(3R,4S)-2-Isopropyl-3-methyl-4-phenyl-3,4-dihydro­isoquinolinium iodide

The title compound, C₁₉H₂₂N⁺·I^-, is a new dihydro­isoquinolinium salt, used as a catalyst in asymmetric epoxidation. It was characterized by NMR spectroscopy and X-ray crystallographic techniques. The absolute configurations of the two stereogenic centres were established by the refinement of the Flack parameter to be 3R and 4S.

Key indicators

• Single-crystal X-ray study
• T = 293 K
• Mean [sigma](C-C) = 0.008 Å
• R factor = 0.038
• wR factor = 0.086
• Data-to-parameter ratio = 19.1

checkCIF/PLATON results

No syntax errors found



Alert level G
REFLT03_ALERT_1_G ALERT: Expected hkl max differ from CIF values
           From the CIF: _diffrn_reflns_theta_max           27.48
           From the CIF: _reflns_number_total               3694
           From the CIF: _diffrn_reflns_limit_ max hkl   12.   10.   34.
           From the CIF: _diffrn_reflns_limit_ min hkl  -12.  -10.  -42.
           TEST1: Expected hkl limits for theta max
           Calculated maximum hkl   12.   12.   42.
           Calculated minimum hkl  -12.  -12.  -42.
REFLT03_ALERT_4_G Please check that the estimate of the number of Friedel pairs is
            correct. If it is not, please give the correct count in the
            _publ_section_exptl_refinement section of the submitted CIF.
           From the CIF: _diffrn_reflns_theta_max           27.48
           From the CIF: _reflns_number_total               3694
           Count of symmetry unique reflns         2102
           Completeness (_total/calc)            175.74%
           TEST3: Check Friedels for noncentro structure
           Estimate of Friedel pairs measured      1592
           Fraction of Friedel pairs measured     0.757
           Are heavy atom types Z>Si present        yes
PLAT199_ALERT_1_G Check the Reported _cell_measurement_temperature        293 K
PLAT200_ALERT_1_G Check the Reported _diffrn_ambient_temperature .        293 K
PLAT791_ALERT_1_G Confirm the Absolute Configuration of C3     = .          R
PLAT791_ALERT_1_G Confirm the Absolute Configuration of C4     = .          S
PLAT860_ALERT_3_G Note: Number of Least-Squares Restraints .......          1

   0 ALERT level A = In general: serious problem
   0 ALERT level B = Potentially serious problem
   0 ALERT level C = Check and explain
   7 ALERT level G = General alerts; check

   5 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   0 ALERT type 2 Indicator that the structure model may be wrong or deficient
   1 ALERT type 3 Indicator that the structure quality may be low
   1 ALERT type 4 Improvement, methodology, query or suggestion
   0 ALERT type 5 Informative message, check

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S1. Comment

Catalytic asymmetric epoxidation of alkenes is an exceptionally valuable synthetic transformation (Xia et al.,2005). The development of efficient methods for asymmetric epoxidation of simple, 'unfunctionalized' alkenes is a particular challenge, and some of the most spectacular progress in recent years has come from the use of oxaziridinum salts generated in situ by oxidation of chiral iminium salts (Bohé et al., 1999). As part of our interest in oxaziridinium chemistry and particularly in the rational design of dihydroisoquinolinium-derived catalysts able to improve the catalytic oxygen transfer process, we examined the influence of the exocyclic substituent on the nitrogen atom on the ee induced in an epoxidation reaction. Thus we prepared the iminium salt (2) and evaluated its behavior in the catalytic system (Fig. 1). We report herein the synthesis and the crystal structure determination of the title compound. Synthesis of the title compound involved heating a mixture of the corresponding diydroisoquinoline (2) and isopropyl iodide for 24 h. Imine (2) was prepared as described by Bohé et al.(1999), in four steps from (1S, 2R)-norephedrine (1).

In the title compound, the tetrahydroisoquinoline unit is substituted by a methyl group in position 3, a phenyl substituent in position 4, and a cyclohexane ring at the nitrogen (Fig. 2). The heterocyclic ring adopts a half-chair conformation as indicated by puckering analysis [QT= 0.458 (5)Å and θ= 62.1 (6)°] (Cremer & Pople, 1975). The substituents in positions 3 and 4 of the heterocyclic ring are in axial conformation with respect to this ring and the X-ray analyses allowed to define the absolute configuration of C3(R) and C4(S).

Related literature

For general background see: Bohé et al. (1999); Xia et al. (2005). For related literature, see: Cremer & Pople (1975).

S2. Experimental

Compound (3) was prepared by reaction of imine (2) (3.470 g, 16 mmol), and isopropyl iodide (8 ml, 80 mmol) in acetonitrile (80 ml).The mixture was heated at reflux for 24 h. On completion of the reaction, as monitored by TLC, the solvent was removed in vacuum and the product purified by flash chromatography on silica, with dichloromethane/methanol (90/10) as eluent (yield 95%). m.p. 457 K. [α] _D²² – 62 (c 1; CHCl3). Spectroscopic analysis, 1H NMR (400 MHz; CDCl3, p.p.m): 1.23 (d, J = 6.2, 3H, Me20); 1.24 (d, J = 6.2,3H, Me19); 1.58 (d, J = 6.7, 3H, Me11); 4.37 (q, J = 6.7, 1H, H3); 4.47 (s,1H, H4); 4.54 (dq, J = 6.2, J = 6.2, 1H, H18); 6.87 (d, J = 6.5, 2H, aromatic H); 7.30 (m, 3H, aromatic H); 7.40 (d, J = 7.5, 1H, aromatic H); 7.63 (t, J = 7.3, 1H, aromatic H); 7.80 (t, J = 7.6, 1H, aromatic H); 8.70 (d, J = 7.2, 1H, aromatic H); 10.54 (s, 1H, H1). 13 C NMR (62.5 MHz; CDCl3): 18.92, 20.33,21.12, 48.12, 61.61, 62.67, 125.10, 127.69, 128.51, 129.48, 129.74, 130.16, 135.75, 136.22, 138.78, 163.74. m/z (ESI+): 264 (M—I)+. Anal.: Calcd for C19H22NI: C 58.32%; H 5.67%; N 3.58%. Found: C 58.44%; H 5.79%; N 3.44% Recrystallization from acetone afford yellow crystals suitable for diffraction.

S3. Refinement

All H atoms were positioned geometrically and treated as riding, with C—H = 0.93 (aromatic), 0.96 (methyl), or 0.98 Å (methine), with U_iso(H) = xU_eq(C) where x = 1.5 for methyl H and 1.2 for all other H atoms. Friedel opposites were not merged. The absolute configuration C3(R),C4(S) was determined from the anomalous scattering contribution of the iodide anion, using 1602 Friedel pairs.

Computing details

Data collection: COLLECT (Hooft, 1998); cell refinement: DENZO (Otwinowski & Minor, 1997); data reduction: DENZO; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997); software used to prepare material for publication: SHELXL97.

Figures

	Fig. 1. Chemical pathway of the formation of (3).
	Fig. 2. Molecular view of the title compound showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level.H atoms are represented as small spheres of arbitrary radii.

(3R,4S)-2-Isopropyl-3-methyl-4-phenyl-3,4-dihydroisoquinolinium iodide

Crystal data

C19H22N^+·I^−	Dx = 1.444 Mg m^−3
Mr = 391.28	Melting point: 457 K
Hexagonal, P61	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 61	Cell parameters from 3639 reflections
a = 9.773 (4) Å	θ = 1.0–27.5°
c = 32.630 (12) Å	µ = 1.77 mm^−1
V = 2699.0 (19) Å^3	T = 293 K
Z = 6	Prism, yellow
F(000) = 1176	0.40 × 0.35 × 0.35 mm

Data collection

Nonius KappaCCD diffractometer	3694 independent reflections
Radiation source: fine-focus sealed tube	2992 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.014
φ and ω scans	θmax = 27.5°, θmin = 2.4°
Absorption correction: multi-scan (SCALEPACK; Otwinowski & Minor, 1997)	h = −12→12
Tmin = 0.491, Tmax = 0.540	k = −10→10
6545 measured reflections	l = −42→34

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.038	H-atom parameters constrained
wR(F^2) = 0.086	w = 1/[σ^2(Fo^2) + (0.0277P)^2 + 2.172P] where P = (Fo^2 + 2Fc^2)/3
S = 1.02	(Δ/σ)max = 0.002
3694 reflections	Δρmax = 0.55 e Å^−3
193 parameters	Δρmin = −1.01 e Å^−3
1 restraint	Absolute structure: Flack (1983), 1602 Friedel pairs
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: 0.01 (3)

Special details

Refinement. Refinement of F² against ALL reflections except one truncated by the beamstop. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
I1	0.64454 (5)	0.68377 (4)	0.139072 (16)	0.1060 (2)
C1	0.7788 (5)	0.4692 (5)	0.20412 (13)	0.0535 (10)
H1	0.8142	0.5730	0.2121	0.060*
N2	0.8719 (4)	0.4388 (4)	0.18374 (10)	0.0528 (8)
C3	0.8106 (5)	0.2778 (5)	0.16614 (15)	0.0599 (11)
H3	0.9006	0.2622	0.1610	0.067*
C4	0.7003 (5)	0.1521 (5)	0.19702 (15)	0.0606 (11)
H4	0.6446	0.0516	0.1822	0.068*
C5	0.4251 (6)	0.0766 (6)	0.22239 (18)	0.0740 (14)
H5	0.3941	−0.0298	0.2198	0.083*
C6	0.3199 (6)	0.1186 (8)	0.23685 (19)	0.0853 (17)
H6	0.2183	0.0406	0.2440	0.096*
C7	0.3627 (6)	0.2737 (9)	0.24090 (19)	0.0837 (17)
H7	0.2898	0.3009	0.2505	0.094*
C8	0.5150 (6)	0.3917 (6)	0.23068 (16)	0.0692 (13)
H8	0.5454	0.4976	0.2341	0.078*
C9	0.6205 (5)	0.3492 (5)	0.21536 (13)	0.0508 (9)
C10	0.5777 (5)	0.1908 (5)	0.21141 (14)	0.0543 (10)
C11	0.7318 (7)	0.2690 (7)	0.12538 (15)	0.0827 (16)
H11A	0.6999	0.1688	0.1127	0.099*
H11B	0.8049	0.3525	0.1078	0.099*
H11C	0.6407	0.2800	0.1298	0.099*
C12	0.7885 (5)	0.1284 (5)	0.23205 (16)	0.0582 (11)
C13	0.8437 (6)	0.2279 (6)	0.26558 (16)	0.0666 (12)
H13	0.8217	0.3098	0.2678	0.075*
C14	0.9315 (6)	0.2078 (7)	0.29619 (18)	0.0766 (14)
H14	0.9722	0.2789	0.3179	0.086*
C15	0.9572 (7)	0.0836 (9)	0.2941 (2)	0.094 (2)
H15	1.0137	0.0679	0.3147	0.105*
C16	0.8997 (7)	−0.0179 (8)	0.2617 (3)	0.096 (2)
H16	0.9167	−0.1033	0.2605	0.108*
C17	0.8179 (6)	0.0037 (6)	0.2311 (2)	0.0740 (14)
H17	0.7812	−0.0663	0.2091	0.083*
C18	1.0400 (5)	0.5578 (6)	0.17395 (16)	0.0718 (13)
H18	1.0601	0.5393	0.1456	0.080*
C19	1.0690 (7)	0.7252 (6)	0.1764 (2)	0.097 (2)
H19A	1.1722	0.7972	0.1659	0.116*
H19B	1.0622	0.7510	0.2044	0.116*
H19C	0.9908	0.7333	0.1604	0.116*
C20	1.1482 (6)	0.5291 (9)	0.2014 (2)	0.097 (2)
H20A	1.1392	0.5570	0.2291	0.116*
H20B	1.2554	0.5927	0.1923	0.116*
H20C	1.1185	0.4196	0.2003	0.116*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
I1	0.0964 (3)	0.0813 (3)	0.0739 (2)	−0.00536 (18)	−0.0301 (2)	0.0212 (2)
C1	0.064 (3)	0.052 (2)	0.047 (2)	0.031 (2)	−0.0024 (19)	−0.0007 (18)
N2	0.0505 (19)	0.0547 (19)	0.0459 (19)	0.0208 (16)	−0.0008 (15)	−0.0027 (15)
C3	0.062 (3)	0.071 (3)	0.050 (2)	0.036 (2)	−0.004 (2)	−0.018 (2)
C4	0.062 (3)	0.050 (2)	0.067 (3)	0.026 (2)	−0.010 (2)	−0.020 (2)
C5	0.057 (3)	0.063 (3)	0.082 (4)	0.016 (2)	−0.006 (3)	0.010 (3)
C6	0.052 (3)	0.111 (5)	0.081 (4)	0.031 (3)	0.007 (3)	0.027 (3)
C7	0.066 (3)	0.128 (5)	0.075 (4)	0.061 (4)	0.010 (3)	0.020 (3)
C8	0.079 (3)	0.082 (3)	0.065 (3)	0.053 (3)	0.012 (3)	0.013 (3)
C9	0.052 (2)	0.057 (2)	0.046 (2)	0.030 (2)	0.0008 (17)	0.0041 (18)
C10	0.049 (2)	0.058 (2)	0.054 (3)	0.025 (2)	−0.0067 (19)	0.0007 (19)
C11	0.081 (3)	0.103 (4)	0.051 (3)	0.036 (3)	−0.013 (2)	−0.019 (3)
C12	0.057 (2)	0.048 (2)	0.076 (3)	0.030 (2)	0.004 (2)	0.002 (2)
C13	0.078 (3)	0.061 (3)	0.068 (3)	0.039 (2)	−0.011 (3)	−0.002 (2)
C14	0.070 (3)	0.096 (4)	0.070 (4)	0.045 (3)	0.000 (2)	0.018 (3)
C15	0.061 (3)	0.119 (5)	0.116 (5)	0.057 (3)	0.027 (3)	0.063 (4)
C16	0.083 (4)	0.083 (4)	0.151 (7)	0.062 (3)	0.032 (4)	0.040 (4)
C17	0.070 (3)	0.059 (3)	0.101 (4)	0.038 (3)	0.015 (3)	0.002 (3)
C18	0.052 (3)	0.094 (4)	0.050 (3)	0.023 (2)	0.003 (2)	−0.005 (2)
C19	0.082 (4)	0.073 (3)	0.081 (4)	−0.002 (3)	0.005 (3)	0.004 (3)
C20	0.057 (3)	0.141 (6)	0.083 (4)	0.042 (3)	−0.009 (3)	−0.019 (4)

Geometric parameters (Å, º)

C1—N2	1.276 (5)	C11—H11B	0.9600
C1—C9	1.445 (6)	C11—H11C	0.9600
C1—H1	0.9300	C12—C13	1.381 (7)
N2—C3	1.491 (5)	C12—C17	1.385 (6)
N2—C18	1.497 (5)	C13—C14	1.393 (7)
C3—C11	1.517 (7)	C13—H13	0.9300
C3—C4	1.537 (7)	C14—C15	1.359 (8)
C3—H3	0.9800	C14—H14	0.9300
C4—C10	1.501 (6)	C15—C16	1.364 (9)
C4—C12	1.518 (7)	C15—H15	0.9300
C4—H4	0.9800	C16—C17	1.361 (9)
C5—C6	1.367 (8)	C16—H16	0.9300
C5—C10	1.391 (6)	C17—H17	0.9300
C5—H5	0.9300	C18—C20	1.516 (8)
C6—C7	1.362 (8)	C18—C19	1.516 (8)
C6—H6	0.9300	C18—H18	0.9800
C7—C8	1.393 (8)	C19—H19A	0.9600
C7—H7	0.9300	C19—H19B	0.9600
C8—C9	1.383 (6)	C19—H19C	0.9600
C8—H8	0.9300	C20—H20A	0.9600
C9—C10	1.393 (6)	C20—H20B	0.9600
C11—H11A	0.9600	C20—H20C	0.9600
N2—C1—C9	122.8 (4)	C3—C11—H11C	109.5
N2—C1—H1	118.6	H11A—C11—H11C	109.5
C9—C1—H1	118.6	H11B—C11—H11C	109.5
C1—N2—C3	119.3 (4)	C13—C12—C17	117.2 (5)
C1—N2—C18	124.3 (4)	C13—C12—C4	122.8 (4)
C3—N2—C18	116.3 (4)	C17—C12—C4	120.0 (5)
N2—C3—C11	108.8 (4)	C12—C13—C14	121.3 (5)
N2—C3—C4	110.0 (3)	C12—C13—H13	119.3
C11—C3—C4	113.3 (4)	C14—C13—H13	119.3
N2—C3—H3	108.2	C15—C14—C13	119.5 (6)
C11—C3—H3	108.2	C15—C14—H14	120.3
C4—C3—H3	108.2	C13—C14—H14	120.3
C10—C4—C12	112.9 (4)	C14—C15—C16	119.7 (6)
C10—C4—C3	109.4 (4)	C14—C15—H15	120.2
C12—C4—C3	113.0 (4)	C16—C15—H15	120.2
C10—C4—H4	107.1	C17—C16—C15	121.1 (5)
C12—C4—H4	107.1	C17—C16—H16	119.4
C3—C4—H4	107.1	C15—C16—H16	119.4
C6—C5—C10	120.9 (5)	C16—C17—C12	121.0 (6)
C6—C5—H5	119.5	C16—C17—H17	119.5
C10—C5—H5	119.5	C12—C17—H17	119.5
C7—C6—C5	120.6 (5)	N2—C18—C20	109.0 (4)
C7—C6—H6	119.7	N2—C18—C19	111.5 (4)
C5—C6—H6	119.7	C20—C18—C19	113.4 (5)
C6—C7—C8	120.2 (5)	N2—C18—H18	107.5
C6—C7—H7	119.9	C20—C18—H18	107.5
C8—C7—H7	119.9	C19—C18—H18	107.5
C9—C8—C7	119.1 (5)	C18—C19—H19A	109.5
C9—C8—H8	120.4	C18—C19—H19B	109.5
C7—C8—H8	120.4	H19A—C19—H19B	109.5
C8—C9—C10	120.8 (4)	C18—C19—H19C	109.5
C8—C9—C1	120.2 (4)	H19A—C19—H19C	109.5
C10—C9—C1	118.9 (4)	H19B—C19—H19C	109.5
C5—C10—C9	118.3 (4)	C18—C20—H20A	109.5
C5—C10—C4	123.3 (4)	C18—C20—H20B	109.5
C9—C10—C4	118.4 (4)	H20A—C20—H20B	109.5
C3—C11—H11A	109.5	C18—C20—H20C	109.5
C3—C11—H11B	109.5	H20A—C20—H20C	109.5
H11A—C11—H11B	109.5	H20B—C20—H20C	109.5
C9—C1—N2—C3	7.8 (6)	C1—C9—C10—C4	2.1 (6)
C9—C1—N2—C18	−175.7 (4)	C12—C4—C10—C5	−85.0 (6)
C1—N2—C3—C11	83.8 (5)	C3—C4—C10—C5	148.2 (5)
C18—N2—C3—C11	−92.9 (5)	C12—C4—C10—C9	92.6 (5)
C1—N2—C3—C4	−40.9 (5)	C3—C4—C10—C9	−34.1 (5)
C18—N2—C3—C4	142.4 (4)	C10—C4—C12—C13	−44.2 (6)
N2—C3—C4—C10	51.6 (5)	C3—C4—C12—C13	80.7 (5)
C11—C3—C4—C10	−70.5 (5)	C10—C4—C12—C17	136.4 (4)
N2—C3—C4—C12	−75.1 (5)	C3—C4—C12—C17	−98.8 (5)
C11—C3—C4—C12	162.8 (4)	C17—C12—C13—C14	2.9 (7)
C10—C5—C6—C7	−0.1 (9)	C4—C12—C13—C14	−176.6 (5)
C5—C6—C7—C8	−0.7 (9)	C12—C13—C14—C15	−3.2 (8)
C6—C7—C8—C9	1.8 (9)	C13—C14—C15—C16	1.4 (8)
C7—C8—C9—C10	−2.2 (7)	C14—C15—C16—C17	0.6 (9)
C7—C8—C9—C1	179.3 (5)	C15—C16—C17—C12	−0.9 (9)
N2—C1—C9—C8	−168.1 (5)	C13—C12—C17—C16	−0.9 (7)
N2—C1—C9—C10	13.4 (6)	C4—C12—C17—C16	178.6 (5)
C6—C5—C10—C9	−0.3 (8)	C1—N2—C18—C20	104.5 (5)
C6—C5—C10—C4	177.4 (5)	C3—N2—C18—C20	−79.0 (5)
C8—C9—C10—C5	1.5 (7)	C1—N2—C18—C19	−21.5 (6)
C1—C9—C10—C5	179.9 (4)	C3—N2—C18—C19	155.0 (4)
C8—C9—C10—C4	−176.3 (4)