Stereocontrolled palladium-catalysed umpolung allylation of aldehydes with allyl acetates
Graphical abstract
Introduction
Trost and Tsuji pioneered the Pd(0)-catalysed asymmetric allylic alkylation of malonic esters and other nucleophiles (Nu−) (1→2→3; Scheme 1), which has become one of the most studied C–C-bond-forming reactions in current asymmetric catalysis.1, 2
In 1987, Brown and co-workers3 published the first example of an umpolung allylation which was studied in detail by Tamaru et al.4, 4(a), 4(b), 4(c), 4(d), 4(e), 4(f) They showed that the latent reactivity of the palladium allyl complex 2 can be reversed from electrophilic to nucleophilic in the presence of dialkylzinc or trialkylboron species. In situ formation of allylcopper and allyliridium species has recently been added in elegant works mainly by the group of Krische to the list of organometallic nucleophiles.5, 5(a), 5(b), 5(c) Importantly, Szabó and co-workers disclosed an efficient one-pot electrophilic allylation procedure (1→4→5) applying palladium–pincer complexes and diboranes 6.6, 6(a), 6(b)
The resulting umpolung reactions represent a complementary reaction to the existing allylation methodologies. In fact, it resembles the nucleophilic allylation of aldehydes (E+) developed by Hoffmann, Roush and others, except that the allylborane/boronate is formed in situ from an electrophilic allyl precursor 1.7d To date, there have been a few enantioselective examples of the dialkylzinc-mediated umpolung allylation (2→5) reported in the literature, namely by Zanoni, Zhou, and Feringa,7, 7(a), 7(b), 7(c), 7(d) while the Szabó approach has not been tested in asymmetric allylations for constructing complex fragments of natural products.8 One noteworthy feature of this umpolung reaction is the exclusive generation of the branched product 5b due to formation of the sterically less hindered allyl boronate 4 (Scheme 1).4(a), 4(b), 4(c), 4(d), 4(e), 4(f) Thus, a terminal double bond and two new stereogenic centers are formed, which makes the transformation highly attractive for natural product synthesis, namely polyketides. Here, we disclose different strategies to control the relative and absolute configuration of the newly formed stereogenic centers during the palladium-catalysed umpolung with in situ generation of allyl boronates 4.
Section snippets
Results and discussion
One major advantage of this one-pot procedure stems from the fact that isolation of the labile boronate intermediates can be avoided. Preliminary optimisation studies were carried out based on known procedures5(a), 5(b), 5(c) using aldehyde 7, cinnamyl acetate 8, and diboronate 10 as a model system (Table 1). In addition to different catalytic systems, the catalyst loading and reaction times were modified. Pd2dba3 (10 mol %) or Pd(allyl)2Cl2 in DMSO were found to be the best combinations (entries
Conclusion
In summary, we disclosed the stereochemical outcome of the palladium-catalysed umpolung allylation of aldehydes with allyl acetates. This protocol has several beneficial features compared to classical crotylations such as the possibility of the in situ generation of allyl boronates and the option of employing racemic allyl acetates.18 Remarkably, an unprecedented high 4,5-syn selectivity was found for selected chiral aldehydes. In conclusion, the umpolung procedure can become a promising tool
General
All experiments were performed under a nitrogen atmosphere in oven-dried glassware. Anhydrous THF was obtained by distillation from sodium and benzophenone. All other chemicals and solvents were purchased from Acros, Sigma–Aldrich, and ABCR. HRMS data were obtained on a Micromass LCT electrospray ionisation spectrometer. 1H NMR and 13C NMR spectra were recorded on a Bruker DPX-400 (400 MHz and 100 MHz). Compounds 7, 8, 10, l-12, and (−)-13 are commercially available. Compounds 26, 28, and 30 were
Acknowledgements
The work was funded by the Fonds der Chemischen Industrie.
References and notes (24)
- et al.
J. Am. Chem. Soc.
(2007)et al.J. Am. Chem. Soc.
(2006) - et al.
Tetrahedron Lett.
(1996) - et al.
Chem. Rev.
(2003)J. Org. Chem
(2004) Pure Appl. Chem
(1982)- et al.
J. Org. Chem.
(1987) - et al.
Angew. Chem., Int. Ed.
(2003)J. Organomet. Chem.
(1999)et al.Angew. Chem., Int. Ed. Engl.
(1995)et al.Tetrahedron Lett.
(1993)et al.Tetrahedron: Asymmetry
(2009)et al.Angew. Chem.
(2010)Angew. Chem., Int. Ed.
(2010) - et al.
Angew. Chem.
(2009)Angew. Chem., Int. Ed.
(2009)et al.Org. Lett.
(2009)et al.Chem. Commun.
(2009) - Asymmetric umpolung... et al.
Angew. Chem., Int. Ed.
(2004)et al.Org. Lett.
(2005)et al.Org. Biomol. Chem.
(2006)et al.Chem. Rev.
(2003) - et al.
Eur. J. Org. Chem.
(2006)