Article pubs.acs.org/joc
Palladium-Catalyzed Intramolecular Diamination of Acrylic Esters Using Sulfamates as Nitrogen Source Patricia Chávez,† Jonathan Kirsch,† Jan Streuff,‡ and Kilian Muñiz*,†,§ †
Institute of Chemical Research of Catalonia (ICIQ), Av. Països Catalans, 16, E-43007 Tarragona, Spain Albert-Ludwigs-Universität Freiburg, Albertstr. 21, 79104 Freiburg, Germany § Catalan Institution for Research and Advanced Studies (ICREA), Pg. Lluís Companys 23, 08010 Barcelona, Spain ‡
S Supporting Information *
ABSTRACT: An intramolecular diamination of acrylates is reported using sulfamates as nitrogen sources. This reaction proceeds under palladium(II) catalysis with copper bromide as oxidant and gives rise to anti-configured 2,3-diamino carboxylates as bicyclic sulfamate derivatives. An aminobrominated intermediate within the diamination reaction was isolated that allowed to clarify the reaction mechanism and to rationalize the observed preferential product stereochemistry.
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INTRODUCTION The 2,3-diamino carboxylic acid motif represents an interesting nonproteinogenic amino acid1 that has attracted attention for its presence in biologically active compounds.2 Mannich-type reactions under transition-metal catalysis or organocatalysis have been described as particularly suitable approaches to this class of compounds.3 Oxidative metal catalysis for diamination of alkenes has recently emerged as a powerful tool for the synthesis of heterocycles that incorporate the vicinal diamine structural motif.4 Reactions to this end include palladium,5 nickel,6 gold,7 and copper8 catalysis.9,10 Within this context, some time ago we reported the diamination of acrylates using ureas as nitrogen sources (Scheme 1).11 This reaction proceeds under palladium catalysis with copper bromide as terminal oxidant and allows us to selectively generate syn-configured 2,3-diamino esters. One of these compounds served as building block in the synthesis of the natural product absouline.
Starting materials 2 are available from cross-metathesis between alkyl acrylate and previously described ω-alkenyl sulfamides (Scheme 2).6 The reaction employs an excess of the corresponding acrylate leading to fumarate as an easily removable byproduct. After some experimentation, conditions were found under which the diamination reaction of 2a to cyclized 3a proceeded under palladium catalysis with high yield and good diastereoselectivity. Initial attempts to employ high oxidation state catalysis12 and acetate base did not meet with success (Table 1, entry 1). Instead, use of copper bromide as oxidant resulted more convenient (entry 2). Solvent exploration revealed DMF to be superior than dichloromethane or THF, respectively (entries 2−4). Further optimization addressed the nature of base and cesium carbonate was identified as optimum base in comparison to acetate and hydrogenphosphate (entries 4−6). Complete conversion was observed for a reaction at slightly enhanced temperature of 40 °C (entry 7). This optimization process hence identified cesium carbonate as optimum base and DMF as best solvent generating product 3a in 83% isolated yield. No reaction was observed in the absence of a palladium catalyst (entry 8). As a usual feature in the intramolecular diamination under palladium catalysis,5a−d,6 the presence of base is required (entry 9). Under the optimized conditions, the diamination reaction of 2a reaches full completion, and an overall yield of 83% (76% for 3a and 7% for 4a) is obtained. The high yield of 3a is
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RESULTS AND DISCUSSION We now became interested in the use of the corresponding sulfamates as nitrogen sources, which are more conveniently accessible and usually show a broader potential for structural diversification. They were already employed in oxidative diamination reactions of terminal alkenes using nickel catalysis.6 Herein, we describe the application of intramolecular diamination of acrylates using sulfamate groups as nitrogen source. © 2012 American Chemical Society
Received: December 12, 2011 Published: January 18, 2012 1922
dx.doi.org/10.1021/jo202507d | J. Org. Chem. 2012, 77, 1922−1930
The Journal of Organic Chemistry
Article
Scheme 1
as a single diastereomer displaying syn-configuration (Scheme 1). We had observed in an earlier case of a different palladium catalysis that the carbamate nitrogen of the sulfamate group displays rather low nucleophilic character for a direct C−N bond formation.6 Assuming a related behavior for the present reaction, we set to investigate potential intermediates by conducting the diamination reaction of 2a at lower reaction temperature (Figure 1). Indeed, when 2a was oxidized at room temperature (Scheme 3), the corresponding aminobrominated product 5 was the major product (65% isolated yield) together with 3a (23%). Compound 4a was not observed. If formed, its amount was below detection level. Treatment of the isolated aminobrominated intermediate 5 with base in DMF gave the expected product 3a as single isomer in 92% isolated yield. This reaction outcome suggests that the present diamination reaction proceeds through a catalytic cycle of syn-aminopalladation5b,d,e,14,15 to A followed by copper-mediated transient palladium oxidation with concomitant C−Br bond formation.16 This latter step proceeds with clean SN2 chemistry leading to inversion of configuration at carbon. Subsequent C− N bond formation from B under a second inversion of configuration leads to anti-3a. The minor isomer 4a is either generated from B within a minor pathway of direct C−N bond formation or from C within an epimerization of the brominated center. The reaction is general for a range of different substrates. Table 2 shows representative examples of several sulfamates with variation of backbone substitution, the ester groups and the carbamate group of the sulfamate. All these reactions proceed with good to high isolated yields. An anti-configuration was obtained for all major products as judged from the respective 3J coupling constants and confirmed by an additional X-ray analysis of product 3l. Diastereomeric ratios range from
Scheme 2. Metathesis Approach to Starting Materials 2
particularly remarkable in view of the lower yielding transformation of parent terminal alkenes 1 under similar conditions.11 The observed coupling constant of 3J = 4 Hz between the two hydrogen atoms at the newly formed tetrahedral carbon atoms suggested that the reaction leads to preferential formation of a trans-configured diamination product 3a. The corresponding cis-isomer 4a is the minor product and is generated in less than 10% yield. Both relative configurations were unambiguously assured from X-ray analyses (Scheme 3).13 This reaction outcome constitutes a noteworthy difference to the one from the previous reactions using ureas as nitrogen source, where the corresponding product was obtained Table 1. Optimization of Reaction Conditions
entry
conditions
conversiona (%)
yieldb (%)
1 2 3 4 5 6 7 8 9
10 mol % Pd(OAc)2, PhI(OAc)2 (1.2 equiv), NaOAc (2 equiv), CH2Cl2, 30 °C 10 mol % Pd(OAc)2, CuBr2 (2 equiv), NaOAc (2 equiv), CH2Cl2, 30 °C 10 mol % Pd(OAc)2, CuBr2 (2 equiv), NaOAc (2 equiv), THF, 30 °C 10 mol % Pd(OAc)2, CuBr2 (2 equiv), NaOAc (2 equiv), DMF, 30 °C 10 mol % Pd(OAc)2, CuBr2 (2 equiv),Na2HPO4 (2 equiv), DMF, 30 °C 10 mol % Pd(OAc)2, CuBr2 (2 equiv), Cs2CO3 (2 equiv), DMF, 30 °C 10 mol % Pd(OAc)2, CuBr2 (2 equiv), Cs2CO3 (2 equiv), DMF, 40 °C CuBr2 (2 equiv), Cs2CO3 (2 equiv), DMF, 30 °C 10 mol % Pd(OAc)2, CuBr2 (2 equiv), DMF, 40 °C
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