Ester stabilized ylide

Stabilized ylides react with aldehydes in water to give Wittig products, sometimes with remarkable acceleration.260 For example, pentafluorobenzaldehyde reacts with ester-stabilized ylide, Ph3P=CHC02Me, at 20 °C in 5 min in 86% yield, with 99 1 E Z-selectivity. Water s ability to stabilize the polar transition state of the reaction, and its participation in the reaction (as determined by deuterium exchange), are discussed. 

To explain the enantioselectivity obtained with semi-stabilized ylides (e.g., benzyl-substituted ylides), the same factors as for the epoxidation reactions discussed earlier should be considered (see Section 10.2.1.10). The enantioselectivity is controlled in the initial, non-reversible, betaine formation step. As before, controlling which lone pair reacts with the metallocarbene and which conformer of the ylide forms are the first two requirements. The transition state for antibetaine formation arises via a head-on or cisoid approach and, as in epoxidation, face selectivity is well controlled. The syn-betaine is predicted to be formed via a head-to-tail or transoid approach in which Coulombic interactions play no part. Enantioselectivity in cis-aziridine formation was more varied. Formation of the minor enantiomer in both cases is attributed to a lack of complete control of the conformation of the ylide rather than to poor facial control for imine approach. For stabilized ylides (e.g., ester-stabilized ylides), the enantioselectivity is controlled in the ring-closure step and moderate enantioselectivities have been achieved thus far. Due to differences in the stereocontrolling step for different types of ylides, it is likely that different sulfides will need to be designed to achieve high stereocontrol for the different types of ylides. 

The N-metallated azomethine ylides having a wider synthetic potential are N-lithiated ylides 141, derived from the imines of a-amino esters, lithium bromide, and triethylamine, and 144 from the imines of a-aminonitriles and LDA (Section II,G). Ester-stabilized ylides 144 undergo regio- and endo-selective cycloadditions, at room temperature, to a wide variety of unsym-metrically substituted olefins bearing a carbonyl-activating substituent, such as methyl acrylate, crotonate, cinnamate, methacrylate, 3-buten-2-one, ( )-3-penten-2-one, ( )-4-phenyl-3-buten-2-one, and ( )-l-(p-tolyl)-3-phenyl-propenone, to give excellent yields of cycloadducts 142 (88JOC1384). 

Tables 6 and 7 summarize results from stereochemical equilibration studies performed over the past decade by MaryanofT et al. (22,23), and Vedejs et al. (20, 21c, 39-42). A few other convincing examples are included to expand the scope of the systems covered. Table 6 lists those examples where control experiments establish at least 90% retention of stereochemistry from intermediates-to alkene products. As already discussed, the percentage of equilibration represents the upper limit for loss of stereochemistry from all possible pathways in the control experiments. No attempt has been made to determine whether the minor levels of stereochemical leakage in Table 6 occur at the stage of oxaphosphetanes, betaines, or other potential intermediates. Table 6 includes entries corresponding to all of the principal families of Wittig reagents nonstabilized ylides (entries 1-12, 24, 25, 29, and 30), benzylic ylides (entries 13-17 and 28), allylic ylides (entries 22, 23, 26, and 27), and ester-stabilized ylides (entries 18-21). The corresponding Wittig reactions must take place under dominant kinetic control.

Oxaphosphetanes containing an unsaturated substituent R at Cj are exceptionally short-lived. Only the unusually stable dibenzophosphole derivatives 52c, 53c, and 53b can be detected, but not even this phosphorus environment provides sufficient stabilization to allow detection of 53d, the oxaphosphetane that would be formed from an ester-stabilized ylide (21c). Strongly electron-withdrawing substituents are required in addition to a five-membered ring, as in structure F (Tables 4 and 5), the first known... 

Most of the a-oxygenated aldehydes in Table 19 display the characteristic trend toward (Z)-enoate formation with Ph3P=CHC02R" (2j). A simple example of this phenomenon was discussed in connection with Table 16 (2-formyltetrahydropyran entries), but a number of others had been reported much earlier (Table 19, entries 61-93) (126-127). Table 19 also includes the first systematic solvent comparisons (entries 61-67) for an a-alkoxy aldehyde reaction with an ester-stabilized ylide (126). This series of experiments represents the most dramatic known example of solvent effects on selectivity (92 8 Z E in methanol 14 86 Z E in DMF), but the results are qualitatively similar to the solvent study in Table 16. In several other examples, the isomer ratios in methanol are reported to reach synthetically useful levels (> 90%) of the (Z)-enoate (Table 19, entries 19, 20, 23-25). However, most of the methanol entries fall in the more typical range of 70-85% (Z)-enoate. No similar trend is seen with p or y-oxygenated aldehydes (Table 19, entries 102-113) that lack an a-alkoxy group. 

Kinetic control is plausible in many, if not all, of the other E-selective ylide reactions. It follows that the exceptionally solvent- and substrate-dependent reactions of the a-unsubstituted ester-stabilized ylides (Ph3P= CHCO2R", Ph2MeP=CHC02R", etc.) reflect transition state preferences... 

Reactions of 2,3-di(methoxycarbonyl)-2/f-azirine with keto-stabilized and ester-stabilized ylides give, respectively, substituted pyrroles and iminophos-phoranes (76). A similar reaction of the ketene-stabilized ylide (77) with 3.3-dimethyl-2-phenyl-l-azirine forms the oxaphospholene (78). ... 

Photochemical Reactions with Alkoxychromium Carbene Complexes. Photolysis of chromium alkoxycarbene complexes in the presence of tosylmethylene phosphorane [or ester stabilized ylides such as (methoxycarbonylmethylene)-triphenylphosphorane] under an atmosphere of carbon monoxide produced aflenes. Such reactive allenes (EWG at C1 and electron donating group at C3) hydrolyzed to give y-keto-a. -unsaturated sulfones with. stereoselectivity (eq 6). ... 

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