A New and Efficient Method for the Isomerization of Secondary Functional Allylic Alcohols into their Primary Isomers

Abstract

The first efficient tandem: "bromination-formylationhydrolysis" for the 1,3-transposition of acyclic allylic alcohols 1 and 2 bearing a nitrile and an ester group is reported.While the Baylis-Hillman reaction produces highly functionalized alkenes 1 of types 1 and 2, which have been demonstrated to be versatile and useful intermediates in the synthesis of natural products 2 and biologically active compounds, 3 this methodology is not efficient for the production of the corresponding 3-substituted allylic alcohols 3 and 4 . The latter compounds are important raw materials for the food industry, 4 as well as intermediates for the synthesis of Nuciferol derivatives, 5 sesquiterpenes lactones, 6 and antifungal and antibacterial products. 7 To our knowledge, few preparations of 3 8 or 4 9 (Scheme 1) have been described.A recent publication 10 on the first synthesis of 3-substituted 2-cyanoallylic alcohols 3 based on reduction of 2-cyano-2,3-epoxy esters prompts us to describe our own results. As part of our ongoing work on the synthesis of novel 2-functional allylic alcohols 3 and 4 , we report here a general and convenient method to accomplish the rearrangement of Baylis-Hillman products 1 and 2 to the corresponding primary allylic alcohols 3 and 4 using a threestep reaction sequence (bromination-formylation-hydrolysis). 11 The sequence involves a regiospecific 1,3-allylic transposition of the hydroxy group (Scheme 2).Our methodology is based on the treatment of 2-(hydroxyalkyl)acrylic compounds 1 and 2 with PBr 3 in diethyl ether at 0°C leading respectively to allylic bromides 5 as a mixture of E , Z-isomers in which the E -isomer is strongly predominant (EWG = CN) and exclusively the Zisomer when EWG = CO 2 Et. The stereochemistry of allyl bromides was assigned by comparing 1 H and 13 C NMR spectral data of these molecules reported in literature. 12 Thus, the displacement of bromide using triethylammonium formate (TEAF; 2 Et 3 N-5 HCO 2 H) as formylating reagent 13 , has been carried out in refluxing acetonitrile. The formyloxy nitriles and esters 6 are hydrolyzed to the corresponding alcohols 3a-g and 4a-h upon hydrolysis in the presence of one drop of concentrated hydrochloric acid at room temperature. 2-(Hydroxymethyl)alk-2-enenitriles 3a-g and ethyl 2-(hydroxymethyl)alk-2-enoates 4a-h prepared are summarized in Table 1.The E -and Z -structure is determined from spectroscopic data 4, 5, 10, 14 of the functional allylic alcohols 3 and 4 and by comparison with data of various authentic samples. 15From Table 1, it is clear that the stereochemistry of the formylation reaction is dependent on the nature of electron-withdrawing group. With EWG = CN, the stereoselectivity of the new allylic alcohols 3a-g seems to depend both on steric and electronic effects and gives E -functional olefins for an electron-withdrawing group (R = p -CF 3 C 6 H 4 ). In contrast, the transformation of secondary alcohols 2 into the corresponding primary alcohols 4a-h is highly stereoselective, independent of the nature of the R group and lea...

An Expeditious Synthesis of [1,2]Isoxazolidin-5-ones and [1,2]Oxazin-6-ones from Functional Allyl Bromide Derivatives

“…Most of the reagents and solvents were obtained from commercial sources (Aldrich, Merck, Fluka) and used as received. Except for the commercially available dimethyl itaconate, allyl bromides 1 and 2 were prepared as described in references [ 16 ] and [ 8 ], respectively.…”

“…Acrylic compounds have become highly attractive and building blocks for the synthesis of several biologically active molecules such as α-methylene-γ-butyrolactones [ 1 , 2 , 3 , 4 , 5 ] and γ-butyrolactams [ 6 , 7 , 8 , 9 ]. Several studies have proposed methods for the preparation of compounds bearing a α-bromomethyl moiety [ 10 , 11 , 12 , 13 , 14 ] commonly called Baylis-Hillman bromides [ 15 , 16 , 17 , 18 , 19 ]. In an ongoing project aimed at further illustrating the potential of readily prepared α-bromomethylated esters analogs 2 [ 9 , 20 ], we have shown the importance of functional allylic bromide 2 as an electrophilic reagent for access to pyrrolidin-2-ones [ 9 ], α-alkyl-β-carbomethoxy-γ-butyrolactams [ 21 , 22 ], ( E , Z )-α-alkylidene-γ-butyro-lactones [ 23 ] and 4-methoxycarbonyl-1- N -alkyl-∆ 2 -pyrrolidin-2-ones.…”

The Baylis-Hillman Reaction: One-Pot Stereoselective Synthesis of Methyl (2E)-3-Aryl-2-hydroxymethylprop-2-enoates

“…[15][16][17][18][19][20][21][22] However, there are only a few methods available in the literature for synthesis of these important molecules. [18][19][20][21][22] It is interesting to note that (m)ethyl 3-hydroxy-2-methylenealkanoates, the Baylis-Hillman adducts obtained from (m)ethyl acrylate, have been a major source for obtaining these (2E)-2-hydroxymethylalk-2-enoic acid derivatives. Thus, (m)ethyl 3-hydroxy-2-methylenealkanoates have been transformed into the desired (m)ethyl (2E)-2-hydroxymethylalk-2-enoates in three different elegant ways.…”

Applications of the Baylis-Hillman Adducts in Organic Synthesis: A Facile Synthesis of [E]-α-Cyanocinnamyl Alcohols and [E]-α-Cyanocinnamic Aldehydes

“…[1][2][3][4][5][6][7][8] The Baylis-Hillman reaction is a novel carbon-carbon bond forming reaction providing a useful class of multifunctional molecules which have been successfully employed in several different stereoselective processess. [9][10][11][12][13][14][15][16][17][18][19][20] In continuation of our interest in the Baylis-Hillman reaction, [12][13][14][15][16][17] we herein report an aqueous sulfuric acid (20%) mediated isomerization of the BaylisHillman adducts, i.e.…”