Carbamoyl radical-mediated synthesis and semipinacol rearrangement of β-lactam diols

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Carbamoyl radical-mediated synthesis and semipinacol rearrangement of β-lactam diols. / Betou, Marie; Male, Louise; Steed, Jonathan W.; Grainger, Richard S.

In: Chemistry: A European Journal, Vol. 20, No. 21, 19.05.2014, p. 6505-6517.

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Betou, Marie ; Male, Louise ; Steed, Jonathan W. ; Grainger, Richard S. / Carbamoyl radical-mediated synthesis and semipinacol rearrangement of β-lactam diols. In: Chemistry: A European Journal. 2014 ; Vol. 20, No. 21. pp. 6505-6517.

Bibtex

@article{8e26c059a16f4ed3a170467a124a61d5,
title = "Carbamoyl radical-mediated synthesis and semipinacol rearrangement of β-lactam diols",
abstract = "In an approach to the biologically important 6-azabicyclo[3.2.1]octane ring system, the scope of the tandem 4-exo-trig carbamoyl radical cyclization—dithiocarbamate group transfer reaction to ring-fused β-lactams is evaluated. β-Lactams fused to five-, six-, and seven-membered rings are prepared in good to excellent yield, and with moderate to complete control at the newly formed dithiocarbamate stereocentre. No cyclization is observed with an additional methyl substituent on the terminus of the double bond. Elimination of the dithiocarbamate group gives α,β- or β,γ-unsaturated lactams depending on both the methodology employed (base-mediated or thermal) and the nature of the carbocycle fused to the β-lactam. Fused β-lactam diols, obtained from catalytic OsO4-mediated dihydroxylation of α,β-unsaturated β-lactams, undergo semipinacol rearrangement via the corresponding cyclic sulfite or phosphorane to give keto-bridged bicyclic amides by exclusive N-acyl group migration. A monocyclic β-lactam diol undergoes Appel reaction at a primary alcohol in preference to semipinacol rearrangement. Preliminary investigations into the chemo- and stereoselective manipulation of the two carbonyl groups present in a representative 7,8-dioxo-6-azabicyclo[3.2.1]octane rearrangement product are also reported.",
keywords = "cyclization, fused-ring systems, nitrogen heterocycles, ring expansion, strained molecules",
author = "Marie Betou and Louise Male and Steed, {Jonathan W.} and Grainger, {Richard S.}",
year = "2014",
month = may,
day = "19",
doi = "10.1002/chem.v20.21",
language = "English",
volume = "20",
pages = "6505--6517",
journal = "Chemistry: A European Journal",
issn = "0947-6539",
publisher = "Wiley-VCH Verlag",
number = "21",

}

RIS

TY - JOUR

T1 - Carbamoyl radical-mediated synthesis and semipinacol rearrangement of β-lactam diols

AU - Betou, Marie

AU - Male, Louise

AU - Steed, Jonathan W.

AU - Grainger, Richard S.

PY - 2014/5/19

Y1 - 2014/5/19

N2 - In an approach to the biologically important 6-azabicyclo[3.2.1]octane ring system, the scope of the tandem 4-exo-trig carbamoyl radical cyclization—dithiocarbamate group transfer reaction to ring-fused β-lactams is evaluated. β-Lactams fused to five-, six-, and seven-membered rings are prepared in good to excellent yield, and with moderate to complete control at the newly formed dithiocarbamate stereocentre. No cyclization is observed with an additional methyl substituent on the terminus of the double bond. Elimination of the dithiocarbamate group gives α,β- or β,γ-unsaturated lactams depending on both the methodology employed (base-mediated or thermal) and the nature of the carbocycle fused to the β-lactam. Fused β-lactam diols, obtained from catalytic OsO4-mediated dihydroxylation of α,β-unsaturated β-lactams, undergo semipinacol rearrangement via the corresponding cyclic sulfite or phosphorane to give keto-bridged bicyclic amides by exclusive N-acyl group migration. A monocyclic β-lactam diol undergoes Appel reaction at a primary alcohol in preference to semipinacol rearrangement. Preliminary investigations into the chemo- and stereoselective manipulation of the two carbonyl groups present in a representative 7,8-dioxo-6-azabicyclo[3.2.1]octane rearrangement product are also reported.

AB - In an approach to the biologically important 6-azabicyclo[3.2.1]octane ring system, the scope of the tandem 4-exo-trig carbamoyl radical cyclization—dithiocarbamate group transfer reaction to ring-fused β-lactams is evaluated. β-Lactams fused to five-, six-, and seven-membered rings are prepared in good to excellent yield, and with moderate to complete control at the newly formed dithiocarbamate stereocentre. No cyclization is observed with an additional methyl substituent on the terminus of the double bond. Elimination of the dithiocarbamate group gives α,β- or β,γ-unsaturated lactams depending on both the methodology employed (base-mediated or thermal) and the nature of the carbocycle fused to the β-lactam. Fused β-lactam diols, obtained from catalytic OsO4-mediated dihydroxylation of α,β-unsaturated β-lactams, undergo semipinacol rearrangement via the corresponding cyclic sulfite or phosphorane to give keto-bridged bicyclic amides by exclusive N-acyl group migration. A monocyclic β-lactam diol undergoes Appel reaction at a primary alcohol in preference to semipinacol rearrangement. Preliminary investigations into the chemo- and stereoselective manipulation of the two carbonyl groups present in a representative 7,8-dioxo-6-azabicyclo[3.2.1]octane rearrangement product are also reported.

KW - cyclization

KW - fused-ring systems

KW - nitrogen heterocycles

KW - ring expansion

KW - strained molecules

U2 - 10.1002/chem.v20.21

DO - 10.1002/chem.v20.21

M3 - Article

C2 - 24711140

VL - 20

SP - 6505

EP - 6517

JO - Chemistry: A European Journal

JF - Chemistry: A European Journal

SN - 0947-6539

IS - 21

ER -