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Synlett 2006(13): 2104-2108  
DOI: 10.1055/s-2006-949609
LETTER
© Georg Thieme Verlag Stuttgart · New York

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

Giuseppe Bartoli*a, Marcella Boscoa, Armando Carlonea, Renato Dalpozzob, Manuela Locatellia, Paolo Melchiorrea, Paolo Palazzia, Letizia Sambria
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
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Publication History

Received 12 April 2006
Publication Date:
09 August 2006 (online)

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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

5

Ref. 4, page 281.

17

Unpublished results.

18

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.

19

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.

20

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.

22

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.

23

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).

24

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

25

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.