Functionalized Organolithium Compounds Through an Arene-Catalyzed Lithiation

Departamento de Química Orgánica, Universidad de Alicante. E-03080 Alicante, Spain. Tel. +96 590-3548, Fax +96 590-3549, E-mail yus@ua.es

Received: 14 July 1997 / Uploaded: 21 July 1997 / Updated 18 September 1997

With one biographical summary

Abstract: Naphthalene- or DTBB-catalyzed lithiation of chloroimines 1, deprotonated chlorobenzyl alcohols, mercaptanes or amines 4, and 3-phenylthiopropylamine 7 in THF at -78deg.C leads to the formation of the corresponding intermediates 2, 5 and 8, which by reaction with carbonyl compounds as electrophiles afford the expected bifunctionalized compounds 3, 6 and 9, respectively.

Keywords: Fuctionalized organolithiums, arene-catalyzed lithiation

Introduction

Functionalized organolithium compounds [1] are versatile intermediates in synthetic organic chemistry due to their ability to transfer their own functionality to electrophilic reagents, so making possible to prepare polyfunctionalized molecules in only one reaction step. In this communication we report our last findings in this field.

Results and Discussion

Chloroimine 1 was lithiated under naphthalene catalysis (4 mol%) [2] in THF at -78[integral]C leading to the formation of the acyllithium-type intermediate [3] 2, which by reaction with different electrophiles [PrⁱCHO, Bu^tCHO, PhCHO, Et₂CO, (CH₂)₅CO at the same temperature, followed by final hydrolysis with water, afforded the corresponding functionalized imines 3 (Scheme 1).

The successive reaction of chlorinated benzylic derivatives 4 with n-butyllithium and lithium in the presence of a catalytic amount of 4,4'-di-tert-butylbiphenyl (DTBB, 4 mol %) in THF at -78deg.C led to a solution of the corresponding dianion 5, which by treatment with different electrophiles [Bu^tCHO, PhCHO, (CH₂)₅CO yielded, after hydrolysis with water at the same temperature, the expected products 6 (Scheme 2).

Deprotonation of amine 7 with n-butyllithium in THF at -78[integral]C followed by lithiation in the presence of a catalytic amount (2.5 mmol%) of DTBB led to the dianionic intermediate 8, which reacted with carbonyl compounds [Bu^tCHO, PhCHO, Me₂CO, (CH₂)₅CO at the same temperature giving, after hydrolysis with water, the expected aminoalcohols 9 (Scheme 3).

To a solution of amine 7 (0.21g, 2mmol) in THF (2ml) was added a solution of n-butyllithium in hexane (1.25ml, 2mmol) at -78deg.C for 10 min. The resulting mixture was transferred via cannula to a suspension of lithium powder (0.1g, 14mmol) and DTBB (0.03g, 0.1mmol) in THF (5ml) at -78deg.C, being it then stirred for 1 hr at the same temperature. Then, benzaldehyde (0.2ml, 2mmol) was added and the mixture was stirred overnigth, allowing the temperature to rise to 20deg.C. The resulting mixture was then hydrolyzed with water (5ml), followed by addition of HCl 3M (50ml) and extracted with ethyl acetate (3x10ml). To the acid aqueous layer was added Na₂CO₃ until basic pH and then, the mixture was extracted with ethyl acetate (3x10ml), this organic layer was dried over anhydrous sodium sulfate and evaporated (15Torr) to give the pure title compound (0.29g, 70%).

IR (film): 3372 (OH, NH), 3084, 3061, 1657 (HC=C).

¹H-NMR (CDCl₃): 1.11 (d, 6H), 1.6 (m, 4H), 2.6 (m, 1H), 2.85 (m, 2H), 3.75 (br s, 2H), 4.65 (dd, 1H), 7.30 (m, 5H).

¹³C-NMR (CDCl₃): 22.35, 22.55, 27.45, 39.6, 46.9, 48.65, 73.45, 125.7, 126.6, 128.05, 145.75.

MS (EI): 207 (M⁺, 7%), 72 (100).

References and Notes

1. For reviews, see: a) N.jera, C.; Yus, M. Functionalized organolithium compounds in synthetic organic chemistry. Trends Org. Chem. 1991, 2, 155-181. b) N.jera, C.; Yus, M. Recent developments in the chemistry of functionalized organolithium compounds. Recent Res. Devel. Org. Chem. 1997, 1, 67-96.

2. For a review, see: Yus, M. Arene-catalyzed lithiation reactions. Chem. Soc. Rev. 1996, 155-161.

3. For a review, see: N.jera, C.; Yus, M. Acyl main group metal and metalloid derivatives in organic synthesis. A review. Org. Prep. Proced. Int. 1995, 27, 383-456.

4. Almena, J.; Foubelo, F.; Yus, M. Reductive opening of phenyl substituted thiacycloalkanes: New way for sulphur-containing organolithium compounds. Tetrahedron 1997, 53, 5563-5572.

Miguel Yus

Miguel Yus was born in Zaragoza in 1947, and received BSc (1969), MSc (1971) and PhD (1973) degrees from the University of Zaragoza. After spending two years as a postdoctoral fellow at the Max Planck Institut fuer Kohlenforschung in Mulheim a.d. Ruhr he retourned to Spain to the University of Oviedo where he became assistant professor in 1977, being promoted to full professor in 1987 at the same university. In 1988 he moved to a chair in organic chemistry at the University of Alicante where he is currently the head of the Organic Chemistry Department. Professor Yus has been visiting professor at different institutions such as ETH-Zurich and the universities of Oxford, Harvard, Uppsala, Marseille and Tucson. He is a menber or fellow of the chemical societies of Argentina, UK, Germany, Japan, Spain, Switzerland and USA. He is coauthor of about 200 papers mainly in the field of development of new methodologies involving organometallic intermediates. His current research interest is focused on the preparation of very reactive functionalized organolithium compounds and their use in synthetic organic chemistry.

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