Ammonium ylide intermediates

Wittig rearrangement of benzylic quaternary ammonium salts upon treatment with alkali metal amides via the ammonium ylide intermediates. 

Cinchona alkaloids possess a nucleophilic quinuclidine structure and can perform as versatile Lewis bases to react with ketenes generated in situ from acyl halides in the presence of an acid scavenger. The resulting ketene enolates can react with electrophilic C=0 or C=N bonds to deliver chiral [i-lactones [5] or [i-lactams [6], respectively, in a [2 + 2] cycloaddition manner, which is discussed in Chapter 5 in detail. Gaunt et al. also developed practical one pot cydopropanation processes mediated by the modified cinchona alkaloids via ammonium ylide intermediates [7]. Although the catalytic strategy has been well established, the utilization of ammonium enolate based [4 + 2] cycloaddition is rare probably because of the relative unreactivity of the... 

A three-component Mannich-type reaction of a diazo compound, Ph-C(=N2)-C02Me, a carbamate, Bn02CNH2, and an imine, PhCH=NPh, gives access to both syn- and anP-Q ,jS-diamino acid derivatives (20). Co-catalysed by Rh2(OAc)4 and BINAP-derived phosphoric acids, the reaction involves diastereoselectively switch-able enantioselective trapping of proton carbamate ammonium ylide intermediates. (J) High levels of chemo-, diastereo-, and enantio-selectivities were achieved... 

Rhodium-Catalyzed Reactions via Ammonium Ylide Intermediates The chemistry of ammonium ylides, which are generated from a diazo compound and an amine in presence of a rhodium catalyst, has been less explored than that of the oxonium analogues. This is probably due to the lower stability of ammonium ylides, which are prone to undergo 1,2-proton transfer. Since Hu et al. [167] discovered that rhodium(II) acetate can promote the formation of an ammonium ylide, the subsequent trapping of which with benzaldehydes affords p-aryl-p-hydroxy a-amino acids, only a limited number of related reactions have been described. 

Failure to obtain the desired azacarbacephem 331 had to be accepted with the diazetidinone 330. Instead of the hoped-for N/H insertion, the ketocarbenoid derived from 330 attacked the more nucleophilic N-l atom to give an intermediate ammonium ylide which then went on to the products 332 and 334 as suggested... 

Photolysis or thermolysis of heteroatom-substituted chromium carbene complexes can lead to the formation of ketene-like intermediates (cf. Sections 2.2.3 and 2.2.5). The reaction of these intermediates with tertiary amines can yield ammonium ylides, which can undergo Stevens rearrangement [294,365,366] (see also Entry 6, Table 2.14 and Experimental Procedure 2.2.1). This reaction sequence has been used to prepare pyrrolidones and other nitrogen-containing heterocycles. Examples of such reactions are given in Figure 2.31 and Table 2.21. 

Natural (-l-)-polyzonimine (19) has been synthesized by a reaction sequence using the asymmetric [2,3]sigmatropic rearrangement of the ammonium ylide to generate the chiral intermediate. The Homer-Emmons reaction of the ketone... 

The reaction of dichlorocarbene with A, A -diethyl-3-methyl-2-butenamine (100) produced A V-diethyl-4-methyl-2-pentenamide (103) as the major product.51 The formation of this material was attributed to the generation of ammonium ylide 101 followed by a [l,2]-allylic shift to give intermediate 102 which then hydrolyzed during workup to produce amide 103. No product resulting from a [2,3]-sigmatropic rearrangement of ylide 101 was detected in the crude reaction mixture. 

Another interesting use of nitrogen ylides in synthesis was reported by Williams and Miller who employed this intermediate in the preparation of a bicyclo P-lactam. P-Lactam 152 was formed in a single step from the diazo precursor 150.68 The proposed mechanism involves a Rh(II)-catalyzed generation of ammonium ylide 151 which abstracts a proton from the benzylic position and then undergoes N-0 bond heterolysis to generate the cyclized product and benzaldehyde. 

These rearrangement reactions are interpretable in terms of [2.3] sigmatropic shifts of the intermediate ylides. A number of such rearrangements of open-chain systems have been described, involving sulfonium ylides [43] [44] [45], ammonium ylides [46] [57], anions in a-position to oxygen (Wittig rearrangement) [48] [49], and fluorenyl carbanions [50]. 

Allenes can be easily prepared using the 3,2-sigmatropic rearrangement of ylidic intermediates. This methodology also provides a general route towards the synthesis of cumulenes. Some examples using sulfonium and ammonium ylides are collected in Table 5. ... 

West and Naidu found that the diazoketone 358, prepared by alkylating the benzyl ester of L-proline with 5-bromo-l-diazopentan-2-one, cyclized to give a transient spirobicyclic ammonium ylide 359 when heated with coppeifll) acetylacetonate in toluene (Scheme 44) (355,356). This unstable ylide underwent a diastereoselective [1,2]-Stevens rearrangement to give the quinolizidinone 360 and its bridgehead epimer in a ratio of 95 5. However, some racemization (possibly through an achiral diradical intermediate) must have occurred, since 360 had an ee of only 75%. Reduction of the ester and defimctionalization of thioketal 361 with the unusual combination of sodium and hydrazine in hot ethylene glycol completed a synthesis of the unnatural (- )-enantiomer of epilupinine (ent-331). 

A mild and simple reaction of dimethyl acetylenedicarboxylate with ammonium ylides produced tri substituted furans in good yields <05S391>. Reaction of acetylenedicarboxylate with a-bromoketones in the presence of DABCO gave similar products in good yields <05JOC8204>. It seems that the intermediate is the same in both reactions. 

The above results are consistent with formation of an intermediate lithiated epoxide which rearranges via an ammonium ylide 88 (Scheme 15). The ketone 90 then arises from addition of the organolithium (present in excess) to the ester 89 (OH=OLi). Using -PrLi in combination with (-)-sparteine at -98°C yielded 54% of the ester-subsituted indolizidine 89 in 89% ee. A sub-stoichiometric amount of (-)-sparteine (24%) also allowed conversion to proceed to 89 with high ee (82 %), albeit at lower rate. Similarly, a sub-stoichiometric amount of (-)-a-isosparteine (24 mol %) proved to be as good as the stoichiometric combination of (-)-sparteine and i-PrLi. 

To address the need for a more general catal)Tic method of s)mthesizing allylic ammonium ylides for [2,3]-rearrangements that is amenable to enantioselective catalysis, our group recently developed a palladium-catalyzed tandem allylic amination/[2,3]-Stevens rearrangement of tertiary amines that proceeds through a palladium-n-allyl intermediate rScheme 15.34T Metal-catalyzed allylic aminations between primary or secondary amines... 

Based on early mechanistic experiments, we propose that aminoester 139 and palladium(II)-n-allyl conplex 140 establish an unfavorable equilibrium with palladium(0) and ammonium salt 141 (Scheme 1 S.3ST As soon as this unstable ammonium intermediate is formed, it undergoes a rapid deprotonation to generate ammonium ylide 142, which is transformed into the observed [2,3]-rearrangement product 143 through an exo transition state. An unfavorable equilibrium for the palladium-catalyzed ammonium salt formation, in conjunction with the facile conversion of ammonium salts into the [2,3]-rearrangement products, could explain the difficulty in observing any ammonium intermediates. This mechanistic proposal also accounts for why catalytic intermolecular allylic amination with tertiary amines has never been reported before. 

Several years later, Liu and coworkers reported another synthesis of cephalotaxine 172 that relied on a distinct [2,3]-Stevens rearrangement fScheme 1 S.4QL ° Proline derivative 173 was transformed into ammonium ylide 174 in the presence of allyl bromide and K2CO3. This zwitterion rearranged to a-allyl aminoester 175. Hydration of the olefin and reduction of the ester furnished diol 176, which was converted to aminoketone 177 via oxidation and aldol condensation. The assembly of this spirocyclic intermediate represented a formal synthesis of cephalotaxine 172. ... 

Such a reaction course dependence has also been observed in the case of the Rh- or Cu-catalysed three-component reaction of diazoacetates (60) with anilines and p,y-unsaturated a-keto esters (61) (Scheme 8). Depending on the electronic nature of (60) and to a lesser extent on the metal nature of the catalyst (Rh or Cu), the three-component reaction can be directed selectively towards acyclic products (62) or cyclic products (63). The observed regioselectivity has been attributed to the inherent reactivity of the intermediate ammonium ylides (64) according to HSAB principles. 

The [2,3]-Stevens rearrangement is a thermal sigmatropic rearrangement of an ammonium ylide (38) to form unnatural amino acid derivatives 39 (Scheme 12). Traditionally, the ammonium ylides have been formed through alkylation of aminoesters 36 with aUcyl halides 37 to form quaternary salts followed by treatment with base. Although effective, the harsh conditions lead to side products and limited substrate scope. More recently, the coupling of diazoesters 40 and allylic amines 41 in the presence of metals like copper, rhodium, and palladium has been developed for the direct constmction of ammonium ylides 38 via metal carbenoid intermediates. " Although this approach represented an advance over the traditional alkylation chemistry, the use of diazoesters still limits the synthetic utility of these reactions. 

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