Betaine formation

Betaine formation is reversible and the reaction becomes under thermodynamic control to give the most stable product. 

The fourth factor becomes an issue when anti betaine formation is reversible or partially reversible. This can occur with more hindered or more stable ylides. In these cases the enantiodifferentiating step becomes either the bond rotation or the ring-closure step (Scheme 1.12), and as a result the observed enantioselectivities are generally lower (Entry 5, Table 1.5 the electron-deficient aromatic ylide gives lower enantioselectivity). However the use of protic solvents (Entry 6, Table 1.5) or lithium salts has been shown to reduce reversibility in betaine formation and can result in increased enantioselectivities in these cases [13]. Although protic solvents give low yields and so are not practically useful, lithium salts do not suffer this drawback. [18]... 

As the formation of betaines from amide-stabilized ylides is known to be reversible (in contrast with aryl- or semistabilized ylides, which can exhibit irreversible anti betaine formation see Section 1.2.1.3), the enantiodifferentiating step cannot be the C-C bond-forming step. B3LYP calculations of the individual steps along the reaction pathway have shown that in this instance ring-closure has the highest barrier and is most likely to be the enantiodifferentiating step of the reaction (Scheme 1.16) [25]. 

Large concentrations of halide ions, preferably iodide, favour the formation of /ra/i5-stilbene from benzaldehyde and benzyltriphenylphosphonium halides in methanol with methoxide as base, whereas large concentrations of methoxide ions slightly favour formation of the m-isomer. These effects have been explained by the preferential solvation of P+ by halide ions, leading to greater reversibility of betaine formation. Methoxide ions, on the other hand, are preferentially solvated by methanol. 

A computational study has probed the origin of the diastereoselectivity in aziridine formation from sulfur ylides, Me2S+-CH -R, and imines.62 For semi-stabilized cases (R = Ph), betaine formation is non-reversible, so that selectivity is determined in the (g) initial addition step. In contrast, for stabilized ylides (R = C02Me), betaine formation is endothermic, and the elimination step becomes rate and selectivity determining. 

There are four main factors that control the enantioselectivity in the sulfur ylide-mediated epoxidation (1) selectivity for one sulfide lone pair (2) control of ylide conformation (3) control of facial selectivity and (4) the reversibility of anti-betaine formation. 

Fig. 10.4 Approaches in betaine formation. (A) favored head-on for ont/ -betaine (B) favored head-to-tail for syn-betaine formation ...

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. 

To explain the observed selectivities, a similar model was proposed as for the epoxidation reactions (see Section 10.2.1.10) [96]. In this model, the ylide conformation is controlled as before, and the alkene selectively attacks one face in an analogous manner to the aldehyde in the epoxidation reactions. It was noted that in this case betaine formation was non-reversible so the diastereoselectivity is controlled by non-bonding interactions during the betaine-formation step [79]. 

Betaine, formation of, 260 Betaine aldehyde, choline dehydrogenase and, 261, 262... 

Pyridine (p/fa 5.2) causes more rapid polymerization than dimethyl-tert-butylamine (P a 10.5). It is difficult to reconcile this observation with the idea that the initiating species is a hydroxyl ion formed by hydrolysis of the amine. On the other hand the structure of an amine might be expected to influence its rate of addition to the carbonyl double bond. The first and rate determining step in the formation of a long chain polymer is apparently betaine formation ... 

Ionization and dissociation take place every time a macrozwitterion is formed. Therefore, both the solvating power and dielectric constant of the solvent will influence the polymerization rate. Strong solvating power will favour betaine formation, high dielectric constant chain growth. 

The ideal addition polymerization is one in which there are no termination or transfer reactions, initiation (betaine formation) is instantaneous and kp lies between 102 and 104 1 moP1 s-1. Such polymerizations can be conveniently followed by adiabatic calorimetry. At very high initiator concentrations it should be possible to measure the rates of the first monomer additions and isolate zwitterion oligomers for study. Cyanoacrylate polymerizations initiated by phosphine satisfy all these conditions except the last. kp is 1051 mol-1 s-1 at —78°C. However, cyanoacrylates with more bulky alkyl substituents may have smaller kp s. It is possible that methylene malonate polymerizations may fulfil the above requirements. 

The first step in this reaction is probably betaine formation. 

---