Diastereoselective Approach

Chiral L-a-MiV-dibenzylaminophenylalaninal has been also used as a chiral auxiliary for the synthesis of o-l,2-diaminoalkyl phenols by combination of an electron-rich phenol with an amine [13]. 

---

Over the past two decades, chiral allyl- and crotyl-boron reagents have proved to be extremely valuable in the context of acyclic stereoselection. The development of superior allyl-boron reagents, which can give enantio- and diastereoselectivities approaching 100%, has become both challenging and desirable.68... 

Asymmetric aza Diels-Alder reactions provide a useful route to optically active heterocyclics such as piperidines and tetrahydroquinolines.45 Although successful examples of diastereoselective approaches had been reported as early as 10 years ago,46 only recently have enantioselective reactions been accomplished.47 For example, the reaction of chiral amine-derived aromatic imine 115 with Brassard s diene 116 gives adduct 117 with up to 95% diaster-eoselectivity (Scheme 5-37).48... 

The synthesis of aldehyde 48 proceeds in 16 steps from (S)-39 in 15% yield and 75% stereoselectivity. The brevity, efficiency, and selectivity of this synthesis rivals alternative acyclic diastereoselective approaches to the rifamycin ansa chain, (see footnote 4 in reference 3i), thereby providing a clear testimony to the potential of the tartrate allylboronates as reagents for complex synthetic problems. 

Scheme 10.4 The diastereoselective approach to quaternary carbon stereogenic centers.

The room-temperature Lewis acid-mediated diastereoselective [1,3] ring contraction of 2,5-dihydrooxepins has been investigated as a diastereoselective approach to tri-, tetra-, (g) and penta-substituted cyclopentanes from readily available precursors (Scheme 28).50 The structural features that facilitate this reaction in contrast to competing processes have been reported. 

An original diastereoselective approach to the synthesis of steganone analogues was reported by Motherwell and co-workers, Fig. (29) [144], The diyne 135 was obtained from bromide 133 and lactone 134 via diastereoselective alkylation and deprotection of the alkyne groups. A cobalt-mediated [2+2+2] cycloaddition of 135 with... 

The intramolecular alkoxypalladation has been developed into a remarkable (catalytic) methodology which exhibits a great synthetic potential, especially in combination with carbonyla-tion. This is reflected by convincing applications in natural product syntheses. This chemistry opens reliable and highly diastereoselective approaches to several hydropyran and hydrofuran systems. The development of efficient enantioselective protocols for the various chirogenic transformations is still a challenging goal for the future. 

Harada, M., Nakai, T., Tomooka, K. Stevens rearrangement of a cyclic hemiacetal system Diastereoselective approach to chiral -amino ketone. Synlett 2004, 365-367. 

Aside from these findings, the diastereoselective approach to alkenes by photochemically generated free carbenes cannot be controlled by experimental conditions. In contrast, the dia-stereomer ratio of the cyclopropanes formed can be varied within wide limits by conducting the cyclopropanation in the presence of an appropriate catalyst rather than photochemically (see Section 1.2.1.2.4.2.6.3.2.). 

A diastereoselective approach to y-butyrolactones is presented in Scheme 27. 4-Pentenoic acid was coupled to Merrifield resin via prolinol as a chiral linker unit. a-Methyladon and treatment of the amides 103 with iodine in TH F/water mixtures hberated substituted butyrolactones 104a-d as a mixture in which the trans diaster-eomers predominated [42]. 

Guanti, G., and Riva, R., A new diastereoselective approach to simplified dynemicin analogues, J. Chem. Soc., Chem. Commun., 1171, 2000. 

The diastereoselectivity approaches 1 1 upon increased reaction time, indicative of acid-catalyzed isomerization of the ester. 

Phospholane derivatives were obtained by a diastereoselective approach. In the first step benzothiadiphosphole was reacted with an unsymmetrical bis-Grignard reagent. In the second step, the pentavalent, pentacoordinated phosphorus intermediate so obtained was reacted with a mono-Grignard reagent to afford another intermediate with a hexacoordinate phosphorus atom whose collapse resulted in the phospholanes isolated as sulfides. The starting materials and the products are outlined in Scheme 3. ... 

Evans DA, Trotter BW, Cote B (1998) Addition of allylstannanes to glycal epoxides. A diastereoselective approach to p-C-glycosidation. Tetrahedron Lett 39 1709-1712... 

Ketones have been also used as electrophiles for the synthesis of natural products. Thus, the partial synthesis of oxybutynin (ditropan) has been accomplished by the aldol reaction between cyclohexanone (3b) and ethyl phenylglyoxylate (23, R = Ph, R =EtO, Scheme 4.9) [69]. Also using a diastereoselective approach the synthesis of 3-functionalized 3-hydroxy-P-lactams has been achieved with good yields and total diastereoselectivity [70]. 

Sun and coworkers established an alternative diastereoselective approach to 3-amino-l-indanols that proceeds under mild conditions. They employed chalcone-derived aldehydes 71 and treated them with weak nitrogen nucleophiles and catalytic amounts of base (Scheme 8.20) [34]. Electron-rich and -deficient substrates as well as several amines were tolerated and gave rise to 72 in very good yields and diastereoselectivities up to >30 1. Sulfonamides were shown to be the best choice with respect to their abihty to add to the a,P-unsaturated ketone. The generated enolate subsequently attacked the aldehyde in an intramolecular aldol reaction. The alternative reaction pathway involving an initial aldehyde attack followed by an intramolecular oxa-Michael addition could be suppressed by using DBU (l,8-diazabicyclo[5.4.0]undec-7-ene) as the appropriate base. 

A diastereoselective approach to these chiral building blocks was developed by Ellman (Scheme 8.15) [40]. Thus, N-tert-butylsulfinyl aldimines 57 were employed as electrophiles in the rhodium/phosphine 58-catalyzed addition of arylboronic acids. Whereas Ellman s procedure requires heating, Batey discovered that an amine base allows the reaction to take place at ambient temperature [41]. However, it is worth noting that Ellman s process can also be carried out in an enantioselec-tive way by using N-diphenylphosphinoyl aldimines 48 as substrate and Degu-PHOS (56) as ligand (87-97% yield, 88-94% ee) (Scheme 8.14 Figure 8.4). 

In sharp contrast to the importance acquired by asymmetric catalysis in the last decades, and although asymmetric induction has been achieved in Passerini reaction through diastereoselective approaches by using chiral substrates and/or chiral auxiliaries [33], the number of catalytic asymmetric procedures reported is still limited for this reaction and it remains as a significant challenge [34], Several drawbacks exist that make this task particularly difficult to... 

In elucidating a synthetic pathway to enantiopure biaryl 14, the key intermediate on the pathway to vancomycin, Uemura et al developed a powerful diastereoselective approach, corresponding to method a in Scheme 5.5. The most important aspects of this approach are presented in Schemes 5.6 and 5.7 [49-51]. 

---