The First Simple Method of Protection of Hydroxy Compounds as their O-Boc Derivatives under Lewis Acid Catalysis

Giuseppe Bartoli; Marcella Bosco; Armando Carlone; Renato Dalpozzo; Manuela Locatelli; Paolo Melchiorre; Paolo Palazzi; Letizia Sambri

doi:10.1055/s-2006-949609

LETTER

The First Simple Method of Protection of Hydroxy Compounds as their O-Boc Derivatives under Lewis Acid Catalysis

Giuseppe Bartoli*^a, Marcella Bosco^a, Armando Carlone^a, Renato Dalpozzo^b, Manuela Locatelli^a, Paolo Melchiorre^a, Paolo Palazzi^a, Letizia Sambri^a
^a Dipartimento di Chimica Organica ‘A. Mangini’, Università di Bologna, viale Risorgimento 4, 40136 Bologna, Italy
Fax: +39(051)2093654; e-Mail: giuseppe.bartoli@unibo.it;
^b Dipartimento di Chimica, Università della Calabria, Ponte Bucci, cubo 12C, 87036 Arcavacata di Rende (Cs), Italy

Abstract

Alle Artikel dieser Rubrik

Abstract

The first Lewis acid catalyzed protection of alcohols as Boc derivatives is described. Zinc acetate is a very efficient catalyst for this transformation and the reaction can be applied to primary, secondary and aromatic alcohols, providing the first example of a generally applicable method.

Key words

alcohols - esterification - protecting groups - Lewis acids - zinc acetate

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Referenzen

References and Notes

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Unpublished results.

In a two-necked flask equipped with a magnetic stirring bar, alcohols 1a-m (1 mmol), di-tert-butyl dicarbonate (1.1 mmol), and Zn(OAc)₂·2H₂O (0.1 mmol) were dissolved in CH₂Cl₂ (1 mL). The mixture was stirred and refluxed until the GC-MS analysis revealed the presence of 1 or Boc₂O for diols (Table [1] ). The crude reaction mixture was diluted with H₂O and extracted twice with CH₂Cl₂. The organic layer was separated, dried over MgSO₄, filtered and the solvent was removed by rotary evaporation. The Boc alcohols 2a-m were purified, when necessary, by flash chromatography on silica gel with a mixture of PE-Et₂O = 8:2.

Product ratio was calculated by integration of the triplet at δ = 3.64 ppm (2 H, J = 6.6 Hz, CH₂O of 1l) and doublets at δ = 1.26 ppm (d, 3 H, MeCH, 3l) and δ = 1.19 ppm (d, 3 H, MeCH, 2l) in the ¹H NMR spectrum of the crude reaction mixture. Products were then separated by flash chromatography and recovered amounts confirmed the calculated ratio.

Product ratio was calculated by integration of the triplet at δ = 3.68 ppm (2 H, J = 6.6 Hz, CH₂O of 1m) and singlets at δ = 1.49 ppm (9 H, aromatic Boc) and δ = 1.55 ppm (9 H + 9 H, aliphatic Boc) in the ¹H NMR spectrum of the crude reaction mixture. Products were then separated by flash-chromatography and recovered amounts confirmed the calculated ratio.

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<A NAME="RG10906ST-21B">21b</A> Dean CS. Tarbell DS. Friedergang AW. J. Org. Chem. 1970, 35: 3393

All the reactions were carried out without solvent. A mixture of alcohols 1a-d,f,g,n-z,aa (1 mmol), di-tert-butyl dicarbonate (1.1 mmol), and Zn(OAc)₂·2H₂O (0.1 mmol) were melted (50-60 °C) in a two-necked flask equipped with a magnetic stirring bar. The mixture was stirred until the GC-MS analysis revealed the presence of 1 (Table [2] ). The crude reaction mixture was diluted with H₂O and extracted twice with CH₂Cl₂. The organic layer was separated, dried over MgSO₄, filtered and the solvent was removed by rotary evaporation. The Boc alcohols 2a-d,f,g,n-z,aa were purified, when necessary, by flash chromatography on silica gel with a mixture of PE-Et₂O = 8:2.

Benzyl tert-butyl carbonate (2c), [6] (4-methoxyphenyl) tert-butyl carbonate (2f), [10] phenyl tert-butyl carbonate (2g), [25] (4-nitrophenyl) tert-butyl carbonate (2h) [10] and (2-phenylethyl) tert-butyl carbonate (2o) [12] are known compounds. Physical data for new compounds follow.
Octyl tert-butyl carbonate (2a): oil. ¹H NMR: δ = 0.88 (t, 3 H, J = 7.1 Hz, Me), 1.20-1.40 [m, 10 H, (CH₂)₅], 1.49 (s, 9 H, t-Bu), 1.60-1.70 (m, 2 H, CH₂), 4.05 (t, 2 H, J = 6.8 Hz, CH₂O) ppm. ¹³C NMR: δ = 14.0 (Me), 22.6 (CH₂), 25.7 (CH₂), 27.6 (3 Me), 28.7 (CH₂), 29.1 (CH₂), 29.2 (CH₂), 31.7 (CH₂), 67.2 (CH₂), 81.7 (C), 153.7 (C=O). MS (EI): m/z (%) = 113 (5), 112 (8), 84 (19), 83 (19), 71 (16), 70 (24), 69 (24) 57 (100).
[(E)-3-Hexenyl] tert-butyl carbonate (2b): oil. ¹H NMR: δ = 0.97 (t, 3 H, J = 7.5 Hz, Me), 1.49 (s, 9 H, t-Bu), 1.95-2.10 (m, 2 H, CH₂), 2.30-2.40 (m, 2 H, CH₂), 4.06 (t, 2 H, J = 6.8 Hz, CH₂O), 5.30-5.45 [dtt, 1 H, J = 15.2 (d), 6.8 (t), 1.6 (t)Hz, CH=], 5.50-5.65 [dtt, 1 H, J = 15.2 (d), 6.3 (t), 1.4 (t)Hz, CH=] ppm. ¹³C NMR: δ = 13.7 (Me), 25.7 (CH₂), 27.9 (3 Me), 32.1 (CH₂), 66.7 (CH₂), 81.8 (C), 123.8 (CH=), 135.3 (CH=), 153.7 (C=O) ppm. MS (EI): m/z (%) = 144 (1), 82 (100), 67 (74), 57 (64), 55 (44).
Ethyl (S)-2-(tert-butoxycarbonyloxy)propanoate (2d): oil; [α]_D ²⁰ (solv) -34.3 (c 1.02, CHCl₃). ¹H NMR: δ = 1.28 (t, 3 H, J = 7.2 Hz, Me), 1.51 (d, 3 H, J = 7.1 Hz, Me) ppm. ¹³C NMR: δ = 14.0 (Me), 16.9 (Me), 27.6 (3 Me), 61.3 (CH₂), 70.8 (CH), 82.8 (C), 152.7 (C=O), 170.7 (C=O) ppm. MS (EI): m/z (%) = 163 (3), 145 (10), 101 (16), 87 (3), 75 (5), 73 (13), 57 (100).
2-(tert-Butoxycarbonyloxy)-1,2-diphenylethanone (2e): mp 147-148 °C. ¹H NMR: δ = 1.49 (s, 9 H, t-Bu), 6.70 (s, 1 H, CHO), 7.30-7.50 and 7.92-7.96 (m, 8 H + 2 H, ArH) ppm. ¹³C NMR: δ = 27.7 (3 Me), 79.7 (CH), 83.2 (CH), 128.6 (2 CH), 128.7 (2 CH), 128.8 (2 CH), 129.1 (2 CH), 129.3 (CH),133.2 (C), 133.4 (CH), 134.6 (C), 152.9 (C=O), 193.9 (C=O) ppm. MS (EI): m/z (%) = 256 (1), 195 (3), 167 (2), 165 (3), 105 (100), 79 (17), 77 (44), 57 (14), 51 (13).
(2-Naphthyl) tert-butyl carbonate (2i): mp 77-78 °C. ¹H NMR: δ = 1.58 (s, 9 H, t-Bu), 7.31 (dd, 1 H, J = 8.9, 2.5 Hz, H-3), 7.40-7.55 (m, 2 H, H-6, H-7), 7.64 (d, 1 H, J = 2.4 Hz, H-1), 7.75-7.85 (m, 3 H, H-4, H-5, H-8) ppm. ¹³C NMR: δ = 27.7 (3 Me), 83.6 (C), 118.1 (CH), 120.8 (CH), 125.6 (CH), 126.5 (CH), 127.6 (CH), 127.7 (CH), 129.3 (CH), 131.3 (C), 133.7 (C), 148.7 (C), 152.0 (C=O) ppm. MS (EI): m/z (%) = 244 (1) [M⁺], 185 (4), 144 (100), 127 (7), 115 (45), 89 (6), 63 (5), 57 (24).
Cholesteryl tert-butyl carbonate (2j): mp 141-142 °C; [α]_D ²⁰ (solv) -30.6 (c 0.99, CHCl₃). ¹H NMR: δ = 0.68 (s, 3 H, H-18), 0.86 (d, 6 H, J = 6.2 Hz, H-26, H-27), 0.91 (d, 3 H, J = 6.4 Hz, H-21), 1.00 (s, 3 H, H-19), 1.49 (s, 9 H, t-Bu), 0.80-2.06 (m, 27 H), 2.33-2.42 (m, 2 H), 4.34-4.49 (m, 1 H, H-3), 5.39 (d, 1 H, J = 4.7 Hz, H-6) ppm. ¹³C NMR: δ = 12.1 (C-18), 18.9 (C-21), 19.4 (C-19), 21.1 (C-11), 22.8 (C-26), 23.0 (C-27), 24.0 (C-23), 24.5 (C-15), 28.0 (C-2, C-25), 28.1 (3 Me), 28.2 (C-16), 32.1 (C-7, C-8), 36.0 (C-20), 36.4 (C-22), 36.8 (C-10), 37.2 (C-4), 38.3 (C-1), 39.7 (C-24), 39.9 (C-12), 42.5 (C-13), 50.2 (C-9), 56.4 (C-17), 56.9 (C-14), 77.6 (C-3), 81.9 (C), 122.9 (C-6), 139.8 (C-5), 153.1 (C=O) ppm. MS (EI): m/z (%) = 429 (1), 405 (4), 386 (57), 301 (55), 275 (60), 255 (51), 213 (63), 207 (47), 159 (59), 145 (75), 107 (87), 105 (77), 57 (70), 55 (88), 44 (100).
(3-Hydroxy-3-methylbutyl) tert-butyl carbonate (2k): oil. ¹H NMR: δ = 1.27 (s, 6 H, 2 e), 1.49 (s, 9 H, t-Bu), 1.87 (t, 2 H, J = 6.8 Hz, CH₂), 4.25 (t, 2 H, J = 6.8 Hz, CH₂O) ppm. ¹³C NMR: δ = 27.7 (3 Me), 29.5 (2 Me), 41.5 (CH₂), 63.9 (CH₂), 69.8 (C), 82.0 (C) ppm. MS (EI): m/z (%) = 148 (5), 133 (15), 89 (16), 84 (16), 71 (52), 59 (100), 57 (78). (5-Hydroxyhexyl) tert-butyl carbonate (2l): oil. ¹H NMR: δ = 1.19 (d, 3 H, J = 6.1 Hz, MeCH), 1.61-1.74 (m, 4 H, CH₂CH₂), 1.49 (s, 9 H, t-Bu), 1.61-1.74 (m, 2 H, CH₂), 1.79 (br s, 1 H, disappears with D₂O, OH), 3.85-3.74 (m, 1 H, CHO), 4.07 (t, 2 H, J = 6.5 Hz, CH₂O) ppm. ¹³C NMR: δ = 21.9 (Me), 23.4 (CH₂), 27.7 (3 Me), 28.6 (CH₂), 38.7 (CH₂), 66.9 (CH₂), 67.8 (CH), 81.8 (C), 153.6 (C=O) ppm. MS (EI): m/z (%) = 162 (2) [M⁺ - 56], 145 (3), 119 (8), 100 (7), 85 (20), 83 (28), 57 (100), 56 (61).
Bis(1,5-tert-butoxycarbonyloxy)hexane (3l): oil. ¹H NMR: δ = 1.26 (d, 3 H, J = 6.7 Hz, MeCH), 1.49 (s, 18 H, 2 t-Bu), 1.50-1.76 (m, 6 H, 3 CH₂), 4.06 (t, 2 H, J = 6.4 Hz, CH₂O), 4.64-4.76 (m, 1 H, CHO) ppm. ¹³C NMR: δ = 19.9 (Me), 21.7 (CH₂), 27.72 (3 Me), 27.74 (3 Me), 28.5 (CH₂), 35.5 (CH₂), 66.7 (CH₂), 73.7 (CH), 81.6 (C), 81.8 (C), 153.2 (C=O), 153.6 (C=O) ppm. MS (EI): m/z (%) = 206 (3) [M⁺ - (56 × 2)], 145 (11), 119 (9), 101 (7), 83 (35), 57 (100), 56 (38).
3-(4-Hydroxyphenyl)propyl tert-butyl carbonate (2m): oil. ¹H NMR: δ = 1.49 (s, 9 H, t-Bu), 1.93 (quint, 2 H, J = 7.0 Hz, CH₂), 2.63 (t, 2 H, J = 7.1 Hz, CH₂), 4.07 (t, 2 H, J = 7.0 Hz, CH₂O), 5.17 (br s, 1 H, disappears with D₂O, OH), 6.70 and 7.04 (A₂B₂ system, 2 H + 2 H, ArH) ppm. ¹³C NMR: δ = 27.8 (3 Me), 30.4 (CH₂), 31.0 (CH₂), 66.4 (CH₂), 82.1 (C), 115.3 (2 CH), 129.5 (2 CH, C), 133.4 (C), 153.9 (C=O) ppm. MS (EI): m/z (%) = 252 (1) [M⁺] 196 (7), 152 (25), 133 (50), 107 (100), 77 (18), 57 (14), 56 (14).
3-(4-tert-Butoxycarbonyloxyphenyl)propyl tert-butyl carbonate (3m): oil. ¹H NMR: δ = 1.49 (s, 9 H, t-Bu), 1.55 (s, 9 H, t-Bu), 1.90-2.02 (m, 2 H, CH₂), 2.63-2.73 (m, 2 H, CH₂), 4.08 (t, 2 H, J = 6.4 Hz, CH₂O), 7.08 and 7.18 (A₂B₂ system, 2 H + 2 H, ArH) ppm. ¹³C NMR: δ = 27.6 (3 Me), 27.7 (3 Me), 30.3 (CH₂), 31.4 (CH₂), 66.3 (CH₂), 81.9 (C), 83.4 (C), 121.2 (2 CH), 129.2 (2 CH,), 138.6 (C), 149.3 (C), 152.2 (C=O), 153.6 (C=O) ppm. MS (EI): m/z = (%) 280 (1) [M⁺ - 72], 262 (10), 150 (48), 133 (10), 104 (100), 91 (58), 71 (20), 57 (25).
[(Z)-3-Hexenyl] tert-butyl carbonate (2n): oil. ¹H NMR: δ = 0.97 (t, 3 H, J = 7.5 Hz, Me), 1.48 (s, 9 H, t-Bu), 2.06 (quint, 2 H, J = 7.5 Hz, CH₂), 2.41 (q, 2 H, J = 7.1 Hz, CH₂), 4.05 (t, 2 H, J = 7.1 Hz, CH₂O), 5.27-5.38 (m, 1 H, CH=), 5.46-5.57 (m, 1 H, CH=) ppm. ¹³C NMR: δ = 14.2 (Me), 20.6 (CH₂), 26.8 (CH₂), 27.4 (3 Me), 66.4 (CH₂), 81.8 (C), 123.3 (CH=), 134.8 (CH=), 153.6 (C=O) ppm. MS (EI): m/z (%) = 144 (1), 82 (100), 67 (86), 57 (88), 55 (54).
4-(tert-Butoxycarbonyloxy)-3-methyl-2-butanone (2p): oil. ¹H NMR: δ = 1.15 (d, 3 H, J = 7.3 Hz, Me), 1.48 (s, 9 H, t-Bu), 2.21 (s, 3 H, MeCO), 2.85-2.95 (m, 1 H, CH), 4.07 (dd, 1 H, J = 11.0, 5.8 Hz, CHO), 4.27 (dd, 1 H, J = 11.0, 7.4 Hz, CHO) ppm. ¹³C NMR: δ = 13.6 (Me), 27.9 (3 Me), 29.0 (Me), 46.2 (CH), 67.9, (CH₂), 82.5 (C), 153.5 (C=O), 209.5 (C=O) ppm. MS (EI): m/z (%) = 146 (2), 105 (11), 85 (30), 69 (11), 57 (100).
3-(tert-Butoxycarbonyloxy)-2-methyl-1-phenylpropene (2q): oil. ¹H NMR: δ = 1.51 (s, 9 H, t-Bu), 1.91 (s, 3 H, Me), 4.62 (s, 2 H, CH₂O), 6.55 (s, 1 H, CH=), 7.20-7.35 (m, 5 H, ArH) ppm. ¹³C NMR: δ = 15.5 (Me), 27.8 (3 Me), 72.7 (CH₂), 82.1 (C), 126.7 (CH), 128.1 (2 CH), 128.6 (CH), 128.9 (2 CH), 132.5 (C), 137.0 (C), 153.5 (C=O) ppm. MS (EI). m/z (%) = 192 (47), 148 (26), 131 (61), 130 (100), 129 (67), 115 (60), 91 (58), 57 (23).
[3-(N,N-Dimethylamino)propyl] tert-butyl carbonate (2r): oil. ¹H NMR: δ = 1.47 (s, 9 H, t-Bu), 1.75-1.90 (m, 2 H, CH₂), 2.21 (s, 6 H, NMe₂), 2.34 (t, 2 H, J = 7.4 Hz, CH₂N), 4.10 (t, 2 H, J = 6.7 Hz, CH₂O) ppm. ¹³C NMR: δ = 27.1 (CH₂), 27.8 (3 Me), 45.5 (2 Me), 56.2 (CH₂), 65.5 (CH₂), 81.9 (C), 153.6 (C=O). MS (EI): m/z (%) = 203(5) [M⁺], 130 (5), 86 (12), 58 (100).
Menthyl tert-butyl carbonate (2s): oil; [α]_D ²⁰ (solv) -42.5 (c 0.97, CHCl₃). ¹H NMR: δ = 0.79 (d, 3 H, J = 6.9 Hz, Me), 0.89 (d, 3 H, J = 7.1 Hz, Me), 0.91 (d, 3 H, J 6.4 Hz, Me), 0.95-1.10 (m, 2 H), 1.35-1.45 (m, 2 H), 1.48 (s, 9 H, t-Bu), 1.60-1.70 (m, 2 H), 1.90-2.10 (m, 2 H), 4.47 [dt, 1 H, J = 11.2 (t), 4.4 (d)Hz, CHO] ppm. ¹³C NMR: δ = 16.1 (Me), 20.7 (Me), 21.9 (Me), 23.2 (CH₂), 26.0 (CH), 27.8 (3 Me), 31.4 (CH), 34.1 (CH₂), 40.9 (CH₂), 46.9 (CH), 77.0 (CH), 81.4 (C), 153.3 (C=O) ppm. MS (EI): m/z (%) = 138 (64), 123 (28), 95 (56), 81 (54), 71 (24), 57 (100).
2-Octyl tert-butyl carbonate (2t): oil. ¹H NMR: δ = 0.88 (t, 3 H, J = 7.1 Hz, Me), 1.25 (d, 3 H, J = 6.2 Hz, Me) 1.25-1.35 [m, 8 H, (CH₂)₄], 1.48 (s, 9 H, t-Bu), 1.44-1.70 (m, 2 H, CH₂), 4.66-4.74 (m, 1 H, CHO) ppm. ¹³C NMR: δ = 14.0 (Me), 20.0 (Me), 22.5 (CH₂), 25.4 (CH₂), 27.8 (3 Me), 29.1 (CH₂), 31.7 (CH₂), 36.0 (CH₂), 74.2 (CH), 81.5 (C) 153.3 (C=O). MS (EI): m/z (%) = 129 (4), 113 (7), 112 (10), 97 (6), 84 (6), 83 (6), 71(14), 57 (100).
(3-Methoxyphenyl) tert-butyl carbonate (2u): oil. ¹H NMR: δ = 1.56 (s, 9 H, t-Bu), 3.79 (s, 3 H, OMe), 6.70-6.80 (m, 3 H, H-2, H-4, H-6), 7.26 (t, 1 H, J = 8.4 Hz, H-5) ppm. ¹³C NMR: δ = 27.7 (3 Me), 55.4 (OMe), 83.5 (C), 107.3 (CH), 111.6 (CH), 113.5 (CH), 129.7 (CH), 151.7 (C), 152.0 (C=O), 160.4 (C) ppm. MS (EI): m/z (%) = 165 (10), 124 (100), 95 (17), 94 (25), 81 (13), 57 (34).
(4-Fluorophenyl) tert-butyl carbonate (2v): oil. ¹H NMR: δ = 1.55 (s, 9 H, t-Bu), 7.00-7.15 (m, 4 H, ArH) ppm. ¹³C NMR: δ = 27.7 (3 Me), 83.7 (C), 116.0 (d, J _C-F 23.6 Hz, 2 CH), 122.7 (d, J _C-F = 9.0 Hz, 2 CH), 147.0 (d, J _C-F = 3.3 Hz, C), 151.9 (C=O), 160.1 (d, J _C-F = 246.0 Hz, C) ppm. MS (EI): m/z (%) = 197 (6), 139 (15), 119 (95), 95 (29), 83 (26), 57 (100).
5-Indolyl tert-butyl carbonate (2w): mp 111-112 °C. ¹H NMR: δ = 1.57 (s, 9 H, t-Bu), 6.53 (br s, 1 H, H-3), 6.99 (dd, 1 H, J = 8.7, 2.2 Hz, H-6), 7.22 (t, 1 H, J = 2.9 Hz, H-2), 7.33 (d, 1 H, J = 8.7 Hz, H-7), 7.41, (d, J = 2.1 Hz, H-4), 8.17 (br s, 1 H, NH) ppm. ¹³C NMR: δ = 27.7 (3 Me), 83.1 (C), 102.8 (C-3), 111.3 (C-4), 112.4 (C-7), 115.8 (C-6), 125.6 (C-2), 128.0 (C-3′), 133.6 (C-7′), 144.8 (C), 153.0 (C) ppm. MS (EI): m/z (%) = 233 (2) [M⁺], 174 (4), 133 (100), 116 (5), 104 (16), 77 (6), 57 (20).
2,2-Dimethyl-4-(tert-butoxycarbonyloxymethyl)-1,3-dioxolane (2x): oil. ¹H NMR: δ = 1.36 (s, 3 H, Me), 1.43 (s, 3 H, Me), 1.49 (s, 9 H, t-Bu), 3.78 (dd, 1 H, J = 8.5, 5.9 Hz, H-5a), 4.04-4.16 (m, 3 H, CH₂ and H-5b), 4.33 (quint, 1 H, J = 5.7 Hz, H-4) ppm. ¹³C NMR: δ = 25.2 (Me), 26.6 (Me), 27.6 (3 Me), 66.3 (CH₂), 66.9 (CH₂), 73.3 (CH), 82.3 (C), 109.7 (O-C-O), 153.2 (C=O). MS (EI): m/z (%) = 217 (5) [M⁺ - 15], 161 (67), 117 (100), 101 (64), 57 (64).
4-(Tetrahydropyranyloxy)butyl tert-butyl carbonate (2y): oil. ¹H NMR: δ = 1.49 (s, 9 H, t-Bu), 1.45-1.88 (m, 10 H, 5 CH₂), 3.36-3.55 (m, 2 H, CH₂), 3.70-3.90 (m, 2 H, CH₂), 4.10 (t, 2 H, J = 6.80 Hz, CH₂-OBoc), 4.58 (t, 1 H, J = 3.50 Hz, CH) ppm. ¹³C NMR: δ = 19.5 (CH₂), 25.4 (CH₂), 25.7 (CH₂), 26.0 (CH₂), 27.7 (3 Me), 30.6 (CH₂), 62.2 (CH₂), 66.8 (CH₂), 66.9 (CH₂), 81.7 (C), 98.7 (O-C-O), 153.6 (C=O) ppm. MS (EI): m/z (%) = 217 (1) [M⁺ - 57], 160 (1), 117 (18), 101 (31), 85 (100), 73 (35), 57 (57), 55 (67).
6-(Triisopropyloxy)hexyl tert-butyl carbonate (2z): oil. ¹H NMR: δ = 0.97-1.08 (m, 21 H), 1.30-1.41 (m, 4 H, 2 CH₂), 1.48 (s, 9 H, t-Bu), 1.43-1.58 (m, 2 H, CH₂), 1.59-1.70 (m, 2 H, CH₂), 3.66 (t, 2 H, J = 6.9, CH₂OSi), 4.05 (t, 2 H, J = 7.3 Hz, CH₂OBoc) ppm. ¹³C NMR: δ = 12.0 (3 CH), 18.0 (6 Me), 25.5 (CH₂), 25.6 (CH₂), 27.8 (3 Me), 28.7 (CH₂), 32.8 (CH₂), 63.3 (CH₂), 67.1 (CH₂), 81.7 (C), 153.7 (C=O) ppm. MS (EI): m/z (%) = 275 (3) [M⁺ - 99], 231 (13), 171 (12), 149 (16) 131 (83), 119 (51), 103 (44), 83 (93), 75 (50), 55 (100).
tert-Butyl 3-(tert-butoxycarbonyloxy)-2-(tert-butoxy-carbonylamino)propanoate (2aa): mp 85-87 °C. ¹H NMR: δ = 1.45 (s, 9 H, t-Bu), 1.47 (s, 18 H, 2 t-Bu), 4.23 (dd, 1 H, J = 11.0, 3.0 Hz, CHH), 4.43 [dt, 1 H, J = 8.0 (d), 3.0 (t) Hz, CH], 4.51 (dd, 1 H, J = 11.0, 3.0 Hz, CHH), 5.34 (br d, 1 H, J = 8.0 Hz, NH) ppm. ¹³C NMR: d = 27.6 (3 Me), 27.8 (3 Me), 28.2 (3 Me), 53.5 (CH), 66.7 (CH₂), 79.9 (C), 82.4 (C), 82.6 (C), 153.0 (C=O), 155.1 (C=O), 168.5 (C=O) ppm. MS (EI): m/z (%) = 234 (2) [M⁺ - 127], 232 (2), 204 (11), 176 (9), 148 (8), 104 (36), 59 (23), 57 (100).

In a blank run, octanol and Boc₂O were stirred together for 144 h and only 13% conversion to carbonate was detected by NMR.

Product ratio was calculated by integration of the triplets at δ = 4.10 (J = 6.7 Hz) and 4.18 (J = 6.4 Hz) ppm (typical of 2r and 4r, respectively) in the ¹H NMR spectrum of the crude reaction mixture.

<A NAME="RG10906ST-26">26</A> Nakamura K. Nakajima T. Kayahara H. Nomura E. Taniguchi H. Tetrahedron Lett. 2004, 45: 495