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Carbohydrate-Catalyzed Enantioselective Alkene Diboration

Transforming Unsaturated Hydrocarbons into Chiral Building Blocks

Enantioselective diboration of olefins is a valuable strategy for transforming unsaturated hydrocarbons into useful chiral building blocks. Typically, the process is carried out via transition-metal based activation of diboron reagent. Prof. James Morken has developed metal-free, affordable, enantioselective, 1,2-diboration of alkenes cocatalyzed by carbohydrate-derived catalysts and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU, 139009). This process employs pseudoenantiomeric glycols, 6-tert-butyldimethylsilyl-1,2-dihydroglucal (THS-DHG, 901235) and dihydrorhamnal (DHR, 901237), derived from D-glucal and L-rhamnal, respectively as chiral catalysts to enhance the reactivity of the diboron nucleus and to control the facial selectivity of the diboration reaction. Among various organoboronic esters studied for this reaction, 2,2′-bi-1,3,2-dioxaborinane (B2(pro)2, 901464) was found to be versatile in promoting reaction efficiency while maintaining high enantioselectivity. Reaction byproducts arising from B2(pro)2, namely, 1,3-propanediol and boric acid are relatively innocuous and easily removable by an aqueous wash. Carbohydrate-derived catalysts, TBS-DHG and DHR, offer not only greener means but also promote highly enantioselective 1,2-diboration of both terminal and internal alkenes at a modest temperature and a shorter reaction time.

tbs-dhg-catalyst

THS-DHG catalyst 901235

dhr-catalyst

DHR catalyst 901237

b-pro

B2(pro)2 901464

Advantages of Carbohydrate-Derived Catalysts

  • Operationally simple, greener, and scalable protocol
  • Highly enantioselective products from a broad range of alkenes
  • Innocuous water-soluble byproducts facilitate clean reactions
  • Requires low catalyst loading, moderate temperature, and a short reaction time

Procedure for the Enantioselective Diboration of Alkenes

enantioselective-diboration-alkenes-scheme

Scheme 1:General scheme for the enantioselective diboration of alkenes with B2(pro)2 and carbohydrate-derived catalysts, TBS-DHG and DHR.

  1. Charge TBS-DHG or DHR catalyst (0.10–0.15 eq), propanediol diboron, B2(pro)2 (2.0–3.0 eq), 4A molecular sieves, and the alkene substrate (1.0 eq) into a dry reaction flask in the glove box.
  2. Dissolve the above in ethyl acetate or THF, and add 0.10–0.15 eq of DBU.
  3. Stir the reaction mixture for 12h (at room temperature or 40 0C).
  4. Cool the reaction mixture to 0 0C, dilute with the solvent, and add 3 M sodium hydroxide solution followed by dropwise addition of 30% hydrogen peroxide.
  5. Warm to room temperature, stir for another 4h.
  6. Cool to 0 0C and add saturated aqueous sodium thiosulfate, dropwise over 5 min.
  7. Dilute with ethyl acetate and separate the organic and aqueous layers. Extract the organic layer, dry over sodium sulfate, and evaporate the solvents to afford the final product.

Scheme of Enantioselective Diboration of Internal and Terminal Alkenes

enantioselective-diboration-terminal-alkenes

Scheme 2:Enantioselective diboration of terminal alkenes by carbohydrate-derived catalysts

enantioselective-diboration-internal-alkenes

Scheme 3:Enantioselective diboration of internal alkenes by a carbohydrate-derived catalyst, TBS-DHG

Materials
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References

1.
Morgan JB, Miller SP, Morken JP. 2003. Rhodium-Catalyzed Enantioselective Diboration of Simple Alkenes. J. Am. Chem. Soc.. 125(29):8702-8703. http://dx.doi.org/10.1021/ja035851w
2.
Kliman LT, Mlynarski SN, Morken JP. 2009. Pt-Catalyzed Enantioselective Diboration of Terminal Alkenes with B2(pin)2. J. Am. Chem. Soc.. 131(37):13210-13211. http://dx.doi.org/10.1021/ja9047762
3.
Toribatake K, Nishiyama H. 2013. Asymmetric Diboration of Terminal Alkenes with a Rhodium Catalyst and Subsequent Oxidation: Enantioselective Synthesis of Optically Active 1,2-Diols. Angew. Chem. Int. Ed.. 52(42):11011-11015. http://dx.doi.org/10.1002/anie.201305181
4.
Lee Y, Jang H, Hoveyda AH. 2009. Vicinal Diboronates in High Enantiomeric Purity through Tandem Site-Selective NHC?Cu-Catalyzed Boron?Copper Additions to Terminal Alkynes. J. Am. Chem. Soc.. 131(51):18234-18235. http://dx.doi.org/10.1021/ja9089928
5.
Fang L, Yan L, Haeffner F, Morken JP. 2016. Carbohydrate-Catalyzed Enantioselective Alkene Diboration: Enhanced Reactivity of 1,2-Bonded Diboron Complexes. J. Am. Chem. Soc.. 138(8):2508-2511. http://dx.doi.org/10.1021/jacs.5b13174
6.
Yan L, Meng Y, Haeffner F, Leon RM, Crockett MP, Morken JP. 2018. Carbohydrate/DBU Cocatalyzed Alkene Diboration: Mechanistic Insight Provides Enhanced Catalytic Efficiency and Substrate Scope. J. Am. Chem. Soc.. 140(10):3663-3673. http://dx.doi.org/10.1021/jacs.7b12316