Subject ylide form

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... 

Due the nature of the substituents, all the stable singlet carbenes exihibit some carbon-heteroatom multiple-bond character and for some time their carbene nature has been a subject of controversy. One has to keep in mind that apart from dialkyl-carbenes, all the transient singlet carbenes present similar electronic interactions. As early as 1956, Skell and Garner drew the transient dibromocarbene in its ylide form based on the overlap of the vacant p-orbital of carbon with the filled p orbitals of the bromine atoms (Scheme 8.31). 

Aldol addition and related reactions of enolates and enolate equivalents are the subject of the first part of Chapter 2. These reactions provide powerful methods for controlling the stereochemistry in reactions that form hydroxyl- and methyl-substituted structures, such as those found in many antibiotics. We will see how the choice of the nucleophile, the other reagents (such as Lewis acids), and adjustment of reaction conditions can be used to control stereochemistry. We discuss the role of open, cyclic, and chelated transition structures in determining stereochemistry, and will also see how chiral auxiliaries and chiral catalysts can control the enantiose-lectivity of these reactions. Intramolecular aldol reactions, including the Robinson annulation are discussed. Other reactions included in Chapter 2 include Mannich, carbon acylation, and olefination reactions. The reactivity of other carbon nucleophiles including phosphonium ylides, phosphonate carbanions, sulfone anions, sulfonium ylides, and sulfoxonium ylides are also considered. 

Possibly, the most common protocols used in the generation of azomethine ylides are those based on the in situ, fluorine-mediated desilyation of cyanoami-nosilanes developed by Padwa et al. (2). Typically, treatment of precursor 1 with AgF, in the presence of dimethyl acetylenedicarboxylate (DMAD), led to the formation of the intermediate cycloadduct 2, which was subjected to immediate DDQ oxidation to give pyrrole 3. The mechanistic rationale invokes fluoride-mediated desilyation to form the intermediate anion 4, which then undergoes loss of cyanide furnishing the corresponding azomethine yhde (Scheme 3.1). 

There are very few examples of photolysis being used for preparation of a carbonyl ylide. The Dittami protocol follows work completed from his lab with aryl vinyl sulfides. Photolysis, followed by cycloaddition, led to the cycloadduct 305 in excellent yield and stereoselectivity. If the aryl vinyl ether 304 was subjected to irradiation in a mixed solution of toluene-methanol at 366 nm rather than a single solvent of toluene, cyclized product was obtained, but no cycloadduct was formed. If a simple phenyl aryl ether was subjected to the same tandem conditions, the cyclized product was generated, but no cycloadduct was detected. 

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). 

The mechanism has been the subject of much study.282 That the rearrangement is intramolecular was shown by crossover experiments, by 14C labeling,283 and by the fact that retention of configuration is found at R1.284 The first step is loss of the acidic proton to give the ylide 71, which has been isolated.285 The finding286 that CIDNP spectra287 could be obtained in many instances shows that in these cases the product is formed directly from a free-radical precursor. The following radical pair mechanism was proposed 288... 

Tetraene 12 is formed following the Willig protocol Deprotonation of the phosphonium salt 8 yields a phosphorus ylide which is subjected to condensation with aldehyde 11 (see Chapters 9 and 13). 

Mechanistic studies have been the subject of a great deal of recent work." Although at one time the Wittig reaction was thought to occur through the formation of zwitterionic betaine intermediates (100) and (101), the reaction of a nonstabilized triphenylphosphorus ylide (99) with an aldehyde forms observable (by NMR) 1,2-oxaphosphetanes (104) and (105), which eliminate to produce the alkene (102) and phosphine oxide (103) (Scheme 21). "... 

Selenium and tellurium ylides take part in chemistry which is analogous to the reactions discussed thus far, and the subject has been well reviewed. Both alkenes and epoxides are formed in their reactions. 

A derivative of (S)-prolinol 10.23, quartemized by CICH2CN and then transformed into the ammonium ylide by KO-fert-Bu in DMSO, has been subjected to a [2,3]-sigmatropic rearrangement at -90°C. After hydrolysis of the aminoni-trile formed in this way, an a-chiral P,y-unsaturated aldehyde is formed with an excellent selectivity [261,290, 1008, 1062] (Figure 10.9). 

Enals generated by oxidation of allylic alcohols with Mn02 in the presence of azolium ylides are trapped to form secondary allylic alcohols. These are subject to further oxidation and the resulting ketones undergo alcoholysis in situ. ... 

The addition of aldehydes to carbenoids derived from the Cu-catalyzed decomposition of ArCHNj to form stilbene epoxides is subject to asymmetric induction by 1,3-oxathiane 47 prepared from 10-mercaptoisobomeol and acetaldehyde. The attack of sulfonium ylides derived from 48 on aldehydes also affords epoxides of high optical purity. The same principle underlies a synthesis of chiral aziridines. ... 

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