Synthesis and Photocleavage of a New Dimeric Bis(o-Nitrobenzyl) Diether Tether

Transcription

1 Supporting Information Synthesis and Photocleavage of a New Dimeric Bis(o-Nitrobenzyl) Diether Tether Nandita Madhavan and Mary S. Gin * Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL mgin@scs.uiuc.edu Experimental Section General. All starting materials were obtained from commercial suppliers and were used without further purification unless otherwise stated. All air- or moisture-sensitive reactions were performed using oven-dried or flame-dried glassware under an inert atmosphere of dry argon or nitrogen. Air- or moisture-sensitive liquids and solutions were transferred via syringe or cannula. Tetrahydrofuran (THF) was distilled from sodium benzophenone ketyl, methanol was distilled from magnesium methoxide, pyridine and dichloromethane were distilled from calcium hydride, benzene was distilled from sodium, and 1,4-dioxane was distilled from lithium aluminum hydride. Cyclohexanol, and propanol were distilled prior to use. Dimethyl sulfoxide and dimethylformamide were stored over 4 Å molecular sieves. N-Bromosuccinimide, benzoyl peroxide, and AIBN were recrystallized using standard techniques. 1 Analytical thin layer chromatography (TLC) was performed using EM Science F54 precoated silica gel 60 plates. Eluting solvents are reported as volume ratios or volume percents. Compounds were visualized using UV light, cerium ammonium molybdate (CAM), potassium permanganate, or iodine stains. Flash column chromatography was performed using silica gel 60 ( mesh). Melting points were taken on a 115V 50/60 Hz Fisher-Johns melting point apparatus from Fisher- Scientific. All 1 H and C NMR spectra were recorded on Varian Unity 400 or Varian Unity 500 spectrometers using CDCl 3, CD 3 D, C 6 D 6 or dioxane-d8 as solvent. The NMR spectra were referenced using residual solvent peaks as the standard. Chemical shifts are expressed in parts per million (δ), coupling constants (J) are reported in Hertz (Hz), and splitting patterns are reported as singlet (s), doublet (d), triplet (t), quartet (q), multiplet (m), and apparent (app). High-resolution mass spectra were obtained from the University of Illinois mass spectrometry lab. The UV spectra were 1 Armarego, W. L. F.; Perrin, D. D. Purification of Laboratory Chemicals, 4 th Ed; Butterworth- Heinemann: xford,

2 recorded at room temperature on a Hewlett-Packard 8453 UV-visible spectrophotometer using a 1 cm quartz cuvette. IR spectra were recorded using a Perkin Elmer Spectrophotometer referenced to a polystyrene standard. Samples were prepared as thin films on a NaCl salt plate by evaporation of chloroform or dichloromethane solutions. Peaks are reported in wavenumbers (cm -1 ) as strong (s), medium (m), weak (w), and broad (br). Photolyses were performed using a Rayonet Photochemical Reactor (Rayonet, The Southern Co., Middletown, Conn.). NH I b a c CH 3 CH Iodo--nitrotoluene (5): To a solution of 4 (.0 g, mmol, 1 equiv) and concentrated HCl (4 ml) in water (45 ml) at 0 C was added a cold solution of sodium nitrite (1.0 g, 15 mmol, 1.1 equiv) in water (5 ml). The resulting solution was allowed to stir for 35 min then KI (3.0 g, 19 mmol, 1.4 equiv) in saturated aqueous sodium acetate (68 ml) at 0 C was added in one portion. The contents of the flask were warmed to room temperature and allowed to stir until effervescence ceased (1 h). The reaction mixture was then extracted with CH Cl. The combined organic layers were washed with saturated aqueous NaHC 3, water, and saturated aqueous NaCl, then dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to give a dark brown solid. Purification of the crude solid by flash column chromatography (30:1 hexane/etac), followed by recrystallization from ethanol afforded.1 g (61%) of the aryl iodide 5 as a pale yellow solid: TLC R f = 0.5 (6:1 hexane/etac); m.p C 1 H NMR (500 MHz, CDCl 3 ) δ 8.3 (d, 1H, J =.0 Hz, H a ), 7.8 (dd, 1H, J = 8.0,.0 Hz, H b ), 7.11 (d, 1H, J = 8.5 Hz, H c ),.57 (s, 3H, CH 3 ); C NMR (16 MHz, CDCl 3 ) δ 164.5, 141.8, 4., 3., 3., 89.7, 0.1; IR (thin film) ν 3094(m), 98(m), 864(m), 151(s), 44(s), 175(m), 1087(w) cm -1 ; HRMS (EI + ) calcd for C 7 H 6 NI (M + ) , found I B 6 B H 3 C b c CH 3 5 N 7 a 3,3 -Dinitroditoluene (7): Aryl iodide 5 (50 mg, mmol, 1 equiv) and DMS (1.5 ml) were added to a mixture of PdCl (dppf) CH Cl (40 mg, 0.05 mmol, 0.05 equiv), potassium carbonate

3 (393 mg,.84 mmol, 3 equiv) and bis(pinacolato)diboron 6 (68 mg, 1.05 mmol, 1.1 equiv). The resulting solution was heated to 80 C for 5 h. Water was added to the reaction mixture and the organics were extracted with benzene. The combined organic layers were washed with water and saturated aqueous NaCl, then dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give a dark brown solid. Purification by flash column chromatography (gradient elution, 30:1 15:1 hexane/etac) afforded 104 mg (81%) of the coupled product 7. The biaryl could be purified further by recrystallization from benzene (yellow crystals, 60%). TLC R f = 0.3 (6:1 hexane/ EtAc); m.p C; 1 H NMR (400 MHz, CDCl 3 ) δ 8. (d, 1H, J =.0 Hz, H a ), 7.75 (dd, 1H, J = 8.0, 1.8 Hz, CH b ), 7.47 (d, 1H, J = 8.0 Hz, H c ),.66 (s, 3H, CH 3 ); IR (thin film) ν 309(m), 969(m), 157(s), 44(s), 896(w) cm -1 ; HRMS (EI + ) calcd. for C 14 H 1 N 4 (M + ) , found H 3 C N 7 CH 3 Br N 8 b a c Br o-nitrobenzyl bromide dimer (8): To a solution of the biaryl 7 (50 mg, mmol, 1 equiv) in benzene (5 ml), N-bromosuccinimide (408 mg,.30 mmol,.5 equiv), benzoyl peroxide (ca 10 mg) and AIBN (ca 10 mg) were added. The resulting mixture was heated to reflux for days, then cooled to room temperature. The solvent was removed in vacuo to give a yellow solid. Purification by flash column chromatography (1:1 benzene/hexane) afforded 40 mg (61%) of dibromide 8 as a pale yellow solid: TLC R f = 0.3 (3:1 hexane/ EtAc); 1 H NMR (400 MHz, CDCl 3 ) δ 8.9 (d, 1H, J =.0 Hz, H a ), 7.86 (dd, 1H, J = 8.0 Hz, H b ), 7.7 (d, 1H, J = 8.0 Hz, H c ), 4.88 (s, H, CH Br); C NMR (16 MHz, CDCl 3 ) δ 164.5, 9.5, 3.6, 3.1, 1.8, 13.9, 8.; IR (thin film) ν 309(m), 907(m), 1704(m), 154(s), 1436(m), 58(s), 1174(w) cm -1 ; HRMS (EI + ) calcd. for C 14 H 10 N 4 Br (M + ) , found General procedure for synthesis of monomeric o-nitrobenzyl ethers of primary alcohols a, b and e. To a solution of the primary alcohol (1 equiv) in CH Cl (0.088 M), was added an aqueous solution of NaH (10% wt/vol, 15 equiv). o-nitrobenzyl bromide (5 equiv) and tetrabutylammonium The corresponding monobromide :TLC R f = 0.9 (3:1 hexane/ EtAc); and tribromide: TLC R f = 0.5 (3:1 hexane/ EtAc); were also isolated. 3

4 hydrogensulfate (1.4 equiv) were added to the above solution. The reaction was stopped when TLC indicated consumption of the alcohol. Water was added and the resultant mixture was extracted with CH Cl. The combined organic layers were washed with saturated aqueous NaCl, then dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude mixture was then subjected to flash column chromatography in order to yield the pure compound. H Bn Bn a 9a Serine ether (9a): The alcohol a 3 (50 mg, 0.18 mmol) was reacted for 4 h following the general procedure. Purification using flash column chromatography (9:1 hexane/etac) afforded 66 mg of the desired ether 9a (90%): TLC R f = 0.5 (3:1 hexane/etac); 1 H NMR (400 MHz, CDCl 3 ) δ 8.1 (dd, 1H, J = 8.1, 1.1 Hz, H Ar ), 7.7 (d, 1H, J = 7.6 Hz, H Ar ), 7.6 (td, 1H, J = 7.8, 1 Hz, H Ar ), 7.4 (t, 1H, J = 8.1 Hz, H Ar ), (m, 5H, H Ph ), 4.96 (d, 1H, J = 7. Hz, NH), 4.89 (d, H, J = 4.3 Hz, CH Ph), 4.54 (s, H, CH Ar), 4.0 (m, 1H, BocHNCHCH ), (m, 4H, CH CH()CH ), 1.44 (s, 9H, C(CH 3 ) 3 ); C NMR (16 MHz, CDCl 3 ) δ 155.4, 147., 8.0, 4.9, 3.6, 18.6, 18.4, 17.9, 17.68, 17.65, 14.6, 73.5, 73., 69.9, 69.8, 68.8, 49.7, 8.3; IR (thin film) ν 3441(br), 3337(br), 976(m), 867(m), 17(s), 154(s), 1504(m), 66(m), 4(m) cm -1 ; HRMS (FAB + ) calcd. for C H 9 N 6 (MH + ) , found H CH 3 b CH 3 9b Hexadecanol ether (9b): Hexadecanol b (50 mg, 0.1 mmol) was reacted for 48 h following the general procedure. Purification using flash column chromatography (40:1 hexane/etac) afforded 34 mg of ether 9b (44%): TLC R f = 0.7 (3:1 hexane/etac); 1 H NMR (500 MHz, CDCl 3 ) δ 8.06 (dd, 1H, J = 6.9, 1.4 Hz, H Ar ), 7.81 (dd, 1H, J = 8.1, 0.7 Hz, H Ar ), 7.65 (td, 1H, J = 7.6, 1.1 Hz, H Ar ), 7.43 (td, 1H, J = 8., 0.8 Hz H Ar ), 4.87 (s, H, CH Ar), 3.56 (t, H, J = 6.6 Hz, CH (CH ) 14 ), 1.66 (m, H, CH CH CH ), 1.39 (m, H, (CH ) CH CH ), 1.5 (m, 4H, (CH ) 3 (CH ) 1 CH 3 ), 0.88 (t, 3H, 3 Sowinski, J. A.; Toogood, P. L. J. rg. Chem. 1996, 61,

5 J = 6.5 Hz, CH 3 ); C NMR (16 MHz, CDCl 3 ) δ 147.3, 5.6, 3.6, 18.6, 17.8, 14.6, 71.5, 69.3, 63.1, 3.8, 31.9, 9.7, 9.65, 9.6, 9.58, 9.56 (overlapping signals), 9.43, 9.39, 9.33, 6., 5.7,.7, 14.1; IR (thin film) ν 953(m), 910(s), 849(s), 156(s), 147(w), 40(s), 1116(m) cm -1 ; HRMS (CI + ) calcd. for C 3 H 40 N 3 (MH + ) , found e H 9e Benzyl ether (9e): Benzyl alcohol e (6.1 mg, 0.4 mmol) was reacted for 4 h following the general procedure. Purification using flash column chromatography (1:1 hexane/benzene) afforded 44 mg of ether 9e (74%): TLC R f = 0.66 (3:1 hexane/etac); 1 H NMR (500 MHz, CDCl 3 ) δ 8.08 (dd, 1H, J = 8.5, 1.3 Hz, H Ar ), 7.87 (dd, 1H, J = 7.5, 1.4 Hz, H Ar ), 6.55 (td, 1H, J = 9., 0.61 Hz, H Ar ), 7.44 (td, 1H, J = 8., 1.4 Hz, H Ar ), (m, 5H, H Ph ), 4.96 (s, 1H, CH Ar), 4.67 (s, H, CH Ph) ; C NMR (16 MHz, CDCl 3 ) δ 147.5, 8.0, 5.4, 3.9, 19.0, 18.8, 18., 18.1, 17.96, 14.9, 73.4, 69.1; IR (thin film) ν 3064(w), 303(w), 860(w), 155(s), 41(s), 110(m), 107(m) cm -1 ; HRMS (EI + ) calcd. for C 14 H 14 N 3 (MH + ) , found H d 9d Cyclohexyl ether (9d): To a solution of the cyclohexanol d (47 mg, 0.47 mmol, 1 equiv) in CH Cl at -10 C was added tri-tert-butyl pyridine (93 mg, 1.18 mmol,.5 equiv), silver triflate (07 mg, mmol, 1.7 equiv), and o-nitrobenzyl bromide (04 mg, mmol, equiv). The resulting solution was stirred at -10 C for 10 min, then was allowed to slowly warm to room temperature. After 48 h, the mixture was filtered through a column of celite. The reaction flask was rinsed with CH Cl and the filtrate and the washings were concentrated in vacuo. The crude mixture was then subjected to flash column chromatography (18:1 hexane/etac) to yield 39 mg cyclohexyl ether 9d (35%): TLC R f = 0.77 (3:1 hexane/etac); 1 H NMR (400 MHz, CDCl 3 ) δ 8.04 (dd, 1H, J = 8., 1. Hz, H Ar ), 7.85 (dd, 1H, J = 7.9, 1.1 Hz, H Ar ), 7.64 (td, 1H, J = 7.7, 1.3 Hz, H Ar ), 7.4 (td, 1H, J = 6.6, 1.5 Hz, H Ar ), 4.91 (s, H, CH Ar), 3.4 (tt, 1H, J = 9.1, 3.8 Hz, CH), 1.97 (m, H, CH cyc ), 1.76 (m, H, CH cyc ), 1.58 (m, H, CH cyc ),1.40 (m, H, CH cyc ), 1.8 (m, H, CH cyc ); C NMR (16 MHz, CDCl 3 ) δ 147.3, 5

6 6.1, 3.5, 18.8, 17.6, 14.5, 78.0, 66.5, 3.1, 5.7, 3.9; IR (thin film) ν 933(s), 857(s), 158(s), 1449(m), 6(m), 4(s), 1103(s), 1076(m) cm -1. H c 9c Propyl ether (9c): To a solution of o-nitrobenzyl bromide (50 mg, 0.3 mmol, 1 equiv) in 10 ml of propanol c was added AgCl 4 (144 mg, mmol, 3 equiv). The solution was heated to 70 C for 3 h 4, after which the solution was filtered through a column of celite. The flask was rinsed with acetone (3 ml), and the filtrate and the washings were concentrated in vacuo. The crude mixture was then subjected to flash column chromatography (4:1:0.1 hexane/etac/chcl 3 ) to afford 37 mg (8%) of ether 9c as an oil: TLC R f = 0.88 (3:1 hexane/etac); 1 H NMR (400 MHz, CDCl 3 ) δ 8.06 (dd, 1H, J = 8., 1. Hz, H Ar ), 7.81 (dd, 1H, J = 7.8, 1.0 Hz, H Ar ), 7.64 (td, 1H, J = 7.5, 1.3 Hz, H Ar ), 7.43 (td, 1H, J = 7.5, 1.4 Hz, H Ar ), 4.88 (s, H, CH Ar), 3.53 (t, H, J = 6.6 Hz, CH CH ), 1.69 (m, H, CH CH 3 ), 0.98 (t, 3H, J = 7.7 Hz, CH 3 ); C NMR (16 MHz, CDCl 3 ) δ 147.5, 5.8, 3.8, 18.8, 18.0, 14.8, 73., 69.5, 3.1, 10.8; IR (thin film) ν.933(m), 964(m), 877(m), 156(s), 4(s), 1110(m), 1077(w) cm -1 ; HRMS (EI + ) calcd. for C 10 H 1 N 3 (M-H + ) , found H 3 C Br N N 15 + H CH 3 H 3 C b N N 11 CH 3 Monohexadecanol ether (11): To a solution of the monobromide 15 5 (5 mg, 0.07 mmol, 1 equiv) in hexadecanol b (4.0 g, 16 mmol) 6 was added silver perchlorate (45 mg, 0.1 mmol, 6 equiv). The resulting solution was heated to 80 C for 48 h, after which the solution was filtered through a column of celite. The flask was rinsed with dichloromethane (3 ml), and the filtrate and the washings were concentrated in vacuo. The crude mixture was then subjected to flash column chromatography (40:1 hexane/etac) to afford 3 mg (88%) of ether 11 as a pale yellow solid: TLC R f = 0.7 (3:1 4 As a precautionary measure a blast shield was used. 5 Isolated during the synthesis of o-nitrobenzyl bromide dimer 8. 6 In the case of hexadecanol b, the solid was heated to melting before the bromide was added. 6

7 hexane/etac); 1 H NMR (400 MHz, CDCl 3 ) δ 8.30 (d, 1H, J = 1.8 Hz, H Ar ), 8.4 (d, 1H, J = 1.9 Hz, H Ar ), 7.93 (d, 1H, J = 8. Hz, H Ar ), 7.88 (dd, 1H, J = 8.1, 1.9 Hz, H Ar ), 7.76 (dd, 1H, J = 7.9, 1.9 Hz, H Ar ), 7.48 (d, 1H, J = 8.0 Hz, H Ar ) 4.9 (s, H, CH Ar), 3.60 (t, H, J = 6.6 Hz, CH (CH ) 14 ),.67 (s, 3H, CH 3 Ar), 1.69 (m, H, CH CH CH ), 1.41 (m, H, (CH ) CH CH ), 1.5 (m, 4H, (CH ) 3 (CH ) 1 CH 3 ), 0.88 (t, 3H, J = 7.1 Hz, CH 3 ); C NMR (16 MHz, CDCl 3 ) δ 149.9, 147.9, 8.7, 7.8, 5.8, 3.9, 3.85, 1.9, 1.3, 19.8, 13., 13, 71.8, 69.3, 3.1, 9.88 (overlapping signals), 9.87, 9.84, 9.81, 9.8, 9.67, 9.55, 6.4,.9, 0.4, 14.3; IR (thin film) ν 918(s), 850(s), 155(m), 1470(m), 4(m), 17(m), 110(w) cm -1 ; HRMS (CI + ) calcd. for C 30 H 45 N 5 (MH + ) 5.338, found H a Bn Bn 1a Dimeric serine ether (1a): To a solution of the alcohol a (33 mg, 0.1 mmol,.5 equiv) in 1 ml of CH Cl at -10 C was added tri tert-butyl pyridine (39 mg, 0.16 mmol, 3.4 equiv), silver triflate (30 mg, 0.1 mmol,.5 equiv), and o-nitrobenzyl bromide dimer 8 (0 mg, 0.05 mmol, 1 equiv). The resulting solution was stirred at -10 C for 10 minutes, then was slowly allowed to warm to room temperature. After 48 h the mixture was filtered through a column of celite. The flask was rinsed with CH Cl, and the filtrate and the washings were concentrated in vacuo. Purification using flash column chromatography (9:1 hexane/etac) yielded 6.0 mg of the serine ether 1a (15%) as an oil: TLC R f = 0.67 (1:1 hexane/etac); 1 H NMR (400 MHz, CDCl 3 ) δ 8.8 (d, H, J =.0 Hz, H Ar ), 7.83 (d, H, J = 8.3 Hz, H Ar ), 7.76 (dd, H, J = 8., 1.8 Hz H Ar ), (m, 10H, H Ph) ), 4.98 (d, H, J = 6.3 Hz, NH), 4.96 (d, 4H, J = 5.1 Hz, CH Ph), 4.56 (s, 4H, CH Ar), 4.06 (s, H, BocHNCHCH ), (m, 8H, CH CH()CH ), 1.45 (s, 18H, C(CH 3 ) 3 ); C NMR (16 MHz, CDCl 3 ) δ 155.7, 147.8, 8.6, 8., 5., 1.9, 19.9, 18.6, 17.97, 17.89, 13.1, 79.8, 73.5, 70.3, 69.8, 69.1, 49.9, 8.6; IR (thin film) ν 3445(br), 3343(br), 97(m), 171(s), 1530(s), 1500(m), 65(m), 1170(m), 1057(m) cm -1 ; LRMS (FD + )

8 General procedure for synthesis of dimeric o-nitro benzyl ethers 1b-1d. To a solution of the o-nitrobenzyl bromide dimer 8 (1 equiv) in the alcohol was added silver perchlorate (6 equiv). The resulting solution was heated to 100 C (80 C for hexadecanol) until TLC indicated consumption of starting materials. The reaction mixture was filtered through a column of celite after which the flask was rinsed with acetone or dichloromethane. The filtrate and the washings were concentrated in vacuo. The crude mixture was then subjected to flash column chromatography to afford the corresponding product. H CH 3 b CH 3 1b Hexadecanol ether (1b): Dibromide 8 (00 mg, mmol) was reacted with 9 g of hexadecanol b and silver perchlorate for h following the general procedure. Purification using flash chromatography (40:1 hexane/etac) yielded 167 mg (48%) of the ether 1b as a white solid: TLC R f = 0.75 (3:1 Hexane/EtAc); m.p. = C; 1 H NMR (500 MHz, CDCl 3 ) δ 8.33 (d, H, J = 1.8 Hz, H Ar ), 7.95 (d, H, J = 7.9 Hz, H Ar ), 7.9 (dd, H, J = 8.1, 1.9 Hz, H Ar ), 4.9 (s, 4H, CH Ar), 3.60 (t, 4H, J = 6.7 Hz, CH (CH ) 14 ), 1.69 (m, 4H, CH CH CH ), 1.41 (m, 4H, (CH ) CH CH ), 1.6 (m, 48H, (CH ) 3 (CH ) 1 CH 3 ), 0.88 (t, 6H, J = 7. Hz, CH 3 ); C NMR (16 MHz, CDCl 3 ) δ 147.7, 8.4, 5.7, 1.7, 19.6, 1.9; 71.6, 69.1, 31.9, 9.67 (overlapping signals), 9.63, 9.60, 9.58, 9.45, 9.3, 6.,.7, 14.1; IR (thin film) ν 90(s), 848(s), 153(m), 1467(m), 6(m), 31(m), 187(m), 1119(w), 110(m) cm -1 ; LRMS (FD + ) H c 1c Propyl ether (1c): Dibromide 8 (0 mg, 0.05 mmol) was reacted with 5 ml n-propanol c and silver perchlorate for 3 h following the general procedure. The crude mixture was then subjected to flash column chromatography (4:1:0.1 hexane/etac/chcl 3 to afford 18 mg (> 99%) of the product 1c as a white solid: TLC R f = 0.65 (3:1 hexane/etac); m.p.= C; 1 H NMR (400 MHz, CDCl 3 ) δ 8.3 (d, H, J = 1.8 Hz, H Ar ), 7.95 (d, H, J = 7.8 Hz, H Ar ), 7.89 (dd, H, J = 8.1, 1.9 Hz, H Ar ), 4.93 (s, 4H, CH Ar), 3.57 (t, 4H, J = 6.6 Hz, CH ), 1.73 (m, 4H, CH CH ), 0.99 (t, 6H, J = 7.3 Hz, CH 3 ); 8

9 C NMR (100 MHz, CDCl 3 ) δ 147.9, 8.6, 5.9, 1.9, 19.9, 13.1, 73.3, 69.3, 3., 10.9; IR (thin film) ν.963 (m), 934 (m), 876(m), 176(w), 1531(s), 44(s), 17(w), 1110(m), 1079(w) cm -1 ; MS (EI + ) calcd for C 0 H 3 N 6 (M-H + ) , found H d 1d Cyclohexyl ether (1d): Dibromide 8 (0 mg, 0.05 mmol) was reacted with 1. ml of cyclohexanol d and silver perchlorate for 16 h following the general procedure. Purification using flash column chromatography (18:1 hexane/etac) yielded 16 mg (68%) of the cyclohexyl ether 1d as a pale yellow solid: TLC R f = 0.61 (3:1 hexane/etac); m.p.= C; 1 H NMR (500 MHz, CDCl 3 ) δ 8.30 (d, H, J = 1.9 Hz, H Ar ), 7.99 (d, H, J = 8. Hz, H Ar ), 7.89 (dd, H, J = 8., 1.9 Hz, H Ar ), 4.96 (s, 4H, CH Ar), 3.45 (tt, H, J = 9., 3.8 Hz, CH), 1.99 (m, 4H, CH cyc ), 1.78 (m, 4H, CH cyc ), 1.44 (m, 4H, CH cyc ), (m, 8H, CH cyc ); IR (thin film) ν 93(s), 856(m), 158(s), 1450(w), 6(m), 46(s), 110(s), 1076(s) cm -1 ; MS (FAB + ) calcd for C 6 H 33 N 6 (MH + ) , found N X X 8 X = Br 1e X =H Benzyl ether (1e): To a solution of dibromide 8 (400 mg, mmol, 1 equiv) in dioxane (. ml), water (. ml) and calcium carbonate (960 mg, 9.6 mmol, 10.3 equiv) were added. The resulting solution was heated to reflux for days, then the solution was cooled and the salts formed were dissolved using dilute HCl. The solution was extracted with CH Cl followed by 10% MeH/CH Cl. The combined organic layers were washed with water, and saturated aqueous NaCl, then dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to afford a 6 mg (9%) of the product as a pale yellow solid: TLC R f = 0.15 (1:1 hexane/etac); m.p.= C; 1 H NMR (400 MHz, CD 3 D) δ 8.93 (d, H, J= Hz, H Ar ), 8.09 (dd, H, J = 8, Hz, H Ar ), 7.99 (d, H, J = 8 Hz, H Ar ), 5.0 (s, 4H, CH H). 9

10 To a solution of the diol (0 mg, 0.07 mmol, 1 equiv) in 1 ml CH Cl, was added an aqueous solution of NaH (656 µl, 10% wt/vol, 5 equiv). Benzyl bromide (68 mg, 0.40 mmol, 6 equiv) and tetrabutylammonium iodide (68 mg, 0.19 mmol,.8 equiv) were added to the above solution and the contents were stirred for h. Water was added to the solution and the resultant mixture was extracted with CH Cl. The combined organic layers were washed with saturated aqueous sodium chloride, then dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude mixture was then subjected to flash column chromatography (18:1 hexane/etac) to yield 11 mg (35%) of the pure compound 1e was a pale yellow solid. TLC R f = 0.5 (3:1 hexane/etac); m.p C; 1 H NMR (400 MHz, CDCl 3 ) δ 8.34 (d, H, J = 1.8 Hz H Ar ), 8.01 (d, H, J = 8.1 Hz, H Ar ), 7.91 (dd, H, J = 8.0,.0 Hz, H Ar ), (m, 10H, H Ph ), 5.01 (s, 4H, CH Ar), 4.71 (s, 4H, CH Ph); C NMR (16 MHz, CDCl 3 ) δ 147.8, 8.5, 7.6, 5., 1.7, 19.8, 18.5, 17.9, 17.7, 1.9, 73.3, 68.6; IR (thin film) ν.9(m), 857 (m), 1747(w), 155(s), 37(s), 11(w) cm -1 ; LRMS (FD + ) General procedure for the photochemical reactions of 1a, 1b, 9a, 9b and 11. In a schlenk flask a M solution of the o-nitrobenzyl ether in benzene was deoxygenated by argon sparge for min. The resulting solution was subjected to UV radiation using F8T5 GE bulbs (black light) which emit maximally at 350 nm in a Rayonet Photochemical Reactor (Rayonet, the Southern Co., Middletown, Conn.). After h of irradiation, the solution was concentrated in vacuo. The crude mixture was purified using flash column chromatography and yields were determined based on the amount of alcohol isolated. H 9a Bn a Bn Serinol (a) from monomer: The serine ether 9a (9.0 mg, 0.0 mmol) was subjected to photolysis in benzene following the general procedure. Purification using flash column chromatography (9:1 hexane/etac) afforded the 4.0 mg of the alcohol a (66%): TLC R f = 0.14 (3:1 hexane/etac), 1 H NMR (500 MHz, CDCl 3 ) δ (m, 5H, H Ph ), 5.18 (s, 1H, NH), 4.53 (s, H, CH Ph), 3.81 (m, 1H, BocHNCHCH ), (m, 4H, CH CH(BocNH)CH ),.57 (s, 1H, H H ), 1.46 (s, 9H, C(CH 3 ) 3 ). 10

11 H Bn 1a a Bn Serinol (a) from dimer: The serine ether 1a (4.0 mg, mmol) was subjected to photolysis in benzene following the general procedure. Purification using flash column chromatography (9:1 hexane/etac) afforded 3.0 mg of the alcohol a (> 99%). TLC: R f = 0.14 (3:1 hexane/ EtAc); 1 H NMR (500 MHz, CDCl 3 ) δ (m, 5H, H Ph ), 5.18 (s, 1H, NH), 4.53 (s, H, CH Ph), 3.81 (m, 1H, BocHNCHCH ), (m, 4H, CH CH(BocNH)CH ),.57 (s, 1H, H H ), 1.46 (s, 9H, C(CH 3 ) 3 ). CH 3 H CH 3 9b b Hexadecanol (b) from monomer: The hexadecanol ether 9b (10.0 mg, 0.06 mmol) was subjected to photolysis in benzene following the general procedure. Purification using flash column chromatography (40:1 hexane/etac) afforded 5.0 mg of hexadecanol b (78%): TLC R f = 0.34 (3:1 hexane/ EtAc), 1 H NMR (500 MHz, CDCl 3 ) δ 3.64 (t, H, J = 6.6 Hz, HCH (CH ) 14 ), 1.56 (m, 4H, HCH CH CH (CH ) 1 ), 1.5 (m, 4 H, H(CH ) 3 (CH ) 1 CH 3 ), 0.88 (t, 3H, J = 6.6 Hz), CH 3 ). CH 3 1b H CH 3 b Hexadexanol (b) from dimer: The dimeric ether 1b (4.0 mg, mmol) was subjected to photolysis in benzene following the general procedure. Purification using flash column chromatography (40:1 hexane/etac) afforded 3 mg of the alcohol b (>99%): TLC R f = 0.34 (3:1 hexane/etac); 1 H NMR (500 MHz, CDCl 3 ) δ 3.64 (t, H, J = 6.6 Hz, HCH (CH ) 14 ), 1.56 (m, 4H, HCH CH CH (CH ) 1 ), 1.5 (m, 4 H, H(CH ) 3 (CH ) 1 CH 3 ), 0.88 (t, 3H, J = 6.7 Hz), CH 3 ). 11

12 H 3 C CH 3 N N 11 H CH 3 b Hexadecanol (b) from monoether 11: The hexadecanol ether 11 (7.70 mg, mmol) was subjected to photolysis in benzene following the general procedure. Purification using flash column chromatography (40:1 hexane/etac) afforded.0 mg of hexadecanol b (56%): TLC R f = 0.34 (3:1 hexane/ EtAc), 1 H NMR (500 MHz, CDCl 3 ) δ 3.64 (t, H, J = 6.6 Hz, HCH (CH ) 14 ), 1.56 (m, 4H, HCH CH CH (CH ) 1 ), 1.5 (m, 4 H, H(CH ) 3 (CH ) 1 CH 3 ), 0.88 (t, 3H, J = 6.6 Hz), CH 3 ). General procedure for the photochemical reactions of 1c-e, 9c-e. In an NMR tube, a M solution of the o-nitrobenzyl ether in the specified deuterated solvent was deoxygenated by argon sparge for min. The resulting solution was subjected to UV radiation for h. Upon completion of the reaction, a known amount of an internal standard was added to the solution and yields were determined by comparing 1 H NMR integrations of the alcohol and the standard. 7 9c H c Propanol (c) from monomer. The propyl ether 9c (4.5 mg, 0.03 mmol) was subjected to photolysis in d 6 -benzene following the general procedure. o-nitrobenzyl chloride (6 mg) was added as an internal standard. Comparison of the integrations of 1 H NMR peaks at δ 4.39 (o- PhCH Cl) and δ 3.4 (C 3 H 7 H) indicated 0.56 mg (40%) of propanol c was formed: TLC R f = 0.34 (3:1 hexane/etac); 1 H NMR (400 MHz, C 6 D 6 ) δ 3.4 (t, H, J = 6.6 Hz, CH ), 1.33 (m, H, CH CH ), 0.76 (t, 3H, J = 7.4 Hz, CH 3 ). 7 The reliability of the internal standards was gauged by taking 1 H NMR of a known amount of alcohol with the internal standard in it. The amount of the alcohol calculated using 1 H NMR integration matched the amount added. 1

13 Propanol (c) from dimer: H 1c c (a) The propyl ether 1c (4.7 mg, 0.01 mmol) was subjected to photolysis in d 6 -benzene as following the general procedure. o-nitrobenzyl chloride (4 mg) was added as an internal standard. Comparison of the integrations of 1 H NMR peaks at δ 4.39 (o- PhCH Cl) and δ 3.4 (C 3 H 7 H) indicated 0.84 mg (60%) of propanol c was formed: TLC R f = 0.34; 1 H NMR (400 MHz, C 6 D 6 ) δ 3.4 (t, H, J = 6.6 Hz, CH ), 1.33 (m, H, CH CH ), 0.76 (t, 3H, J = 7.4 Hz, CH 3 ). (b) The propyl ether 1c (7.8 mg, 0.0 mmol) was subjected o photolysis in d 8 -dioxane following the general procedure. o-nitrobenzyl chloride (7.9 mg) was added as an internal standard. Comparison of the integrations of 1 H NMR peaks at δ 5.0 (o- PhCH Cl) and δ 3.4 (C 6 H 11 H) indicated 1.9 mg (78%) of propanol c was formed: TLC R f = 0.34; 1 H NMR (400 MHz, C 4 D 8 ) δ 3.4 (t, H, J = 6.6 Hz, CH ), 1.47 (m, H, CH CH ), 0.88 (t, 3H, J = 7.4 Hz, CH 3 ). H 9d d Cyclohexanol (d) from monomer. The cyclohexyl ether 9d (14.5 mg, 0.09 mmol) was subjected to photolysis in d 6 -benzene following the general procedure. o-nitrobenzyl chloride (8 mg) was added as an internal standard. Comparison of the integrations of 1 H NMR peaks at δ 4.39 (o- PhCH Cl) and δ 3.36 (C 6 H 11 H) indicated 4 mg (71%) of cyclohexanol d was formed: TLC R f = 0.41 (3:1 hexane/etac); 1 H NMR(500 MHz, C 6 D 6 ) δ 3.36 (m, 1H, CHH), 1.68 (m, H, CH ), 1.56 (m, H, CH ), 1.33 (m, H, CH ), (m, 4H, CH CH ). H 1d d Cyclohexanol (d) from dimer: (a) The cyclohexyl ether 1d (4.4 mg, mmol) was subjected to photolysis in d 6 -benzene following the general procedure. o-nitrobenzyl chloride (4 mg) was added as an internal standard. Comparison of the integrations of 1 H NMR peaks at δ 4.39 (o- PhCH Cl) and δ 3.36 (C 6 H 11 H) indicated 1.3 mg (7%) of cyclohexanol d was formed: TLC R f = 0.41 (3:1 hexane/etac);

14 1 H NMR (500 MHz, C 6 D 6 ) δ 3.36 (m, 1H, CHH), 1.68 (m, H, CH ), 1.56 (m, H, CH ), 1.33 (m, H, CH ), (m, 4H, CH CH ). (b) The cyclohexyl ether 1d (.5 mg, mmol) was subjected to photolysis in d 8 -dioxane following the general procedure. o-nitrobenzyl chloride (3 mg) was added as an internal standard. Comparison of the integrations of 1 H NMR peaks at δ 5.0 (o- PhCH Cl) and δ 1.50 (C 6 H 11 H) indicated 0.97 mg (98%) of cyclohexanol d was formed: TLC R f = 0.41 (3:1 hexane/etac); 1 H NMR (500 MHz, C 4 D 8 ) δ 3.44 (m, 1H, CHH), (m, 4H, CH CH ), 1.50 (m, H, CH ), (m, 4H, CH CH ) 9e e H Benzyl alcohol (e) from monomer. The benzyl ether 9e (10.5 mg, mmol) was subjected to photolysis in d 6 -benzene following the general procedure. p-toluenesulfonyl chloride (9 mg) was added as an internal standard. Comparison of the integrations of 1 H NMR peaks at δ 1.71 (TsCH 3 ) and δ 4.31 (PhCH H) indicated 1.9 mg (40%) of benzyl alcohol e was formed: TLC R f = 0.6 (3:1 hexane/etac); 1 H NMR (500 MHz, C 6 D 6 ) δ (m, 5H, H Ar ), 4.31 (s, H, CH Ph). 1e e H Benzyl alcohol (e) from dimer: (a) The benzyl ether 1e (6 mg, 0.01 mmol) was subjected to photolysis in d 6 -benzene following the general procedure. p-toluenesulfonyl chloride (8.6 mg) was added as an internal standard. Comparison of the integrations of 1 H NMR peaks at δ 1.71 (TsCH 3 ) and δ 4.31 (PhCH H) indicated 1.6 mg (59%) of benzyl alcohol e was formed: TLC R f = 0.6 (3:1 hexane/etac); 1 H NMR (500 MHz, C 6 D 6 ) δ (m, 5H, H Ar ), 4.31 (s, H, CH Ph). (b) The benzyl ether 1e (4.8 mg, 0.01 mmol) was subjected to photolysis in d 8 -dioxane following the general procedure. DMF (10 µl) was added as an internal standard. Comparison of the integrations of 1 H NMR peaks at δ.85 (DMF) and δ 4.54 (PhCH H) indicated.4 mg (> 99%) of benzyl alcohol 14

15 e was formed: TLC R f = 0.6 (3:1 hexane/etac); 1 H NMR(500 MHz, C 4 D 8 ) δ (m, 5H, H Ar ), 4.54 (s, H, CH Ph). Comparison of UV spectra of o-nitrobenzyl alcohol dimer and o-nitrobenzyl alcohol 14 UV sample preparation and measurement. Solutions (10 ml) containing 5. µmol of each compound in ethanol were prepared using serial dilutions from an intial stock solution. The UV absorption spectra were recorded using 1 cm quartz cells on a Hewlett Packard UV spectrophotometer in the right angle geometry at room temperature. The data is presented graphically with absorbance plotted versus the wavelength in nm (figure 1) Dimer Monomer 14 Absorbance H N 14 H H Wavelength (nm) Figure 1: Comparison of UV spectra of monomer Vs. dimer 15