Nucleophiles Pauson-Khand reaction

Scheme 6/4.8. Combination of a nucleophilic substitution and a Pauson-Khand reaction.

Also alkynylcarbene complexes can react as Michael acceptors with nucleophiles, forming 1,3-dien-l-ylcarbene complexes (Figure 2.17). Both carbon nucleophiles, such as, e.g., enamines [246-249], and non-carbon nucleophiles, such as imidates [250], amines [64,131,251], aliphatic alcohols [48,79,252], phenols [252], and thiols [252] can add to the C-C triple bond of alkynylcarbene complexes. Further reactions of the C-C triple bond of alkynylcarbene complexes include 1,3-dipolar [253,254], Diels-Alder [64,234,238,255-258] and [2 -i- 2] cycloadditions [259 -261], intramolecular Pauson-Khand reactions [43,262], and C-metallation of ethynylcarbene complexes [263]. 

The asymmetric reactions discussed in this chapter may be divided into three different types of reaction, as (1) hydrometallation of olefins followed by the C—C bond formation, (2) two C C bond formations on a formally divalent carbon atom, and (3) nucleophilic addition of cyanide or isocyanide anion to a carbonyl or its analogs (Scheme 4.1). For reaction type 1, here described are hydrocarbonyla-tion represented by hydroformylation and hydrocyanation. As for type 2, Pauson-Khand reaction and olefin/CO copolymerization are mentioned. Several nucleophilic additions to aldehydes and imines (or iminiums) are described as type 3. 

Deoxypolypropionates, via ZACA reaction, 10, 273 13-Deoxyserratine, via Pauson-Khand reaction, 11, 360 2-Deoxy sugars, via rhodium(II)-catalyzed intramolecular nitrene C-H insertions, 10, 203-204 Deprotection reactions, by nucleophilic tellurium species,... 

Some of the most exciting reactions in organic chemistry are based on transition metals. How about these two for example The first is the Heck reaction, which allows nucleophilic addition to an unactivated alkene. Catalytic palladium (Pd) is needed to make the reaction go. The second, the Pauson-Khand reaction, is a special method of making five-membered rings from three components an alkene, an alkyne, and carbon monoxide (CO). It requires cobalt (Co). Neither of these reactions is possible without the metal. 

From alcohols. Alcohols can be transformed into phenylselenides in a stepwise manner via mesylation and reaction with lithium phenylselenolate. This procedure offers obvious advantages over the formation of the corresponding bromides or iodides when subsequent reaction with strong nucleophiles, such as organolithium compounds, are necessary to prepare the radical precursors. The diol 8 is converted to the bis(phenylselenide) 9 via the corresponding bis(mesylate) as shown in Scheme 2 [6]. Compound 9 is converted to the radical precursor 11 via reaction with lithium phenylacetylide followed by alkylation with allylbromide and a Pauson-Khand reaction. Such a reaction sequence would not be feasible with an alkyl halide. The cyclization afforded the expected tricyclic compound 12 in 95% yield. 

Tandem Nucleophilic Coupling/Pauson-Khand Reaction... 

Advantage can be taken of several effects of the cobalt complexation of alkynes (Scheme 7.23). This is most often by using the cation stabilization effect to form the substrate for the Pauson-Khand reaction. The dicobalt complex of vinyl acetylene 7.82 underwent a Friedel-Crafts like acylation reaction, via a cobalt-stabilized cation 7.83." The cation was then trapped by an added nucleophile, methanol. Reduction of the ketone 7.84, followed by an intramolecular Pauson-Khand reaction yielded the tricyclic compound 7.85. 

The Nicholas and Pauson-Khand reactions, as well as the bond-angle effect, have been combined in a single synthetic scheme to make more efficient use of the cobalt. This has been done in a synthesis of epoxydictamine 7.90 (Scheme 7.24)." The Nicholas reaction was employed, in which a carbocation 7.87, generated from acetal 7.86, was trapped by an allylsilane nucleophile intramolecularly, to form the eight-membered ring... 

A similar Nicolas-Pauson-Khand combination was used in a synthesis of the ketone analogue of biotin 7.98, required for biochemical studies (Scheme 7.25). In this case, the Nicholas reaction was intermolecular, between allyl thiol as the nucleophile and carbocation 7.94 generated from alcohol 7.93. The Pauson-Khand reaction was then between the dicobalt complexed alkyne 7.95 and the double bond from the thiol moiety. The Pauson-Khand reaction proceeded with no stereoselectivity, and the diastereoisomers had to be chromatographically separated at a later stage. The synthesis was completed by reduction of the alkene of cyclopentenone 7.96, without using palladium-catalysed hydrogenation due to the sulfide moiety, and ester hydrolysis. 

Numerous carbon nucleophiles participate in the Nicholas reaction the most popular are electron rich aromatics, enamines, enol ethers, ketene acetals, alkenes, allylsilanes, allylstannanes, and organoaluminum compounds. Upon completion of the substitution reaction, the cobalt complex can be oxidatively removed with E, Fe(III), or Ce(IV). Additional chemistry based on cobalt-complexed alkynes, like the Pauson-Khand reaction, can also be performed to further increase molecular complexity. 

The most impressive use of a tandem strategy involving the Nicholas reaction in a total synthesis project is Schreiber s preparation of (+)-epoxydict5miene (61). Cobalt complexation of 58 followed by an endocyclic intramolecular Nicholas reaction with an allylsilane nucleophile yields Pauson-Khand precursor 59. Treatment of 59 with iV-methylmorpholine-iV-oxide (NMO) promotes the Pauson-Khand reaction to furnish tetracycle 60 which was ultimately converted to the target natural product 61. ... 

Other synthetic reactions. Catalyzed elimination of allylic carbonates occurs in the absence of nucleophiles. Alkynediols undergo isomerization and dehydration, furnishing 2,5-disubstituted furans as a result. 1-Carboranyltributyltin adds to aldehydes under the influence of the Pd catalyst to form carbinols. The Pd version of a Pauson-Khand cyclopentenone synthesis is accomplishable in the presence of CO, and actually this version is specially suited for a one-step construction of a -methylenecyclopentenones. ... 

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