Pivaldehyde conditions

Unlike the straightforward chemistry observed with rhodium hydrides and ArOH, the reaction with pivaldehyde is quite complex (143,144). The observed rate constants, and even the shape of kinetic curves, change with reaction conditions and the presence of scavengers for various intermediates. Figure 10 shows some examples. 

Aryl-vinyl coupling fi-aryl-fi-amino acids.2 A novel route to P-amino acids is based on the formal conjugate addition of an aryl iodide to an enantiomerically pure dihydropyrimidinone such as 1, prepared by pivaldehyde acetalization of (R)-aspara-gine (c/., 14, 69-70). Thus 4-iodoanisole couples with 1 under Heck conditions, Pd(OAc)2, Ar3P, triethylamine, and DMF to give 2 in 78% yield. Reduction of 2... 

As a second example, we recently used the readily available (W)-phenylglycine amide as a Chirality Transfer reagent (see Chapter 25).43 In this case, a Strecker reaction is performed on pivaldehyde under equilibrium conditions resulting in two covalent diastereoisomeric products (Scheme 7.9). The lower solubility of the (.S. /H-diastereoisomer results in transformation of the (R,/H-diastereoisomer into the (.S. /H-diastereoisomer in 93% yield and >99% diastereoselectivity. 

An as yet unexplicable drawback of the described catalytic system (S,S)-5/pivaldehyde/dioxygen is its limitation to 2-aryl substituted cyclohexanones the positional isomer 4-phenylcyclohexanone or 2-alkyl substituted cyclohexanones are not converted. The strained cyclobutanones, however, will almost always react under the catalytic conditions. Thus, the racemic bicyclic cyclobu-... 

Monocyclic cyclobutanones 9 (Fig. 1) with alkyl, aryl, or carboxylato substituents at C3 gave under the usual catalytic conditions optically active lactones with only moderate enantiomeric excesses (up to 47% ee) [25]. Increasing the amount of pivaldehyde used in the catalysis led to higher yields without a significant decline in enantioselectivity. For instance, 3-phenylcyclobutanone (9, R= Ph) was converted to the corresponding (S)-lactone in 66% yield with either... 

Malic acid (1) reacts with aldehydes or ketones under acidic catalysis to form dioxo-lanones. Of particular interest is the reaction of 1 with pivaldehyde in the presence of PTSA and sulfuric acid, which produces cw-dioxolanone 170 in 67% yield [59]. The choice of solvent is crucial to ensuring high cw-stereoselectivity. If the reaction is carried out in benzene, a 3 2 equilibrium mixture of cis and trans isomers is obtained. Under heterogeneous conditions in pentane the ratio of cis to trans isomers increases dramatically to 50 1 ( > 98% ds). 

In support of the proposed scheme, whereby CMesOO and CraqOO compete for the intermediate CMe3C(0)00, the change of aldehyde to CH3CHO resulted in predictable changes in kinetic behavior. Because there are no persistent radicals in the CH3CHO system, and CraqOO is the only scavenger for peroxyacetyl radicals produced in Eq. (29), the consumption of CraqOO is much larger than in the pivaldehyde reaction. As shown in Fig. 13, all the CraqOO was consumed before the reaction was completed, as shown by the sudden break in the kinetic trace at 9 s. Under comparable conditions in... 

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