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Proceeding Paper

Zn–Catalyzed Direct Synthesis of 3-Iodo-1,3-dienes from α-Allenols †

by
Mireia Toledano-Pinedo
1,*,
Beatriz Peñín
1,
Teresa Martínez del Campo
1 and
Pedro Almendros
2
1
Grupo de Lactamas y Heterociclos Bioactivos, Unidad Asociada al CSIC, Departamento de Química Orgánica, Facultad de Ciencias Químicas, Universidad Complutense de Madrid, 28040 Madrid, Spain
2
Instituto de Química Orgánica General, IQOG-CSIC, Juan de la Cierva 3, 28006 Madrid, Spain
*
Author to whom correspondence should be addressed.
†
Presented at the 24th International Electronic Conference on Synthetic Organic Chemistry, 15 November–15 December 2020; Available online: https://ecsoc-24.sciforum.net/.
Chem. Proc. 2021, 3(1), 113; https://0-doi-org.brum.beds.ac.uk/10.3390/ecsoc-24-08091
Published: 13 November 2020
(This article belongs to the Proceedings of The 24th International Electronic Conference on Synthetic Organic Chemistry)
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Abstract

:
We wish to report herein a new protocol that allows one to obtain 3-iodo-1,3-dienes through a sustainable process starting from α-allenols. In this new synthetic route, zinc (II) derivatives are used as metallic promoter, which are an inexpensive and environmentally friendly species.

1. Introduction

In recent years, the chemistry of allenes has attracted the attention of many chemists giving rise to numerous studies. The presence of a cumulated diene in the structure of the allene compound allows for the selective synthesis of different functionalized organic molecules [1,2,3].
Allenes are the starting point of a large number of synthetic routes, due to the possibility of having four substituents in its structure. Furthermore, both the electronic density and the reactivity of each carbon of the allenes can be modulated as a function of the substitution. Besides, the inherent axial chirality allows the stereoselective synthesis of optically active allenes and the transfer of chirality from the allenes to the final product.
On the other hand, iododienes are interesting species for organic chemistry because of their wide reactivity. These compounds are precursors in Diels–Alder reactions [4], palladium-catalyzed reactions [5] such as Stille [6], Negishi [7], and Sonogashira [8] and carbonylation cross-couplings [9,10], solvolysis [11,12], and metalation reactions [8].
In the literature there are several methods of synthesis of iododienes from allenes. Okamoto et al. described the oxidative addition of (η2-propene)Ti(O-i-Pr)2 to α-allenyl carbonates to form titanium complexes that by reacting with molecular iodine resulted in 2-iodo-1,3-dienes (Scheme 1a) [13]. Nishimaya et al. observed the formation of 2-iodo-1,3-butadiene by treatment of 1-trimethylsilyl-2,3-butadiene with I2 and tetra-n-butylammonium fluoride (TBAF) (Scheme 1b) [9].
Based on these precedents, the main aim of this project is the development of a new synthetic method that allows one to obtain 3-iodo-1,3-dienes directly from α-allenols through a sustainable process.
First, the allenylation reaction was carried out on the aldehydes 1 (Scheme 2). Experiments were performed according to previous conditions developed in our research group [14,15]. Barbier-type conditions [16] were used where aldehydes 1 reacted with differently substituted propargyl bromides, using indium and a THF/NH4Cl mixture (1:5) as a metal promoter and solvent, respectively. In this way, α-allenols 2 were prepared with total regioselectivity.
Once the starting materials were synthesized, allenol 2a was selected as model substrate. Initial experiments were performed though the reaction of 2a with ZnI2 and p-toluenesulfonic acid monohydrate in dichloromethane (Scheme 3), which provided the 3-iodo-1,3-diene 3a as the only reaction product.
This reactivity involving addition of the iodine atom and double bond rearrangement was surprising, because it was expected to obtain the corresponding dihydrofuran through the well-developed metal-catalyzed oxycyclization of α-allenols [17].
However, the yield was very low and the reaction conditions were optimized (see Table 1). The highest yield of the product was achieved by employing 1.2 equiv. of ZnI2 at room temperature in dichloromethane without the presence of p-toluenesulfonic acid (Table 1, entry 4).
The scope of the reaction was explored in different α-allenols giving rise to the corresponding 3-iodo-1,3-dienes 3a–h in reasonable yields (22–69%) and good (E)-diastereoselectivity (Scheme 4). It should be noted that in products 3a and 3b the reaction temperature had to be increased to 80 °C to consume the starting material.
A possible pathway for the generation of 3-iodo-1,3-dienes 3 from α-allenols 2 is outlined in Scheme 5. It is assumed that the initial step is the coordination of the zinc salt to the terminal double bond of the allene to give the corresponding complex 2-Zn. Subsequently, the loss of HI occurs followed by an addition of an iodine atom. Final elimination of the hydroxyl group of the former α-allenol assisted by Zn generated the iododiene.

2. Experimental Section

General methods: 1H NMR and 13C NMR spectra were recorded on a Bruker Avance-300 spectrometer. NMR spectra were recorded in C6D6, except otherwise stated. Chemical shifts are given in ppm relative to TMS (1H, 0.00 ppm), or C6D6 (1H, 7.16 ppm; 13C, 128.0 ppm). Low and high resolution mass spectra were taken on an AGILENT 6520 Accurate-Mass QTOF LC/MS spectrometer using the electrospray mode (ES) unless otherwise stated. IR spectra were recorded on a Bruker Tensor 27 spectrometer. All commercially available compounds were used without further purification.

2.1. General Procedure for the Preparation of α-Allenols 2a–h

These precursors were readily obtained as described in the literature [14,15].

2.2. General Procedure for the Preparation of 3-Iodo-1,3-dienes 3a–h

ZnI2 (1.2 mmol) was added to a well stirred solution of α-allenol (1 mmol) in CH2Cl2 (10 mL). After the disappearance of the starting material (TLC) the mixture was filtered through a short pad of celite, washed with CH2Cl2, and then concentrated under reduced pressure to give the product.
Chromatography of the residue eluting with hexanes/ethyl acetate mixtures gave analytically pure compounds 3. It should be noted that in products 3a and 3b the reaction temperature had to be increased to 80 °C to consume the starting material.
Chemproc 03 00113 i001
3-iodo-1,3-diene 3a. From 40 mg (0.23 mmol) of allenol 2a, and after chromatography of the residue using hexanes/ethyl acetate (60:1) as the eluent gave compound 3a (31 mg, 48%) as a yellow oil; 1H NMR (300 MHz, C6D6, 25 °C): δ = 6.95 (s, 1H), 6.88 (d, 2H, J = 6.0 Hz), 6.78 (d, 2H, J = 6.1 Hz), 5.87 (d, 1H, J = 3.2 Hz), 5.70 (d, 1H, J = 3.0 Hz), 1.94 (s, 3H), 1.70 (s, 3H); 13C NMR (75 MHz C6D6, 25 °C): δ = 137.0, 136.5, 136.3 (CH), 134.8, 129.6 (2CHAr), 129.2 (2CHAr), 126.3 (CH2), 114.6, 21.1 (CH3), 15.6 (CH3); IR (CHCl3, cm–1): υ = 3051, 2898, 553.
Chemproc 03 00113 i002
3-iodo-1,3-diene 3b. From 100 mg (0.53 mmol) of allenol 2b, and after chromatography of the residue using hexanes/ethyl acetate (60:1) as the eluent gave compound 3b (50 mg, 32%) as a yellow oil; 1H NMR (300 MHz, C6D6, 25 °C): δ = 7.08 (s, 1H), 7.04 (d, 2H, J = 8.4 Hz), 6.72 (d, 2H, J = 8.8 Hz), 6.04 (d, 1H, J = 1.5 Hz), 5.87 (d, 1H, J = 1.6 Hz), 3.28 (s, 3H), 1.87 (d, 3H, J = 1.1 Hz); 13C NMR (75 MHz, C6D6, 25 °C): δ = 159.3, 136.0 (CH), 135.6, 131.0 (2CHAr), 130.0, 128.5 (2CHAr), 126.0 (CH2), 114.9, 54.7 (CH3), 15.7 (CH3); IR (CHCl3, cm–1): υ = 3079, 2854, 554.
Chemproc 03 00113 i003
3-iodo-1,3-diene 3c. From 100 mg (0.46 mmol) of allenol 2c, and after chromatography of the residue using hexanes/ethyl acetate (13:1) as the eluent gave compound 3c (62 mg, 41%) as a yellow oil; 1H NMR (300 MHz, C6D6, 25 °C): δ = 8.06 (m, 2H), 7.16 (s, 1H), 6.93 (m, 2H), 6.00 (d, 1H, J = 1.7 Hz), 5.85 (d, 1H, J = 1.7 Hz), 3.51 (s, 3H), 1.69 (d, 3H, J = 1.1 Hz); 13C NMR (75 MHz, C6D6, 25 °C): δ = 166.4, 142.0, 138.7, 135.1 (CH), 129.8 (2CHAr), 129.4 (2CHAr), 129.1, 127.7 (CH2), 113.6, 51.6 (CH3), 15.6 (CH3); IR (CHCl3, cm–1): υ = 3001, 2854, 760, 548.
Chemproc 03 00113 i004
3-iodo-1,3-diene 3d. From 75 mg (0.39 mmol) of allenol 2d, and after chromatography of the residue using hexanes/ethyl acetate (60:1) as the eluent gave compound 3d (38 mg, 32%) as a yellow oil; 1H NMR (300 MHz, C6D6, 25 °C): δ 7.03 (d, 2H, J = 8.5 Hz), 6.85 (s, 1H), 6.71 (d, 2H, J = 8.2 Hz), 5.99 (d, 1H, J = 1.6 Hz), 5.84 (d, 1H, J = 1.7 Hz), 1.67 (d, 3H, J = 1.2 Hz); 13C NMR (75 MHz, C6D6, 25 °C): δ = 137.6, 135.9, 134.9 (CH), 131.2, 130.8 (2CHAr), 128.6 (2CHAr), 126.9 (CH2), 113.8, 15.5 (CH3); IR (CHCl3, cm–1): υ = 3047, 2937, 1095, 564.
Chemproc 03 00113 i005
3-iodo-1,3-diene 3e. From 50 mg (0.21 mmol) of allenol 2e, and after chromatography of the residue using hexanes/ethyl acetate (16:1) as the eluent gave compound 3e (32 mg, 44%) as a yellow oil; 1H NMR (300 MHz, C6D6, 25 °C): δ = 7.53 (d, 2H, J = 8.5 Hz), 7.50 (s, 1H), 6.98 (d, 2H, J = 8.2 Hz), 6.33 (d, 1H, J = 1.6 Hz), 6.18 (d, 1H, J = 1.7 Hz), 1.00 (d, 3H, J = 1.2 Hz); 13C NMR (75 MHz, C6D6, 25 °C): δ = 137.7, 136.3, 134.9 (CH), 131.5 (2CHAr), 131.0 (2CHAr), 127.0 (CH2), 121.5, 113.8, 15.4 (CH3); IR (CHCl3, cm–1): υ = 3047, 2900, 1100, 528.
Chemproc 03 00113 i006
3-iodo-1,3-diene 3f. From 100 mg (0.51 mmol) of allenol 2f, and after chromatography of the residue using hexanes as the eluent gave compound 3f (35 mg, 22%) as a yellow oil; 1H NMR (300 MHz, C6D6, 25 °C): δ = 7.04 (m, 1H), 6.99 (ddd, 1H, J = 7.5, 2.6, 1.0 Hz), 6.77 (m, 3H), 5.95 (d, 1H, J = 1.6 Hz), 5.82 (d, 1H, J = 1.7 Hz), 1.64 (d, 3H, J = 1.1 Hz); 13C NMR (75 MHz, C6D6, 25 °C): δ = 139.4, 138.3, 134.6 (CH), 134.4, 129.6 (CH), 129.4 (CH), 127.5 (CH), 127.3 (CH), 127.1 (CH2), 113.5, 15.4 (CH3); IR (CHCl3, cm–1): υ = 3052, 2958, 1073, 601.
Chemproc 03 00113 i007
3-iodo-1,3-diene 3g. From 100 mg (0.57 mmol) of allenol 2g, and after chromatography of the residue using hexanes as the eluent gave compound 3g (54 mg, 33%) as a yellow oil; 1H NMR (300 MHz, C6D6, 25 °C): δ = 7.09 (s, 1H), 7.00 (m, 4H), 6.03 (d, 1H, J = 1.5 Hz), 5.87 (d, 1H, J = 1.7 Hz), 2.07 (s, 3H), 1.71 (d, 3H, J = 1.1 Hz); 13C NMR (75 MHz, C6D6, 25 °C): δ = 136.9, 136.8, 136.7 (CH), 130.2 (CHAr), 129.3 (CHAr), 128.0, 127.7 (CHAr), 126.5 (CH2), 125.7 (CHAr), 114.4, 19.9 (CH3), 15.2 (CH3); IR (CHCl3, cm–1): υ = 3039, 2906, 587.
Chemproc 03 00113 i008
3-iodo-1,3-diene 3h. From 50 mg (0.24 mmol) of allenol 2h, and after chromatography of the residue using hexanes/ethyl acetate (12:1) as the eluent gave compound 3h (53 mg, 69%) as a yellow oil; 1H NMR (300 MHz, C6D6, 25 °C): δ = 7.42 (s, 1H), 7.24 (m, 1H), 7.02 (m, 3H), 6.15 (m, 1H), 5.94 (d, 1H, J = 1.7 Hz), 1.99 (s, 3H), 1.81 (d, 3H, J = 1.1 Hz); 13C NMR (75 MHz, C6D6, 25 °C): δ = 139.5, 137.6, 136.2, 135.2 (CH), 129.7 (CHAr), 128.1 (CHAr), 126.7 (CH2), 125.4 (CHAr), 124.4 (CHAr), 113.7, 15.4 (CH3), 15.1 (CH3); IR (CHCl3, cm–1): υ = 3100, 2252, 524.

3. Conclusions

In conclusion, we present the controlled preparation of 3-iodo-1,3-dienes, directly from allenes through the coordination of the zinc salt to the double terminal bond of the allene by a subtle variation of the substituents.

Supplementary Materials

The poster presentation is available online at https://0-www-mdpi-com.brum.beds.ac.uk/article/10.3390/ecsoc-24-08091/s1.

Author Contributions

M.T.-P. and B.P. planned and conducted experiments. M.T.-P. and B.P. analyzed the data for the compounds and compiled most of the Supplementary Information. T.M.d.C. analyzed data to support the mechanistic proposal. P.A. designed and directed the project. M.T.-P. wrote the manuscript. T.M.d.C. and P.A. contributed to discussion. All authors have read and agreed to the published version of the manuscript.

Funding

This work was supported in part by AEI (MICIU) and FEDER (Project PGC2018-095025-B-I00).

Conflicts of Interest

The authors declare no conflict of interest.

References

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Chemproc 03 00113 sch001 550
Scheme 1. Previous reports on the synthesis of iododienes from allenes [9,13].
Scheme 1. Previous reports on the synthesis of iododienes from allenes [9,13].
Chemproc 03 00113 sch001
Chemproc 03 00113 sch002 550
Scheme 2. Synthesis of α-allenols [14,15].
Scheme 2. Synthesis of α-allenols [14,15].
Chemproc 03 00113 sch002
Chemproc 03 00113 sch003 550
Scheme 3. Synthesis of 3-iodo-1,3-diene 3a.
Scheme 3. Synthesis of 3-iodo-1,3-diene 3a.
Chemproc 03 00113 sch003
Chemproc 03 00113 sch004 550
Scheme 4. Preparation of 3-iodo-1,3-dienes 3a–h.
Scheme 4. Preparation of 3-iodo-1,3-dienes 3a–h.
Chemproc 03 00113 sch004
Chemproc 03 00113 sch005 550
Scheme 5. Possible mechanism for the formation of 3-iodo-1,3-dienes 3.
Scheme 5. Possible mechanism for the formation of 3-iodo-1,3-dienes 3.
Chemproc 03 00113 sch005
Table
Table 1. Optimization of reaction conditions for the formation of 3-iodo-1,3-dienes 3.
Table 1. Optimization of reaction conditions for the formation of 3-iodo-1,3-dienes 3.
EntryZnI2 (Equiv.)TsOH·H2O (Equiv.)Yield (%)
10.0250.0252
20.10.133
31.20.137
41.2-48
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Toledano-Pinedo, M.; Peñín, B.; Campo, T.M.d.; Almendros, P. Zn–Catalyzed Direct Synthesis of 3-Iodo-1,3-dienes from α-Allenols. Chem. Proc. 2021, 3, 113. https://0-doi-org.brum.beds.ac.uk/10.3390/ecsoc-24-08091

AMA Style

Toledano-Pinedo M, Peñín B, Campo TMd, Almendros P. Zn–Catalyzed Direct Synthesis of 3-Iodo-1,3-dienes from α-Allenols. Chemistry Proceedings. 2021; 3(1):113. https://0-doi-org.brum.beds.ac.uk/10.3390/ecsoc-24-08091

Chicago/Turabian Style

Toledano-Pinedo, Mireia, Beatriz Peñín, Teresa Martínez del Campo, and Pedro Almendros. 2021. "Zn–Catalyzed Direct Synthesis of 3-Iodo-1,3-dienes from α-Allenols" Chemistry Proceedings 3, no. 1: 113. https://0-doi-org.brum.beds.ac.uk/10.3390/ecsoc-24-08091

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