Annulations phosphine-catalyzed

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. 

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... 

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... 

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). 

The phosphine-catalyzed [4-1-2] annulation of allenoates with activated olefins 427 affords the annulation products 428 or 429 depending on the phosphine catalyst being used... 

The multifunctional thiourea-phosphine-catalyzed asymmetric [3-1-2] annulation of MBH carbonates with maleimides affords functionalized fused cyclopentenes bearing three contiguous stereogenic centers with high enantiomeric excess (Scheme 6.29) [33]. 

D-Threonine-L-tert-leucine-derived bifunctional phosphine catalyzes highly enan-tioselective [3+2] annulation of maleimides with allenes, allowing the synthesis of optically active, functionalized bicyclic cyclopentenes containing two tertiary stereogenic centers (Scheme 6.30) [34],... 

Zhou, R., Wang, J., Song, H., He, Z. (2011). Phosphine-catalyzed cascade [3 -(- 2] cyclization-allylic alkylation, [2 -F 2 -F 1] annulation, and [3 -F 2] cyclization reactions between aUylic carbonates and enones. Orgaiuc Letters, 13, 580-583. 

Tian, J., He, Z. (2013). Phosphine-catalyzed [3-f2] annulation of a-substituted aUenoates with ester-activated a,f)-unsaturated imines a novel variation of the Lu [3-f2] cycloaddition reaction. Chemical Communications, 49, 2058-2060. 

Deng, H.-R, Wei, Y, Shi, M., (2011). Highly regio- and diastereoselective construction of spirocyclopenteneoxindoles through phosphine-catalyzed [3 -l- 2] annulation of Morita-Baylis-Hillman carbonates with isatylidene malononitriles. Organic Letters, 13, 3348-3351. 

Duvvuru, D., Pinto, N., Gomez, C., Betzer, J.-F., RetaUleau, R, Voituriez, A., Marinetti, A. (2012). Heterocyclic spiranes and dispiranes via enantioselective phosphine-catalyzed [3+2] annulations. Advanced Synthesis Catalysis, 354, 408-414. 

SCHEME 2.104 Synthesis of bicyclic heterocycles through a phosphine-catalyzed annulation... 

In 2003, Lu and coworkers reported the first phosphine-catalyzed yhde reactions in an aUyhc yhde [3-1-2] annulation reaction. AUyhc bromides 26 reacted with dually activated olefins 27 or 28 smoothly at 90 C in the presence of a catalytic amount of PPh3, affording the [3-1-2] cydoaddition products 29 and 30 respectively, in moderate to good yields with high diastereoselectivily (Scheme 20.24) [4d, 44]. 

Scheme 20.24 Phosphine-catalyzed ylide annulation reaction of allylic bromide.

Scheme 20.25 Proposed mechanism of the phosphine-catalyzed annulation reaction.

The introduction of the activated allylic bromides and Morita-Baylis-HiUman acetates and carbonates pioneered the development of a number of phosphine-catalyzed reactions in subsequent years [45]. Interestingly, the asymmetric variant of this type of transformation only appeared in the literature seven years later. In 2010, Tang, Zhou, and coworkers disclosed a highly enantioselective intramolecular ylide [3-1-2] annulation using spirobiindane-based phosphine catalyst 31 (Scheme 20.27). BINAP was found inactive in this reaction even at an elevated temperature (70°C). Notably, both optically active benzobicyclo[4.3.0] compounds 32 and 32 with three continuous stereogenic centers could be obtained as major products in high yields and stereoselectivities just by a choice of an additive [Ti(OPr )4], which can block the isomerization of the double bond [46]. 

Scheme 20.27 Spiro-phosphine-catalyzed asymmetric annulation reactions.

Based on the bicyclic structure of the octahydro-1,6-naphthyridin-4-one 92, a chemical library was prepared by employing a solid-phase synthesis technique and evaluated by an EC activation assay that measured the production of macrophage inflammatory protein 1 beta (MIPljS), a marker of EC activation by IFNy. Reaction conditions were first established by using SynPhase lanterns as solid supports. Allenoate 93 was subjected to a phosphine-catalyzed [4 + 2] annulation reaction with A-tosylbenzaldimine 94. 

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

Yao et al. [35] developed a highly efficient annulation of 2-(l-hydroxy-3-aiyl-prop-2-ynyl)phenols leading to the key intermediates to synthesize aiuones catalyzed by silver NPs/carbon black-supported silver NPs (Scheme 5.7). In the presence of a phosphine ligand, both the catalysts show excellent catalytic activities in the reaction and give the products with good yields as well as excellent legioselec-tivities and stereoselectivities in a water-toluene mixed solvent. 

Zhao, Q., Han, X., Wei, Y., Shi, M., Lu, Y. (2012). Asymmetric [3-1-2] annulation of allenes with maleimides catalyzed by dipeptide-derived phosphines facile creation of functionalized bicyclic cyclopentenes containing two tertiary stereogenic centers. Chemical Communications, 48, 970-972. 

In this work, the combination of cinchona-alkaloid-derived primary amine and Au(I) phosphine complex has been employed to effect two consecutive Friedel-Crafts-type reactions of pyrrole in one pot to furnish 2,3-annulated pyrroles containing a seven-membered ring (eq 1) This reaction proceeds through initial asymmetric 1,4-addition of p)rrole to enones catalyzed by the primary amine followed by an intramolecular 7-c/ido-dig cycliza-tion catalyzed by the Au(I) phosphine complex. 

A phosphane-catalyzed [4 - -1] annulation between nitroalkenes and Morita-Baylis-Hillman carbonates was performed by He and co-workers. " The authors claimed the in situ formation of an allylic phosphorus ylide as an active intermediate. Allenoates and enones were able to form cyclopentenes via two cycloaddition reactions they underwent a [3 -F 2] or a [2 -F 4] process in the presence of catalytic phosphines or amines, respectively (Scheme 15). To explain such a different reactivity, Huang, Lankau and Yu, carried out M06-2X/6-31- -G calculations to study the role of ylide intermediates. ... 

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