Derived from Prolinol

Richter was the first to study these reactions and was able to prepare the t-Bu derivative of 39 from r-BuPC, but not the Me or Ph analogues, which had to be prepared following method B. Since this report others have prepared a small family of compounds (Table 3.10). 

A variety of monodentate ligands (entries 1-9) and P,N-bidentate ligands (entries 10 and 11) have been suceessfully prepared. Some have also been oxidised to the P(V) compounds (entries 12 16) or boronated (entry 17). Interestingly, entry 18 shows the single example of a C2 bidentate ligand prepared from prolinol. 

In most of the cases (except entries 4 and 8-10), the reaetions provide the desired compound in high or complete stereoselectivity towards the tram diastereomer (represented in the table), which is the thermodynamie product. Some early papers report the formation of much larger quantities of the cis epimer at the beginning of the reaction, suggesting that it is the kinetic product. 

Some oxides and sulfides have also been prepared from phosphoryl or thiophosphoryl ehlorides, but very low or no diastereoseleetivity has been found. This class of compounds were also found to suffer the [1,3] P-O 

---

As with the above pyrrolidine, proline-type chiral auxiliaries also show different behaviors toward zirconium or lithium enolate mediated aldol reactions. Evans found that lithium enolates derived from prolinol amides exhibit excellent diastereofacial selectivities in alkylation reactions (see Section 2.2.32), while the lithium enolates of proline amides are unsuccessful in aldol condensations. Effective chiral reagents were zirconium enolates, which can be obtained from the corresponding lithium enolates via metal exchange with Cp2ZrCl2. For example, excellent levels of asymmetric induction in the aldol process with synj anti selectivity of 96-98% and diastereofacial selectivity of 50-200 116a can be achieved in the Zr-enolate-mediated aldol reaction (see Scheme 3-10). 

Non-catalyzed aldol reactions via hypervalent silicon species have also been studied. An aldol reaction between aldehydes and silyl enol ethers of amides was reported by Myers [105]. The reaction can be conducted under mild conditions to produce anti aldol without Lewis acid or base catalysts (Sch. 62). Asymmetric induction was particularly high when the (Z)-silyl ketene A/,0-acetal derived from prolinol was used. 

Formation of Chiral Quaternary Carbon. Birch reduction-alkylation of benzoic acids and esters establishes quaternary carbon centers. Neighboring stereocenters will influence the stereochemical outcome of the tandem reaction sequence. The following example illustrates how a chiral auxiliary (derived from prolinol) controls the stereoselection in the Birch reduction-alkylation step. ... 

Recently, two other groups have shown that exocyclic iminium salts can be useful mediators in asymmetric epoxidation. Komatsu has developed a system based on ketiminium salts [14], prepared through the condensation of aliphatic cyclic amines with ketones. A chiral variant was also produced, derived from prolinol and cyclohexanone, which gave 70% yield and 39% ee for cinnamyl alcohol (Scheme 5.7). 

This reduction method has a number of advantages that include wide scope, predictable absolute stereochemistry, ready availability of the chiral catalyst in both enantiomeric forms, high yields, experimental ease, recovery of the catalyst (as the amino alcohol), and low cost of goods. The most common form of the chiral oxazaborolidine is derived from prolinol and has a methyl substituent on the boron atom (B-Me-CBS) 1. When one conducts a reduction on a novel system for the first time, this catalyst provides a good compromise of cost, enantioselectivity, and experimental ease. If sufficient control is not observed with this reagent, one can then systematically evaluate the numerous variations of this framework. 

The equilibria between bicyclic oxazolidines and enamines derived from prolinol derivatives and aldehydes have been studied spectroscopically by Schmid et al. [44] In the case of prolinol, the less stable c db-oxazolidinone is the kinetic product, which is in equilibrium with the aw/f-enamine conformer. The zwitterionic amonium alkoxide, not detected, is the key intermediate in the oxazolidine-enamine equilibrium. For diarylprolinol derivatives, minor amounts of en amine can be detected, and only the e/J[Pg.27]

The conformational preferences of enamines derived from prolinol, diarylpro-lynols, prolinol ethers, diarylprolynol ethers, and chiral imidazolidinones have been... 

Hydroxy-amides. - Wittig rearrangement of acetamide (424) [LDA, -85 C] provides almost exclusively the erythro-a-hydroxy-amide (425). The likely transition-state geometry suggests that the presence of vinylic substituents larger than methyl should at least maintain this level of selectivity during rearrangement. Unfortunately similar reactions of chiral amides derived from prolinol result in only moderate asymmetric induction. 

TMS acetylene has been added to aromatic aldehydes in high ee, using an amino alcohol/zinc complex derived from prolinol. ... 

High e/y/firo-selectivity has been obtained using optically active zirconium enolates (18) derived from prolinol in an enantioselective aldol condensation (Scheme 14). Much lower selectivity was obtained using the corresponding lithium enolate. 

A number of chiral catalysts originally devised for aldol reactions (see Chapter 4) have also successfully been deployed in enantioselective Mannich additions. One such example is the dinuclear zinc complex 220 developed by Trost (Equation 18) [154]. The complex is generated in situ from Et2Zn and the corresponding chiral diamino triol ligand derived from prolinol. Excellent enantio- and diastereoselectivity were obtained in reactions with a-hydroxyketones such as 218. From imine 219, the syn a-hydroxy-/l-amino ketone 221 was isolated in > 99% ee and > 15 1 dr. Additional investigations revealed that appropriate choice of the N-substituent on the imine could selectively provide either the anti or the syn a-hydroxy- -amino ketones [155]. 

---