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. 2017 Nov 3;19(21):6024-6027.
doi: 10.1021/acs.orglett.7b03193.

Direct, Mild, and General n-Bu4NBr-Catalyzed Aldehyde Allylsilylation with Allyl Chlorides

Makeda A Tekle-Smith  1 , Kevin S Williamson  1 , Isaac F Hughes  1 , James L Leighton  1
Affiliations

Direct, Mild, and General n-Bu4NBr-Catalyzed Aldehyde Allylsilylation with Allyl Chlorides

Makeda A Tekle-Smith et al. Org Lett. .

Abstract

A direct, mild, and general method for the enantioselective allylsilylation of aldehydes with allyl chlorides is reported. The reactions are effectively catalyzed by 5 mol % of n-Bu4NBr, and this rate acceleration allows the use of complex allyl donors in fragment-coupling reactions and of electron-deficient allyl donors. The results are (1) significant progress toward a "universal" asymmetric aldehyde allylation reaction that can reliably and highly stereoselectively couple any allyl chloride_aldehyde combination and (2) the discovery of a novel mode of nucleophilic catalysis for aldehyde allylsilylation reactions.

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Conflict of interest statement

Notes

The authors declare no competing financial interests.

Figures

Figure 1
Figure 1
(a) A hypothetical direct complex fragment coupling allylation of aldehyde 1 with stereochemically and functionally complex allyl chloride 2. (b) Desirable attributes of a “universal” and direct aldehyde allylation reaction. (c) Our allylsilylation method entails preformation and isolation of the allyl trichlorosilanes, and has a limited scope with respect to the allyl donor.
Figure 2
Figure 2
Model fragment coupling allylation reaction for the synthesis of the EF-half of spongistatin 1.
Figure 3
Figure 3
Rate measurements of the crotylation of PhCHO. Each data point is the average of 3 runs (2 in the case of chloride-free silane 10), measuring the disappearance of PhCHO (measuring the appearance of product gives similar results) against a quantitative internal standard by 1H NMR spectroscopy
Figure 4
Figure 4
(a) Mechanistic scheme for Denmark’s LB-catalyzed allylation and aldol reactions. (b) Proposed mechanism of the anion-catalyzed allylation reaction. (c) Spectroscopic evidence for the formation of B and G.
See this image and copyright information in PMC

References

    1. Denmark SE, Almstead NG. In: Modern Carbonyl Chemistry. Otera J, editor. Wiley-VCH; Weinheim, Germany: 2000. Chapter 10.
    2. Chemler SR, Roush WR. In: Modern Carbonyl Chemistry. Otera J, editor. Wiley-VCH; Weinheim, Germany: 2000. Chapter 11.
    1. Yamamoto Y, Asao N. Chem Rev. 1993;93:2207–2293.
    2. Masse CE, Panek JS. Chem Rev. 1995;95:1293–1316.
    3. Ramachandran PV. Aldrichimica Acta. 2002;35:23–35.
    4. Denmark SE, Fu J. Chem Rev. 2003;103:2763–2794. - PubMed
    5. Kennedy JWJ, Hall DG. Angew Chem Int Ed. 2003;42:4732–4739. - PubMed
    6. Hall DG. Synlett. 2007:1644–1655.
    7. Lachance H, Hall DG. Org React. 2008;73:1–573.
    8. Leighton JL. Aldrichimica Acta. 2010;43:3–12.
    9. Yus M, González-Gómez JC, Foubelo F. Chem Rev. 2011;111:7774–7854. - PubMed
    1. Brown HC, Bhat KS. J Am Chem Soc. 1986;108:293–294. - PubMed
    2. Brown HC, Bhat KS. J Am Chem Soc. 1986;108:5919–5923. - PubMed
    3. Garcia J, Kim BM, Masamune S. J Org Chem. 1987;52:4831–4832.
    4. Roush WR, Ando K, Powers DB, Palkowitz AD, Halterman RL. J Am Chem Soc. 1990;112:6339–6348.
    5. Roush WR, Palkowitz AD, Ando K. J Am Chem Soc. 1990;112:6348–6359.
    6. Hafner A, Duthlaer RO, Marti R, Rihs G, Rothe-Streit P, Schwarzenbach F. J Am Chem Soc. 1992;114:2321–2336.
    7. Jain NF, Takenaka N, Panek JS. J Am Chem Soc. 1996;118:12475–12476.
    8. Denmark SE, Fu J. J Am Chem Soc. 2001;123:9488–9489. - PubMed
    9. Lachance H, Lu X, Gravel M, Hall DG. J Am Chem Soc. 2003;125:10160–10161. - PubMed
    10. Burgos CH, Canales E, Matos K, Soderquist JA. J Am Chem Soc. 2005;127:8044–8049. - PubMed
    11. Kim H, Ho S, Leighton JL. J Am Chem Soc. 2011;133:6517–6520. - PMC - PubMed
    1. Kim IS, Ngai MY, Krische MJ. J Am Chem Soc. 2008;130:6340–6341. - PMC - PubMed
    2. Kim IS, Ngai MY, Krische MJ. J Am Chem Soc. 2008;130:14891–14899. - PMC - PubMed
    3. Kim IS, Han SB, Krische MJ. J Am Chem Soc. 2009;131:2514–2520. - PMC - PubMed
    4. Han SB, Han H, Krische MJ. J Am Chem Soc. 2010;132:1760–1761. - PMC - PubMed
    5. Zhang YJ, Yang JH, Kim SH, Krische MJ. J Am Chem Soc. 2010;132:4562–4563. - PMC - PubMed
    6. Han SB, Gao X, Krische MJ. J Am Chem Soc. 2010;132:9153–9156. - PMC - PubMed
    7. Gao X, Zhang YJ, Krische MJ. Angew Chem Int Ed. 2011;50:4173–4175. - PMC - PubMed
    8. Hassan A, Townsend IA, Krische MJ. Chem Commun. 2011;47:10028–10030. - PMC - PubMed
    9. Gao X, Han H, Krische MJ. J Am Chem Soc. 2011;133:12795–12800. - PMC - PubMed

    1. For examples of indirect fragment coupling allylation reactions with pre-formation and isolation of the complex allylmetal(loid) species, see:

    2. Williams DR, Meyer KG. J Am Chem Soc. 2001;123:765–766. - PubMed
    3. Wender PA, Hegde SG, Hubbard RD, Zhang L. J Am Chem Soc. 2002;124:4956–4957. - PubMed

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