Decomposition of Alkynyl Hydrazones: Synthesis of Allenoates, Dihaloallenoates, and Angularly Fused Tricyclic Azepines

Abstract

An unprecedented decomposition of unprotected alkynyl hydrazones is attempted that has provided allenoates, tetrasubstituted α,γ-dihaloallenoates, and functionalized tricyclic azepines. A reaction of alkynyl hydrazones with N-halosuccinimides captures the electrophile in 2-fold that delivers fully substituted dibromo-and diiodoallenoates in good yields. In addition, a DABCO-promoted Wolff−Kishner reduction of hydrazones, followed by isomerization, provides versatile allenoates under mild conditions. In contrast, a similar decomposition with ambiphilic DBU furnishes a completely different tricyclic azepine scaffold in excellent yield and diastereoselectivity.

Synthesis of Tetrasubstituted 1,4-Dicarbonyl (Z)-2,3-Dihaloalkenes via Electrophilic Halogenation of Alkynyl Hydrazones

“…Then, 1.3 equiv of NBS and H 2 O (4 equiv) were added, and the reaction mixture was allowed to stir at the given temperature for 3 h. As a continuation of our research interest in exploring the reactivity of unprotected alkynyl hydrazones, 16 we attempted their decomposition in the presence of NBS (2 equiv) and observed α,γ-dibromoallenoates 3a. 17 During the optimization of 3a, we also observed an interesting side product 4a in trace amounts (Table 1, entry 1). Keeping in mind the invaluable synthetic potential of 1,4-dicarbonyl dihaloalkenes, we turned our attention toward obtaining 4a as a sole product.…”

“…As a continuation of our research interest in exploring the reactivity of unprotected alkynyl hydrazones, we attempted their decomposition in the presence of NBS (2 equiv) and observed α,γ-dibromoallenoates 3a . During the optimization of 3a , we also observed an interesting side product 4a in trace amounts (Table , entry 1).…”

“…First, hydrazone 1a undergoes a 2-fold electrophile trapping reaction that provides dihaloallenoate 3a. 17 Then, a third equivalent halonium source could form a complex with allenoate 3a to afford transient cyclic halonium ion species B that could engender an electrophile-trapped oxocarbenium ion C. 24 Subsequently, it could undergo a reversible nucleophilic addition with water that would generate dihydrofuran D. The presence of nonbonded electron pairs on the heterocyclic oxygen and the leaving ability of halide trigger an another oxocarbenium ion E that results in the desired product 4a.…”

“…A plausible mechanism for electrophilic halogenation of alkynyl hydrazone is depicted in Scheme . First, hydrazone 1a undergoes a 2-fold electrophile trapping reaction that provides dihaloallenoate 3a . Then, a third equivalent halonium source could form a complex with allenoate 3a to afford transient cyclic halonium ion species B that could engender an electrophile-trapped oxocarbenium ion C .…”

Electroreductive Carboxylation of Propargylic Acetates with CO2: Access to Tetrasubstituted 2,3-Allenoates

“…Among the methods developed, traditional methods for the 2,3-allenoates and their derivatives’ construction involve the Wittig or Horner-Wadsworth-Emmons reactions of ketenes or ketene equivalents, isomerization of alkynoates, − β-hydride elimination of ( E )-enol triflates, , cross-coupling of α-diazoesters with alkynes, , and caboxylation with CO − or CO 2 . − However, these approaches suffer from poor step-economy, unsatisfactory selectivity, harsh reaction conditions, and/or limited substrate scope. Moreover, it is still a high challenge to synthesize tetrasubstituted 2,3-allenoates, especially when operating in a cis / trans stereoselectivity-controlled fashion. , Typically, methods that consist of base-mediated trapping of allenyl anions from 2,3-allenoates with electrophiles (Scheme a) − or transition-metal-catalyzed cross coupling of propargylic acetates with arylboronic acids (Scheme b) have been established to furnish the challenging tetrasubstituted 2,3-allenoates, with all relying on the use of inherent-ester-group-containing starting materials. Alternatively, Ma and co-workers have reported a Pd/H + -cocatalyzed carboxylation of 2-alkynols with CO and nucleophiles (such as alcohols and H 2 O) by incorporation of external ester groups for the preparation of tetra- or trisubstituted allenoates and 2,3-allenoic acids (Scheme c) .…”