Total Synthesis of (+)-Preussin: Control of the Stereogenic Centers by Enantioselective Allyltitanations

 

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Abstract

(+)-Preussin was synthesized in ten steps with an overall yield of 6.4% from phenylacetaldehyde. The three stereogenic centers were controlled by enantioselective allyltitanations of aldehydes.

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Complex (R,R)-Ia (R = MOM) was formed in situ after deprotonation of 3-methoxymethoxypropene by s-BuLi and transmetallation with the correponding chlorocyclo-pentadienyldialkoxytitanium(IV) complex.

The enantiomeric excess of (+)-3 was determined by ¹H NMR after its derivatization with (S)- and (R)-methoxy-phenylacetic acid.

Secondary alcohol 4′ was isolated as a mixture of two diastereomers in a 75:25 ratio. After debenzylation (H₂,
Pd/C, quantitative yield), the resulting 1,3-diols were transformed to the corresponding acetonides (dimethoxypropane, PPTS, 90%). According to the ¹H NMR and ¹³C NMR data, the major product has the anti-anti structure (Figure [3] ):

Decomposition of the starting material or non-reactivity were observed when other boranes were used [9-BBN, (Cy)₂BH].

The formation of tetrahydrofuran B as secondary product could be observed during the cyclization process (Figure [4] ).