Planar chiral hydroxy derivatives of [2.2]paracyclophane as auxiliaries for asymmetric allylboration

Abstract

Allylboronic esters with various structures were synthesized for the first time based on [2.2]paracyclophane derivatives containing one or two hydroxy groups. It was demonstrated that these esters can be used as chiral inductors in the asymmetric allylboration of benzalde hyde. The highest enantiomeric excess of 1 phenylbut 3 en 1 ol (60%) was achieved in the reactions with acyclic bis O,O´ (paracyclophanyl) allylboronates based on (S) 4 hydroxy and (S) 12 bromo 4 hydroxy[2.2]paracyclophanes. (S) 4 Hydroxy[2.2]paracyclophane was studied by X ray diffraction.The allylboration of aldehydes is one of the most widely used approaches to the stereoselective C-C bond forma tion. 1-4 Generally, enantiomerically pure compounds (diols, diamines, sulfamides, and amino alcohols) pos sessing central 4 or (more rarely) axial chirality 5 are used for the design of reagents for the asymmetric allylboration.Earlier, 6,7 we have demonstrated for the first time that planar chiral [2.2]paracyclophane derivatives can be used in this reaction. For example, diastereomerically pure diallylborinate 2 was synthesized starting from 4 acetyl[2.2]paracyclophane (1) 8,9 (Scheme 1).Compound 2 was used in the allylboration of 4 for myl[2.2]paracyclophane (4) (de of rel (R p ,R) 4 (1 hydr oxybut 3 enyl)[2.2]paracyclophane (5) 50%) and benz aldehyde (6) (ee of 1 phenylbut 3 en 1 ol (7) was 18%). Homoallylic alcohol 3 produced in the reaction is a re cyclable auxiliary because it again gives ester 2 in the reaction with triallylborane (see Scheme 1).In alcohol 3, the hydroxy group is two bonds from the paracyclophane moiety. In the present study, we investi gated the influence of the distance between the functional group and the paracyclophane moiety on the stereochemi cal result of asymmetric allylboration of benzaldehyde. For this purpose, we examined for the first time the possi bility of designing reagents for the asymmetric allyl boration based on chiral phenols, viz., (S) 4 hydr oxy[2.2]paracyclophane (8) and (S) 12 bromo 4 hydr oxy[2.2]paracyclophane (9), in which the hydroxy group is directly fixed in the aromatic ring of [2.2]paracyclo phane.An important feature, which distinguishes phenols 8 and 9 from alcohol 3 containing two stereogenic centers, is that they contain only one (planar) chirality center, which eliminates the question about the possible coop erative effect of the planar and central chirality in the asymmetric process. Results and DiscussionSynthesis of starting phenols 8 and 9. Racemic phenol 8 was synthesized according to a known procedure. 10 To synthesize its enantiomers, we have developed 11-14 a pro cedure for the resolution of rac 8 into enantiomers through esters with (1S) (-) camphanic acid 10 (Scheme 2). 15, 16 Diastereomeric esters 10 were separated by fractional crystallization 15 followed by the preparative separation of the mother liquor by silica gel column chromatography. 16 In the present study, we improved the procedure for the isolation of enantiomers of phenol 8 from diastereo merically pure esters by us...

Synthesis and application of the first planar chiral strong brønsted acid organocatalysts

“…A Suzuki coupling of enantiopure ( S P )‐ 20 with 2‐hydroxyphenyl boronic acid ( 21 ) gave the diol ( S P )‐ 22 in 70% yield (Scheme ). This compound has been mentioned in the literature several times,27–29 but no characterization has been published so far.…”

Enantiopure planar chiral [2.2]paracyclophanes: Synthesis and applications in asymmetric organocatalysis

“…ester adducts formed upon treatment with activated camphanoyl derivatives. [54][55][56][57][58][59][60] This quite general approach can be exemplified by the chemical resolution of 4-hydroxy[2.2]paracyclophane (±)-16. 57 This compound has been submitted to a reaction with (1S)-(À)-camphanoyl chloride ((S)-17, Scheme 8) to form a couple of diastereomers, which can be easily separated by silica gel column chromatography (Scheme 8).…”

Novel strategy for the synthesis of chiral pseudo-ortho-substituted hydroxy[2.2]paracyclophane-based ligands from the resolved 4-bromo-12-hydroxy[2.2]paracyclophane as a parent compound

“…Recently, 26 we have shown that, similarly to phenol 1, the enantiomerically pure compound 12 can be used as a chiral inductor, namely, recoverable auxiliary reactant in the asymmetric allylboronation of benzaldehyde (ee of the product, 3-buten-1-phenyl-1-ol, up to 59%).…”

“…Colourless, needle-like crystals were obtained from EtOH, C 26 The structures were solved by direct method and refined by the full-matrix least-squares against F 2 in anisotropic (for no-hydrogen atoms) approximation. The H(C) atoms were placed in geometrically calculated positions and were refined in isotropic approximation in riding model with the U iso (H) parameters equal to 1.2 U eq (Ci), for methyl groups equal to 1.5 U eq (Cii), where U(Ci) and U(Cii) are, respectively, the equivalent thermal parameters of the atoms to which the corresponding H atoms are bonded.…”