Two-Step, Stereoselective Hydrazidoarylation of 1,3-Cyclopentadiene

Abstract

The first palladium-catalyzed reductive phenylation of norbornene (1) was published by Larock and Johnson [1] in 1989; since then the high synthetic potential of the hydroarylation [2] and especially its asymmetric variant [3] with bicyclic alkenes for the one-step construction of three asymmetric centers has induced a line of follow-up papers. This situation is especially true for the hydroarylation of the 7-aza-and oxabicyclic alkenes 2 (Scheme 1) [2b±d, 3c] as this synthetic route even in the case of the asymmetric pathway leads directly to the biologically highly active alkaloid Epibatidine [4] and its analogues.As we are interested in both the hydroarylation of bicyclic alkenes and, herein, in the use of these products in the stereoselective synthesis of substituted cyclopentane derivatives, we have investigated the hydroarylation followed by reductive cleavage of the easily accessible [5] 2,3-diazabicyclo[2.2.1]heptenes 3, [6] in which the N À N [7] or C À N bond [8] represents an internal point of fracture.Recently, we have reported the first palladium-catalyzed hydroarylation of the N,N'-diethoxycarbonyl-substituted derivative 4 of 3 with triethylamine as a base. [6] The following selective NÀN bond cleavage opens a highly stereoselective way to the trans-4-aryl-cis-1,3-diaminocyclopentanes 6 (Scheme 2).Encouraged by this initial result, we turned to the hydroarylation of the sterically more hindered and more rigid, trior tetracyclic Diels±Alder adducts of 1,3-cyclopentadiene with the very reactive azodienophiles 4-phenyl-1,2,4-triazoline-3,5-dione (7 a) and 2,3-phthalazine-1,4-dione (7 b). The reaction of 7 a with iodobenzene was chosen as a model system with which to optimize the reaction conditions; selected experiments are shown in Table 1.We started with the reaction conditions (Et 3 N, DMF, 65 8C, entry 1) which were optimal in case of the hydroarylation of 4; besides 21 % of the expected hydroarylation product 8 a, compound 9 a was formed in 9 % as the product of a CÀN cleavage reaction. Formally, the formation of 9 a is the result of a 1,2-hydrazidoarylation on the primarily employed 1,3-cyclopentadiene. From the 1 H and 13 C NMR spectroscopic data it appeared that the trans isomer 9 a was formed exclusively. The structural assignment is difficult in case of five-membered ring systems; however, the stereochemistry was unambiguously supported by an X-ray analysis (Figure 1). [9,10] COMMUNICATIONS

Carbon–Nitrogen Bond‐Forming Reactions of Dialkyl Azodicarboxylate: A Promising Synthetic Strategy

“…(22)]. 33 Radhakrishnan and co‐workers reported the palladium(0)/Lewis acid mediated ring opening of azabicyclic olefin with organostannane, leading to the synthesis of 3,4‐disubstituted hydrazinocyclopentene derivative 49 in excellent yield 34. The reaction of phenyl boronic acid with bicyclic alkene in the presence of a Pd(OAc) 2 /PPh 3 /I 2 catalyst system afforded 3‐phenyl‐4‐hydrazino cyclopentene 48 [Eq.…”

Chemodivergence in Enantioselective Desymmetrization of Diazabicycles: Ring‐Opening versus Reductive Arylation

“…[7] Conversely, the racemic hydroarylation of diazabicycles using Pd was reported by Kaufmann and co-workers, but the reaction led to mixtures of 2 and 3. [8] We found that the hydroarylation products are formed through a mechanism that is markedly different from the one proposed with Pd, thus opening up new synthetic opportunities. [9] We focused on finding a solution to the challenging problem of enantioselective ring-opening of diazabicyclo-[2.2.1]heptanes to provide a rapid synthesis of optically active trans-2-arylated cyclopentyl amines 4, which are known to be biologically active small molecules (Scheme 1).…”

Palladium‐Catalyzed Cross‐Coupling of Aryl Iodides with Heterobicyclic Olefins: Access to Hydroarylated and Heteroannulated Motifs

“…by various research groups . Kaufmann and co‐workers explored the palladium catalyzed hydroarylation of diazabicyclic olefins . Our group has demonstrated the utility of mono and bi‐functional aryl iodides with diazabicyclic olefins toward the construction of 3,4‐disubstituted cyclopentenes, indanones and indoline/benzofuran fused cyclopentenes…”

“…[8] Kaufmann and co-workers explored the palladium catalyzed hydroarylation of diazabicyclic olefins. [9] Our group has demonstrated the utility of mono and bi-functional aryl iodides with diazabicyclic olefins toward the construction of 3,4-disubstituted cyclopentenes, [10] indanones [11] and indoline/ benzofuran fused cyclopentenes. [12] Urea and its cyclic derivatives represent a class of biologically relevant molecules, widely occurring in natural products and have been studied for various biological activities such as antibiotic hypoglycemic effects, anti-cancer, antidiabetic, antimicrobial, antibacterial activities etc.…”