Letter Cite This: Org. Lett. XXXX, XXX, XXX−XXX
pubs.acs.org/OrgLett
Trisulfur Radical Anion (S3•−) Involved [1 + 2 + 2] and [1 + 3 + 1] Cycloaddition with Aromatic Alkynes: Synthesis of Tetraphenylthiophene and 2‑Benzylidenetetrahydrothiophene Derivatives Jing-Hao Li, Qi Huang, Shun-Yi Wang,* and Shun-Jun Ji*
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Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science & Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou 215123, China S Supporting Information *
ABSTRACT: S3•−-mediated [1 + 2 + 2] and [1 + 3 + 1] cycloaddition reactions of aromatic alkynes to give tetraphenylthiophene and 2benzylidenetetrahydrothiophene derivatives via two C−S bond formations are developed. These two protocols provide new, simple, and straightforward strategies to construct tetraphenylthiophene and 2-benzylidenetetrahydrothiophene derivatives under transition-metal-free conditions. This study also expands the application of S3•− in organic reactions.
S
catalyzed dual C−S bond formation reactions of 1,4-diiodo1,3-diene with K2S (Scheme 1a-2).8 However, the limited reported methods have some drawbacks such as multireaction steps, low total product yields, long reaction times, and use of transition metal catalysts. It is more desirable to develop new simple strategies to construct these compounds in one step under mild conditions. The S3•− species has been known for more than 40 years and can be very easily formed by the reaction of elemental sulfur with KOH in DMF at room temperature.9 However, applications for the synthesis of organosulfur compounds involving S3•− via C−S bond formation are very rare.10 Recently, Lei’s group reported an S8 and base in situ generated S3•−-mediated [4 + 1] cycloaddition with 1,3-diynes for synthesis of 2,5-substituted thiophene.10b More recently, our group developed an in situ generated S3•− from a K2S-initiated [5 + 1] cycloaddition reaction with enaminones to afford benzothiazine derivatives (Scheme 1b).10d As part of our continued efforts on the reactions involving S3•−, herein, we describe a S3•− in situ generated from S2−-mediated [1 + 2 + 2] and [1 + 3 + 1] cycloaddition with aromatic alkynes to give tetraphenylthiophene and 2-benzylidenetetrahydrothiophene derivatives via two C−S bond formations (Scheme 1c). Initially, we investigated the reaction of 1,2-diphenylethyne 1a and K2S 2a in DMF at 120 °C for 12 h under Ar atmosphere. To our delight, the [2 + 2 + 1] cycloaddition product tetraphenylthiophene 3a was obtained in 65% liquid chromatography yield (LC-yield). The structure of 3a was confirmed by NMR, IR, HRMS, and X-ray analyses. With this promising result in hand, we further screened the reaction conditions to optimize the reaction. It was found that the reaction was very messy without argon protecting. Next, other
ubstituted thiophenes and tetrahydrothiophenes have emerged as a class of important heterocycles because of their presence in a broad spectrum of natural and synthetic molecules with diverse biological properties,1 material characteristics,2 and utility in organic synthesis as versatile intermediates.3 In particular, poly- and oligoarylthiophenes have recently attracted much attention due to their useful electronic and optical properties.4 What is more, tetraarylthiophenes can also be used as an important reactant for the synthesis of special full substituted aromatic benzenes,5 naphthalenes, and anthracenes.6 The general synthetic approach to such tetra-arylthiophenes involves multiple C−H coupling reactions from 3-methoxythiophene.5,6 It can also be synthesized by palladium-catalyzed coupling of 3-thiophenecarboxylic acid with aryl halides (Scheme 1a-1)7 and copperScheme 1. Approaches to Tetra-arylthiophenes and Our Works on C−S Bond Construction by S3•−
Received: July 2, 2018
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.8b02066 Org. Lett. XXXX, XXX, XXX−XXX
Letter
Organic Letters sulfur reagents such as cyclo-S8, Na2S·9H2O, and Na2S2O3 were applied in the reaction (Table 1, entries 2−4). The Table 1. Optimization of the Reaction Conditionsa
entry
S reagent
solvent
temperature (°C)
3a (%)a,b
1 2 3 4 5 6 7 8 9 10 11d
K2S S8 + NaOtBu Na2S·9H2O Na2S2O3 K2S K2S K2S K2S K2S K2S K2S
DMF DMF DMF DMF DMSO DMA toluene DMF DMF DMF DMF
120 120 120 120 120 120 120 80 130 140 130
65(48)c
