Cohalogenation of alkenes with DMF: an easy vicinal haloformyloxylation reaction

Abstracts

The reaction of alkenes with trichloroisocyanuric acid or N-bromosaccharin or I2 / Fe2(SO4)3 in the presence of DMF followed by aqueous work-up led to the corresponding beta-haloformate in high regio- and stereoselectivity.

addition reaction; alkenes; halogenation; esters; beta-haloformyloxylation

A reação de alquenos com o ácido tricloro-isocianúrico ou N-bromo-sacarina ou I2 / Fe2(SO4)3 na presença de DMF, seguida de tratamento em meio aquoso, leva à formação dos respectivos beta-halo-formatos com alta regio- e estereosseletividade.

SHORT REPORT

Cohalogenation of alkenes with DMF: an easy vicinal haloformyloxylation reaction

Adriana V. A. de Souza; Gabriela F. Mendonça; Rafael B. Bernini; Marcio C. S. de Mattos^*

Instituto de Química, Universidade Federal do Rio de Janeiro, CP 68545, 21945-970 Rio de Janeiro-RJ, Brazil

ABSTRACT

The reaction of alkenes with trichloroisocyanuric acid or N-bromosaccharin or I₂ / Fe₂(SO₄)₃ in the presence of DMF followed by aqueous work-up led to the corresponding b-haloformate in high regio- and stereoselectivity.

Keywords: addition reaction, alkenes, halogenation, esters, b-haloformyloxylation

RESUMO

A reação de alquenos com o ácido tricloro-isocianúrico ou N-bromo-sacarina ou I₂ / Fe₂(SO₄)₃ na presença de DMF, seguida de tratamento em meio aquoso, leva à formação dos respectivos b-halo-formatos com alta regio- e estereosseletividade.

Introduction

The vicinal functionalization of alkenes is an important process in synthetic organic chemistry and several methodologies are described in the literature.¹ Among them, the so-called "cohalogenation" (halogenation of an alkene in the presence of a nucleophilic solvent) is an attractive tool to produce vicinal halo-functionalized compounds regioselectively, which are useful intermediates for diverse organic transformations.² A proposed mechanism goes through formation of a halonium ion intermediate followed by ring opening promoted by the nucleophilic solvent.² Thus, DMF can act as a nucleophile in the cohalogenation reaction³ and so the halonium ion intermediate can be attacked by the oxygen of DMF to produce an iminium ion, which upon hydrolysis gives a vicinal haloformate⁴ (Scheme 1). In spite of its synthetic potential, this reaction has received little attention, being the vicinal haloformyloxylation of alkenes achieved using DMF / HCl and an oxidizing agent⁴ or DMF / N-halosuccinimides.^5-7

Alternative sources of electrophilic halogen species (halenium ions) are of great interest from both mechanistic and green synthesis points of view.⁸ Trichloroisocyanuric acid (TCCA, Figure 1) is a stable and inexpensive solid frequently found in a large number of commercial products for swimming pool disinfection.^9,10N-bromosaccharin (NBSac, Figure 1) is a stable solid, easily prepared from saccharin¹¹ and much more reative than its analogue NBS.¹² On the other hand, I₂ / Fe(III) salts are mild reagents for iodination of alkenes¹³ that avoid the utilization of oxidizing reagents and heavy-metal salts.¹⁴

During our investigation on cohalogenation reactions,¹⁵ we had shown that TCCA, NBSac, and I₂ / Fe₂(SO₄)₃ are efficient sources of electrophilic chlorine,¹⁶ bromine,¹⁷ and iodine¹⁸ species, respectively, that react with alkenes in the presence of diverse oxygenated solvents to give vicinal halofunctionalyzed structures (halohydrins, b-haloethers, and b-haloacetates).

Herein we communicate our results on the cohalogenation of alkenes with TCCA, NBSac, and I₂ / Fe₂(SO₄)₃ in the presence of DMF to produce vicinal haloformates.

Results and Discussion

The reactions of representative alkenes (cyclohexene, styrene, a-methylstyrene, and 1-octene) with the sources of electrophilic halogens in DMF afforded, after work up, the b-haloformates in 42-82% isolated yields, as shown in Table 1. The reactions were carried out stirring together the alkene with TCCA or NBSac or I₂ / Fe₂(SO₄)₃ in DMF for 1.5 h at room temperature, followed by addition of water and the products were analyzed by HRGC and characterized by spectroscopic methods (Table 2).

The orientation in the reaction follows the Markovnikoff pattern, with the expected exception¹⁹ of the aliphatic monosubstituted 1-octene that afforded a regioisomeric mixture of b-haloformates in which the secondary formate predominated (2-5:1). The process is also stereoselective, with cyclohexene yielding exclusively the trans-isomer, as can be seen (Figure 2) by the high values of the coupling constants²⁰ for adjacent hydrogens of the haloformates derived from cyclohexane.

No diol, arising from Prèvost-Woodward reaction,²¹ was detected on the crude reaction mixture, but variable amounts of the corresponding halohydrins were observed, specifically in the cases of the iodoformate derived from a-methylstyrene (16% yield from a-methylstyrene) and the chloroformate derived from 1-octene (20% yield from 1-octene), that could explain the low yields of b-haloformates obtained in these cases. The formation of the halohydrins could be rationalized by hydrolysis of the haloformate or its precursors during the work up.⁶ Alternatively, its formation by addition of water to the halonium ion seems to be improbable because, although we have used DMF without further purification and in an open flask, no loss of stereoselectivity in the reactions of cyclohexene (arising from small amounts of water²²) was detected either.

Conclusions

In summary, we have developed a convenient route to vicinal haloformates from alkenes. The reaction conditions are mild, the work up process is very simple, the reagent employed are stable, cheap, and readily available and, furthermore, there is no need of special techniques and conditions.

Experimental

General

NBSac was prepared from saccharin, KBr and oxone^®, as early described.¹¹ Trichloroisocyanuric acid (commercial grade, 98%), and other chemicals and solvents were used as received. The ¹H and ¹³C NMR spectra were recorded on a Bruker AC-200 (200MHz and 50MHz, respectively) spectrometer in CDCl₃ solution with TMS as internal standard. High-resolution GC was performed on a HP-5890-II gas chromatograph with FID using a 30 m (length), 0.25mm (ID), and 25 µm (phase thickness) RTX-5 capillary column and H₂ (flow rate 50 cm s^-1) as carrier gas (split: 1:10). Mass spectra were obtained on a Hewlett-Packard HP 5896-A HRGC-MS using electron impact (70 eV).

Preparation of b-chloroformates

To a stirred solution of the alkene (5 mmol) in DMF (50 cm³), TCCA (2.5 mmol) was added at room temperature in small portions. After 1.5 h, water (10 cm³) was added and the solution was extracted with CH₂Cl₂ (20 cm³). The organic layer was washed with satd NaHSO₃, water and then dried (anhyd Na₂SO₄). After rotaevaporation of the solvent, the product was purified by radial chromatography on a Chromatotron^®. Spectral data of the products are shown in Table 2.

Preparation of b-bromoformates

Same as above, NBSac (7.5 mmol) used instead of TCCA.

Preparation of b-iodomoformates

Same as above, I₂ (7.5 mmol) and Fe₂(SO₄)₃ (6.0 mmol) used instead of TCCA.

Acknowledgments

A.V.A.S. and R.B.B. thank PIBIC-UFRJ; G.F.M. and M.C.S.M. thank CNPq.

References

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Received: July 10, 2007

Web Release Date: December 6, 2007

Publication Dates

• Publication in this collection
  12 Feb 2008
• Date of issue
  2007

History

• Accepted
  10 July 2007
• Received
  10 July 2007