Phosphine-Promoted Divergent Annulations of δ‑Acetoxy Allenoates

Letter Cite This: Org. Lett. XXXX, XXX, XXX−XXX

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Phosphine-Promoted Divergent Annulations of δ‑Acetoxy Allenoates with α‑Hydroxy-β-carbonyl Ester Derivatives: Synthesis of Tetrasubstituted Cyclopentadienes and Benzenes Tong Xu, Dong Wang, Wei Liu, and Xiaofeng Tong* Jiangsu Key Laboratory of Advanced Catalytic Materials & Technology, School of Petrochemical Engineering, Changzhou University, 1 Gehu Road, Changzhou 213164, China

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S Supporting Information *

ABSTRACT: The substrate-dependent annulations of δacetoxy allenoates with α-hydroxy-β-carbonyl ester derivatives are reported. 2-[(Methoxycarbonyl)oxy]malonate as a C1 partner is able to undergo (1 + 4) annulations with allenoates in the presence of a catalytic amount of phosphine, affording cyclopentadienes in good yields. However, (2 + 4) annulations of allenoates with 2-(tosyloxy)-3-ketoesters are instead observed with the assistance of stoichiometrical phosphine and base, leading to tetrasubstituted benzene products. In these two reactions, δ-acetoxy allenoate serves as a 1,4-disubstituted diene synthon.

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ince the pioneering report of Lu’s (3 + 2) cycloaddition,1 the phosphine-catalyzed annulations of allenoates (PCAA) have been extensively developed, which have become a solid synthetic tool for the construction of a wide range of carboand heterocycles.2 These methods are also highlighted by their success in natural product synthesis as a key step.3 Nevertheless, construction of the cyclopentadiene scaffold remains an unmet challenge in PCAA. Cyclopentadienes are very attractive organic compounds as they have versatile applications in the fields of synthesis, catalysis, as well as material science.4 From a mechanistic viewpoint, the catalytic cycles of PCAA involve various zwitterion intermediates.2 It is interesting to note that these highly reactive species play pivotal roles, which generally undergo nucleophilic addition to the CX bond. In addition, the class of zwitterions exhibits an alternative potential for nucleophilic substitution (SN), which, however, is rarely observed in PCAA. In 2009, Kwon and co-workers reported an elegant phosphine-promoted (3 + 3) annulation of aziridine with α-substituted allenoate, in which the involved zwitterion intermediate A was observed to undergo nucleophilic aromatic substitution (SNAr) (Scheme 1a).5 This reaction firmly established the concept that the zwitterion intermediate is able to engage in nucleophilic substitution in addition to nucleophilic addition. A similar SNAr was also observed in our phosphine-catalyzed (3 + 2) annulation of δacetoxy allenoate 1a with 2-sulfonamido-2-benzoyl acetate (Scheme 1b).6a With these two precedents and our ongoing interest in acetoxy allenoates,6 we envisioned that malonate derivative 2 bearing a leaving group at αC would undergo a similar addition reaction with the phosphonium diene intermediate C to generate zwitterion intermediate D, which would be competent for intramolecular SN2 (Scheme 1c). © XXXX American Chemical Society

Scheme 1. Nucleophilic Substitution (SN) in the PhosphineCatalyzed Annulations of Allenoates

Herein, we report a phosphine-catalyzed (4 + 1) annulation of δ-acetoxy allenoates 1 with malonate 2, which provides facile access to tetrasubstituted cyclopentadiene under mild conditions. In view of its well-known dual reactivity, bromomalonate 2a would be an appropriate candidate to test the feasibility of our working hypothesis as depicted in Scheme 1c. However, no reaction was detected when 2a was subjected to react with allenoate 1a in toluene in the presence of PPh3 (20 mol %) and Received: November 28, 2018

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DOI: 10.1021/acs.orglett.8b03808 Org. Lett. XXXX, XXX, XXX−XXX

Letter

Organic Letters K2CO3 (1.2 equiv) (Table 1, entry 1). Unfortunately, 2tosyloxy malonate 2b was also unable to react with 1a (Table

Scheme 2. Scope of (4 + 1) Annulations

Table 1. Condition Optimization for the PhosphineCatalyzed (4 + 1) Annulation of 1a and 2a

entry

2 (LG)

PR3

additiveb

yieldd (%)

1 2 3 4 5 6 7 8 9 10 11 12

2a (Br) 2b (OTs) 2c (OCO2Me) 2c (OCO2Me) 2c (OCO2Me) 2c (OCO2Me) 2c (OCO2Me) 2c (OCO2Me) 2c (OCO2Me) 2c (OCO2Me) 2c (OCO2Me) 2c (OCO2Me)

PPh3 PPh3 PPh3 PPh3 PPh3 PPh3 P(4-F-Ph)3 P(4-Me-Ph)3 P(4-MeO-Ph)3 PPh2Me PPhMe2 PnBu3

K2CO3 K2CO3 K2CO3 NaHCO3 t BuOK c c c c c c c

0 0 7 18