Stereodivergent synthesis

Scheme 2.19 A highly stereodivergent synthesis of cis- and tram-2-alkenylaziridines.

Scheme 2.32 Stereodivergent synthesis of threo- and erythro-sphingosines 124.

Scheme 2.35 Stereodivergent synthesis of syn- and anti-amino alcohols.

The antiviral agent virantmycin is an unusual chlorinated tetrahydroquinoline isolated from a strain of Streptomyces (Figure 6.10). Hydrolysis of a prochiral 2,2-disubstituted dimethyl malonate with PLE in DMSO-pH 8 phosphate buffer (1 4) was a key step in a stereodivergent synthesis of this natural product [57]. 

A new stereodivergent synthesis of optically pure 4-alkylisoxazolidin-4-ols starting from enantiopure 2-(alkyloxiran-2-yl)methanols has been reported. In particular, the (2/ )-glycidyl... 

A stereodivergent synthesis of derivatives of 1,2-diols with an Se 2-retention pathway can be performed via a-alkoxyorganolead compounds. 

Stereodivergent synthesis of almost enantiomerically pure and stereospecifically deuterium-labeled 2,2-dimethylcyclopropanols has been achieved by treating 2,2-dimethylpropane-l,3-diol dicarbamate with alkyllithium in the presence of (-)-sparteine (equation 17)29. 

Being restricted to DHAP as the nucleophile, aldol additions will only generate ketoses and derivatives from which aldose isomers may be obtained by biocatalytic ketol isomerization (cf. Sect. 7.1) [306]. For a more direct entry to aldoses the inversion strategy may be followed (Scheme 19) [290] which utilizes monoprotected dialdehydes. After aldolization and stereoselective chemical or enzymatic ketone reduction, the remaining masked aldehyde function is deprotected to provide the free aldose. Further examples of the directed, stereodivergent synthesis of sugars and related compounds such as aza- or thiosugars are collected in Sect. 7. 

The availability and the rather similar substrate tolerances exhibited by most members within the families of related lyases fulfills the demand for a complete set of catalysts for a directed stereodivergent synthesis of a set of diastereomeric products from common synthetic building blocks [189]. The verification of this concept ( combinatorial synthesis ) has indeed been pursued in a different respect, and will be highlighted by pertinent examples for the synthesis of simple sugars and for the synthesis of azasugars , an emerging class of glycosidase inhibitors. 

Scheme 23. Stereodivergent synthesis of all eight possible hexokctoses from glyceraldehyde by DHAP aldolases...

Scheme 25. Stereodivergent synthesis of 1-dcoxy azasugars of the nojirimycin type by enzymatic aldolization followed by catalytic reductive amination. a) 1. Aldolase, DHAP 2. phosphatase 3. H2/Pd-C...

Scheme 17 Stereodivergent synthesis of spiro- [S-lactams using ester enolates and chiral imines...

Fujisawa et al. [89] have reported the stereodivergent synthesis of spiro-[S-1 act a ms 64, 65 (Scheme 17) by reaction of lithium or titanium ester enolates 62 with single chiral imines 63 by taking advantage of different coordination states of the enolate metals. Almost complete reversal of the diastereofacial-discrimination with respect to the C-4 of the (3-lactam skeleton has been attained in this reaction coupled with flexibility in the selection of the enolates and ready removal of the chiral auxiliary. 

With the enantiomeric pair of 1 in hand, we examined the stereodivergent synthesis of a,a -disubstitued 3-piperidinol alkaloids. The basic strategy we used to prepare the building blocks (I-IV) from (-)-1 is presented in Figure 3. 

Fig. (3). Basic strategy for the stereodivergent synthesis of 3-piperidinol alkaloids...

An attractive flexibility in using anomeric phenyl sulfones is that a stereodivergent synthesis of C-glycosides is available by alkylation before the reductive desulfonylation event. Thus, a one-pot four-step sequence of sulfone deprotonation-electrophile quenching-reductive lithiation-methanol quenching on sulfone 14 provides stereoselectively P-C-glycosides 19 as shown with aldehyde 16 (Fig. 

Related reactions of acyclic unsaturated amide derivatives S show a reversal of the diastereofa-cial selection according to the geometry of the double bond. This is in contrast to the carbamate series (vide infra)13 which is dependent on the nature of the nucleophile68. The most remarkable feature is the formation of 1,2-syvj-products 6B from the A-isomers. This may be best explained by the steric repulsion between the ester and acyl groups. This complementary and effective diastereoselection provides a stereodivergent synthesis of 2,3-disubstituted piperidines (see also Section D.7.3.1.1.2.2.). 

An aldol reaction with chiral /3-benzyloxy aldehyde provides a method for the stereodivergent synthesis of both syn and anti diastereomers [97] with high diastereo-selectivity dictated primarily by the chirality of the BINOL-Ti catalyst (1) rather than the /1-benzyloxy aldehyde (Sch. 37) [98]. The aldol products can be used as useful key intermediates for /1-lactone synthesis [99]. 

Gomez, A M, Moreno, E, Valverde, S, Lopez, J C, Stereodivergent synthesis of carbasugars from d-mannose. Syntheses of 5a-carba-alpha-D-allose, beta-L-talose, and alpha-L-gulose pentaacetates, Synlett, 891-894, 2002. 

A stereodivergent synthesis was developed by H. Nemoto and co-workers for the preparation of c/s-fused 2,5-disubstituted octahydroquinolines, which constitute the core structure of certain dendrobatid aikaioids. The instaiiation of the C5 methyi group was achieved by 1,4-cuprate addition and the resuiting enoiate was trapped with TMSCi. The siiyi enoi ether was then oxidized to the enone with Pd(OAc)2. 

Oliana M, King F, Horton PN, Hursthouse MB, Hii KK (2006) Practical synthesis of chiral vinylphosphine oxides by direct nucleophilic substitution. Stereodivergent synthesis of aminophosphine ligands. J Org Chem 71 2472-2479... 

Table 10.2 Stereodivergent Synthesis of Epoxy Alcohols (E)-92 and Their Payne Rearrangement Tsee Scheme 10.211...

The efficient stereodivergent synthesis of cis-(2R,4S)- and fr t i-(2/, 4/ )-4-phos-phonomethyl-2-piperidine carboxylic acid (122) and (123) from the same chiral imine derived from (if)-gliceraldehyde has been elaborated (Scheme 42). ... 

Scheme 34.9 Stereodivergent synthesis of [60]fuUeropyrrolidines by asymmetric catalysis.

Yu, S. H. Ferguson, M. J. McDonald, R. Hall, D. G. Bronsted Acid-Catalyzed Allylboration Short and Stereodivergent Synthesis of All Four Eupomatilone Diastereomers with Crystallographic Assignments. J. Am. Chem. Soc. 2005, 127,12808-12809. 

---