Stereospecific conversion of alcohols into pinacol boronic esters using lithiation–borylation methodology with pinacolborane

Roesner, Stefan; Brown, Christopher; Mohiti, Maziar; Pulis, Alexander P.; Rasappan, Ramesh; Blair, Daniel J.; Essafi, Stéphanie; Leonori, Daniele; Aggarwal, Varinder K.

doi:10.1039/c4cc00993b

Cited by 41 publications

(15 citation statements)

References 26 publications

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“…After protection as the t-butyldiphenylsilyl (TBDPS) ether, hydrolysis of the ester and carbamoylation led to carbamate 16. Lithiation followed by treatment with pinacolborane (HBpin) gave pinacol boronic ester 17 in good yield 36 followed by the addition of pinacol boronic ester 17 and heating gave the homologated product 14 in 92% yield and 99:1 d.r.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of hydroxyphthioceranic acid using a traceless lithiation–borylation–protodeboronation strategy

Rasappan¹,

Aggarwal²

2014

Nature Chem

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101

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In planning organic syntheses, disconnections are most often made adjacent to functional groups, which assist in C-C bond formation. For molecules devoid of obvious functional groups this approach presents a problem, and so functionalities must be installed temporarily and then removed. Here we present a traceless strategy for organic synthesis that uses a boronic ester as such a group in a one-pot lithiation-borylation-protodeboronation sequence. To realize this strategy, we developed a methodology for the protodeboronation of alkyl pinacol boronic esters that involves the formation of a boronate complex with a nucleophile followed by oxidation with Mn(OAc)3 in the presence of the hydrogen-atom donor 4-tert-butylcatechol. Iterative lithiation-borylation-protodeboronation allows the coupling of smaller fragments to build-up long alkyl chains. We employed this strategy in the synthesis of hydroxyphthioceranic acid, a key component of the cell-wall lipid of the virulent Mycobacterium tuberculosis, in just 14 steps (longest linear sequence) with full stereocontrol.

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Section: Resultsmentioning

confidence: 99%

Synthesis of hydroxyphthioceranic acid using a traceless lithiation–borylation–protodeboronation strategy

Rasappan¹,

Aggarwal²

2014

Nature Chem

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101

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“…Aggarwal has recently developed an alternative approach that gives access to similar substrates in high selectivity (Scheme 11) [27]. In this example, the configurationally stable tertiary benzylic α-O organolithium (vide infra) was reacted with H-B(pin).…”

Section: Scheme 4 Chiral Diamines Used In Asymmetric Deprotonationmentioning

confidence: 99%

Reagent-Controlled Lithiation–Borylation

Leonori

Aggarwal

2015

Synthesis and Application of Organoboron Compounds

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“…This methodology enabled the diastereoselective synthesis of a range of b-methyl-substituted allylic boronic esters, of which only a few examples have been reported to date. [12] The proposed mechanism for the 1,3 rearrangement is shown in Scheme 3. A transmetalation between B 2 pin 2 and Pd(OAc) 2 gives the Bpin-bound Pd II intermediate 12.…”

Section: IImentioning

confidence: 99%

Stereocontrolled Synthesis of 1,5‐Stereogenic Centers through Three‐Carbon Homologation of Boronic Esters

2014

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Allylic pinacol boronic esters are stable toward 1,3-borotropic rearrangement. We developed a Pd II -mediated isomerization process that gives di-or trisubstituted allylic boronic esters with high E selectivity. The combination of this method with lithiation-borylation enables the synthesis of carbon chains that bear 1,5-stereogenic centers. The utility of this method has been demonstrated in a formal synthesis of (+)-jasplakinolide.Polyketide natural products are replete with carbon chains that bear 1,5-stereogenic centers connected by alkyl, di-or trisubstituted alkenyl groups (Figure 1).[1] Numerous ingenious strategies have been devised for the synthesis of these natural products, but control of the double-bond geometry, especially in the case of tri-substituted alkenyl groups, can sometimes be challenging. [2] Recently, lithiation-borylation has emerged as a powerful tool to control the stereochemistry along a carbon chain and to build up multiple stereogenic centers with high stereocontrol. [3] In order to use lithiation-borylation to create compound arrays that bear 1,5-stereogenic centers, a threecarbon homologation of boronic ester 1 to an allylic boronic ester intermediate 2 would be required, which would then be set up for further homologations (Scheme 1 a). While there was one report of a three-carbon homologation of a boronic ester, this homologation required the use of unstable and difficult-to-handle propylene glycol boronic esters 3 (Scheme 1 a).[4] Furthermore, these substrates perform poorly in lithiation-borylation processes, thus limiting their use in asymmetric synthesis. In contrast, pinacol boronic esters perform well in lithiation-borylation processes, and so we needed to find conditions under which such esters could be employed in three-carbon homologations.In order to achieve our goal, we needed to 1) carry out a homologation to give allylic boronic ester 4 followed by 2) a diastereoselective 1,3-borotropic shift to give boronic ester 5 (Scheme 1 c). Both steps presented challenges. First of all, we needed to establish a general and efficient protocol for the homologation of a broad range of pinacol boronic esters to allylic boronic esters 4.[5] Secondly, conditions for the key 1,3-borotropic shift needed to be identified to maximize the reaction efficiency and more importantly to control the olefin geometry. It is important to note that while less sterically hindered allylic boronic esters (and boranes) [6] are known to undergo a 1,3-borotropic shift upon heating, pinacol allylic boronic esters have been shown to be thermally stable. [7] Despite the limited precedence, we initiated a research program aimed at addressing this challenge, anticipating that its solution would be highly useful for the synthesis of many relevant molecules. Herein we describe the first threecarbon homologation of pinacol boronic esters, introducing a di-or tri-substituted alkenyl unit with high stereocontrol over the double-bond geometry. This methodology was

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Stereospecific conversion of alcohols into pinacol boronic esters using lithiation–borylation methodology with pinacolborane

Cited by 41 publications

References 26 publications

Synthesis of hydroxyphthioceranic acid using a traceless lithiation–borylation–protodeboronation strategy

Synthesis of hydroxyphthioceranic acid using a traceless lithiation–borylation–protodeboronation strategy

Reagent-Controlled Lithiation–Borylation

Stereocontrolled Synthesis of 1,5‐Stereogenic Centers through Three‐Carbon Homologation of Boronic Esters

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