F
R. Ding et al.
Paper
Synthesis
5-(Bromomethyl)-3,3-dimethyldihydrofuran-2(4H)-one (2d)18
[CAS Reg. No. 174362-60-8]
13C NMR (75 MHz, CDCl3): δ = 179.10 (C-1), 51.29 (C-4), 35.89 (C-5),
31.69 (C-2), 31.13 (C-3).
Colorless oil; yield: 980 mg (95%).
5,6-Dibromohexanoic Acid (3f)21
[CAS Reg. No. 279214-91-4]
1H NMR (300 MHz, CDCl3): δ = 4.66–4.57 (m, 1 H, H-C-5), 3.54 (dd,
J = 10.8, 5.1 Hz, 1 H, H-CH2Br, A part of ABX), 3.47 (dd, J = 10.8, 6.0 Hz,
1 H, H′-CH2Br, B part of ABX), 2.25 (dd, J = 12.9, 6.3 Hz, 1 H, H-C-4),
1.91 (dd, J = 12.9, 9.3 Hz, 1 H, H′-C-4), 1.28 (s, 3 H, CH3), 1.26 (s, 3 H,
CH3).
13C NMR (75 MHz, CDCl3): δ = 180.97 (C-2), 74.74 (C-5), 41.87 (C-4),
40.61 (C-3), 33.74 (CH2Br), 24.96 (CH3), 24.91 (CH3).
Colorless oil; yield: 1.16 g (85%).
1H NMR (300 MHz, CDCl3): δ = 4.21–4.11 (m, 1 H, H-C-5), 3.86 (dd,
J = 10.2, 4.5 Hz, 1 H, H-C-6), 3.62 (t, J = 10.2 Hz, 1 H, H′-C-6), 2.47–2.40
(m, 2 H, H-C-2), 2.27–2.18 (m, 1 H, H-C-4), 2.01–1.92 (m, 1 H, H-C-3),
1.89–1.71 (m, 2 H, H′-C-3 and H′-C-4).
13C NMR (75 MHz, CDCl3): δ = 179.64 (C-1), 52.06 (C-5), 36.05 (C-6),
HRMS (ESI): m/z [M + Na]+ calcd for C7H11BrNaO2: 228.98401; found:
35.35 (C-4), 33.26 (C-2), 22.16 (C-3).
228.98355.
2-(2,3-Dibromocyclopentyl)acetic Acid (3h/3h′)
6-Bromohexahydro-2H-3,5-methanocyclopenta[b]furan-2-one
(2g)19
White solid; yield: 1.28 g (90%); obtained as a mixture of isomers 3h
and 3h′ in a ratio of 1:0.41.
[CAS Reg. No. 16512-03-1]
Light yellow oil; yield: 995 mg (92%).
2-[(1S*,2S*,3S*)-2,3-Dibromocyclopentyl]acetic Acid (3h)
1H NMR (300 MHz, CDCl3): δ = 4.90 (d, J = 5.1 Hz, 1 H, H-CH-O-), 3.82
(d, J = 2.1 Hz, 1 H, H-CH-Br), 3.21 (tq, J = 4.8, 1.5 Hz, 1 H, H-CHCH-Br),
2.66–2.64 (m, 1 H, H-CH-CO), 2.57–2.51 (m, 1 H, H-CHCH-O), 2.30
(dq, J = 11.4, 1.5 Hz, 1 H, H-CH2CH-CO), 2.12 (ddd, J = 13.8, 11.4, 4.2
Hz, 1 H, H-CH2CHCH-Br), 1.80–1.69 (m, 2 H, H′-CH2CHCH-Br and H′-
CH2CH-CO).
13C NMR (75 MHz, CDCl3): δ = 179.29 (C=O), 87.69 (CH-O), 53.58 (CH-
Br), 45.93 (CHCH-Br), 45.55 (CH-CO), 37.56 (CHCH-O), 35.78 (CH2CH-
CO), 33.99 (CH2CHCH-Br).
1H NMR (300 MHz, CDCl3): δ = 4.77 (d, J = 3.9 Hz, 1 H, H-C2-cyclopen-
tyl), 4.70 (d, J = 6.3 Hz, 1 H, H-C3-cyclopentyl), 3.13–2.98 (m, 1 H, H-
C1-cyclopentyl), 2.83–2.71 (m, 1 H, H-C4-cyclopentyl), 2.71 (dd,
J = 17.1, 7.8 Hz, 1 H, H-C-2), 2.62 (dd, J = 17.1, 6.9 Hz, 1 H, H′-C-2),
2.26–2.10 (m, 2 H, H-C5- and H′-C4-cyclopentyl), 1.70–1.52 (m, 1 H,
H′-C5-cyclopentyl).
13C NMR (75 MHz, CDCl3): δ = 178.83 (C-1), 64.07 (C2-cyclopentyl),
55.71 (C3-cyclopentyl), 38.05 (C1-cyclopentyl), 37.68 (C-2), 33.45
(C4-cyclopentyl), 27.27 (C5-cyclopentyl).
HRMS (ESI): m/z [M + Na]+ calcd for C8H9BrNaO2: 238.96836; found:
238.96767.
2-[(1S*,2R*,3R*)-2,3-Dibromocyclopentyl]acetic Acid (3h′)
1H NMR (300 MHz, CDCl3): δ = 4.41–4.34 (m, 1 H, H-C3-cyclopentyl),
4.11 (dd, J = 7.2, 5.7 Hz, 1 H, H-C2-cyclopentyl), 2.87 (dd, J = 16.2, 5.1
Hz, 1 H, H-C-2), 2.72–2.62 (m, 1 H, H-C1-cyclopentyl), 2.54–2.45 (m,
2 H, H-C4-cyclopentyl and H′-C-2), 2.27–2.08 (m, 2 H, H-C5- and H′-
C4-cyclopentyl), 1.78–1.69 (m, 1 H, H′-C5-cyclopentyl).
13C NMR (75 MHz, CDCl3): δ = 178.04 (C-1), 59.95 (C2-cyclopentyl),
55.72 (C3-cyclopentyl), 45.33 (C1-cyclopentyl), 38.68 (C-2), 34.43
(C4-cyclopentyl), 29.21 (C5-cyclopentyl).
trans-3,4-Dibromopentanoic Acid (3b)
Colorless oil; yield: 1.16 g (90%).
1H NMR (300 MHz, CDCl3): δ = 11.21 (s, 1 H, COOH), 4.41 (dt, J = 8.7,
3.0 Hz, 1 H, H-C-3), 4.33 (dq, J = 8.7, 6.3 Hz, 1 H, H-C-4), 3.50 (dd,
J = 17.1, 3.0 Hz, 1 H, H-C-2), 3.03 (dd, J = 17.1, 9.0 Hz, 1 H, H′-C-2),
1.90 (d, J = 6.3 Hz, 3 H, CH3).
13C NMR (75 MHz, CDCl3): δ = 176.07 (COOH), 52.31 (C-3), 51.17 (C-
4), 43.08 (C-2), 25.37 (CH3).
(3S*,4S*)-3,4-Dibromocyclopentanecarboxylic Acid (3i)14a
[CAS Reg. No. 140451-75-8]
trans-3,4-Dibromononanoic Acid (3c)
Colorless oil; yield: 1.35 g (86%).
White solid; yield: 1.30 g (96%).
1H NMR (300 MHz, CDCl3): δ = 4.50–4.41 (m, 1 H, H-C-3), 4.25 (td,
J = 8.7, 3.0 Hz, 1 H, H-C-4), 3.50 (dd, J = 17.1, 3.0 Hz, 1 H, H-C-2), 3.03
(dd, J = 17.1, 9.6 Hz, 1 H, H′-C-2), 2.21–2.10 (m, 1 H, H-C-5), 1.99–1.85
(m, 1 H, H′-C-5), 1.70–1.55 (m, 1 H, H-C-6), 1.54–1.41 (m, 1 H, H′-C-
6), 1.40–1.27 (m, 4 H, H-C-7 and H-C-8), 0.91 (t, J = 6.9 Hz, 3 H, CH3).
13C NMR (75 MHz, CDCl3): δ = 176.33 (C-1), 58.68 (C-4), 50.64 (C-3),
42.97 (C-2), 36.95 (C-5), 31.12 (C-7), 26.56 (C-6), 22.56 (C-8), 14.11
(CH3).
1H NMR (300 MHz, CDCl3): δ = 4.64–4.62 (m, 1 H, H-C-3), 4.57–4.54
(m, 1 H, H-C-4), 3.45–3.34 (m, 1 H, H-C-1), 3.07–2.99 (m, 2 H, H-C-2
and H-C-5), 2.65–2.57 (m, 1 H, H′-C-2 or H′-C-5), 2.48 (ddt, J = 15.0,
8.7, 1.5 Hz, 1 H, H′-C-2 or H′-C-5).
13C NMR (75 MHz, CDCl3): δ = 180.68 (COOH), 56.34 (C-3), 54.45 (C-
4), 40.83 (C-1), 37.27, 37.08 (C-2 and C-5).
(1R*,3S*,4S*)-3,4-Dibromocyclohexanecarboxylic Acid (3j)14a
[CAS Reg. No. 38361-06-7]
4,5-Dibromopentanoic Acid (3e)20
[CAS Reg. No. 78181-02-9]
White solid; yield: 1.14 g (80%).
1H NMR (300 MHz, CDCl3): δ = 4.71–4.68 (m, 1 H, H-C-3), 4.62–4.59
(m, 1 H, H-C-4), 3.02–2.90 (m, 1 H, H-C-1), 2.62 (ddd, J = 14.7, 11.7,
3.3 Hz, 1 H, H-C-2), 2.56–2.44 (m, 1 H, H-C-5), 2.28–2.17 (m, 1 H, H′-
C-2), 2.08–2.03 (m, 1 H, H′-C-5), 2.01–1.94 (m, 2 H, H-C-6).
Colorless oil; yield: 1.02 g (79%).
1H NMR (300 MHz, CDCl3): δ = 4.23 (tdd, J = 9.6, 4.2, 2.7 Hz, 1 H, H-C-
4), 3.86 (dd, J = 10.5, 4.5 Hz, 1 H, H-C-5), 3.61 (t, J = 10.2 Hz, 1 H, H′-C-
5), 2.74–2.47 (m, 3 H, H-C-2 and H-C-3), 2.09–1.94 (m, 1 H, H′-C-3).
13C NMR (75 MHz, CDCl3): δ = 180.78 (COOH), 52.01, 51.96 (C-3 and
C-4), 37.50 (C-1), 30.75 (C-2), 28.28 (C-5), 23.13 (C-6).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–K