Letter pubs.acs.org/OrgLett
Catalytic Tandem C−C Bond Formation/Cleavage of Cyclopropene for Allylzincation of Aldehydes or Aldimine Using Organozinc Reagents Takeo Nakano,† Kohei Endo,†,*,‡ and Yutaka Ukaji† †
Division of Material Sciences, Graduate School of Natural Science and Technology, Kanazawa University, Kakuma, Kanazawa 920-1192, Japan ‡ PRESTO, Japan Science and Technology Agency (JST), 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan S Supporting Information *
ABSTRACT: The tandem allylation of aldehydes or an aldimine with allylzinc intermediates derived from organozinc reagents and cyclopropenes is described. The present three-component reaction involves carbozincation of cyclopropene and sequential cleavage of a cyclopropylzinc intermediate in situ without a transition-metal catalyst. The allylzinc intermediates generated in situ, which is an α,β-unsaturated acylanion equivalent, gave the corresponding homoallylic alcohols or amine in good yields.
A
Scheme 1. Allylzincation via Sequential Carbozincation and C−C Bond Cleavage of Cyclopropylzinc Intermediate
ctivation of a C−C single bond in highly strained molecules is a powerful approach to the construction of structurally complex molecules in a single operation. However, previous reports have typically achieved C−C bond cleavage with the use of an expensive transition-metal catalyst, such as Pt, Rh, Ru, or Ir.1 We previously reported the cleavage of cyclopropylzinc intermediates without a transition-metal catalyst to give allylzinc intermediates, which can take part in the allylzincation of β-hydrazoneamide derivatives in a single operation.2 The transition-metal-free carbozincation of cyclopropene in the presence of β-hydrazoneamide derivatives is a key factor in our approach to the tandem C−C bond cleavage in cyclopropylzinc intermediates. Nucleophilic addition to electronically unactivated cyclopropene typically requires a transition metal as a catalyst.3,4 Marek and co-workers reported the Cu-catalyzed carbometalation of cyclopropene, oxidation, and retro aldol-type C−C bond cleavage.5 In contrast, our strategy using cyclopropenone acetal (CPA)6 as a cyclopropene for the carbozincation proceeded without any metal catalyst to give a cyclopropylzinc intermediate in the presence of a β-hydrazoneamide, and subsequent C−C bond cleavage of a cyclopropylzinc intermediate took place in situ.7 Our previous report showed that the carbozincation2,8 of CPA proceeded to give cyclopropylzinc intermediate A, the subsequent ring-opening of which generated allylzinc intermediate B for the chemoselective allylzincation of hydrazone (Scheme 1, a). Chemoselective C− C bond cleavage without a transition-metal catalyst gave the sterically congested hydrazine in a single operation. Although we have described the allylation of benzaldehyde in the presence of a stoichiometric amount of β-hydrazoneamide, the yield of the desired product was low. Since β-hydrazoneamides take part in the reaction as ligands as well as electrophiles, the allylation to other electrophiles may be difficult to control. We © 2014 American Chemical Society
report here the β-hydrazoneamide-catalyzed tandem carbozincation of cyclopropene and the subsequent allylzincation of Received: January 21, 2014 Published: February 24, 2014 1418
dx.doi.org/10.1021/ol500208r | Org. Lett. 2014, 16, 1418−1421
Organic Letters
Letter
ligands L2 or L3 promoted unidentified side reactions (entries 2−4). The ligands gradually gave a trace amount of byproducts via allylation to hydrazone and/or cyclopropylation, as reported previously.2 The use of acyclic β-hydrazoneamide L4 or L5 gave the desired product 2a in lower yields (entries 5 and 6). On the other hand, β-ketoamide L6, β-hydroxyhydrazone L7, amino alcohol L8, and N,N,N′,N′-tetramethylethylenediamine (TMEDA) did not give the product 2a (entries 7−10). Therefore, the amounts of L1, diethylzinc, and CPA were examined. The reaction in the presence of a catalytic amount of L1 (15 mol %) gave 2a in 56% yield (entry 11). When the reaction was carried out at 0 °C, the yield of 2a decreased (entry 12). Further screening of the reaction conditions in the presence of L1 (25 mol %) showed that the reaction using diethylzinc (1.3 equiv) and CPA (1.3 equiv) gave the desired product 2a in 76% yield (entries 13−17). The use of a coordinative solvent slowed the reaction (entries 18−23). Under the optimized conditions, a catalytic tandem allylation reaction was performed using various aromatic and aliphatic aldehydes (Table 2). The reaction typically gave the (E)-isomer
additional aldehydes and an aldimine as 3-component reactions in a single operation (Scheme 1, b). The reaction conditions were examined for the βhydrazoneamide-mediated or -catalyzed tandem allylzincation of benzaldehyde (1a) using diethylzinc and CPA (Table 1, Figure 1). The reaction without a ligand gave product 2a in poor yield (entry 1).9 The use of cyclic hydrazoneamide L1 as a ligand gave the desired product 2a in moderate yield; other Table 1. Optimization of Reaction Conditions
entry
ligand
solvent
X
Y
yield (%)
1 2 3 4 5 6 7 8 9 10 11 12a 13 14 15 16 17 18 19 20 21 22 23
L1 L2 L3 L4 L5 L6 L7 L8 TMEDAb L1 L1 L1 L1 L1 L1 L1 L1 L1 L1 L1 L1 L1
toluene toluene toluene toluene toluene toluene toluene toluene toluene toluene toluene toluene toluene toluene toluene toluene toluene benzene hexane THF Et2O MTBE CH2Cl2
1.1 1.1 1.1 1.1 1.1 1.1 1.1 1.1 1.1 1.1 1.1 1.1 1.1 1.2 1.3 1.4 1.5 1.3 1.3 1.3 1.3 1.3 1.3
0 110 110 110 110 110 110 110 110 110 15 15 25 25 25 25 25 25 25 25 25 25 25
