Enantioselective Michael reactions. Diastereoselective reactions of chlorotitanium enolates of chiral N-acyloxazolidinones with representative electrophilic olefins

Evans, David A.; Bilodeau, Mark T.; Somers, T. C.; Clardy, Jon; Cherry, David T.; Kato, Yōkō

doi:10.1021/jo00020a007

Cited by 141 publications

(48 citation statements)

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“…), along with competitive removal of the p -methoxybenzyl-acetal (PMB-acetal). Gratifyingly, we found that Ti(O i -Pr)Cl 3 , thought to generate a more nucleophilic enolate,26 provided the necessary syn-syn aldol adduct 11 in good yield (88%) and selectivity (95:5 d.r.). This is a notable example of a β -keto imide-based aldol on a stereochemically complex aldehyde.…”

Section: Resultsmentioning

confidence: 87%

Total synthesis and study of 6-deoxyerythronolide B by late-stage C–H oxidation

2009

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Among the frontier challenges in chemistry in the 21st century are the interconnected goals of increasing synthetic efficiency and diversity in the construction of complex molecules. C—H Oxidation reactions, particularly when applied at late-stages of complex molecule syntheses, hold special promise for achieving both these goals. Here we report a late-stage C—H oxidation strategy in the total synthesis of 6-deoxyerythronolide B (6-dEB), the aglycone precursor to the erythromycin antibiotics. An advanced intermediate is cyclized to the 14-membered macrocyclic core of 6-dEB using a late-stage (step 19 of 22) C—H oxidative macrolactonization reaction that proceeds with high regio-, chemo-, and diastereoselectivity (>40:1). A chelate-controlled model for macrolactonization predicted the stereochemical outcome of C—O bond formation and guided the discovery of conditions for synthesizing the first diastereomeric 13-epi-6-dEB precursor. Overall, this C—H oxidation strategy affords a highly efficient and stereochemically versatile synthesis of the erythromycin core.

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Section: Resultsmentioning

confidence: 87%

Total synthesis and study of 6-deoxyerythronolide B by late-stage C–H oxidation

2009

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“…[121a] It works efficiently in alkylation reactions, conjugate addition reactions [122] and of course, in aldol reactions. [123] Resin-bound Evans× auxiliaries have been reported by Shuttleworth et al for alkylation reactions in 1996, [124] Burgess et al in 1997 [125] and Davies et al [126] In 1998, Abell et al reported about a resin-bound Evans× oxazolidinone in aldol and conjugate addition reactions [127] synthesized on a solid support in three steps starting with tyrosine (122, Scheme 20).…”

Section: Classical Aldol Reactionsmentioning

confidence: 99%

“…[123] This solid phase-supported Evans× auxiliary can also be used in conjugated addition reactions (Scheme 22). [122] In 1999, Fujii and Sodeoka introduced a polystyrenesupported BINAP-Pd(II) complex 128 in asymmetric aldol reactions. [128] In comparison with the soluble complex 129…”

Section: Classical Aldol Reactionsmentioning

confidence: 99%

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Recent Advances in Asymmetric CC and C‐Heteroatom Bond Forming Reactions using Polymer‐Bound Catalysts

2003

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Dedicated to Professor Dieter Seebach for his achievements in asymmetric catalysis.Abstract: The synthesis of enantiomerically pure compounds is one of the major challenges in organic synthesis. In this review, we present the state of the art in asymmetric catalysis using immobilized chiral ligands and complexes for asymmetric C À C and Cheteroatom bond forming reactions. Chiral catalysts based on dendrimers and soluble polymeric supports are considered. In particular, addition reactions to carbon-carbon double bonds, asymmetric 1,2-addition reactions using, e.g., dialkylzinc reagents, metalcatalyzed substitution reactions and cycloaddition reactions are covered. Specific emphasis is placed on enantioselective epoxidation and aldol reactions. A further aspect is the (hetero) Diels±Alder reaction catalyzed by immobilized ligands.

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“…The synthesis of the requisite ester 54 commenced with introduction of (R)-4-benzyl-2-oxazolidinone to 4-ethylpent-4-enoic acid 44 [14] via its mixed anhydride (Scheme 10) [15]. According to Evans' method [16], diastereoselective cyanoethylation of the resulting imide 45 afforded the adduct 46 as the sole isomer. Reduction of 46 [17], followed by protection of the resulting alcohol 47 as its t-butyldiphenylsilyl (TBDPS) ether furnished 48.…”

Section: Total Synthesis Of (+)-Vinblastine (1)mentioning

confidence: 99%

Stereocontrolled total synthesis of (+)-vinblastine

Yokoshima

Ueda

Kobayashi

et al. 2003

Pure and Applied Chemistry

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Stereocontrolled total synthesis of (+)-vinblastine (1) has been achieved using a novel radical-mediated indole synthesis developed in our laboratories. The isothiocyanate 18, prepared readily from quinoline 17, underwent a facile addition of the malonate anion to give 19. The o-alkenylthioanilide 19 was then converted to indole 20 by radical cyclization and protection. (-)-Vindoline (2) was prepared from this key intermediate 20 in a highly efficient manner. The indole core of the 11-membered intermediate 3 was constructed similarly from quinoline. The critical coupling reaction between 2 and the chloroindolenine derived from 3 proceeded with complete control of stereochemistry to give the desired product 66 in 97 % yield, which could be successfully converted to (+)-vinblastine (1).Vinblastine (1), isolated from Catharanthus roseus [1], has been widely known as a prominent agent for cancer chemotherapy. Since chemical modifications of the natural product have been the major means for exploration of the more potent analogs, a limited number of its derivatives have so far been accessible [2a]. Total synthesis of vinblastine, on the other hand, has been the subject of intensive investigations in the area of alkaloid synthesis [2b]. Despite the endeavors spanning the past three decades, only four syntheses have been reported to date [3]. In all cases, however, the supply of the lower half of vinblastine (i.e., vindoline) relied upon the natural sources. The major challenges in the total synthesis of 1 include controlling the stereochemistry of C18′ as well as establishment of efficient routes to the two halves of the indole units.Our synthetic plan is shown in Scheme 1. Model studies by Schill [4] as well as our molecular modeling study strongly suggested that a stereocontrolled coupling with vindoline (2) could be per-*Lecture presented at the

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Enantioselective Michael reactions. Diastereoselective reactions of chlorotitanium enolates of chiral N-acyloxazolidinones with representative electrophilic olefins

Cited by 141 publications

References 0 publications

Total synthesis and study of 6-deoxyerythronolide B by late-stage C–H oxidation

Total synthesis and study of 6-deoxyerythronolide B by late-stage C–H oxidation

Recent Advances in Asymmetric CC and C‐Heteroatom Bond Forming Reactions using Polymer‐Bound Catalysts

Stereocontrolled total synthesis of (+)-vinblastine

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