Cycloisomerization reactions phosphine

In contrast to chiral amines, phosphine-based chiral catalysts were less developed for asymmetric MBH transformations. In the first asymmetric cycloisomerization reaction, the cyclopentenol derivative 233 was prepared from 232 in the presence of (-)-CAMP (Scheme 2.114). ° ° The low asymmetric control (14% ee) was attributed to the reversibility of the cyclization. Notably, this reaction is not suitable for the preparation of six-membered rings. 

Using a protocol for tandem carbonylation and cycloisomerization, Mandai et al.83 were able to synthesize cyclopentene and cyclohexene derivatives in high yield, including fused and 5/>/>0-bicycles (Scheme 25). The cyclohexene Alder-ene products were not isolable methanol addition across the exocyclic double bond (in MeOH/ toluene solvent) and olefin migration (in BuOH/toluene solvent) were observed. The mechanism of methanol addition under the mild reaction conditions is unknown. In contrast to many of the other Pd conditions developed for the Alder-ene reaction, Mandai found phosphine ligands essential additionally, bidentate ligands were more effective than triphenylphosphine. 

The heteroatom-tethered enynes, If-i, were converted to the corresponding bicyclic heterocycles 2f-i without event, thereby further illustrating the scope of this transformation. The [RhCl(CO)2]2-catalyzed PK reaction with the 1,6-enynes Ij and Ij, which have a methyl group at a terminal position of the olefin moiety, furnishes the corresponding bicyclopentenone 2j and 2j in good to excellent yield. Interestingly, treatment of 1 j with a phosphine ligand-bound catalyst, such as 10, affords a mixture of the desired cyclopentenone 2j with the cycloisomerization product 2j (Eq. 1). 

A novel route to biaryls has been reported starting from 1,4-epoxy-1,4-dihydroarenes. These substrates participate in a symmetrical coupling reaction in the presence of Pd(dba)2, Zn, and HSiCls (eq 28). Finally, a heterogeneous catalyst prepared from Pd(dba)2 and a phosphine-containing polymer resin has been found to facilitate the cycloisomerization of enynes in water. ... 

A number of interesting applications of cycloisomerization to natural product syntheses have been carried out by Trost. As an example, total synthesis of picro-toxinin has been achieved based on cycloisomerization (Alder-ene reaction) of the 1,6-enyne system 141 as a key reaction. No satisfactory cyclization of 141 occurred when phosphine ligands such as P(o-Tol)3, DPPB, and triisopropyl phosphite were used. However, smooth cyclization took place to give the Alder-ene product in a quantitative yield at 50 °C when A,A -bis(benzylidene)ethylenediamine (BBEDA) was used as a ligand, and the triol 142 was obtained in 75 % yield after... 

RajanBabu has developed an asymmetric protocol for the heterodimerization of vinyl-arenes and ethenej The use of Hayashi s novel, weakly chelating phosphine 91 is critical to the success of this asymmetric reaction (Scheme 68). 1,6-Dienes (e.g., 92) also undergo direct cycloisomerization in the presence of bis[allyl(bromo)nickel] to afford meth-ylenecyclopentane products (e.g., 93 Scheme 69). The scope of the intramolecular process allows preparation of a variety of carbocyclic and heterocyclic ring systems. A reaction mechanism involving in situ generation of a nickel hydride catalyst, alkene hydro-metalation, cyclization, and p-hydride elimination has been proposed. ... 

Under these conditions, no reaction occurred with the phosphine-based bimetallic species 15a (Table 3, entries I and 2). With the NHC-containing catalyst precursor 16a, full consumption of the starting materials took place within 2 h. The expected RCM cycloadducts 18a,b were, however, accompanied by rearranged products 19a,b formed in almost equimolar proportion (entries 3 and 4). Thus, Ru complex 16a acted as catalyst precursor for both RCM and cycloisomerization of the acyclic a,(o-dienes. A similar twofold... 

There are many examples of preparing cyclopentane structures from enynes by gold-catalyzed carbocyclization reactions. Toste et al. have reported that Au(l)-phosphine complexes act as superior catalysts for isomerization of 1,5-enynes to bicyclo[3.1.0]hexenes [124]. For example, treatment of 1,5-enyne (86) with 1 mol% of PhsP-AuPFfi in dichloromethane at room temperature results in formation of cyclopropane-fused cyclopentene (87) in 99% yield (Scheme 18.30). 1,6-Enynes also undergo similar cycloisomerization to five-membered cyclic compounds under the influence of cationic gold(l) catalysts [125, 126], Hydroxylated enynes are versatile precursors for cyclopentenones by gold-catalyzed cycloisomerization... 

A catalyst system consisting of Pd2(dba)3 and AcOH or PhC02H effectively promotes the Alder-ene-type cycloisomerization of 1,6-enyne 34 to give 1,4-diene 35 (phosphine ligand is sometimes necessary). A cationic Pd(II) hydride species is believed to be generated in these reactions, the anion of which affects catalyst activity and selectivity (eq 22). 

Polystyrene-supported Au catalysts 17 and 18 have been prepared using the route outlined in Scheme 40. Polystyrene bound triphenyl phosphine was treated with [(Me2S)Au]Cl in dichloromethane at room temperature for 6h to obtain 16. Two different heterogeneously supported Au catalysts, 17 and 18 were obtained by simple ion exchange reaction of AgOTf and AgNTf2 wifh 16. These two catalysts were used to provide the furan derivative by the intramolecular 5-endo-dig cycloisomerization of alkynyl-diol (Scheme 41) [63]. 

Finally, in recent years, intramolecular transformations involving two gold catalyst units have been discovered and studied. While the initial observations were made by Houk and Toste in 2008 when working on the cycloisomerization of enynes with a phosphine-gold complex, numerous further developments were made by the group of Hashmi. More specifically, it was shown that NHC-Au species were the most efficient catalysts to perform the cycloisomerization of a series of diynes (Scheme 11.12). Recently, digold species have been identified as reaction intermediates. Stable digold complexes have also been synthesized and isolated they have proved to be valuable catalyst precursors for a series of transformations. ... 

A related reaction to hydration of alkynes is intramolecular addition of alcohols to a triple bond. This reaction was used for cycloisomerization of homo-propargyl alcohols to the butyrolactones 79 and it was catalyzed by the ruthenium complex (rj -C5H5)Ru(COD)Cl 78 in a combination with tris(furyl) phosphine (TFP), an ammonium salt and an oxidant (NOHS=iV-hydroxysuc-cinimide) (Scheme 31). 

Best results were obtained with Rh(PR3)3Cl and [Rh(COD)Cl]2 catalysts in the presence of an excess of electron-poor triaryl phosphines to avoid undesirable dimerization/oligomerization processes. The proposed reaction mechanism involves the formation of the Rh-vinylidene complex followed by the intramolecular endo-dig cyclization. The protodemetallation of intermediate I seems to be the more plausible path, whereas the formation of the Rh-oxacarbene complex II was excluded because all attempts to generate lactones by using N-hydroxysuccinimide failed and the cycloisomerization product was the only product obtained (Scheme 10). 

Beside ene-type cyclizations, chiral phosphine-palladium complexes have been applied to only a few cycloisomerization processes, leading to 6-membered compounds. In aU these reactions SEGPHOSs are the preferred Ugands (Fig. 10.11). 

From this short overview it appears that the majority of the recent studies on enantioselective cycloisomerizations have been focused so far on asymmetric Alder-ene type cyclizations with Pd and Rh catalysts, since these reactions represent an economical access into synthetically usefiil cyclopentene and cyclohexene frameworks (Sects. 10.2.1 and 10.3.1). For these processes, efficient chiral catalysts have been afforded mainly by atropisomeric diphosphines, but also DuPHOS, Skewphos and phosphine-oxazolines can occasionally represent suitable auxiliaries. 

Uozumi et al. developed paUadium-phosphine complex catalysts supported on amphiphilic polysterol/PEG resins. These polymer-bound amphiphiHc complexes were tested in the Heck reaction of various aryl hahdes and alkenes, giving the corresponding styrene derivahves in quantitative yields (Scheme 8.27a). Other catalytic reactions (e.g., Suzuki, Sonogashira, cycloisomerization, and hydroxycar-bonylation reactions) (Scheme 8.27b-d) were also realized with these amphiphilic palladium-phosphine complexes under mild conditions (room temperature) over long reaction periods [63]. 

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