Complex Boron-Containing Molecules through a 1,2-Metalate Rearrangement/anti-S N 2′ Elimination/Cycloaddition Reaction Sequence

Abstract

The three-component coupling of benzylamines, boronic esters, and 4-phenyl-3H-1,2,4-triazole-3,5(4H)-dione (PTAD) is reported. The boronate complex formed from an ortho-lithiated benzylamine and a boronic ester undergoes a stereospecific 1,2-metalate rearrangement/anti-S N 2′ elimination in the presence of an N-activator to provide a dearomatized tertiary boronic ester. Interception of this dearomatized intermediate with a dienophile leads to stereopredictable cycloaddition reactions to generate highly complex three-dimensional boron-containing molecular structures. When enantioenriched α-methyl-substituted benzylamines are employed, the corresponding cycloaddition adducts are formed with excellent enantiospecificities.

Computational assessments of diastereoselective [4+2] cycloaddition and 1,3-borotopic shift of a dearomatized tertiary boronic ester intermediate: reactivities explained through transition-state distortion energies

“…This activation energy difference between the isomeric pathways would reect the experimental diastereoselectivity (>20 : 1 d.r.). 10 Computational evaluations about the origin behind the high selectivity indicate that, along TS, the bulk steric between the dienophile and quaternary substituted group is responsible for the isomeric preference. Along TS 12b-syn the steric distance between CH 3 group in the Bpin of the diene moiety and N-N moiety in the dienophile (PTAD) is 3.39 A and 2.55 A for N1-H[CH 3 ]Bpin and N2-H[CH 3 ] Bpin respectively.…”

“…Very recently, they published a simple one-pot procedure through the interception of the dearomatized intermediate 3 with a dienophile (PTAD) in a diastereoselective [4+2] cycloaddition to generate highly complex three-dimensional boron-containing molecular structures (Scheme 1-c). 10 This intermediate has been used in total syntheses 11 and different transition metal-catalyzed transformations. 12 We were then captivated in a number of issues arising from these transformations; (1) realizing the formation of this intermediate in a compelling mechanism, (2) understanding the facial selectivity in the Diels-Alder cycloaddition which should give us a clue to rationalize the origin behind high diastereoselectivity, (3) realizing the reactivity of cycloaddition and 1,3-borotopic in the absence and presence of a Lewis acid, and (3) due to the notably limited reactivity of cyclohexadienes evaluation of the other dienophiles in [4+2] cycloaddition have raised further questions corresponding to the demand of matched/mismatched reactivities between the HOMO and LUMO orbitals.…”

How Big is the Pinacol Boronic Ester as a Substituent?

“…The percent buried volume (%V Bur ) steric parameter describes the percentage of a sphere ( r =3.5 Å) around the metal centre that is occupied by a given ligand and we postulated that it might better incorporate the effect of the diol backbone [25] . The percent buried volume values, using fully optimized C‐R distances to capture differences in bond lengths as noted above (see Table S3 in ESI), are provided in Figure 2 and show the same trend as the experimental Diels–Alder reaction results, [10] with the Bpin group appearing bigger than unbranched primary alkyl groups (e.g. Me, Et), comparable to a phenyl ring, but significantly smaller than secondary and tertiary alkyl groups (e.g.…”

“…We became interested in the question of Bpin's size during a recent study which engaged the dienyl tertiary pinacol boronic ester 1 with 4‐phenyl‐3 H ‐1,2,4‐triazole‐3,5(4 H )‐dione in a Diels–Alder cycloaddition reaction (Scheme 1 C). [10] The facial selectivity, whether the dienophile approaches past the Bpin or R group, led to mixtures of diastereoisomers, 2 and 3 . Assuming that the approach is governed by steric interactions, we reasoned that the diastereoselectivities could be attributed to the relative sizes of the Bpin and R groups.…”

A unified approach for divergent synthesis of contiguous stereodiads employing a small boronyl group

“…Although the Bpin group contains a five-membered heterocycle and a bulky pinacol moiety, its planar structure combined with substituent-free oxygen atoms might render it a less sterically demanding structural unit than common carbon-centered groups. In a recent report, Tillin et al also noted smaller size effect of Bpin in comparison with groups such as cyclohexyl 58 .…”