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Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
 
J Am Chem Soc. Author manuscript; available in PMC 2010 September 23.
Published in final edited form as:
PMCID: PMC2763309
NIHMSID: NIHMS141496

Pt-Catalyzed Enantioselective Diboration of Terminal Alkenes with B2(pin)2

Abstract

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The Pt-catalyzed enantioselective addition of bis(pinacolato)diboron to simple monosubstituted alkenes is described. This reaction occurs in the presence of a readily available chiral phosphonite ligand and is effective with a variety of terminal alkene substrates. Importantly, the reaction can operate with catalyst loadings of only 1 mol% Pt. While oxidation of the intermediate 1,2-bis(boronate) ester provides the chiral 1,2-diol as the reaction product, the intermediate may also be subjected to homologation/oxidation to furnish a chiral 1,4-diol as the reaction product.

The transition metal catalyzed diboration is an enabling method for the conversion of simple olefins to functionally- and stereochemically-enriched products.1,2 Of the substrate classes that might be considered for this reaction, terminal alkenes are amongst the most attractive. 1,2-Diboration of a terminal olefin provides a reactive intermediate with both primary and secondary boronate groups and the different environment of these elements causes them to exhibit differential reactivity in subsequent transformations.3 To employ these strategies in asymmetric synthesis, the issue of enantioselectivity in alkene diborations is critical. This has been addressed in our laboratory4 where it was determined that enantioselective diboration could be accomplished with bis(catecholato)diboron in the presence of Rh(I) and the chiral ligand Quinap.5 Unfortunately, this process is not only impractical with respect to reaction cost (both B2(cat)2 and the catalyst are expensive), but it also suffers from the fact that low enantioselectivity is observed for most 1-alkene substrates. In this report we describe a practical and economical enantioselective alkene diboration reaction that is highly effective with terminal olefins, occurring with good yield and excellent enantioselectivity.

Recently, we described the Pt-catalyzed enantioselective 1,4-diboration of 1,3-dienes in the presence of taddol-derived phosphonite ligands; after oxidation, the net 1,4-dihydroxylation product is obtained.6 Of interest, was the observation that enantioselective 1,2-diboration occurs as a side reaction with some 1,3-diene substrates. This feature prompted us to examine the asymmetric diboration of 1-alkene substrates under the influence of platinum complexes. Initial experiments with 1-octene showed that this process can be enantioselective and that taddol-derived phosphonite and phosphoramidite ligands7 can provide elevated levels of enantioselection (Table 1). Ligand L2 appeared optimal and was selected for further fine-tuning. Subsequent experiments suggested that several parameters are important for obtaining the highest enantioselectivity. First, 31P NMR analysis revealed that pre-heating Pt2(dba)3 and the phosphonite ligand at 80 °C for 30 minutes is required to achieve complete complexation of the metal and ligand and that the presence of B2(pin)2 aids in this complexation step; without this pre-treatment, diminished enantioselectivity is observed in the diboration. Second, a ligand loading of 1.2 equivalents, relative to platinum, results in optimal selectivity and yield; with two equivalents of ligand pre-complexed to Pt, only 9% yield of product is obtained.8 Lastly, fine-tuning of the R substituent on L2 revealed that the ethyl derivative (L8, Table 2) is more selective than the methyl derivative and leads to the derived 1,2-diol in 92% enantiomeric excess when combined with the above described modifications.

Table 1
Effect of Chiral Ligand on the Catalytic Enantioselective Diboration of 1-Octene.a
Table 2
Catalytic Enantioselective Diboration of 1-Alkenes.a

As depicted in Table 2, Pt-catalyzed diboration of many 1-alkene substrates occurs in a highly enantioselective fashion. Generally, only 1.05 equivalents of the diboron reagent are required and the products can be isolated in good yield. In addition to 1-octene, other aliphatic α-olefins undergo selective diboration.9 Notably, the reaction is insensitive to the nature of the alkyl substituent with large groups (entries 5 and 6) and small groups (entry 1) equally tolerated. Also of note, substrates bearing protected oxygen functionality undergo clean diboration with excellent levels of enantioselection. Surprisingly, substrates with allylic oxygenation do not suffer from competing π-allyl chemistry as has been documented in related catalyzed reactions between diboron reagents and allylic ethers.4b,10 Remarkably, the catalytic diboration of allylic ethers (i.e entry 9) only occurs in the presence of ligand (R,R)-L8; in the absence of (R,R)-L8 or with PCy3 as the ligand, the diboration/oxidation product cannot be detected. Also of note, is that styrene reacts with useful levels of enantioselectivity; in Rh-Quinap catalyzed diboration, this substrate reacts with anomalously low selectivity (33% ee).4a

Operation of the Pt-catalyzed asymmetric diboration on large scale would be most practical with reaction conditions that employ diminished catalyst loading and benign reaction solvent.11 As depicted in Scheme 1, ethyl acetate can also be employed as the reaction solvent, although in this solvent the product is furnished with slightly diminished enantiomeric purity relative to THF. Importantly, the catalyst loading can also be decreased to 0.5 mol% of the Pt dimer and 1.2 mol% ligand. With these conditions the reaction still occurs efficiently and in a reasonable time frame.

An attractive feature of the Pt-catalyzed asymmetric diboration is that the reaction conditions are compatible with many subsequent transformations of the chiral bis(boronate) ester, and thereby enable single-flask transformations without an intermediate reaction work-up. An example of this strategy is depicted in Scheme 2 where 1-octene is subjected to catalytic asymmetric diboration. After 12 hours of reaction at 60 °C, the reaction mixture is cooled to −78 °C and treated with two equivalents of ClCH2Li. Under these conditions, clean methylene insertion12 into each carbon-boron bond occurs and oxidative work-up provides the derived 1,4 diol in good yield and excellent enantiomeric purity.

In conclusion, we have described the first highly enantioselective asymmetric diboration of simple terminal alkenes. In addition to the oxidation and homologation reactions described here, many other transformations should be available to the diboron intermediate. Additional studies in this regard, and on further development of the catalytic reaction are underway.

Supplementary Material

1_si_001

Acknowledgment

Support by the NIGMS (GM-59417) is gratefully acknowledged, as is the NSF (DBI-0619576) for support of the BC Mass Spectrometry Center. We also thank AllyChem, Co., Ltd. for a generous donation of B2(pin)2.

Footnotes

Supporting Information Available: Characterization and procedures. This information is available free of charge through the internet at http://pubs.acs.org.

References

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9. With these conditions, trans-2-octene and α-methyl styrene are unreactive. Reaction of 1-octene with B2(cat)2 occurred in 17% yield and 62% ee. Lower yields in Table 2 reflect a lack of conversion; hydroboration products are not detected.
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11. B2(pin)2 is a readily available inexpensive reagent ($800/kg, AllyChem, Co., Ltd. ( http://www.allychem.com).
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