Urea-derived catalysts addition

A screening of (R)-bis-N-tosyl-BlNAM 151 and axially chiral (thio)urea derivatives 152-162 (10mol% loading 0.36 M catalyst concentration incorporating the N-aryl(alkyl) structural motif was performed at various reaction temperatures in di-chloroform using the asymmetric FC addition of N-methylindole to trans-Ji-nitrostyrene as model reachon (product 1 Scheme 6.158). The structure of bis(3,5-bistrifluoromethyl) phenyl functionalized binaphthyl bisthiourea 158 was identified... 

Using this protocol, primary aliphatic amines, secondary aliphatic amines, and diamines could be converted into the corresponding urea derivatives in moderate yields. Additionally, catalytic efficiency of cations derived from various bases decreases in the order of > diamines > primary amines > secondary amines > aniline, probably being due to the steric effect and basicity. The catalyst could also be recovered after a simple separation procedure, and reused over five times with retention of high activity. This process presented here could show much potential application in industry due to its simplicity and ease of catalyst recycling. 

If the latter reaction proceeds through a closed transition state (e.g., 5 in Scheme 7.2), good diastereocontrol can be expected in the case of trans- and cis-CrotylSiCl3 (2b/2c) [14, 15]. Here, the anh-diastereoisomer 3b should be obtained from trans-crotyl derivative 2b, whereas the syn-isomer 3c should result from the reaction of the cis-isomer 2c (Scheme 7.2). Furthermore, this mechanism creates an opportunity for transferring the chiral information if the Lewis base employed is chiral. Provided that the Lewis base dissociates from the silicon in the intermediate 6 at a sufficient rate, it can act as a catalyst (rather than as a stoichiometric reagent). Typical Lewis bases that promote the allylation reaction are the common dipolar aprotic solvents, such as dimethylformamide (DMF) [8,12], dimethyl sulfoxide (DMSO) [8, 9], and hexamethylphosphoramide (HMPA) [9, 16], in addition to other substances that possess a strongly Lewis basic oxygen, such as various formamides [17] (in a solution or on a solid support [7, 8, 18]), urea derivatives [19], and catecholates [10] (and their chiral modifications [5c], [20]). It should be noted that, upon coordination to a Lewis base, the silicon atom becomes more Lewis acidic (vide infra), which facilitates its coordination to the carbonyl in the cyclic transition state 5. 

One of the most common methods employed for the generation of allylpalladium complexes involves oxidative addition of allylic electrophiles to Pd . This transformation has been explored by several groups, and has been the topic of recent reviews [69]. A representative example of this process was demonstrated in a recent total synthesis of (+ )-Biotin [70]. The key step in the synthesis was an intramolecular amination of 89, which provided bicydic urea derivative 90 in 77% yield (Eq. (1.40)). In contrast to the Pd"-catalyzed reactions of allylic acetates bearing pendant amines described above (Eq. (1.10)), which proceed via alkene aminopalladation, Pd -catalyzed reactions of these substrates occur via initial oxidative addition of the allylic acetate to provide an intermediate Jt-allylpalladium complex (e.g., 91). This intermediate is then captured by the pendant nudeophile (e.g., 91 to 90) in a formal reductive elimination process to generate the product and regenerate the Pd catalyst. Both the oxidative addition and the reductive elimination steps occur with inversion... 

Vilar and coworkers [59] have investigated the use of additives to suppress olefin migration in the self-metathesis of urea derivatives (Scheme 12.33). The Af-allyl urea 109 was found to undergo self-metathesis in the presence of Ru catalyst 3 in 33% yield. The isomerized species 110 was isolated as the major product (55% yield, Z= 1 1). Vilar and coworkers identified phenylphosphoric acid (112) as an effective inhibitor of the undesired alkene isomerization. When the metathesis of Af-allyl urea 109 was performed with phenylphosphoric acid (50mol%), the desired dimer 111 was isolated in 56% yield, and 30% of the starting material 109 could be recovered. The authors also investigated the use of benzoquinone derivatives, and found that 2,6-dichloro-l,4-benzoquinone (10 mol%) was equally... 

Chiral Lewis-basic catalysts, in particular phosphoratnides (1 and 2),2-13c. 16.46,47 pyridine iV,iV-bisoxides (3 and and pyridine iV-monoxides (5, 6 and 7,8),3 exhibit very high enantioselectivities for the allylation of aromatic, heteroaromatic, and cinnamyl-type aldehydes with allyl, ( )- and (Z)-crotyl, and prenyl trichlorosilanes. Chiral formamides, pyridine-oxazolines, urea derivatives, and sulfoxides are generally less enantioselective and effective only in stoichiometric quantities. The reaction is much less efficient with aliphatic aldehydes, which require stoichiometric conditions (vide infra). However, a, -unsaturated aldehydes do react readily and give 1,2-addition products. 

It was in 1994 that urea derivatives were employed as catalysts for the radical addition reactions, where addition of urea increased the reaction rate and also altered the stereochemistry in the allylation reaction of the sufinyl radical with... 

Very recently, Lu et al. reported an asymmetric version of this reaction for the generation of chiral oxazolidin-2-one derivatives [41]. Additionally, C -symmetric urea with a multiple hydrogen-bonding site was exploited as a Bronsted acid catalyst to realize reactivity control and enanlioselectivity induction (Scheme 9.45). 

Recently, enantioselective organo-catalytic procedures for the aza-Henry reaction have been disclosed. The presence of either an acidic or a basic function appears to be a requisite of the catalyst. In fact, the condensation of ni-tromethane with M-phosphinoyl arylimines 72 is catalyzed by the chiral urea 85 derived from (R,R)-l,2-diaminocyclohexane and gives the product (R)-74 with good yield and moderate enantioselectivity (Scheme 15) [50]. The N-phosphinoyl substituent is determinant, as the addition of nitromethane to the N-phenyl benzaldimine failed and the reaction of the N-tosyl ben-zaldimine gave the expected adduct with quantitative yield but almost no... 

Hydroaminomethylahon of alkenes [path (c)j wiU not be considered [12]. This review deals exclusively with the hydroaminahon reaction [path (d)], i.e. the direct addition of the N-H bond of NH3 or amines across unsaturated carbon-carbon bonds. It is devoted to the state of the art for the catalytic hydroamination of alkenes and styrenes but also of alkynes, 1,3-dienes and allenes, with no mention of activated substrates (such as Michael acceptors) for which the hydroamination occurs without catalysts. Similarly, the reachon of the N-H bond of amine derivatives such as carboxamides, tosylamides, ureas, etc. will not be considered. 

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