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Cite This: J. Org. Chem. 2018, 83, 8786−8792
Synthesis of Densely Substituted Conjugated Dienes by TransitionMetal-Free Reductive Coupling of Allenylboronic Acids and Tosylhydrazones Dong Wang, Martin J. M. de Wit, and Kálmán J. Szabó* Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University, SE-10691 Stockholm, Sweden
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ABSTRACT: Tosylhydrazones and allenylboronic acids underwent a transition-metal-free reductive coupling reaction. This process is suitable for synthesis of tetra- and pentasubstituted conjugated dienes. The corresponding allenyl-Bpin substrate showed a very poor reactivity. The reaction is suggested to involve coupling of the in situ formed diazo compound and allenylboronic acid. The intermediate formed in this coupling undergoes allenyl migration followed by protodeboronation to furnish a conjugated diene as major product.
A
llenylboron compounds1 are useful reagents for selective introduction of propargyl, allenyl, and dienyl functional units.2 The most widespread use of these reagents is carbon− carbon bond formation with carbonyl compounds and imines.2c However, recently, even cross-coupling reactions with allenylboron species have attracted interest in organic synthesis.1f,3 As a part of our organoboron chemistry program,1b,4 we reported a new transition-metal-catalyzed method for synthesis of allenylboronic acids.1d We have shown that these species are more reactive and more versatile reagents than the corresponding allenyl-Bpin compounds and other boronates.1d In a couple of recent papers, we showed that Cu- and Pd-catalyzed cross-coupling of allylboronic acids with diazoketones can be easily performed.5 Now, our attention turned to studying transition-metal-free cross-coupling of allenylboronic acids with diazo compounds. The groups of Wang,6 Barluenga,7 Valdés,8 Ley,9 and others10 have demonstrated that transition-metal-free reductive coupling of alkyl-, aryl-, and alkenylboronic acids can be performed by diazo compounds. In many of these reactions, the diazo compounds have been generated in situ, prior to the coupling by the Bamford−Stevens reaction11 using tosylhydrazones in the presence of base. The overall reaction can be used for homologization of alkyl, aryl, and vinyl boronates (Scheme 1a). As far as we know, this method has never been used with allenylboron reagents. We found that the major product of the coupling reaction of diazo compounds and allenylboronic acids are 1,3-dienes (Scheme 1b). Using trisubstituted allenylboronic acid reagents, this process is suitable for synthesis of densely substituted dienes with high diastereoselectivity. Initially, we reacted allenylboronic acid 1a and phenyltosylhydrazone 2a (precursor for the diazo compound11) in the presence of CsF at 110 °C (Table 1, entry 1) in dioxane. The main product (38%) of this reaction was conjugated diene 3a, in which the phenyl group (arising from 2a) and the n-butyl group possess the E-geometry. The Z-isomer 3b was formed as a minor product (6%). © 2018 American Chemical Society
Scheme 1. Transition-Metal-Free Coupling of Tosylhydrazones and Organoboron Compounds
We found that the variation of the base influenced the selectivity and the yield of the reaction (entries 1−10). When CsF was replaced by Bu4NF, the ratio of the E/Z products was improved, but a new regio-isomer, allene 4, appeared as a minor product (entry 2). We also considered application of organic bases such as Et3N and DBU (entries 3 and 4, respectively). The yield and selectivity was poor with Et3N (entry 3), but application of DBU substantially improved the yield of 3a, albeit the selectivity decreased by formation of a considerable amount of allenyl product 4 (entry 4). Application of strong inorganic bases such as NaOMe and KOH led to poor yields (entries 5 and 6, respectively). Although using Na2CO3 (entry 7) was inefficient, application of Cs2CO3 (entry 8) and K2CO3 (entry 9) led to improved yields (up to 49%) and selectivities. The relatively high temperature (110 °C) was important for the successful generation of the diazo compound intermediate from 2a.12 When the reaction was carried out at 80 °C, the yield was sharply decreased (entry 10). The reaction can also be performed in toluene (entry 11). However, we found that Received: May 1, 2018 Published: May 24, 2018 8786
DOI: 10.1021/acs.joc.8b01104 J. Org. Chem. 2018, 83, 8786−8792
Note
The Journal of Organic Chemistry Table 1. Screening of the Conditions for the Reductive Coupling of Allenylboronic Acid 1a and Tosylhydrazone 2aa
entry
base
solvent
1 2 3 4 5 6 7 8 9 10 11 12c 13c 14c 15c 16c,d
CsF Bu4NF Et3N DBU NaOMe KOH Na2CO3 Cs2CO3 K2CO3 K2CO3 K2CO3 K2CO3 K2CO3 K2CO3 K2CO3 K2CO3
1,4-dioxane 1,4-dioxane 1,4-dioxane 1,4-dioxane 1,4-dioxane 1,4-dioxane 1,4-dioxane 1,4-dioxane 1,4-dioxane 1,4-dioxane toluene 1,4-dioxane 1,4-dioxane 1,4-dioxane 1,4-dioxane 1,4-dioxane
additive
temp (°C)
3ab
3bb
4b
10 equiv H2O 1.5 equiv CsF 1.5 equiv CsF, 10 equiv H2O 1.5 equiv CsF, 10 equiv H2O
110 110 110 110 110 110 110 110 110 80 110 110 110 110 110 110
38 37 19 67 18 20
