With K-selectride

The facial selectivity for the reduction of a-(fluoroalkyl)- 3-sulfinylenamine (88) with K-Selectride was controlled by the sulfoxide, and proceeded with high diastereoselectivity to yield product 89 (Scheme 23).57... 

For the preparation of syn isomers, alcohol 62 has to be oxidized into the corresponding ketone, which is reduced with K-Selectride into the syn isomer 64. The a-amino aldehyde L-65, derived from L-serine, was converted into aminotetrose and pentose derivatives 66 and 71, respectively. The anti diastereoselectivity observed for 67 of 61 to the A, W-diprotected Q -amino aldehyde l-65 can be reversed to syn selectivity by using a W-monoprotected derivative [209,210]. 

Conjugate reduction of enones with K-Selectride (K[5ec-Bu3BH]) is a valuable method for regiospecifically generating enolate anions. As illustrated below, the enolate species reacts with an alkyl halide to give the corresponding a-alkylated ketone in good yield. 

Substrates of this class are of considerable importance because of their value as intermediates in the synthesis of carbohydrates and carbohydrate-likc molecules. The detailed interpretation of their behavior presents some difficulty because of potential competition between a- and /f-chelation and 1,2- and 1,3-asymmetric induction. However, this complexity has not prevented the development of methods which show very satisfactory selectivity. Thus, a study involving (/ )-3,4-dibcnzyloxy-2-butanone, one of the simplest of these substrates, revealed that either the ami or the syn reduction product could be obtained by treatment with K-Selectride/magnesi-um(II) bromide or with L-Selectridc, respectively 51. The former was understood to occur via a-chelation, as in transition state 2, while the latter presumably occurred via a Felkin-Anh" transition state 3 which may, or may not. have been reinforced by /1-chelation. 

Chromium trioxide oxidation of the epimeric mixture 95 and 96 followed by highly selective reduction of the resulting ketone with K-Selectride in THF provides a 98 2 ratio of 95 96. Chromatographic purification provides (R) 95 in 75% yield. This is similarly converted to (+ )- jco-brevicomin (90). 

Reduction of the cA/ro-inositol derivative (145), made from quebrachitol, with K-selectride in THF and HMPA gave a high preponderance of the (S)-diastereomer (146). Surprisingly, replacement of the HMPA with 18-crown-6 led to reversal of the diastereoselectivity with up to 92% d.e. of the (/ )-product.il ... 

Protection of D-erythrono-1,4-lactone as its 2,3-0-benzylidene acetal, followed by regioselective reductive acetal opening (triethylsilane-titanium tetrachloride), then hydride reduction of the lactone function gave 2-0-benzyl-L-erythritol. In contrast, tributyltin oxide mediated benzylation of the same 1,4-lactone then hydride reduction of the lactone group gave 2-0-benzyl-D-erythritol. L-Erythrulose has been converted into 2-amino-2-deoxy-L-erythritol in six steps and 35% overall yield, the key step being a stereoselective reduction of the ketoxime orthoformate 11 with K-selectride. ... 

The reaction between ethyl Hthiopropiolate and the N-acylpyridinium salt formed by reaction of 4-methoxy-3-methyl-5-(triisopropylsilyl)pyridine 2363 with (+)-frafis-2-(a-cumyl)-cyclohexyl chloroformate (TCC chloro-formate) was the starting point in the synthesis of (-l-)-aUopumihotoxin 267A (1718) by Comins et al. (Scheme 301). The dihydropyridone product (—)- 2364 was obtained diastereoselectively (>96%) before hydrogenation to the saturated ester (+)-2365. However, some epimerization of the methyl substituent was apparent after cleavage of the TCC carbamate with lithium methoxide and cyclization to the indolizidinone (—)-2366 (dr 8 1). Acetoxylation at C-8 with lead tetraacetate was stereoselective, and introduced the acetate from the axial direction, possibly by stereoelec-tronicaUy-controUed intramolecular transfer of acetate from a lead—enol intermediate. The acetoxy product (—)-2367 was protodesilylated with formic acid, after which a one-pot tandem reduction with K-Selectride followed by hthium aluminum hydride gave diol (- -)-2368 with complete... 

In the effort of total synthesis of discodemolide, the Still-Gennari type HWE reaction was also used by Paterson and Lyothier to form the Cg-C9 olefin. Phosphonate 94 was treated with NaH in THE at 0 °C for 30 min prior to the addition of aldehyde 93. The crude product showed a mixture of (Z)- and ( )-olefins, 95 and 96, in a 5 1 ratio. The desired (Z)-isomer 96 could be isolated by flash chromatography in 73% yield. The (Z)-enone 96 was further treated with K-Selectride at 25 C for 24 h. A single diastereomeric alcohol 97 was formed selectively and isolated in 59% yield. This alcohol processing (7/ )-configuration was leading to 1-epi-discodermolide 98 as final product by four additional reactions. 

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