Pauson-Khand reaction scope

Torres, R. R. The Pauson-Khand Reaction Scope, Variations and Applications, Wiley Hoboken, NJ, 2012. (Review). 

The sequential double migratory insertion of CO into acydic and cydic diorganozircono-cene complexes through acylzirconocene and ketone—zirconocene species provides a convenient procedure for preparing acyclic and cyclic ketones (Scheme 5.6) [8], Thus, the bi-cydic enones from enynes can be obtained through CO insertion into zirconacyclopen-tenes followed by a subsequent rearrangement (Scheme 5.7). The scope and limitations of this procedure have been described in detail elsewhere [8d]. This procedure provides a complementary version of the well-known Pauson Khand reaction [9]. 

Recent developments have impressively enlarged the scope of Pauson-Khand reactions. Besides the elaboration of strategies for the enantioselective synthesis of cyclopentenones, it is often possible to perform PKR efficiently with a catalytic amount of a late transition metal complex. In general, different transition metal sources, e.g., Co, Rh, Ir, and Ti, can be applied in these reactions. Actual achievements demonstrate the possibility of replacing external carbon monoxide by transfer carbonylations. This procedure will surely encourage synthetic chemists to use the potential of the PKR more often in organic synthesis. However, apart from academic research, industrial applications of this methodology are still awaited. 

The asymmetric catalytic Pauson-Khand reaction met success in the late 1990s. Not only the conventional Co catalyst but also other metal complexes, such as Ti, Rh, and Ir, are applicable to the reaction. Asymmetric hydrocyanation of vinylar-enes is accomplished using Ni complex of chiral diphosphite. Further studies on the scope and limitation are expected. 

Increasing reactivity in the Pauson-Khand reaction. The PK reaction originally suffered from a lack of substrate scope and low reaction yields which prevented it from being widely employed. The discovery of new reaction conditions (additives and modified methods) led to an improvement in yields and reaction times, allowing the scope of the reaction to be expanded. 

Few organic transformations add as much molecular complexity in one step as the Pauson-Khand reaction. This reaction is one of the best examples of how organometallic chemistry is useful in modern organic synthesis, and can serve as a key tool for the synthesis of natural products, in this case those possessing cyclopentane units. The limited scope, low yields and lack of efficient catalytic procedures were serious drawbacks in the past that have been... 

Variations on the hydrazulene skeleton have been approached via the Pauson-Khand reaction, several with high regio- and diastereo-selectivity. Pauson s cycloadditions of cycloheptene provided the Brst entries but were limited in scope and efficiency (equation 39).2° Several synthetic equivalents of cyclohep-tenes displaying greater reactivity include 8-oxa- and 8-aza-bicyclo[3.2.1]oct-6-enes (equations 48 and... 

Preston, A. J., Parquette, J. R. A pyridylsilyl group expands the scope of the intermolecular Pauson-Khand reactions. Chemtracts200Z, 16, 435-438. 

Apart from studies by Pauson and coworkers, this reaction was not widely investigated until the seminal report by Schore in 1981 which detailed the first intramolecular example of a Pauson-Khand reaction [10]. Following this report, activity in this area flourished, and the frequent apphcation of this methodology in the total synthesis of natural and unnatural products demonstrated the versatility of this reaction. A detailed discussion of these efforts is beyond the scope of this article, but a number of excellent reviews on the subject have been published [11]. 

While the Pauson-Khand reaction represents a very special cyclopentenone synthesis, our next topic - the metathesis cyclization reaction (MCR) - has the advantage of having a very broad scope in alicyclic as well as heterocyclic chemistry. 

The formal [2 + 2+1] cycloaddition between an alkyne, an alkene and carbon monoxide has become commonly known as the Pauson-Khand (PK) reaction and has undergone extensive investigation since its initial discovery.4 7 Recent improvements in the reaction conditions and an increase in substrate scope has led to the reaction becoming an important method for the preparation of cyclopentenones. 

The first report of a catalytic intermolecular cyclization was made by Pauson and Khand in 1974 [22], but the scope was limited to gaseous acetylene as the alkyne partner, strained olefins such as norbornene and norbornadiene as the alkene component, and TON s (turnover numbers) were modest (8-11). Several subsequent reports detailed the production of cyclopentenones from a substoi-chiometric amount of Co2(CO)g, but none were as efficient as Pauson s initial work [23,24]. Using ethylene as the alkene component, Rautenstrauch demonstrated the first efficient catalytic Pauson-Khand cyclization with a TON of 220, Eq. (5) [25]. A more general catalyst system employing (indenyl)Co(cod) was recently reported by Chung and Jeong, Eq. (6) [26]. The reaction was quite effec-... 

The scope of the intramolecular Pauson-Khand has been rapidly expanded as both more complex and heteroatom-containing substrates have been employed. Cycloadditions involving a cycloalkene reaction partner afford the direct construction of tricyclic systems in a single step. Triquinacene derivatives are efficiently obtained from 3-(3-butynyl)cyclopentenes [Eq. (55)]. An unusual characteristic of this system is the epimerization that occurs at the pro-pargylic position subsequent to cobalt complexation but prior to cyclization. The steric demands on the reaction are evidently so large that one stereoisomer is unable to cyclize and, instead, isomerizes through a cobalt-stabilized propargylic cation [123]. 

The scope of Pauson-Khand type reactions has been expanded by exploring the use of various carbon components. Dienyne 350 is a versatile substrate, which can be subjected to two cycloaddition pathways (Scheme 2-21). In 2003, Wender et al. reported the Rh-catalyzed PK-type reaction of350. Under unoptimized conditions, 350 underwent three competing cycloadditions, i.e., 1) an intramolecular [4+2] cycloaddition to afford product 351, 2) a new version of a [2+2+1] cycloaddition to afford product 352, and 3) an unprecedented [4+2+1] cycloaddition to afford product 353. After further refinement, the [2+2+1] product 352 was obtained in excellent yield.t >... 

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