HETEROCYCLES

■ Contents

■ Natural Product Inspired Enantioselective Synthesis of Hexahydro-aza-pentalenones

Pierre-Yves Dakas, Herbert Waldmann, and Kamal Kumar*

*Chemical Biology, Max Planck Institute of Molecular Physiology, Otto-Hahn Str. 11 44227, Germany

Abstract

An asymmetric synthesis of structurally complex hexahydro-aza-pentalenones embodying four consecutive stereogenic centers including two quaternary centers, one of which is an all-carbon-quaternary center, was developed with an enantioselective [3+2] cycloaddition reaction of azomethine ylides and substituted cyclopentenones.

■ Unexpected Highly Chemoselective Nucleophilic Substitution Reaction of 4-Dimethylamino-2-methoxy-3-trifluoroacetylquinoline with Various Nucleophiles

Etsuji Okada,* Mizuki Hatakenaka, Yoshinori Takezawa, and Keisuke Iwakuni

*Department of Chemical Science and Engineering, Graduate School of Engineering, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan

Abstract

Aromatic nucleophilic substitution reaction of 4-dimethyl-amino-2-methoxy-3-trifluoroacetylquinoline with various nucleophiles (NuH) such as amines, thiols, and alcohols proceeded chemoselectively to give the corresponding Me2N-Nu exchanged products, 2-methoxy-3-trifluoroacetyl-4-quinolylamines, sulfides, and ethers without any formation of MeO-Nu exchanged products in spite of the common knowledge that alkoxy group is the better leaving group than amino group.

■ Palladium-Catalyzed Cross-Coupling Reactions of Brominated Porphyrins with Functionalized Organomagnesium Reagents: Direct Preparation of Functional-Group-Bearing Free Base Porphyrins

Noriaki Sugita, Ikumi Tsuchiya, and Toshikatsu Takanami*

*Pharmaceutical Sciences, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan

Abstract

The direct preparation of free-base porphyrins possessing reactive functional groups such as esters, halides, amide, nitriles, and acetals is described. This method relies on a simple one-pot procedure that involves sequential palladium-catalyzed cross-coupling of brominated free-base porphyrins with functionalized aryl and alkenylmagnesium reagents, which are readily prepared by iodine–magnesium exchange of the corresponding organic iodides with the turbo Grignard reagent i-PrMgCl·LiCl, followed by demetallation of the resulting magnesium porphyrins under very mild conditions involving either a 1.2 M aqueous methanol solution of HCl or a 0.1 M methanol solution of citric acid at ambient temperature.

■ Pd(II)-Catalyzed Ligand-Controlled Synthesis of 2,3-Dihydroisoxazole-4-carboxylates and Bis(2,3-dihydroisoxazol-4-yl)methanones

Tomohiro Ariyama, Taichi Kusakabe,* Keita Sato, Mifuyu Funatogawa, Dong Lee, Keisuke Takahashi, and Keisuke Kato*

*Faculty of Pharmaceutical Sciences, Toho University, 2-2-1, Miyama, Funabashi, Chiba 274-8510, Japan

Abstract

Pd(II)-catalyzed ligand-controlled switching between cyclization–carbonylation and cyclization–carbonylation–cyclization-coupling (CCC-coupling) reactions of propargylic N-hydroxylamines was investigated. The use of a [Pd(tfa)2(box)] catalyst in MeOH afforded symmetric ketones bearing two 2,3-dihydroisoxazoles in good yields; replacing the catalyst and solvent with Pd(tfa)2 and MeOH/DMSO led to the formation of methyl 2,3-dihydroisoxazole -4-carboxylates in good yields.

■ One-Pot Synthesis of Densely Functionalized Thiazoles and syn-3-Thioacrylates

Yi-Jing Dang, Mu-Yan Sun, Xiao-Yan Meng, Fu-Jie Zhao, Wen-Juan Hao, Bo Jiang, Shu-Jiang Tu, and Guigen Li*

*Department of Chemistry & Biochemistry, Texas Tech University, Lubbock, TX 79409-1061, U.S.A.

Abstract

A sequential one-pot, two-step reaction has been established for efficient synthesis of densely functionalized thiazoles and syn-3-thioacrylates. Treatment of cyanoacetamide with isothiocyanates gave rise to 2-cyano-3-mercaptoacrylamides, trapped by but-2-ynedioates through [3+2] cyclization to access functionalized thiazoles. Using propiolates to replace but-2-ynedioates, the reaction resulted in highly substituted syn-3-thioacrylates. The present green synthesis shows several advantages including operational simplicity and fast reaction rates, which makes it a useful and attractive process of library generation for drug discovery.

■ Mechanistic Aspects of the Mild-Condition Phthalimidine Synthesis with Use of 1,2,3-1H-Benzotriazole and 2-Mercaptoethanol as Dual Synthetic Auxiliaries

Ichiro Takahashi,* Teruki Kawakami, Hidehiko Kitajima, Kimio Isa, and Shinzo Hosoi

*Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Fukui University, Bunkyo, Fukui 910-8507, Japan

Abstract

The mild-condition phthalimidine synthesis based on Mannich-type　condensation reaction between o-phthalaldehyde and p-toluidine was first achieved with use of 1,2,3-1H-benzotriazole (Bt-H) and 2-mercaptoethanol (MET) as dual synthetic auxiliaries. Mechanistic aspects based on reaction condition optimization exercises are described.

■ Application of the Mild-Condition Phthalimidine Synthesis with Use of 1,2,3-1H-Benzotriazole and 2-Mercaptoethanol as Dual Synthetic Auxiliaries. Effective Synthesis of Phthalimidines Possessing a Variety of Substituents at 2-Position

Ichiro Takahashi,* Teruki Kawakami, Etsushi Hirano, Mako Kimino, Shigeki Kamimura, Takayuki Miwa, Takanori Tamura, Ryo Tazaki, Hidehiko Kitajima, Minoru Hatanaka, Kimio Isa, and Shinzo Hosoi

*Department of Applied Chemistry and Biotechnology, Faculty of Engineering, Fukui University, Bunkyo, Fukui 910-8507, Japan

Abstract

The mild-condition phthalimidine synthesis based on Mannich type 1:1 condensation reaction between o-phthalaldehyde with a variety of primary amines in the presence of excess 2-mercaptoethanol and 1,2,3-1H-benzotriazole as “dual synthetic auxiliaries” in MeCN for 13 h at room temperature afford 2-substituted phthalimidines (2,3-dihydroisoindol-1-one) in fair to good isolated yields.

■ Photochemical Behavior of 2’-Hydroxychalcone Derivatives Having Pyridyl and Quinolyl Groups

Fumiya Aizawa, Yukino Shinozaki, Yuka Ishida, and Tatsuo Arai*

*Department of Chemistry, Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Ten-nodai, Tsukuba-shi, Ibaraki 305-8571, Japan

Abstract

2'-Hydroxy chalcone derivatives having heteroaromatic rings have been synthesized and their photochemical and photophysical properties have been examined in terms of tautomer produced by intramolecular hydrogen atom transfer reaction.

■ A D3h-Symmetric Macrocycle Alternatingly Composed of Pyridine and Benzyl Alcohol Units Linked with Acetylene Bonds

Hajime Abe,* Ryuta Yumoto, and Masahiko Inouye

*Department of Chemical Biology, Graduate School of Pharmaceutical Sciences, University of Toyama, Sugitani 2630, Toyama, 930-0194, Japan

Abstract

A macrocyclic compound alternatingly composed of three pyridine and three benzyl alcohol units linked with acetylene bonds was developed as a new type of D3h-symmetric hexagonal shape-persistent macrocycles with a host function. The macrocycle was prepared via several steps of Sonogashira reaction and proved to interact with halide anions, especially chloride on the basis of 1H NMR studies.

■ Regioselective Synthesis of 2,4-Differentially Arylated Pyrroles and Its Application to The Synthesis of Lamellarins

Tsutomu Fukuda, Mizuho Anzai, and Masatomo Iwao*

*Division of Chemistry and Materials Science, Graduate School of Engineering, Nagasaki University, 1-14, Bunkyo-machi, Nagasaki 852-8521, Japan

Abstract

An efficient method for the synthesis of 2,4-differentially arylated pyrroles has been developed via stepwise palladium-catalyzed Suzuki–Miyaura coupling of N-benzenesulfonyl-4-bromo-2-iodopyrrole with different arylboronic acids. This method has been applied to the new synthesis of the marine natural products lamellarins.

■ Synthesis of 5-Aminobenzoimidazo[1,2-a]Quinoline Derivatives Through One-Pot Two-Step Cascade Reaction

Jun-ya Kato, Yutaro Ito, Ryosuke Ijuin, Hiroshi Aoyama, and Tsutomu Yokomatsu*

*School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan

Abstract

An efficient method for the synthesis of 5-aminobenzimidazo[1,2-a]quinolines with high diversity has been developed through a cascade reaction involving sequential aromatic nucleophilic substitution and the Dieckmann–Thorpe cyclization. This method is applicable to the synthesis of a wide range of 5-aminobenzimidazo[1,2-a]quinoline derivatives from readily available 2-fluoroarylnitriles and benzimidazole substrates. Moderate light emission was observed for some 5-aminobenzimidazo[1,2-a]quinolines.

■ Chemistry of Polyhalogenated Nitrobutadienes, 15: Synthesis of Novel 4-Nitro-3-amino-1H-pyrazole-5-carbaldehydes and Pyrazolo[3,4-f]indazole-4,8-diones

Viktor A. Zapol'skii, Jan C. Namyslo, Mimoza Gjikaj, and Dieter E. Kaufmann*

*Institute of Organic Chemistry, Clausthal University of Technology, Leibnizstrasse 6, D-38678 Clausthal-Zellerfeld, Germany

Abstract

Condensation of 1-amino-1-(1H-benzo[d][1,2,3]triazol-1-yl)-3,4,4-trichloro-2-nitrobuta-1,3-dienes 3a-e with methylhydrazine leads to a series of uniquely persubstituted 4‑nitropyrazoles 4a-e bearing a dichloromethyl substituent in 5-position. Subsequent hydrolysis of this group applying aqueous sulfuric acid then gives interesting push-pull–substituted pyrazole-5-carbaldehydes 5a-e. Upon hydrolysis of 4a-e at harsher reaction conditions different pyrazolo[3,4-f]indazole-4,8-diones were also formed. A mechanism of the homo-condensation of carbaldehydes 5a,d to the indazole derivatives 8-13 is proposed, and as an example the structure of 3,7-bis(dimethylamino)-1,6-dimethylpyrazolo[3,4-f]indazole-4,8(1H,6H)-dione (9) has been confirmed by X-ray analysis.

■ A New Tactic for Tocopherol Synthesis Using Intramolecular Benzyne Trapping by an Alcohol

David W. Knight* and Qing Xu

*School of Chemistry, Cardiff University, Main Building, Park Place, Cardiff, CF10 3AT, U.K.

Abstract

A formal total synthesis of (S)-α-tocopherol, the major component of natural Vitamin E has been achieved using intramolecular benzyne trapping as a key step to form the chroman ring. The synthesis also features an efficient new method for benzotriazole N-amination using an oxaziridine; chiral, non-racemic intermediates are generated using asymmetric dihydroxylation.

■ Synthesis of 2,3,9,10-Tetraoxygenated Benzo[c]phenanthridine Derivatives via Palladium-Mediated Aryl-Aryl Coupling Reaction

Hitoshi Abe,* Naoko Kobayashi, Yutaka Kadoshima, Yasuo Takeuchi, Takashi Harayama, and Yoshikazu Horino

*Graduate School of Science and Engineering, University of Toyama, 3190 Gofuku, Toyama 930-8555, Japan

Abstract

Two 2,3,9,10-tetraoxygenated benzo[c]phenanthridine alkaloids, 1 and 2, originally reported as zanthoxyline and broussonpapyrine, respectively, were synthesized using the Pd-mediated intramolecular aryl-aryl coupling reaction as the key step.

■ Multi-Substituted Dibenzophosphole Oxide Synthesis by the Catalytic [2+2+2] Cycloaddition of Phosphorylbenzene-Tethered Diynes with Various Alkynes

Yu-ki Tahara, Tatsuki Sato, Riku Matsubara, Kyalo Stephen Kanyiva, and Takanori Shibata*

*Chemistry and Biochemistry, Advanced Research Center of Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku-ku, Tokyo 169-8555, Japan

Abstract

Rhodium-catalyzed intermolecular [2+2+2] cycloaddition of phosphorylbenzene-tethered 1,6-diynes with alkynes gave dibenzophosphole oxide derivatives. Various monoalkynes were applicable in this reaction as coupling partners, and dibenzophosphole oxide derivatives substituted with aromatic ring(s) including dibenzothiophene(s) were obtained. The asymmetric desymmetrization of a prochiral phosphorylbenzene-tethered triyne gave a chiral dibenzophosphole oxide derivative with high ee.

■ Facile Synthesis of 5- to 7-Membered Benzolactam Compounds via Strongly Facilitated Electrophilic Aromtic Substitution Reaction†

Hiroaki Kurouchi, Yuko Otani, and Tomohiko Ohwada*

*Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan

Abstract

We employed our system to activate aromatic ring-tethered carbamate compounds with trifluoromethanesulfonic acid to obtain benzolactams with 5- to 7-membered rings, and examined the substrate scope and limitations of this activation method. In 5-membered ring formation, a halogen group on the aromatic ring did not greatly affect the reaction yield, but other electron-donating groups inhibited the cyclization reaction, and various side-reactions occurred. In 7-membered ring formation, eletron-donating groups on aromatic ring promoted the cyclization reaction, but cyclization of electron-deficient aromatic rings did not proceed well. The 6-membered ring formation reaction showed the greatest substrate generality.

■ Guaiazulenopentathiepin and Related Compounds: Reactions of Guaiazulene with Reactive Sulfuration Reagents

Ohki Sato,* Takahito Saito, Mana Iwase, and Atsushi Sakai

*Department of Chemistry, Graduate School of Science and Engineering, Saitama University, 255 Shimo-okubo, Sakura-ku, Saitama 338-8570 , Japan

Abstract

Guaiazulene reacted with reactive sulfuration reagents to give guaiazulenopentathiepin together with a 1,2-dithiin compound and a mixture of bis(guaiazulyl)sulfides. The yield of the pentathiepin was improved by the reaction with the reagent prepared from sulfur chloride and imidazole in a molar ratio of one to two. Reduction of the pentathiepin and the successive reaction with N,N’-(thio)carbonyldiimidazoles afforded 2-(thi)oxo-1,3-dithioles.

■ Alkoxide-Directed Hydride Addition to α,β-Unsaturated Sultones

Kamal M. Dawood, Andrea Bramborg, Ahmed F. Darweesh, Katrin Spinde, Victor Rogachev, Anne Jäger, and Peter Metz*

*Organic Chemistry I, Department of Chemistry, Technische Universität Dresden, Bergstrasse 66, 01069 Dresden, Germany

Abstract

Seven- and eight-membered β,γ-unsaturated sultones were readily prepared by ring closing metathesis. Epoxidation of these sultones and of an analogous six-membered sultone furnished the corresponding β,γ-epoxy sultones efficiently. Treatment of these epoxides with a suitable base gave α,β-unsaturated γ-hydroxy sultones in high yields. Reduction of both the α,β-unsaturated γ-hydroxy sultones and the epoxy sultones by Red-Al is likely to proceed in a hydroxyl-directed fashion via a mixed aluminate as the reactive intermediate.

■ Synthesis of 2,3-Dihydro-4H-furo[3,2-c]chromen-4-one Derivatives by Oxidative Radical Cyclization of 4-Hydroxy-2H-chromen-2-one with Alkenes

Masahiro Yoshida,* Asuka Kobayashi, and Kosuke Namba

*Graduate School of Pharmaceutical Sciences, The University of Tokushima, Sho-machi, Tokushima 770-8505, Japan

Abstract

Oxidative radical cyclization of 4-hydroxy-2H-chromen-2-one with aryl-substituted alkenes has been developed. 2,3-Dihydro-4H-furo[3,2-c]chromen- 4-ones having substituents at the 2-position were produced when the reactions were carried out in the presence of CAN as an oxidant. Various substituted products were regioselectively synthesized via a successive cyclization.

■ Continuous Flow Microfluidic Chemistry: Synthesis of [18F]-3-Fluoro-2-(4-((2-nitro-1H-Imidazol-1-yl)methyl)-1H-1,2,3-triazol-1-yl)Propan-1-ol, [18F]F-HX4, A Potent Hypoxia Agent

Murthy Akula, David Blevins, and George W. Kabalka*

*Chemistry Department, University of Tennessee, Knoxville, Tennessee, 37996-1600, U.S.A.

Abstract

The microfluidic synthesis of the promising hypoxia imaging agent [18F]-3-fluoro-2-(4-((2-nitro-1H-imidazol-1-yl)methyl)-1H-1,2,3-triazol-1-yl)propan-1-ol, [18F]F-HX4, was successfully accomplished using a commercial microfluidic system. A decay corrected radiochemical yield of 48±4% (n=4) and radiochemical purity of ≥ 98% was obtained. The total reaction time including the HPLC purification was 40 min.

■ Synthesis of Hantzsch 1,4-Dihydropyridines in a Continuous Flow Microreactor

Peiyuan Gao, Xuan Sun, Ming Lei,* and Hong Zhang

*Department of Chemistry, Zhejiang University , 38 Zheda Road, Hangzhou, 310027, China

Abstract

A simple and efficient synthesis of Hantzsch 1,4-dihydropyridines from the condensation of benzaldehydes with alkyl acetoacetates/benzoylacetate and aqueous ammonia in the absence of catalyst has been developed by using a continuous flow microreactor. Under optimized condition, various 1,4-dihydropyridines were obtained in 80-93% yield with high atom efficiency. Compared with using batch system, the present smooth procedure greatly accelerated the reaction due to the excellent mixing and mass transfer of reactant in micro flow system.

■ Unsymmetrical Phthalocyanines With One TTF unit and Octylthio or Octylsulfonyl Groups: Their Optical and Electrochemical Properties

Takeshi Kimura,* Jasmin Kang, and Shidsuko Nakajo

*Center for Instrumental Analysis, Iwate University, 4-3-5 Ueda, Morioka, Iwate 020-8551, Japan

Abstract

Unsymmetrical phthalocyanines fused with a TTF unit and six octylthio or six octylsulfonyl groups were prepared by the reaction of a mixture of phthalonitrile fused with a TTF unit and 4,5-di(octylthio)- or 4,5-di(octyl- sulfonyl)phthalonitrile. The optical and electrochemical properties of the products were determined by UV-vis absorption spectra, cyclic voltammetry, and ESR spectra.

■ Ring-contractive and -Closing Skeletal Rearrangement of 1,1’-Binaphthalene-2,2’-Diamines (Binams) Induced by an Iodine-Containing Oxidant: Synthesis of Spiro[Benzo[e]Indole-1,1'-inden]-2-amines and Application to an Aiee-active BF2 Complex

Masato Okazaki, Kosuke Takahashi, Youhei Takeda, and Satoshi Minakata*

*Department of Applied Chemistry, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan

Abstract

An iodine-containing oxidant-induced ring-contractive and -closing skeletal rearrangement of 1,1’-binaphthalene-2,2’-diamines (BINAMs) to afford spiro[benzo[e]indole-1,1'-inden]-2-amines has been discovered. Furthermore, a spiro product was successfully transformed into a novel luminescent spirocyclic BF2 complex.

■ Construction of cis-Fused Hydrindane Skeleton with a Lactone Tether Utilizing Intramolecular Diels-Alder Reaction

Shuqiang Yin, Kenji Takai, Daishiro Minato, Kenji Sugimoto, Hideki Ohtsu, Kiyoshi Tsuge, and Yuji Matsuya*

*Graduate School of Medicine and Pharmaceutical Sciences for Research, University of Toyama, Sugitani 2630, Toyama, 930-0194, Japan

Abstract

Synthetically important, cis-fused hydrindane skeleton having quaternary angular stereogenic centers was selectively furnished by intramolecular Diels-Alder reaction of ester-tethered precursor via endo transition state. The reaction was applicable for a construction of the steroidal BCD ring system with cis-hydrindane framework.

■ Synthetic Studies toward Concavine: Synthesis of The BCD Ring System

Yosuke Komori, Akitoshi Kozen, and Masahiro Toyota*

*Team TOYOTA, Graduate School of Science, Osaka Prefecture University, 1-1 Gakuencho, Sakai, Osaka 593-8531, Japan

Abstract

The BCD ring system of concavine is realized stereoselectively using a palladium-catalyzed cycloalkenylation to synthesize the CD ring and an intramolecular aza-Michael reaction to append the third ring.

■ Practical Synthesis of Tricyclic Lactam Model of Antitumor Renieramycin-Saframycin Natural Products

Masashi Yokoya, Akiya Fujino, Ayako Yaguchi, Miku Yamazaki, and Naoki Saito*

*Department of Medicinal Chemistry, Pharmaceutical Chemistry, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan

Abstract

A practical synthesis of the tricyclic lactam model compound of antitumor renieramycin-saframycin natural product starting from 2-hydroxy-4,5-dimethoxy-3-methylbenzaldehyde in eleven steps was described. A tosyl group was used for protection of a phenol during this transformation. The overall yield of the target compound was 23%.

■ Yb(OTf)3-Catalyzed Synthesis of 2-Substituted 4(3H)-Quinazolinones via Cleavage of a Carbon-Carbon Bond

Tsutomu Yoshimura, Shun-ichi Naito, Di Yuanjun, Aoi Son, Yu Kimura, Akio Toshimitsu, and Teruyuki Kondo*

*Advanced Biomedical Engineering Research Unit, Kyoto University, Katsura, Nishikyo-ku, Kyoto 615-8510, Japan

Abstract

A general, selective, and practical one-pot synthesis of 2-substituted 4(3H)-quinazolinones by the Yb(OTf)3-catalyzed cyclo-condensation of 2-aminobenzamides with acyclic or cyclic 1,3-diketones (β-diketones) under mild and neutral reaction conditions has been developed, which involves the highly selective cleavage of a C-C bond in 1,3-diketones by Yb(OTf)3 catalyst. For example, the Yb(OTf)3-catalyzed cyclo-condensation of 2-aminobenzamide (1a) with 1-phenylbutane-1,3-dione (2c) gave 2-methyl-4(3H)-quinazolinone (3a) in 90% yield, together with acetophenone in 65% yield. Ring-opening cyclo-condensation of 2-aminobenzamides (1a) with cyclic 1,3-diketones (2i and 2k-m), except for cyclopentane-1,3-dione (2j), gave 2-substitued 4(3H)-quinazolinones (3i and 3k-m) with one carbonyl group.

■ Synthesis of Noroxymorphone by N-Demethylation/ Intramolecular Acylation of Oxymorphone Catalyzed by Iron(II) Chloride

Mary Ann A. Endoma-Arias, Ales Machara, D. Phillip Cox, and Tomas Hudlicky*

*Department of Chemistry, Brock University, 1812 Sir Isaac Brock Way St. Catharines, Ontario, L2R 3K4, Canada

Abstract

Oxymorphone was converted to its 3,14-diacetate and subjected to Fe(II)/t-BuOOH-catalyzed N-demethylation that occurred with concomitant acyl migration from the C-14 hydroxyl to the N-17 nitrogen. The resulting diacetyl compound was hydrolyzed in dilute sulfuric acid to noroxymorphone in good yield.

■ Magnesium-Alkoxide Directed Photoaddition of Tetrahydrofurans to γ,γ-Disubstituted Allylic Alcohols

Yasutaka Watanabe, Takahiro Sakai, Hajime Maeda, Masahito Segi, Takahiro Soeta, and Yutaka Ukaji*

*Division of Material Sciences, Graduate School of Natural Science and Technology, Kanazawa University, Kakuma, Kanazawa, Ishikawa 920-1192, Japan

Abstract

Magnesium-alkoxide directed photoaddition of tetrahydrofurans to γ,γ-disubstituted allylic alcohols was achieved. When the allylic alcohols were treated with Grignard reagent in THF under light, the corresponding γ-(2-tetrahydrofuryl) substituted alcohols were regioselectively obtained in up to 82% yield. The conversion of the hydroxyl group to the corresponding bromomagnesium alkoxide was crucial.