+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

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



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



Proceedings of the National Academy of Sciences of the United States of America 101(16): 5782-5787



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)(2)ZrCl(2)]. In this investigation, attention has been focused on those reduced polypropionates that are alpha-monoheterofunctional and either omega-ethyl or omega-n-propyl. The reaction of 3-buten-1-ol with triethylaluminum (Et(3)Al) or tripropylaluminum ((n)Pr(3)Al) in the presence of (NMI)(2)ZrCl(2) 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)(2)ZrCl(2) 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 approximately 50% 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.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 011748930

Download citation: RISBibTeXText

PMID: 15073327

DOI: 10.1073/pnas.0307514101


Related references

All-catalytic, efficient, and asymmetric synthesis of alpha,omega-diheterofunctional reduced polypropionates via "one-pot" Zr-catalyzed asymmetric carboalumination-Pd-catalyzed cross-coupling tandem process. Journal of the American Chemical Society 127(9): 2838-2839, 2005

An efficient and general method for the synthesis of alpha,omega-difunctional reduced polypropionates by Zr-catalyzed asymmetric carboalumination: synthesis of the scyphostatin side chain. Angewandte Chemie 43(22): 2911-2914, 2004

Efficient and selective synthesis of siphonarienolone and related reduced polypropionates via Zr-catalyzed asymmetric carboalumination. Organic Letters 6(9): 1425-1427, 2004

An efficient route to synthesize isatins by metal-free, iodine-catalyzed sequential C(sp(3))-H oxidation and intramolecular C-N bond formation of 2'-aminoacetophenones. Organic & Biomolecular Chemistry 12(42): 8512-8518, 2015

A general and efficient approach to 2H-indazoles and 1H-pyrazoles through copper-catalyzed intramolecular N-N bond formation under mild conditions. Chemical Communications 47(36): 10133-5, 2011

Practical route to 2-quinolinones via a Pd-catalyzed C-H bond activation/C-C bond formation/cyclization cascade reaction. Organic Letters 17(2): 222-225, 2015

Thiopyran route to polypropionates: an efficient synthesis of serricornin. Journal of Organic Chemistry 71(23): 8989-8992, 2006

Catalytic asymmetric carbon carbon bond formation asymmetric synthesis of cis decalin derivatives by palladium catalyzed cyclization of prochiral alkenyl iodides. Journal of Organic Chemistry 54(20): 4738-4739, 1989

Pd-catalyzed C-H activation/C-N bond formation: a new route to 1-aryl-1H-benzotriazoles. Organic Letters 13(8): 2102-2105, 2011

The asymmetric Cu(II)-indolinylmethanol complex catalyzed Diels-Alder reaction of 2-vinylindoles with β,γ-unsaturated α-ketoesters: an efficient route to functionalized tetrahydrocarbazoles. Organic & Biomolecular Chemistry 12(24): 4172-4176, 2016

Total synthesis of (+)-scyphostatin featuring an enantioselective and highly efficient route to the side-chain via Zr-catalyzed asymmetric carboalumination of alkenes (ZACA). Chemical Communications 46(13): 2200-2202, 2010

Pd-catalyzed dehydrogenative aryl-aryl bond formation via double C(sp(2))-H bond activation: efficient synthesis of [3,4]-fused oxindoles. Organic Letters 17(2): 334-337, 2015

Copper-catalyzed asymmetric three-component borylstannation: enantioselective formation of C-Sn bond. Chemistry 21(13): 4918-4922, 2016

Development of C-C bond formation and asymmetric reactions catalyzed by N-heterocyclic carbenes. Yakugaku Zasshi 128(8): 1179-1185, 2008

Chiral metal nanoparticle-catalyzed asymmetric C-C bond formation reactions. Chemical Society Reviews 43(5): 1450-1461, 2013