6a − d[B] , 92−98/8−2) , of the acylated products ( 6a − d ) with a cis- configuration between the 3-alkyl group and the 4-acyl group, as shown in Table .…”

“…The stereochemistry of 6[A] and 6[B] was determined by detailed analysis of the coupling constants J 3H - 4H between protons at the 3- and 4-positions in their 1 H NMR spectra as reported in the literature . For example, the values of J 3H - 4H for 6a[A] and 6a[B] are 4.88 and 3.91 Hz.…”

A One Pot Synthesis of Dehydrohedione (DHH) from a Hedione® Precursor

“…More than 25 years ago, Naef and Decorzant unsuccessfully attempted the synthesis of dehydrohedione (DHH) 1a via γ ‐halogenation/dehydrohalogenation of the Michael intermediate 2a ,. Subsequently, we also tried unsuccessfully both the dehydrochlorination of 3a (LiCl, Et 2 aniline, 100 °C; or AcONa, Ac 2 O, 20 °C, or DBN, 20 °C), as well as its clean decarbomethoxylation (either LiOH, THF, H 2 O, 20 °C, or H 2 O, 180 °C; or H 2 O, Na 2 CO 3 , NMP, 140 °C; or HCl, AcOH, 100 °C)). It is worth noting that in all cases, the halide elimination was performed under basic conditions.…”