Alper reaction

Alper reaction. The Alper reaction corresponds to the ring expansion of azir-idines by metal-catalyzed CO insertion (Scheme 3). 

In 1991, El-Ali and Alper reported the cyclocarbonylation reaction of terminal propargyl alcohols with formation of 5,5-disubstituted 2(5//)-furanones using Pd(dba)2 and l,4-bis(diphenylphosphino)butane (dppb) (91JOC4099). However, this reaction was not applicable to internal alkynols. 

Cycloadditions of isocyanates and their derivatives with vinyiaziridines were first reported by Alper and coworkers. From their previous studies of cydoadditions to vinylepoxides or alkylaziridines, they investigated cydoadditions to vinyiaziridines and found that such reactions with isocyanates, carbodiimides, or isothiocyanates in the presence of catalytic amounts of Pd(OAc)2 (2 mol%) and PPh3 (10 mol%) at room temperature afforded five-membered ring products 249 in 34—97% yields (Scheme 2.61) [91]. When an aziridine 247 possessing an alkyl substituent at the... 

For a monograph that discusses most of the reactions in this section, see Stowell, J.C. Carbanions in Organic Synthesis Wiley NY, 1979. For a review, see Noyori, R. in Alper Transition Metal Organometallics, in Organic Synthesis, vol. 1 Academic Press NY,... 

Grushin VV, Alper H (1999) Activation of Otherwise Unreactive C-Cl Bonds. 3 193-225 Guitian E, Perez D, Pena D (2005) Palladium-Catalyzed Cycloaddition Reactions of Arynes. 14 109-146... 

Unlike the case of the Ni-catalyzed reaction, which afforded the branched thioester (Eq. 7.1), the PdCl2(PPh3)3/SnCl2-catalyzed reaction with 1-alkyne and 1-alkene predominantly provided terminal thioester 6 in up to 61% yield in preference to 7. In 1983, a similar hydrothiocarboxylation of an alkene was also documented by using a Pd(OAc)2/P( -Pr)3 catalyst system with t-BuSH to form 8 in up to 79% yield (Eq. 7.6) [16]. It was mentioned in the patent that the Pt-complex also possessed catalyhc activity for the transformation, although the yield of product was unsatisfactory. In 1984, the hydrothiocarboxylation of a 1,3-diene catalyzed by Co2(CO)g in pyridine was also reported in a patent [17]. In 1986, Alper et al. reported that a similar transformation to the one shown in Eq. (7.3) can be realized under much milder reaction conditions in the presence of a 1,3-diene [18], and the carboxylic ester 10 was produced using an aqueous alcohol as solvent (Eq. 7.7) [19]. 

Thiol is acting as a co-catalyst in this transformation. In 1997, Alper et al. reported the reaction of thiols, propargyl alcohol, and CO catalyzed by Pd(PPli3)4 (Eq. 7.20)... 

Carbonylation of alkynes is a convenient method to synthesize various carbonyl compounds. Alper et al. found that carbonylation of terminal alkynes could be carried out in aqueous media in the presence of 1 atm CO by a cobalt catalyst, affording 2-butenolide products. This reaction can also be catalyzed by a cobalt complex and a ruthenium complex to give y-keto acids (Scheme 4.8).92... 

The low catalytic reactivity of aryl chlorides in cross-coupling reactions is usually attributed to their reluctance towards oxidative addition to Pd(0). For a discussion, see V. V. Grushin and H. Alper, Chem. Rev., 94, 1047-1062 (1994), and reference therein. 

A typical second step after the insertion of CO into aryl or alkenyl-Pd(II) compounds is the addition to alkenes [148]. However, allenes can also be used (as shown in the following examples) where a it-allyl-r 3-Pd-complex is formed as an intermediate which undergoes a nucleophilic substitution. Thus, Alper and coworkers [148], as well as Grigg and coworkers [149], described a Pd-catalyzed transformation of o-iodophenols and o-iodoanilines with allenes in the presence of CO. Reaction of 6/1-310 or 6/1-311 with 6/1-312 in the presence of Pd° under a CO atmosphere (1 atm) led to the chromanones 6/1-314 and quinolones 6/1-315, respectively, via the Jt-allyl-r 3-Pd-complex 6/1-313 (Scheme 6/1.82). The enones obtained can be transformed by a Michael addition with amines, followed by reduction to give y-amino alcohols. Quinolones and chromanones are of interest due to their pronounced biological activity as antibacterials [150], antifungals [151] and neurotrophic factors [152]. 

The general concept of phase transfer catalysis applies to the transfer of any species from one phase to another (not just anions as illustrated above), provided a suitable catalyst can be chosen, and provided suitable phase compositions and reaction conditions are used. Most published work using PTC deals only with the transfer of anionic reactants using either quaternary ammonium or phosphonium salts, or with crown ethers in liquid-liquid or liquid-solid systems. Examples of the transfer and reaction of other chemical species have been reported(24) but clearly some of the most innovative work in this area has been done by Alper and his co-workers, as described in Chapter 2. He illustrates that gas-liquid-liquid transfers with complex catalyst systems provide methods for catalytic hydrogenations with gaseous hydrogen. 

Similar 0—4 generations silica-supported Pd-PAMAM dendrimers with various spacer lengths were used by Alper et al. as recyclable catalysts for the hydroesterification reaction of alkenes (55) and the oxidation of terminal alkenes to methyl ketones (56). The hydroesterification experiments (Scheme 16) showed that (PPh3)2Pd-PPh2-PAMAM-Si02 complexes were highly active catalysts for styrene derivatives and linear long-chain alkenes (numbers of turnovers up to 1200). 

Since Alper and co-workers reported the first Rh-catalyzed carbonylative ring expansion of aziridines, yielding /3-lactams in 1989, this ring-expansion reaction catalyzed by Rh or Co complexes and its mechanism have been extensively studied. ... 

As an active initiator for a co-polymerization, acyl-cobalt complexes also work well. As demonstrated by Alper and Lee, an equimolar mixture of Go2(GO)s, benzyl bromide (BnBr), and dihydro-1,10-phenanthroline 17, possibly generating BnGOGo(GO)4 under the reaction conditions, co-polymerized PO or 1,2-butene oxide with GO, and the... 

Alper, E., Mass Transfer with Chemical Reaction in Multiphase Systems, NATO ASI Ser., Vol. I, Nijhoff Publishers, The Hague, 1983. 

A surprising variation on the silylformylation reaction has been reported by Zhou and Alper. A zwitterionic rhodium(I) complex, (l,5-COD)Rh+(Tj6-PhBPh3), catalyzes the silylformylation of alkynes under normal reaction conditions. However, if H2 is added to the system, the reaction may proceed to yield silylalkenals of a different structure. Interestingly, although the H2 must play a key role in the reaction, it is not incorporated in the product. At this time, the mechanistic role of the hydrogen remains unclear. The authors term this reaction a silylhydroformylation [Eq. (51)].126... 

El Ali, B. Alper, H. In Transition Metal Catalyzed Reactions IUPAC Monograph Chemistry for the 21st Century"-, Davies, S. G. Murahashi, S. (Ed.) Blackwell Science Oxford, 1999. 

The first account on the carbonylation of heterocyclic compounds with metallo-dendrimers was recently reported by Lu and Alper using Rh-complexed dendrimers on a resin [207]. The building-block techniques of solid-phase chemistry were used to synthesize dendrimers, followed by phosphonation of the dendrimers with diphenylphosphinomethanol. The resulting phosphonated dendrimers were then reacted with chloro(dicarbonyl)rhodium(I) dimer to give dendritic catalysts A and B (31P NMR, 8 - 25 ppm loading of rhodium A, 0.74 mmol g-1 B, 0.83 mmol g ). As a model study, the reaction of l-ferf-butyl-2-phenylaziridine with carbon monoxide in catalytic presence of A afforded the desired [3-lactam... 

The transition metal-catalyzed carbonylation reaction is an important pathway to introduce an extra carbon atom in the heterocyclic ring. Lu and Alper used this reaction with recyclable palladium-complexed dendrimers on silica to synthesize 1,4-oxazepines. Remarkably, starting from iodinated arylamine 121, as a substrate for the intramolecular carbonylation, quantitative conversion to the pentacyclic heterocycle 122, containing two oxazepine rings, was achieved (Equation 11) <2005JA14776>. 

In 2001, Van den Hoven and Alper reported the unexpected 2(Z)-6(ft)-47/-[l,4]-thiazepin-5-one 215, as the major product, from the reaction of acetylenic thiazole 214 with carbon monoxide and hydrogen in presence of a zwitterionic rhodium complex and triphenyl phosphite. After optimization of the reaction condition, the pressure, and the temperature, up to 90% yield is achieved with good selectivity for thiazepine 215 over thiazole side products 216-218 (Scheme 38) <2001 JA1017>. 

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