Phosphines annulations

The annulation reaction of thioamides with 2-alkynoates and 2,3-dienoates under the catalysis of phosphine provides 4,5-dihydro-1,3-thiazoles, particularly those with 2-aryl substituents (Scheme 14).35... 

Conversion of 172 to the tetracyclic benzo-annulated pyrrolizinone 173 was achieved by using the Heck reaction in DMF/H20 (Scheme 38) the best conversion and yield (80%) were observed in the absence of phosphine ligands <2005JOC268>. 

An allenic ester-tropone annulation is also catalyzed by a phosphine in refluxing benzene, providing a single stereoisomer in good yield [194]. 

Contrary to the phosphine-catalyzed reaction of the allene buta-2,3-dienoate, which adds to CgQ in a ]3-i-2] cycloaddihon ]354], the allene amide 317 forms the cyclobutane annulated fuUerene derivahve in good yields (Scheme 4.63) [355]. The reaction was also performed with similar allene amides bearing a six- or seven-membered lactam. 

Phosphine-catalysed annulation between aldehydes (RCHO) and ethyl allenolate (H2C=C=CHC02Et) gives 6-substituted 2-pyrones (52), proceeding via a zwitterionic (g) enolate.201 The product is derived from the -intermediate, which is favoured by the use of sterically demanding trialkylphosphines, such as tri(cyclopentyl). However, overdoing the phosphine bulk with, for example, the tri(r-butyl) derivative gives no yield. 

Allenylation of N-tosylimines 47 has been shown to effect the Kwon annulation with the allene derivative 48 on catalysis with the axially chiral phosphine 50 (Scheme 7.8), affording the piperidine derivative 49 with good diastereocontrol (9 1) and high enantioselectivity (93% ee) [52, 53]. 

A new synthesis of thiazolines has been described. The annulation of thioamides with 2-alkynoates or 2,3-dienoates in the presence of a phosphine catalyst yields thiazolines in a selective manner <02JOC4595>. 

The annulation reaction is applicable to a variety of aromatic thioamides with both electron withdrawing and donating groups and heteroaryl thioamides such as 2-thienyl and 3-pyridyl. Aliphatic thioamides such as thioacetamide did not undergo clean cyclisation though. When triphenylphosphine was used as the catalyst the reaction required refluxing in toluene however, if more nucleophilic phosphines were used such as tributylphosphine the reaction could be carried out at room temperature <02JOC4595>. 

A variety of small-molecule inhibitors of protein geranylgeranyltransfer-ase type-I (GGTase-I) have been developed over the years. In this chapter, we describe our approach to obtain novel inhibitors of GGTase-I (GGTIs). We screened a library of compounds derived from phosphine-catalyzed annulation reactions of allenoates and A-sulfonyl arylamines and obtained hits, P3-E5 and P5-H6, which exhibited specific inhibition of GGTase-I. Further derivatization of P5-H6 based on the C-terminal sequence of the GGTase-I protein substrates led to the synthesis of P61-A6 that has... 

In this chapter, we describe our effort to develop GGTIs with novel scaffolds [13,14]. Our approach commenced with the constrnction of a novel library of dihydropyrroles and tetrahydropyridines derived from the phosphine-catalyzed annulation of resin-bound allenoates and A-sulfonyl imines. Derivatization of one of the initial hits, dihydropyrrole-carboxyhc... 

Enyne cycloisomerizations can also be exploited to annulate a cyclopentane onto an existing ring system. An example drawn from Trost and co-workers asymmetric total synthesis of picrotoxinin (119) is the conversion of bridged bicyclic intermediate 117 into tricycle 118 (Scheme 6-20) [46]. The optimal cyclization conditions in this case were unusual, requiring an internal proton delivery and a bidentate phosphine. A related example is the conversion of 120 to 121, which was the pivotal step in Trost s synthesis of (—)-dendrobine (122) [47]. An all-carbon tether is not required, as is exemplified by the conversion of 123 to 124 in the total synthesis of ( )-phyllanthocin (125) [48]. Note that in-situ reduction of the o-palladium species prior to /5-hydride elimination has occuined in this latter-example. The enyne disconnection in the synthesis of ( )-phyllanthocin was... 

Heck reactions. The o-oxazolinylphenyl(diphenyl)phosphine ligand 11 is an xcellent ligand to direct enantioselective Heck reactions. On the other hand, the iioxazolinylmethane derivative 12 has been used for the annulation of allenes by means of jnctionalized aryl iodides. ... 

Among a host of other phosphine-catalysed reactions in which the initial step is the formation of a reactive phosphoniobetaine intermediate by addition to a carbon-carbon double or triple bond are intramolecular cyclisations leading to benzobicyclo[4,3,0]-compounds, " cyclic ethers " and lactones,and a great many intermolecular reactions, e.g., a [3 -b 3]-annulation of modified t-butyl allylic carbonates and alkylidenemalonitriles to give cyclohexenes,phosphine- (and fluoride)- catalysed routes to 1,4-benzothiazepines from cyclic sulfenamides and alkynes, a [4- -3]-annu-lation of allylic carbonates with methyl coumalate to give functionalised bicyclo[3.2.2]nonadienes, the a-carbon addition of cyanide ion, generated in situ from cyanohydrins, to activated alkynes, and a stereoselective... 

Bicyclic cyclopenta[fc]dihydrofuran derivatives were produced from y-substituted allenoates, as four-carbon synthons, through phosphine-catalyzed sequential [2 + 3] and [3 + 2] annulation reactions in good-to-excellent yields under mild conditions (14CEJ3520). 

In contrast to the reported modes of reactions of dienes and allene with tropone, phosphine-catalyzed reaction of modified allylic compounds, including acetates, bromides, chlorides or /er/-butyl carbonates derived from the MBH reaction with tropone, afforded [3 + 6] annulation products 488 in... 

After screening phosphine catalysts, it was found that the more nucleophilic EtPh2P was the best catalyst for [3 + 2] annulation of allylic compounds, furnishing 2-substituted 1,1-dicyanoalkenes 22 in up to 95% yield (Scheme 4.7). ... 

Lu s group has developed a novel phosphine-catalyzed [3 + 3] annulation. In their first study, the reaction of the t-butyl allylic carbonate 68 and 2-(l-phenylethylidene)malononitrile 69 with PPhs (10 mol.%) in toluene under reflux, unfortunately, offered a non-cyclized product 70 in 95% yield (Scheme 4.23). By screening the solvent effect, it was found that the reactions in polar solvents eould give higher yields of [3 + 3] eycloadducts 71 than those... 

The [4+3] cycloaddition reaction offers a convenient way to prepare relatively complex seven-membered rings from simple starting materials. Using MBH adducts 352 as C3 component, a phosphine-catalyzed [4 + 3] annulation has been developed to construct the bicyclo[3.2.2]nonadiene skeleton (Scheme 4.112). The reactions proceeds smoothly with various MBH adducts as well as various substituted pyrones 353 such as ester, nitrile and amide substituted pyrones, resulting in compounds 354 in moderate to good yields. 

This strategy yielded a small collection ofindoloquinolizines with yields ranging from 20 to 91%. Low yields were observed in the case of halogen-substituted chromones, and the low-yielding step was found to be the phosphine-catalyzed [4-1-2] annulation of 3-formylchromones 36 with acetylene dicarboxylates 37. Therefore, an alternative domino reaction was developed to bypass this phosphine-catalyzed reaction in order to increase the yield of these halogenated indoloquinolizines. 

The first example of [3 -I- 2] cycloaddition reaction was reported in 2010 by Tang and co-workers [145] when they developed a chiral phosphine catalyzed [3 + 2] intramolecular annulation of BH carbonate with a,(3-unsaturated carbonyl compounds. It showed that spirobiindane-based chiral phosphine (S)-DMM-SITCP (78) was an efficient catalyst to promote this reaction in combination with Ti(OrPr)4 as co-catalyst, affording optically active tricyclic compounds in good yields and ee s (Scheme 9.43). 

---