Catalytic, Asymmetric Synthesis of Siphonarienal

Calter, Michael A.; Liao, Wensheng; Struss, John A.

doi:10.1021/jo0160367

Cited by 46 publications

(15 citation statements)

References 22 publications

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“…With an eye toward utilizing the chiral dimers as synthetic intermediates,50 his early work focused on the cinchona alkaloid catalyzed dimerization of pregenerated methylketene (Scheme 3.10). 51 He screened a number of cinchona alkaloid derivatives, finding that quinidine ( 7b ), or its silylated derivative 7d , was most effective, with the two giving the same high selectivity (98% ee).…”

Section: Asymmetric β-Lactone Synthesismentioning

confidence: 99%

Catalytic, asymmetric reactions of ketenes and ketene enolates

2009

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Section: Asymmetric β-Lactone Synthesismentioning

confidence: 99%

Catalytic, asymmetric reactions of ketenes and ketene enolates

2009

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“…One that has been used for the synthesis of (Ϫ)-doliculide (16) makes use of Charette and Juteau's asymmetric cyclopropanation (17) and subsequent ring opening (18), but it requires a seven-step sequence for iteration. Another involves asymmetric dimerization of methylketene in the presence of 0.3 mol% of quinidine, permitting a four-step synthesis of (S)-2-methylpentanol, which is then converted to (2S,4S,6S)-2,4,6-trimethyl-1-nonanol in four additional steps, with a total yield over eight steps of 10% (19,20). Although catalytic asymmetric COC bond formation is not involved, catalytic hydrogenation of oxygenated alkene derivatives (9) is noteworthy.…”

mentioning

confidence: 99%

An efficient and general route to reduced polypropionates via Zr-catalyzed asymmetric C—C bond formation

Negishi

Tan²,

Liang³

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

104

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An efficient and general method for the synthesis of reduced polypropionates has been developed through the application of asymmetric carboalumination of alkenes catalyzed by dichlorobis(1-neomenthylindenyl)zirconium [(NMI) 2ZrCl2]. In this investigation, attention has been focused on those reduced polypropionates that are ␣-monoheterofunctional and either -ethyl or -n-propyl. The reaction of 3-buten-1-ol with triethylaluminum (Et 3 Al) or tripropylaluminum ( n Pr3Al) in the presence of (NMI)2ZrCl2 and isobutylaluminoxane gave, after protonolysis, (R)-3-methyl-1-pentanol as well as (R)-and (S)-3-methyl-1-hexanols in 88 -92% yield in 90 -92% enantiomeric excess in one step. These 3-monomethyl-1-alkanols were then converted to two stereoisomers each of 2,4-dimethyl-1-hexanols and 2,4-dimethyl-1-heptanols via methylalumination catalyzed by (NMI) 2ZrCl2 and methylaluminoxane followed by oxidation with O 2. The four-step (or three-isolation-step) protocol provided syn-2,4-dimethyl-1-alkanols of >98% stereoisomeric purity in Ϸ50% overall yields, whereas (2S,4R)-2,4-dimethyl-1-hexanol of comparable purity was obtained in 40% overall yield. Commercial availability of (S)-2-methyl-1-butanol as a relatively inexpensive material suggested its use in the synthesis of (2S,4S)-and (2R,4S)-2,4-dimethyl-1-hexanols via a three-step protocol consisting of (i) iodination, (ii) zincation followed by Pd-catalyzed vinylation, and (iii) Zr-catalyzed methylalumination followed by oxidation with O 2. This three-step protocol is iterative and applicable to the synthesis of reduced polypropionates containing three or more branching methyl groups, rendering this method for the synthesis of reduced polypropionates generally applicable. Its synthetic utility has been demonstrated by preparing the side chain of zaragozic acid A and the C11-C20 fragment of antibiotics TMC-151 A-F. O ligo-and poly(alkene)s with methyl groups bonded to alternating carbon atoms in the main chain (compound 1 in Fig. 1) are important structural units in both polymer materials chemistry (1) and natural products chemistry. The latter includes those reduced polypropionates that contain (i) two methylbranched asymmetric carbon centers, such as zaragozic acid A (compound 2 in Fig. 1) (2), and (ii) three methyl-branched asymmetric carbon centers, such as antibiotics TMC-151 A-F (compound 3 in Fig. 1) (3). The degree of polymerization of poly(propylene) usually exceeds 10 3 . As a consequence, most of the methyl-branched carbon centers may be considered to be ''virtually achiral,'' rendering their absolute configuration practically insignificant. On the other hand, their relative stereochemistry, termed tacticity, is of crucial importance in various respects. In the cases of reduced polypropionates, where the degree of polymerization is mostly Ͻ10, typically 2-4, both absolute and relative configurations of compound 1 (Fig. 1) are critically important. It is therefore essential to construct each methyl-bearing asymmetric carbon center with the correct absolute configurati...

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“…141 These ketene dimerization-opening-aldol reaction sequences provide a convenient and diastereoselective method for a one-step construction of polypropionate segments. They have demonstrated their usefulness in the total synthesis of natural products such as siphonarienal, 142 siphonarienedione and siphonarienolone 143 and the C21-C34 segment of the aplyronines. 144…”

Section: Scheme 47mentioning

confidence: 99%

Direct Methods for Stereoselective Polypropionate Synthesis: A Survey

Li¹,

Menche²

2009

Synthesis

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Polypropionates are key subunits in structurally diverse polyketide natural products and pharmaceuticals, rendering their synthesis an objective of high priority in synthetic organic and medicinal chemistry. A variety of methods have been devised for the direct and enantioselective assembly of the characteristic sequence of alternating methyl-and hydroxy-bearing stereogenic centers. This review presents a survey of well-established and more recently developed methods for the regio-and stereoselective assembly of polypropionates.

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Catalytic, Asymmetric Synthesis of Siphonarienal

Cited by 46 publications

References 22 publications

Catalytic, asymmetric reactions of ketenes and ketene enolates

Catalytic, asymmetric reactions of ketenes and ketene enolates

An efficient and general route to reduced polypropionates via Zr-catalyzed asymmetric C—C bond formation

Direct Methods for Stereoselective Polypropionate Synthesis: A Survey

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