Butadienyl Ketene: An Unexplored Intermediate in Organic Synthesis

Butadienyl ketene is a useful intermediate for its role as 2- components in cycloaddition reactions with a variety of substrate such as simple/conjugated imines and dienes. The current review article summarizes the different reports on the in-situ generation of butadienyl ketene and their cycloaddition reactions to afford different heterocyclic systems. The chemistry of butadienyl ketene is explored only for their [2+2] and [4+2] cycloaddition with a variety of imines and azadiene such as 1,3-diazabuta-1,3-dienes for the synthesis of four- and six-membered heterocycles respectively.


Introduction
Ketenes are one of the most well-known and versatile organic synthetic intermediates (Figure 1).Ketenes, commonly presented as the 'neutral' cumulene form (H 2 C  =C  =O), are generally in resonance with the 'zwitterionic' form with the oxygen atom bearing a partially positive charge and the C  atom bearing a partial negative charge. 1 Because of the fascinating electronic structure of ketenes, these species have been the subject of intense investigation, 1,2 and the appearance of ketenes in organic synthesis has become more frequent over the past few decades. 3,4A very common reaction of ketenes -the Staudinger reaction -involves [2+2] cycloaddition of ketene derivatives and imines and proceeds via zwitterionic intermediate, 5 providing a useful method for the preparation of biologically potent lactams.The syntheses of carbo-and heterocyclic systems involving the [2+2] cycloaddition of ketenes with alkenes and iminic systems have been explored extensively. 3Furthermore, there are many reports on the exploration of conjugated ketenes, namely vinyl and isopropenyl ketenes, for the synthesis of functionalized heterocyclic compounds. 6,710]

Figure 1 Ketenes explored in chemical reactions
However, compared with other conjugated ketenes such as vinyl and isopropenyl ketene, butadiene ketene has been less extensively explored in [m+n] cycloaddition reactions with different substrates acting as 2-or 4-components.There are some reports on [2+2] and [4+2] cycloaddition reactions of the butadienyl ketene with imines and dienes, respectively, to afford functionalized heterocycles with rich synthetic potential.In an effort to highlight the synthetic potential of butadienyl ketene and to arouse the interest of the synthetic community in capturing the unleashed potential of the butadienyl intermediate, this review article summarizes the generation of butadienyl ketene and applications of the cycloaddition reaction reported since 1982.

Review SynOpen 2 Generation of Butadienyl Ketene
Butadienyl ketene was first observed during the preparation of 3,5-hexadienoic esters by Thomas R. Hoye et al. in 1982.3g Sorboyl chloride 2 was prepared by refluxing sorbic acid and thionyl chloride.For the preparation of conjugated methallyl ester 1a, triethylamine was used to catalyze the acylation of sorboyl chloride 2 using methallyl alcohol.However, the formation of a substantial portion of conjugated isomer 5a was observed in addition to 1a (Table 1).This side reaction proceeded via butadienyl ketene 4. The addition of one equivalent of triethylamine to sorboyl chloride resulted in the formation of acyl triethylammonium ion 3. M. K. Mann et al.

Review SynOpen
addition reaction with alcohol to afford conjugated ester 1; however, acyl triethylammonium ion 3 also formed ketene 4, which, on reaction with a second molecule of triethylamine, resulted in the formation of conjugated ester 5 on reaction with alcohol. 3

Review SynOpen
In 2018, Bhargava et al. explored the reactions of sorboyl tosylate at high temperature (80 °C) with a variety of imines to yield mixtures of 3-dienyl lactam 12 and -alkylidene--lactams 13.The formation of dienyl lactam at elevated temperature was mediated through a [2+2] cycloaddition of in-situ generated butadienyl ketene and imines.However, the formation of -alkylidene--lactams 13 involved the addition of the sorbic tosylate to the imine nitrogen of 11 to afford a zwitterionic intermediate 13A, which collapsed to intermediate 13B by ring-closure electrocyclization.Abstraction of an acidic ring proton by the base led to the formation of 3-but-2-enylidene-azetidin-2ones 13 as the major adduct (Table 4).Density functional theory calculations were performed to understand the outcome of the cycloaddition reaction and the results were used to predict a plausible mechanism for the reaction.As a result, a mixture of 3-butadienyl-azetidin-2-ones 12 and 3but-2-azetidin-2-ones 13 was afforded in appreciable yield at elevated temperature. 19ang et al. designed and synthesized three series of 3dienyl--lactams as inhibitors targeting a binding site of colchicine. 20The imines 16 were accessed via butadienyl ketene generated in situ by the action of sorbic acid and suitable base in dichloromethane to afford 3-(buta-1,3dien-1-yl)azetidin-2-ones 17 (Table 5).Derivatives 17 also exhibited in vitro antitumor activity against the MCF-7 breast cancer cell line, with IC 50 values of 23-33 nM. 20heme 3 [4+2] cycloaddition of butadienyl ketene 4 and 1,3-diazabuta-l,3-dienes 25

Review SynOpen Conclusion
This mini-review has focused on the reactivity of dienyl ketenes.Ketene chemistry is an area of interest for chemists due to the atom-economical formation of cycloadducts with a variety of functionalities at different positions.[2+2] and [4+2] cycloaddition reactions of dienyl ketene with imines and heterodienes, respectively, are well-established methods that afford a variety of four-and six-membered heterocycles.However, the synthesis of carbo-and heterocyclic systems through cycloaddition reactions of dienyl ketene are less extensively explored and cycloaddition reactions of butadienyl ketene with aldehyde, enamine, and ynamines, etc. are potentially useful for the development of new routes to functionalized heterocycles.Moreover, the synthetic potential of dienyl ketene as a 4-component in cycloadditions with various substrates has not yet been tested.We hope that this mini-review has highlighted the work carried out using butadienyl ketene and underscored the synthetic potential of this important compound in organic chemistry.

2
Acyl triethylammonium ion 3 then underwent direct Biographical Sketches Maninderjeet Kaur Mann completed her PhD in chemical sciences under the supervision of Dr. Gaurav Bhargava at IK Gujral Punjab Technical University, Jalandhar.She has research ex-perience in synthetic chemistry.Simranpreet K. Wahan is DST Inspire JRF at IK Gujral Punjab Technical University, Jaland-har.She is a gold medalist in Masters of Science (Chemistry) at Punjab University, Chandi-garh.She has many publications in various reputable journals.Nitin Tandon works as Associate Professor at Lovely Professional University, Jalandhar.His research work includes the synthesis of active pharmaceutical ingredients and the synthesis of novel organic molecules for medicinal use.Gaurav Bhargava is Head of Department in the Department of Applied Sciences, IK Gujral Punjab Technical University, Jalandhar.He has rich research experience in green chemistry and synthetic organic chemistry and various publications in reputable international journals.

Table 1
Generation of Butadienyl Ketene 4 and Conversion into Conjugated Ester 5 19

Table 4
Synthesis of a Series of -Alkylidene--lactam Derivatives