Stannous enolates, stereoselective aldol

The aldol reaction is one of the most fundamental and useful synthetic methods in organic synthesis and boron enolates are known (18) to be the most efficient intermediates in view of their mild reaction conditions and high stereoselectivity. Recently, stannous enolates... 

Stannous ene-diolates also give high yields of aldol products, but with little diastereoselectivity. The stannous ene-diolates were prepared in situ by reduction of a-diketones with activated metallic tin, in turn prepared by the reduction of stannous chloride with potassium metal. Stannous enolates of bromomethyl ketones show good stereoselectivity in aldol reactions with aldehydes when... 

The stannous enolates of Evans (/ )- and (5)-4-benzyl-3-(isothiocyanoacetyl)oxazolidin-2-ones 223 (Figure 11.76) react with aliphatic and aromatic aldehydes to afford 5-substituted 2-thioxo-oxazolidine-4-carboxylates, which are readily hydrolyzed to give syn-(2S,3R)- and (2R,35)-/3-hydroxy-a-amino acids, respectively, in fairly good yields (50-70%) and excellent stereoselectivities (90-99% d.e.) . Although 223 is readily accessible from the respective chloroacetyl precursor through treatment with sodium azide and transformation of the resultant azide with PhsP and CS2, the less commonly used ethyl (lR,2R,5/ )-((2-hydroxypinan-3-ylene)amino)acetate 12241 and its (-l-)-antipode are the only linear chiral glycinate exploited so far in aldol reactions in isotope chemistry. ... 

The aldol reactions of (9-protected (R)- or (5)-hydroxyacetyl 4-substituted 1,3-oxazolidin-2-ones (0-protected chiral glycolates) show some peculiarities. The boron enolates of (S)-and (7 )-3-p-methoxybenzyloxyacetyl-4-benzyl-l,3-oxazolidin-2-one (2381 react with aldehydes to provide the expected syn aldols . In contrast, anti aldols are formed in high stereoselectivities with the corresponding stannous enolates when the reactions are run in the presence of TMEDA °. 

Stereochemically controlled synthesis of this subunit, which contains five stereogenic centers, is important to an efficient bleomycin synthesis. (2S,3S,4i )-4-(/er/-Butoxycarbonyl-amino)-3-hydroxy-2-methylpentanoic acid (15) was obtained via a stereoselective syn aldol addition of a boron Z-enolate with (27 )-2-(tert-butoxycarbonylamino)propanal (Scheme 4). Similarly, the L-threonine subunit 18 was prepared by diastereoselective syn aldol addition of an N- acy I ox azo I i di n one stannous Z-enolate with acetaldehyde. The bithiazole unit 19 was prepared using a direct DCC-promoted condensation of 3-(methylsulfanyl)propylamine. Convergent access to tetrapeptide S was obtained by coupling of acid 15 and deprotected 18 to give dipeptide 20, followed by further coupling with the bithiazole 19 to ultimately give tetrapeptide S (21). 

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