Subject electron-deficient

In a recent study, we showed that the more flexible pyrido[l,2-a]indole-based cyclopropyl quinone methide is not subject to the stereoelectronic effect.47 Scheme 7.17 shows an electrostatic potential map of the protonated cyclopropyl quinone methide with arrows indicating the two possible nucleophilic attack sites on the electron-deficient (blue-colored) cyclopropyl ring. The 13C label allows both nucleophile attack products, the pyrido[l,2-a]indole and azepino [l,2-a]indole, to be distinguished without isolation. The site of nucleophilic is under steric control with pyrido [1,2-a]indole ring formation favored by large nucleophiles. 

The recombinantly expressed nitrilase from Pseudomonas fluorescens EBC 191 (PFNLase) was applied in a study aimed at understanding the selectivity for amide versus acid formation from a series of substituted 2-phenylacetonitriles, including a-methyl, a-chloro, a-hydroxy and a-acetoxy derivatives. Amide formation increased when the a-substituent was electron deficient and was also affected by chirality of the a- stereogenic center for example, 2-chloro-2-phenylacetonitrile afforded 89% amide while mandelonitrile afforded 11% amide from the (R)-enantiomer but 55% amide was formed from the (5)-enantiomer. Relative amounts of amide and carboxylic acid was also subject to pH and temperature effects [87,88]. 

The epoxidation of electron-deficient alkenes, particularly a,P-unsaturated carbonyl compounds, continues to generate much activity in the literature, and this has been the subject of a recent concise review <00CC1215>. Additional current contributions in this area include a novel epoxidation of enones via direct oxygen atom transfer from hypervalent oxido-).3-iodanes (38), a process which proceeds in fair to good yields and with complete retention of... 

It is obvious that studying interligand Si-H interactions has reached a great extent of sophistication. At least three classes of nonclassical Si-H bonding can be identified. These are the electron-deficient residual Si H interactions in silane a-complexes and agostic complexes, electron-rich IHI MH SiX, and the more recent multicenter H Si interactions, which are the subject of current debate and have features common to both IHI and a-complexes. This surprising diversity stems from the special role the substituent at silicon can play in tuning the extent of Si H interaction, and from the propensity of silicon to be hypervalent. 

Zimmerman and Hoffacker also observed a regioselective reaction subjecting various aryl-substituted 1,4-pentadienes to photoinduced electron transfer using DCN and DCA. The radical cations produced underwent a regioselective cyclization wherein one electron-deficient aryl group of one diarylvinyl moiety bonds to the (3-carbon of the second diarylvinyl group (Scheme 30) [41]. 

In the process of developing the Stetter reaction in ionic liquids, Gree and coworkers applied their methodology to the synthesis of haloperidol (Scheme 25) [101], A variety of aromatic aldehydes react with methyl acrylate 160 when butyl-methylimidazolium tetrafluoroborate [bmim][BF ] is used as solvent. In the synthesis of haloperidol, electron-deficient aldehyde 153 was subjected to standard reaction conditions with 160 to provide 161 in good yield. 

Rhodium-catalyzed asymmetric conjugate addition has enjoyed uninterrupted prosperity since the first report by Hayashi and Miyaura [6]. Its high enantioselectivity and wide applicability are truly remarkable. However, some problems still remain, since the carbon atoms that can be successfully introduced by this rhodium-catalyzed reaction have been limited to sp carbons and the substrates employed have been limited mostly to the electron-deficient olefins free from sterically bulky substituents at a- and / -positions. These issues will be the subject of increasing attention in the future. 

Another approach employing chiral acyclic azomethine ylides was published in two recent papers by Alcaide et al. (85,86). The azomethine ylide-silver complex (51) was formed in situ by reaction of the formyl-substituted chiral azetidinone (50) with glycine (or alanine) in the presence of AgOTf and a base (Scheme 12.18). Azomethine ylides formed in this manner were subjected to reaction with various electron-deficient alkenes. One example of this is the reaction with nitrostyrene, as illustrated in Scheme 12.18 (86). The reaction is proposed to proceed via a two step tandem Michael-Henry process in which the products 52a and 52b are isolated in a... 

Other chiral azomethine ylide precursors such as 2-(ferf-butyl)-3-imidazolidin-4-one have been tested as chiral controllers in 1,3-dipolar cycloadditions (89). 2-(ferf-Butyl)-3-imidazolidin-4-one reacted with various aldehydes to produce azomethine ylides, which then were subjected to reaction with a series of different electron-deficient alkenes to give the 1,3-dipolar cycloaddition products in moderate diastereoselectivity of up to 60% de. 

The use of chiral azomethine imines in asymmetric 1,3-dipolar cycloadditions with alkenes is limited. In the first example of this reaction, chiral azomethine imines were applied for the stereoselective synthesis of C-nucleosides (100-102). Recent work by Hus son and co-workers (103) showed the application of the chiral template 66 for the formation of a new enantiopure azomethine imine (Scheme 12.23). This template is very similar to the azomethine ylide precursor 52 described in Scheme 12.19. In the presence of benzaldehyde at elevated temperature, the azomethine imine 67 is formed. 1,3-Dipole 67 was subjected to reactions with a series of electron-deficient alkenes and alkynes and the reactions proceeded in several cases with very high selectivities. Most interestingly, it was also demonstrated that the azomethine imine underwent reaction with the electronically neutral 1-octene as shown in Scheme 12.23. Although a long reaction time was required, compound 68 was obtained as the only detectable regio- and diastereomer in 50% yield. This pioneering work demonstrates that there are several opportunities for the development of new highly selective reactions of azomethine imines (103). 

Recall that the LUMO shows which regions of a molecule are most electron deficient, and hence most subject to nucleophilic attack. One such region is over the carbonyl carbon, consistent with the observation that carbonyl compounds undergo nucleophilic addition at the carbonyl carbon. Another region is over the P carbon, again consistent with the known chemistry of a,P-unsaturated carbonyl compounds, in this case conjugate or Michael addition. 

Condensation products of 4(5//)-oxazolonium salts with aldehydes and orthoesters are the subject of a series of papers by Kosulina and co-workers Reaction of 2-methyl-4(5//)-oxazolonium perchlorates 44 with an ortho ester gives rise to an enol ether, which reacts with furanamides to afford the frani-eneamides 45 (Scheme 6.14). " Using electron deficient anilines in a three component condensation affords either 46 or 47 in 64-80% and 78-84% yields, respectively, depending on whether the reaction is performed in acetic acid or acetic anhydride. Electron-rich anilines are unreactive since they are merely protonated by the perchloric acid present in the reaction medium. ... 

The mechanism for the polymerization probably fits the general pattern of electrophilic attack by the initiator on the carbonyl oxygen atom for the initiation step, with propagation taking place by attack of the electron deficient C-4 of the last unit of the growing chain on the carbonyl group of a monomer molecule. Certain modifications of this general mechanism are apparently observed with specific catalysts, and the subject appears to need further study. 

The LUMO delineates areas which are most electron deficient, hence subject to nucleophilic attack. On the maps above, regions where the absolute value of the LUMO is greatest are indicated in blue , while regions where it is least are indicated in red . As expected, the blue regions are directly over the carbonyl carbon. More interesting, note that the blue spot over the axial face is larger than that over the equatorial face. This suggests that nucleophilic attack onto the axial face is likely to be more favorable than attack onto the equatorial face, in accord with experimental observation. 

The synthetic utility of a-phosphorus- and a-thio-stabilized carbanions is the subject of numerous reviews.21 Notable are additions of phosphonium ylides (237),183 sulfonium ylides (238),l84 ° oxosulfo-nium ylides (239)184 " and sulfoximine ylides (240)184,1 to electron-deficient alkenes which afford nucleophilic cyclopropanation products. In contrast, with a-(phenylthio)-stabilized carbanions, which are not acyl anion equivalents, either nucleophilic cyclopropanation or retention of the hetero substituent occurs, depending on the acceptor and reaction conditions used. For example, carbanion (241) adds to 1,1-... 

A wide range of alkenes may be used as substrates. The reaction is most commonly performed with alkenes of normal electronic nature, but electron deficient alkenes, such as a, 3-unsaturated carbonyl compounds, and very electron rich alkenes, such as enol ethers and enamines, have also been used successfully. Not surprisingly, the cyclopropylcarbinyl ethers and amines that are formed in the latter reactions (see Table S) are subject to facile rearrangements. 

The electron distribution in the vinylidene ligand, which results in a high electron deficiency on the a-carbon, but with considerable electron density on the / -carbon (see Section VII,A), renders this ligand subject to nucleophilic attack on the former, and electrophilic attack on the latter. 

The catalytic asymmetric epoxidation of electron-deficient olefins, particularly a,P-unsaturated ketones, has been the subject of numerous investigations, and as a result a number of useful methodologies have been elaborated [44], Among these, the method utilizing chiral phase-transfer catalysis occupies a unique position in terms of its practical advantages. Moreover, it also allows the highly enantioselective epoxidation of trans-a,P-unsaturated ketones, particularly chalcone. 

Conclusions drawn from the study of nitration are subject to many serious reservations. As discussed in Section III, the several sets of experimental conditions employed for nitration are not equally selective. Experimental discrepancies contribute further uncertainty. In addition, the nature of the transition state for nitration may limit its utility as a model for other substitution processes. This difficulty is developed by small variations in the degree of electron deficiency in the aromatic fragment of the transition state (Stock and Himoe, 1962). In view of these limitations, a plot of the composite data for nitration under several conditions versus the cr+-constants (Fig. 16) is most encouraging. The reaction constant is — 6.0. 

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