Stereoselective synthesis of (2S,3S)‐norstatine derivatives by addition of lithiated methoxyallene to amino aldehydes and subsequent ozonolysis

Abstract

Addition of lithiated methoxyallene 2 to optically active N‐benzyl‐Boc‐protected amino aldehydes 12–14 and to aldehyde 16 provides products 17–20 with good to excellent diastereoselectivity. These adducts are subsequently cleaved by ozonolysis to give α‐hydroxy‐β‐amino acid derivatives 21–25 in good overall yield. By conversion into an oxazolidone derivative, the configuration of the major diastereomer was determined to be anti (2S,3S). Thus, the additions of 2 follow the course proposed by the Felkin‐Anh model and are not ruled by chelation effects. The diastereoselective synthesis of 22 constitutes one of the simplest routes to a protected norstatine derivative.

Bifunctionalized Allenes. Part XIII. A Convenient and Efficient Method for Regioselective Synthesis of Phosphorylated α-Hydroxyallenes with Protected and Unprotected Hydroxy Group

“…There are variety of methods for the construction of hydroxyallenes that include prototropic rearrangement of propargylic alcohols [14,15,16], metal-catalyzed nucleophilic addition of propargylic derivatives to aldehydes [17,18,19,20,21,22,23,24], Cu(I)-catalyzed reaction of propargylic chlorides with Grignard reagents [25,26,27], metal-catalyzed reaction of propargylic oxiranes with organometallic compounds [28,29,30,31,32,33,34,35] and ketones [36,37], reduction of alcohols, ethers, oxiranes etc. with aluminium reagents [38,39,40], Pd(0)-catalyzed reaction of cyclic carbonates with acetylenic compounds [41,42], S N 2’ [43,44] and A N [45,46,47] reactions of metalled alkoxy-allenes with oxiranes and ketones [5], and other routes [48,49].…”

Stereocontrolled synthesis of the taxol C-13 side chain: Methyl (2R,3S)-3-benzoylamino-2-hydroxy-3-phenylpropanoate

“…We have already described preparation of several anti-(2S,3S)-α-hydroxy-β-amino esters by stereoselective addition of lithiated methoxyallene to optically active N-benzyl-BOC-protected amino aldehydes followed by ozonolysis [2]. We anticipated that a modification of the N-protecting group could lead to predominant syn-configurated products and therefore we envisaged a synthesis of (2R,3S)-3-benzoylamino-2-hydroxy-3-phenylpropanoic acid (1) Abstract: Addition of lithiated methoxyallene 5 to literatureknown amino aldehyde 3 followed by ozonolysis provided syn-configurated α-hydroxy-β-amino ester 6 in moderate Lithiation of methoxyallene 4 was performed under standard conditions [6] in THF, and to the resulting solution of 5 freshly prepared aldehyde 3 was added to give a mixture of syn-2 (major) and anti-2 (minor).…”

Lithium Carbenoids

“…As outlined above, the hydroxyalkylated allenes 189/190 can be converted into furanones 191/192 upon treatment with potassium t-butoxide and subsequent acid hydrolysis 410 . When, on the other hand, the adducts of 183 to the aldehydes 193 are submitted to an ozonolysis, N-protected α-hydroxy-β-amino esters 194/195 result (Scheme 25) 415 .…”