Highly Diastereoselective Enolate Addition of O-Protected α-Hydroxyacetate to (S_R)-tert-Butanesulfinylimines:  Synthesis of Taxol Side Chain

Abstract

The taxol side chain (S(R),2R,3S)-N-tert-butanesulfinyl-O-Boc-3-phenylisoserine benzyl ester 4c was synthesized through a lithium enolate addition of O-Boc-alpha-hydroxyacetate benzyl ester 5c to benzylidene (S(R))-tert-butanesulfinamide 6a in excellent yield and diastereoselectivity. By similar approach, a series of enantiopure 3-substituted isoserine benzyl esters 4 useful for the semi-syntheses of taxol derivatives were also prepared in high to excellent yields and diastereoselectivities. The diastereoselective addition mechanism was discussed on the basis of the experimental observation.

Total Synthesis and Configurational Assignment of Chondramide A

“…[15] For example, asymmetric nitroaldol reactions,[16] the Staudinger reaction leading to β-lactam intermediates,[17] the Sharpless asymmetric aminohydroxylation,[18] or asymmetric aldol reactions of glycolates to imines are known to produce these types of structures. [19] And finally, chemoselective substitution reactions on 2,3-dihydroxy-3-arylpropanoates would provide the syn diastereomer of 8 . [20] We opted for the latter due to its operational simplicity (Scheme 2).…”

Total Synthesis of (−)‐Haouamine B Pentaacetate and Structural Revision of Haouamine B

“…Thus, treatment of 17 with a lithium enolate, prepared from O ‐Boc glycolate 11 ,9 provided β‐aminoester 18 as a single isomer in 86 % yield. Interestingly, unlike in the related report by Qin and co‐workers, who used an arylsulfinimine,9 the absolute configuration of the C2 and C3 positions was 2 R and 3 S , which was determined by comparison of specific rotations after transformation of 18 to a known compound 10. Having successfully constructed the consecutive stereogenic centers, we then focused on the intramolecular Friedel–Crafts alkylation of the tertiary alcohol 22 5b.…”

“…Using 17 , we then examined the diastereoselective Mannich reaction. Thus, treatment of 17 with a lithium enolate, prepared from O ‐Boc glycolate 11 ,9 provided β‐aminoester 18 as a single isomer in 86 % yield. Interestingly, unlike in the related report by Qin and co‐workers, who used an arylsulfinimine,9 the absolute configuration of the C2 and C3 positions was 2 R and 3 S , which was determined by comparison of specific rotations after transformation of 18 to a known compound 10.…”

Total Synthesis of (−)‐Haouamine B Pentaacetate and Structural Revision of Haouamine B

“…Chemie related report by Qin and co-workers, who used an arylsulfinimine, [9] the absolute configuration of the C2 and C3 positions was 2R and 3S, which was determined by comparison of specific rotations after transformation of 18 to a known compound. [10] Having successfully constructed the consecutive stereogenic centers, we then focused on the intramolecular Friedel-Crafts alkylation of the tertiary alcohol 22.…”

“…Using 17, we then examined the diastereoselective Mannich reaction. Thus, treatment of 17 with a lithium enolate, prepared from O-Boc glycolate 11, [9] provided b-aminoester 18 as a single isomer in 86 % yield. Interestingly, unlike in the…”