Simple stereoselection

In fact, even if simple stereoselection can be reasonably controlled, using syn and anti selective reagents S mixtures of "Cram " and "anti-Cram" diastereomers are always obtained as shown in Scheme 9.19, where only the (Z)-enolate is formed ... 

Protonolysis in the last step can also be achieved with aqueous silver ammonium nitrate for acid sensitive molecules as in a simple stereoselective route to prostaglandins (Eq. 70) 128>. 

A simple stereoselective synthesis of /ra i-2-oxazolidinones, such as 187, was reported using a PPhs-CCU-TEA mediated cyclization of M-Boc-P-aminoalcohols 186. In the same work cis derivatives were converted into tram by the use of DBU <03TL6323>. 

The Zweifel traws-alkene synthesis from dialkyl-1-alkenylboranes involves the hy-droboration of 1-halo-l-alkynes with dialkylborane (Eq. 69) It is of interest that the base produces a transfer with inversion Protonolysis in the last step can also be achieved with aqueous silver ammonium nitrate for acid sensitive molecules as in a simple stereoselective route to prostaglandins (Eq. 70)... 

In the simple stereoselective total synthesis of salinosporamide A, E.J. Corey and co-workers applied the intramoiecuiar Bayiis-Hiiiman reaction to a ketoamide substrate." The reaction was catalyzed by quinuclidine and the y-lactam product was formed as a 9 1 mixture of diastereomers favoring the desired stereoisomer. 

Simple stereoselective aldol reactions (chapter 3) can also be controlled by tandem conjugate addition. Addition of Me2CuLi to the simple unsaturated ketone 27 gives the lithium enolate 28. It would be very difficult to produce this enolate from the parent ketone MhiCO.Me with regio- or stereoselectivity. The cyclic transition state 29 with zinc replacing lithium then shows the way to the anti-aldol7 30. 

The dianion of the hydroxybutyrolactone (87) reacts with aldehydes with high diastereofacial selectivity to give mixtures of dihydroxy lactones (88) and (89) (equation 76 Table 5). ° The lithium enolate shows little simple stereoselection with the sterically undemanding aldehydes phenylacetaldehyde and tetradecanal. Significant stereoselectivity is seen in the reaction with benzaldehyde, and pivalaldehyde gives only a single product. Because the aldol relative stereochemistry in the reactions with benzalde-... 

Simple amide enolates give poor stereoselection as shown by the examples in equation (S ). " " This low degree of simple stereoselection appears to result from differences in the diastereomeric transition states, since A(-propionylpyrrolidine gives a single enolate. Welch found that the lithium enolates of fluoroacetamides give mixtures of syn and anti aldols, and that the lack of stereoselectivity is due to the fact that enolate mixtures are obtained a typical example is shown in equation (88)." On the other hand, A(-acyl derivatives of 2,3-dihydro-4W-l,4-benzothiazine and phenothiazine react with a variety of aldehydes to give jyn-(3-hydroxy amides (equations 89-90). ... 

If a prochiral silyl enol ether reacts with a prochiral C=X compound, a pair of racemic dia-stereoisomers results (equation 1). A reaction that gives an excess of one of these diastereoisomers is said to exhibit simple stereoselection. In this section we discuss the factors that govern the stereochemistry of this process. Diastereoisomers such as (1) and (2) will be called syn (1) and anti (2) in accord with the convention first proposed by Masamune et al Although only one enantiomer is depicted in each case, all structures in this section represent racemates. 

Silyl enol ethers and silyl ketene acetals add to aldehydes in the presence of a stoichiometric amount of a Lewis acid (generally titanium tetrachloride, boron trifluoride etherate, tin(IV) chloride) with low levels or a complete lack of simple stereoselection. The anti.syn ratios usually range from 25 75 to 80 20, depending on the particular aldehyde, Lewis acid, enol ether and on the double bond stereochem-... 

The TiCU-mediated reaction of enol silanes with imines was first introduced by Ojima and coworkers in 1977. The reaction was then extended to several similar substrates, i.e. nitrones, ot-methoxycarba-mates, aminals, 4-acetoxyazetidin-2-one, 40 anj to different Lewis acids, i.e. SnCU, TiCU-(0PH)2, catalytic ZnX2, catalytic TMSOTf, ° to give good yields of the addition products with low levels ( 80 20) or a complete lack of simple stereoselection. Moderate to good anti selectivities were reported in the addition of silyl ketene acetals to imines under particular reaction conditions (equation 9) significant results are summarized in Table 4. 

Equation (12) illustrates the following general principle electrophiles able to form a chelated complex with the Lewis acid e.g. 28) control (usually invert) the simple stereoselection of the reaction . The major isomer (29) is, in fact, syn. Adducts (29) and (30) were then transformed, by simple functional group chemistry, into (+)-PS-5, a carbapenem antibiotic. Transition structure models for this process are discussed in detail in Section 2.4.4.1. 

Chiral butyrolactone derivatives (32) and (33) react with aldehydes to give the condensation products (34)-(36) as single stereoisomers in high yield (equation 13) both simple stereoselection (TMS and OH syn, see Section 2.4.2.1) and diastereofacial selection are 100%. Another example where a substituent on a cyclic silyl enol ether causes 100% diastereofacial selection is shown in equation (14). ... 

Another case where simple stereoselection is reversed by the use of particular reagents is shown in Scheme 5 (42) was obtained as a single isomer (jy ), in contrast with the anti selectivity shown by achiral silyl ketene acetals with the same catalyst (Table 4, entries 3-5). 

When the electrophile is chiral, besides simple stereoselection a second type of diastereoselectivity, termed diastereofacial selectivity , is possible. This sort of diastereofacial preference, qualitatively predictable by Cram s rule for asymmetric induction or one of its more modem descendants, " is typical for additions to chiral aldehydes. 

Additions of enol silanes to p-alkoxy aldehyde (85 equation 25) are reported in Table 17. High selectivity (chelation control) was obtained with TiCU via complex (78 entries 1, 2). The same preference for isomers (86) and (87) was obtained with BF3 via complex (80), which simulates chelation. The influence of chelation on simple stereoselection is also evident in the reactions of achiral aldehydes (90) and (92) with silyl enol ethers (Z)-(91) and ( )-(93), which are usually moderately anti selective in their reactions with aldehydes incapable of chelation high syn selectivity was obtained irrespective of the enol ether geometry (equations 26 and 27). - ... 

TiCU-mediated addition of silyl enol ether (95) to chiral a-amino aldehyde (94) was reported to proceed with good chelation control, albeit in poor yield (equation 28). Effective chelation control was also reported in the TiCU-mediated reactions of chiral a-alkoxy and p-alkoxy acyl cyanides (96) and (97) with silyl enol ether (95 equations 29 and SO). Reaction of acyl cyanide (97) with the ( )-silyl enol ether (93) gave a single stereoisomer as a result of complete chelation control and syn simple stereoselection (equation 31). Additions of silyl enol ethers and silyl ketene acetals to (-)-menthyl phenyl-glyoxylate and pyruvate were reported to proceed with moderate facial selectivity the best result (84 16) is shown in equation (32). ... 

The pinwheel shape of a f-butyl propionate derived silylketene acetal (see Section 2.4.2.1) was revealed by a single-crystal X-ray diffraction analysis. Several different catalysts were reported to promote the aldol-type condensation of alkyl enol ethersand silyl enol ethers with aldehydes, acetals and various other electrophiles. In some cases the reaction proceeded with high simple stereoselection. The mechanism of the Lewis acid mediated additions to acetals (see Section 2.4.2.3) was investigated in detail, as well as the uncatalyzed aldol reaction of silyl enol ethers with aldehydes promoted by the hydrophobic effect (see Section 2.4.2.1). 

L. Banfi, S. Cardani, D. Potenza and C. Scolastico, Tetrahedron, 1987, 43, 2317 G. Guanti, L. Banfi, E. Narisano and C. Scolastico, Tetrahedron Lett., 1985, 26, 3517. For the addition of nitrogen-substituted silyl ketene acetals to prochiral aldehydes (simple stereoselection), see T. Oesterle and G. Simchen, Synthesis,... 

---