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

: 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.


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.
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. Scheme 1. Previous reports on the synthesis of iododienes from allenes [9,13].
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.

Scheme 4. Preparation of 3-iodo-1,3-dienes 3a-h.
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.

Experimental Section
General methods: 1 H NMR and 13 C 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 ( 1 H, 0.00 ppm), or C6D6 ( 1 H, 7.16 ppm; 13 C, 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.

General Procedure for the Preparation of α-Allenols 2a-h
These precursors were readily obtained as described in the literature [14,15].

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.

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.