Stereoselective Intermolecular Carbolithiation of Open-Chain and Cyclic 1-Aryl-1-alkenyl N,N-Diisopropylcarbamates Coupled with Electrophilic Substitution. Observation of p-Carboxylation in a Benzyllithium Derivative

Abstract

1-Aryl-1-alkenyl N,N-diisopropylcarbamates (1) are obtained from alkyl aryl ketones and N,N-diisopropylcarbamoyl chloride (CbCl) by heating with excess pyridine. These undergo facile syn-carbolithiation by alkyllithium/diamine and produce configurationally stable lithiated benzyl carbamates, which have been trapped with different electrophiles. If the reaction is carried out in the presence of chiral diamines, such as (-)-sparteine or (-)-α-isosparteine, moderate enantiofacial differentiation is observed.

Key words

1-alkenyl carbamates - benzyl carbamates - chiral benzyllithium compounds - carbolithiation - (-)-sparteine

References

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  See Ref. [15]

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• 36a X-ray analysis
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• 36h

  Crystallographic data (excluding structure factors) for the structure reported in this paper have been deposited with Cambridge Crystallographic Data Centre as supplementary publication No. CCDC-156957-156959. Copies of the data can be obtained free of charge on application to The Director, CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (fax: int. code+44(1223)336-033; e-mail: [e-mail]).

6

The sense of diastereoselectivity, by which F is formed, depends on the configuration of intermediate E and the stereochemistry of the substitution step.

14

High simple diastereoselectivity may result from the syn-addition process.

17

X-ray crystal structure analysis of 1d: formula C₂₁H₂₅NO₂, M = 323.42, colourless crystal 0.40 × 0.40 × 0.20 mm, a = 12.118(2), b = 13.509(2), c = 23.090(4) Å, β = 92.32(1)°, V = 3776.8(11) ų, ρ_calc = 1.138 g cm^-3, µ = 0.72 cm^-1, no absorption correction (0.994 ≤ C ≤ 0.999), Z = 8, monoclinic, space group P2₁/c (No. 14), λ = 0.71073 Å, T = 293 K, ω/2θ scans, 6700 reflections collected (+h,+k, ±l), [(sinθ)/λ] = 0.59 Å^-1, 6374 independent (R _int = 0.028) and 3227 observed reflections [I ≥ 2 σ(I)], 441 refined parameters, R = 0.048, wR ² = 0.114, max. residual electron density 0.45 (-0.23) e Å^-3, hydrogens calculated and refined as riding atoms, two almost identical molecules in the asymmetric unit, differences in the torsion angles C1-C2-O2-C3 and C31-C32-O32-C33. [36]

18

If not denoted otherwise in Tables: the first letter corresponds to the substrate and the second letter corresponds to the carbolithiation reagent.

19

X-ray crystal structure analysis of 9a: formula C₂₅H₃₅NO₂, M = 381.54, colourless crystal 0.70 × 0.50 × 0.30 mm, a = 29.416(5), c = 11.006(2) Å, V = 9524(3) ų, ρ_calc = 1.064 g cm^-3, µ = 0.66 cm^-1, empirical absorption correction via ψ scan data (0.928 ≤ C ≤ 0.999), Z = 16, tetragonal, space group I4₁/a (No. 88), λ = 0.71073 Å, T = 293 K, ω/2θ scans, 8176 reflections collected (+h, ±k,+l), [(sinθ)/λ] = 0.59 Å^-1, 4011 independent (R _int = 0.099) and 1859 observed reflections [I ≥ 2 σ(I)], 258 refined parameters, R = 0.062, wR ² = 0.161, max. residual electron density 0.18 (-0.17) e Å^-3, hydrogens calculated and refined as riding atoms. [36]

21

X-ray crystal structure analysis of 17: formula C₂₃H₃₅NO₄, M = 389.52, colourless crystal 0.30 × 0.25 × 0.15 mm, a = 10.689(1), b = 10.717(1), c = 10.953(1) Å, α = 101.53(1), β = 96.47(1), γ = 108.18(1)°, V = 1147.2(2) ų, ρ_calc = 1.128 g cm^-3, µ = 0.76 cm^-1, no absorption correction (0.978 ≤ T ≤ 0.989), Z = 2, triclinic, space group P1bar (No. 2), λ = 0.71073 Å, T = 293 K, ω and φ scans, 8217 reflections collected (±h, ±k, ±l), [(sinθ)/λ] = 0.65 Å^-1, 5220 independent (R _int = 0.020) and 4004 observed reflections [I ≥ 2 σ(I)], 261 refined parameters, R = 0.052, wR ² = 0.138, max. residual electron density 0.17 (-0.16) e Å^-3, hydrogens calculated and refined as riding atoms. [36]

25

Iodide 18 was prepared from 1-phenylprop-2-enol by carbamoylation, a deprotonation-γ-alkylation sequence with a ω-oxy-2-(tetrahydropyranyloxy)propyl iodide, deprotection of the hydroxy group and conversion to the iodide; see experimental section.

27

See also footnote 15 in Ref. [13]