The clean deprotection or desilylation of a silyl-protected functional group is essential to its utility. The relative stability correlation of trisubstituted silyl ethers towards hydrolysis under acid conditions is: TMS ≈ DMPS ≈ MDPS < TES ≈ DMIPS < TPS < TBS < TDS is: TMS ≈ DMPS ≈ MDPS < DMIPS ≈ TES < TBDPS ≈ TBS < TDS < TIPS < DTBMS.59 Denmark and coworkers have looked at the steric and electronic effects influencing the desilylation of silyl ethers under both acid and base conditions.60 In addition the long-range structural effects on the desilylation of silyl ethers has been investigated.61 Typical deprotection protocols for the removal of silyl ethers are acidic aqueous THF, or acidic methanol, alkaline aqueous solutions and sources of fluoride ion, most commonly tetra-n-butylammonium fluoride, TBAF, in various solvents. The TBAF reagent has been used in the deprotection of all silyl ethers though the conditions will change depending on the nature of the silyl ether and its surrounding environment. A selection of some interesting and potentially useful examples of selective removal of one silyl ether in the presence of another are shown here.
Catecholborane in the presence of Wilkinson’s catalyst selectively deprotects TES ethers in the presence of other TES ethers, as well as TBS and TIPS ethers (Eq. 35).62 An excess of the catecholborane is required for good yields. Esters and olefins were shown to be stable to the reaction conditions.
A highly selective deprotection of silyl phenol ethers employs catalytic lithium acetate in moist DMF (Eq. 36).63 The procedure is tolerant of aliphatic silyl ethers, epoxides, and acetates.
Diisobutylalane, DIBAL-H, has been employed in the selective deprotection of primary TES ethers in the presence of secondary TES ethers (Eq. 37).64 The selective removal of TES ethers in the presence of TBS and TBDPS ethers as well as a primary TBS ether in the presence of a secondary TBS ether was also shown to be possible with this reagent (Eq. 38).
Even though the use of TBAF in THF is a common method for the deprotection of nearly all silyl ethers it can also be selective as shown in Eq. 39 where a primary TIPS ether is untouched by the reagent under the conditions employed.65 The strong influence of the environment around a silyl ether is shown in Eq. 40 where a primary TIPS ether is selectively removed in the presence of a tertiary TES ether with the TBAF/THF reagent.66 On the other hand the secondary TES ether in 9 is selectively reacted in the presence of the primary TBDPS ether in quantitative yield (Eq. 41).67 In an extraordinary example of the influence of the surrounding environment is the selectivity shown in the TBAF deprotection of the secondary TBDPS ether of 10 in the presence of a tertiary TMS ether, although the yield is modest (Eq. 42).68
Pyridinium fluoride, HF•pyr has been commonly used for the selective deprotection of silyl ethers in the presence of other silyl ethers as illustrated in Eqs. 43 & 44).69,70
The selective removal of an ethynyl trimethylsilyl group in the presence of silyl ethers was demonstrated with DBU either in stoichiometric or catalytic amounts. When carried out catalytically the required time for complete reaction was increased (Eq. 45).71
1. Acid-catalyzed cleavage of trimethylsilyl ethers.
The silylated alcohol (0.4 mmol) in dichloromethane (4 mL) is treated with a drop of 1N HCl and the reaction mixture is stirred for 30 min. In a transesterification approach a 0.5 M solution of trimethylsilylated alcohol in methanol is treated with pyridinium p-toluenesulfonate (PPTS) at room temperature for 30 min. The lower boiling trimethylmethoxysilane is removed by distillation.
2. Base-catalyzed cleavage of trimethylsilyl ethers.
The mildest conditions for the base-catalyzed deprotection of trimethylsilyl ethers is the treatment of a methanol solution of the silylated alcohol with an excess of potassium carbonate for 1 to 2 h.
3. Selective cleavage of a triethylsilyl ether with hydrogen fluoride-pyridine – representative procedure for the cleavage of silyl ethers with HF•pyr.
Treatment of 180 mmol of the silylated alcohol with 4 mL of the stock solution of HF•pyr (2 mL of HF•pyr, 4 mL pyridine, 16 mL THF) for 2 to 3 h results in the cleavage of the triethylsilyl ether.
4. Acid-catalyzed cleavage of triethylsilyl ethers.
A methanol solution of the silyl ether held at 0 °C is treated with p-toluenesulfonic acid (0.33 eq.) for 1 to 2 h. Alternatively, a THF solution of the triethylsilyl ether is treated with an aqueous solution of trifluoromethanesulfonic acid.
5. Cleavage of a tert-butyldimethylsilyl ether with tetra-n-butylammonium fluoride – representative procedure for the deprotection of silyl ethers with TBAF.
A solution of the silyl ether in THF (approximately 4 M) is treated with 3 equivalents of 1 M TBAF in THF at room temperature until the silyl ether is converted. This depends on the environment of the TBS ether, but usually requires from 2 to 16 h.
6. Cleavage of a tert-butyldimethylsilyl ether with tris(dimethylamino)sulfur(trimethylsilyl)difluoride – representative procedure for the deprotections of silyl ethers with TAS-F.
A 0.4 M solution of the silylated alcohol in THF is added to the TAS-F, SIT8715.0, at room temperature and the resulting solution stirred for 1 to 2 h.
7. Cleavage of a tert-butyldimethylsilyl ether with HF – representative procedure for the deprotection of silyl ethers with HF.
Hydrofluoric acid (49% aqueous solution, excess) is added to the silyl ether in acetonitrile at 0 °C. After stirring for a short time (typically 10 to 30 min) the reaction mixture is carefully quenched by the addition of saturated aqueous sodium hydrogen carbonate (CAUTION: STRONG EVOLUTION OF CARBON DIOXIDE).
8. Cleavage of a tert-butyldiphenylsilyl ether with TBAF in acetic acid.
A stock solution of TBAF in acetic acid is prepared (0.15 mL of HOAc per 1.0 mL of 1M TBAF in THF). The silyl ether is dissolved in THF and reacted with an excess of the stock solution for several hours.
| Deprotection of: | In presence of 1° TMS | In presence of 1° TES | In presence of 1° TIPS | In presence of 1° TBS | In presence of 1° TBDPS |
|---|---|---|---|---|---|
| 1° TMS | [bmim]Cl215, allylPPh3S2O8216 | NaHCO3217, Br2/PVPP218 | NaOH/EtOH219, MCM-41220 | NaOH/EtOH219, Cu(NO3)2221, Ce(NO3)3221, [Bu2(NCS)Sn]2O222BiCl3225, Bi(O2CCF3)3223, K2CO3224, MCM-41220, Br2/PVPP218, K2CO3225, MnIII-Schiff-base/H2O2226 | NaOH/EtOH219, Cu(NO3)2221, Ce(NO3)3133, HCl219,227,K2CO3228, Swern229 |
| 1° TES | TFA230, H2/Pd-C231,232, MCM-41220, HOAc/uw233 MeCHClO2CCl234, flourous TBAF110, FeCl3216, 2-hydroxymethylphenol/hn235, TMS-Br/MeOH236, catecholborane/(PPh3)3RhCl62, FeCl3/Et3SiH/ArCHO237 | HF/pyr238, TCNQ/MeCN/H2O239, DDQ/MeCN/H2O239,240, CSA241,242, IBX/DMSO243, MCM-41220, H2/Pd-C231, HCO2H244, MeCHClO2CCl234, flourous TBAF110, FeCl3216, 2-hydroxymethylphenol/hn235, catecholborane/(PPh3)3RhCl62, Swern245 | SiF4/CH2Cl2246, DDQ/MeCN/H2O239,240, MCM-41/MeOH220, CSA247,248, H2/Pd-C231,232,249, TMSOTf/HCO2DPM/SiO297, ZnBr2/H2O250, HCl251,252, PPTS253-255, CSA256,257, HOAc/uw233, MeCHClO2CCl234, FeCl3216, Fe(OTs)3258, 2-hydroxymethylphenol/hn235, TMS-Br/MeOH236, FeCl3/Et3SiH/ArCHO237, Swern259 | ||
| 1° TIPS | |||||
| 1° TBS | HCl/EtOH219,260,261, H2SiF6/tBuOH262-264, NaOH/EtOH24, Cyclohexene/PdO265 Alumina266, H2SO4267, CSA268,269, PPTS270, H2/Pd-C231,249, TMS-OTf/Et3N/MeOH271, CeCl3•7H2O/NaI157, Decaborane272, AcCl/MeOH, HOAc/uw233, MeCHClO2CCl234, HF•pyr274, FeCl3216, TMS-Br/MeOH236, H2/Pd-C232, TBAF65, pyridinium tribromide275, FeCl3/Et3SiH/ArCHO237 | TsOH/THF/H2O25, Cl2CHCO2H276,277, TBAF278-280, TBSOTf281, HOAC282, PPTS279,283, DDQ284, MnO2/AlCl3285, DMSO/H2O286, H2/Pd-C231, CrO3/H5IO6287 | HCl219,288-291, HOAc31,292-296, CSA242,297-311, PPTS287,312-327 TsOH328-330, MeOH/CCl4331, Cu(NO3)2221, Ce(NO3)3221, Cyclohexene/PdO265, Alumina25, SiF4/CH2Cl2246, DDQ/MeCN/H2O239,240, AcBr/CH2Cl332, TMSOTf333, HF-pyr/THF334, H2SO4335, TFA284,336,337, TsOH338,339, LL-ALPS-SO3H340, AcCl/MeOH341, Zn(BF4)2342, Cu(OTf)2/Ac2O343, InCl3344, CeCl3•7H2O/NaI157,345, H2O/NaI157, Ce(OTf)4/THF/H2O346, PdCl2(MeCN)2347, I2/MeOH348, Br2/MeOH349, IBr350, LiCl/DMF351, CCl4/MeOH352, ZnBr2/H2O250, ZrCl4/Ac2O353, HF-pyr274,354,355, I2/KOH315, H2/Pd-C231,232,249, Bu4NOH/MeOH356, TBAF357, TMSOTf/HCO2DPM/SiO297, Decaborane272, pyridinium tribromide275, MeCHClO2CCl234, 2-hydroxymethylphenol/hn235, FeCl3216, CrO3/H5IO6287, FeCl3/Et3SiH/ArCHO237, TMS-Cl/KF•2H2O358, Cl3CO2H359, BF3•OEt2225,300, TMS-Cl360, TMS-Br/MeOH236, (MeCN)2PdCl2361, SbCl3362, Fe(OTs)3258, NiCl2•6H2O HSCH2CH2SH363, CuBr2364, LiCl/H2O/DMF365, sulfated SnO2366, Bi(OTf)3367, Sc(OTf)3367, SnCl2•2H2O368, TBPA•SbCl6369, CCl4/MeOH370, MeCOPPh3Br371 | ||
| 1° TBDPS | KOH372,373, TBAF/HOAc353,374 | TBAF/HOAc253,254,375-378, TBATB/MeOH356, NaOH376,379-381, Bu4NOH375, KOH/DMPU382 | LiAlH4383, HF-pyr384, TBAF280 |
| Deprotection of: | In presence of 2° TMS | In presence of 2° TES | In presence of 2° TIPS | In presence of 2° TBS | In presence of 2° TBDPS |
|---|---|---|---|---|---|
| 1° TMS | Rexyn 101385, K2CO3/MeOH386, Alumina266, HOAc387 HOAc/ Ac2O388, [bmim]Cl215, NaHCO3389, K2CO3390, Swern391,392 | NaHCO3217, Swern391 | K2CO3393 | BF3OEt2394, HF•pyr395 | |
| 1° TES | Swern391 | HOAc16,396-398, CSA264, PPTS253,254,256, 399-402, HBr/PPh3403HF•pyr217, TBAF404-411, KF412, LiOH217, Swern13,391,400, 413-420, CrO3•2pyr421, HF•pyr241, K2CO3422, DIBAL-H64, DDQ423 | HOAc16, TMSOTf/i-Pr2NEt424, HF•pyr217,425, LiOH217 TMS-Br/MeOH236, HOAc/uw233 , PPTS426 | HOAc/H2O/THF16,427, RMgX428, HCl429, HBr/PPh3403 CSA241,264,430,431, PPTS432, TFA433-435, HF•pyr436-438, HF412, TMSOTf/i-Pr2EtN424, TBAF264,404, KF412, Swern418,419,439-441, HCO2H244, NaClO2438, DIBAL-H64, DDQ441 | SiF4/CH2Cl2442, DDQ239,240, TsOH413, citric acid443 TMSOTf/i-Pr2NEt424, TMSOTf/Et3N271, HCl398, PPTS444, TBAF445, DIBAL-H64 |
| 1° TIPS | TBAF425,446, CSA448, SiF4449, POCl3-DMF102,442 (TfO)2O-DMF102,442, CBr4/MeOH450, CAN/SiO2451, TFA452, HF•pyr453 | TFA/H2O/THF454, TBAF447,455,456 | TFA/H2O/THF458, CSA459 | ||
| 1° TBS | HF•pyr241, HOAc460, pyridinium, tribromide275 | HCl24,261,462,463, HOAc31,166,168,169,370,464-472, TsOH/PPTS473,474, HF•pyr475-485NaOH24, Cyclohexene/PdO265, TsOH486-489, H2SO4490, CSA268-270,304,462,481,482,491-495, PPTS478,496, NH4Cl/MeOH497, TBAF264,498, polymeric DCKA499, HOAc/uw233, Cl3CO2H359, (HF)3•xNEt3500, TMS-Br/TBAB/Ac2O501, (CF3CO)2O/MeOH501, PCC/Celite34 | HCl291,488,502-504, HOAc16,505-515, TFA/H2O/THF516-518, CSA242,268-270,298,306,316,307, 481,482,519-545 PPTS279,283,316,546-587, Acid Amberlite588, NH4F273,549,589-5917, HF598-602, H2SiF6/tBuOH263, HF•pyr381,382,477-479,481-485,498,505,506,532,536-538, 541-545,560-587,603-648, H2/wet Pd649, H2/Pd-C231, NBS/DMSO650, TBAF424,651-665, MeOH/CCl4331, NaOH24, TFA337,615-619, TsOH330,338,339,613,666-672, TsOH/Bu4NHSO4614, Alumina262,663,673,674, (CF3SO22)/DMF102, AgOAc675, CAN/iPrOH451, acidic CHCl3620, Cu(OTf)2/Ac2O92, BCl3621, Cyclohexene/PdO676, H2SiF6677, TAS-F678, CBr4-hν679,680, Jones566, LiBr/18-C-6681, CAN/i-PrOH682, POCl3-DMF102,684, (TfO)2O-DMF102,684, QFC685, Bu4NBr3/MeOH356, MnO2/AlCl3285, Oxone686, CAN/SiO2451, TMS-Cl/KF/MeOH358, pyridinium tribromide275, CBr4/hv687, ZnBr2688, SnCl2688, Bi(OTf)3367, CeCl3•7H2O/NaI688, SbCl3362, flourous TBAF110, LiAlH4689, DIBAL-H64, NaIO4690,691, I2/MeOH692, HClO4/SiO2438, (HF)3•xNEt3628 | HOAc512,693-696, TsOH697-704, TBAF705,706, PPTS313,327,702,707-711 HF•pyr32,69,197,712,714, HF459,715-718, HCl461,719, NaOH720, H2SiF6721, CSA309-311,722-729, BF3•OEt2730, NBS/DMSO452,731, CrO3/H5IO6287, TBPA•SbCl6368, TMSOTf/Et3N271, Cu(OTf)2/Ac2O342, Zn(OTf)2341, K2CO3102,683, TBTU732, QFC poly DCKA733, InCl3343, IBr/DCM158 | |
| 1° TBDPS | TBAF/HOAc377,734,735, NaOH/DMPU736, Hf•pyr27, TMSCN/Sc(OTf)3737 DIBAL-H64 | NaH/HMPA738, Hf•pyr358,739-740, KOH/18-C-6741, KOH273,742, NaOH319,470, TASF639 | TBAF566,571,650,743-746, TBAF/HOAc242,253,254,304,324,374,376,377,561,568,734,735,739,747-758, KOH759-761, KOH/18-C-6741NaOH380,762,763, NaOH/DMPU736, NH4F594,597,764-772, NH4F/HFIP773, TAS-F418,774,775, NaH/propargyl alcohol289, NaH/HMPA759, TMSCN/Sc(OTf)3737, HF•pyr27 | Hf•pyr383,725,776-779, NH4F764,766, TBAF458,208,780, CSA781, alumina33,266,782, POCl3-DMF102.683, (TfO)2O-DMF102,683 |
| Deprotection of: | In presence of 3° TMS | In presence of 3° TES | In presence of 3° TIPS | In presence of 3° TBS | In presence of 3° TBDPS |
|---|---|---|---|---|---|
| 1° TMS | PPTS783, Swern229 | ||||
| 1° TES | PPTS784 | Hf•pyr480,567,575,785,786, CSA248,787, PPTS253,254,398, KF/glycol788 Swern259 | Amberlyst-15789, TBAF/HOAc404, PPTS242 | HOAc790 | |
| 1° TIPS | TBAF66,791 | TBAF785, SiF4783 | |||
| 1° TBS | CSA248,787,794, Hf•pyr479,480,567,575,640,786,795,796, Sc(OTf)3366, TBAF/HOAc555 | TBAF445,585,627,797,798, CSA242,303,308,309,743,799,800, Hf•pyr69,586, H2SiF6330, SiF4/CH2Cl2246, MeOH/CCl4441, NH4F128,801, oxone685, BF3•OEt2802, DDQ803 | |||
| 1° TBDPS | TBAF/HOAc735, HF•pyr27 | TAS-F804, TBAF/HOAc242,253,254,750 |
| Deprotection of: | In presence of 1° TMS | In presence of 1° TES | In presence of 1° TIPS | In presence of 1° TBS | In presence of 1° TBDPS |
|---|---|---|---|---|---|
| 2° TMS | Amberlyst 15384, [bmim]Cl215 | TBAF65,447, PPTS805, NH4F806 | HCl807, K2CO3/MeOH378,808, TsOH809, citric acid676, PPTS388, IBX/4-methoxy-pyridineoxide67, H2SiF6388, NaOH462 | HCl810,811, TsOH809,812-815, Acetone/Me2C(OMe)2/CSA816, PhSeCl/K2CO3785, TBAF817, PPTS818,819, Alumina266, K2CO3/MeOH820, HOAc821, CSA822,823, HF•pyr824, BF3•OEt2821, TMS-OTf573,825 | |
| 2° TES | Hf•pyr17 | TFA453,826, H2SiF6/HF/H2O827, HCl807, HOAc458,713 CSA241,267,828,829, PPTS446,740,830-833, HF-pyr217,264, 424,446, Ph3P-HBr267, HF-Et3N834, TBAF352,372, H2SO4267, TsOH835, FeCl3216, Zn(OTf)2/EtSH836 | DDQ/MeCN/H2O240, HCl/py837, NH4Cl838,839, TBAF/THF838 Hf•pyr224, I2/Ag2CO3840,841, Pd/C, MeOH842, Pd/C,H2231, H2SiF6676, NaOH489, HCO2H244, PPTS843, TiCl4844, MCPBA/NaHCO3556 | HCl227,253,254,562,571,816,845-847, HOAc289,848, Cl3CCO2H441, TsOH269,414,444,813,845,846,849-855, HF/MeCN856,857, Et3N-HF858, Hf•pyr19,228,859,860, TBAF297,352,841,861,862, SiF4/CH2Cl2246, CSA242,299,303,813,863-866, PPTS298,318,784,831,850,867-870, TFA400,871,872, H2SO4861, BF3•OEt2269,850, BF3•OEt2/Et3SiH742, DDQ240,873, tetrabromocyclohexadienone/PPh3874, H2Pd/C875, HOAc876-878, TMS-Br/MeOH236, TMS-OTf860,879-881, TES-OTf882, FeCl3216, Zn(OTf)2/EtSH253,254,836,865, PhSeCl/K2CO3785, ZnBr2/H2O250 | |
| 2° TIPS | TBAF/HOAc392 | ||||
| 2° TBS | H2SiF6/HF/H2O697, CSA830, TMS-OTf883, 2-mercaptobenzothiazole/Ph3P/DIAD833 | DIBAL-H884, MnO2/AlCl3285, LiAlH4885 | HCl24,886, HOAc887-889, TsOH890-893, PPTS304,312,383,894-896, BF3•OEt2897, TMS-OTf271,332,383,725,852,879,880,898, HF/MeCN515, TBAF296,773,899,900, SiF4/CH2Cl2246, CSA/MeOH298, H2SiF6741, Cu(OTf)2/Ac2O92, InCl3343, LiAlH4901,902, IBr903, P2O5/(MeO)2CH2338, LiCl/DMF350, polymeric DCKA733, ZnBr2/H2O250, Zn(BF4)2341, Amberlyst-15639, AcCl/MeOH904, SnCl4905, [PdCl2(MeCN)2]906, CrO3/H5IO6287, DDQ907,908, NaIO4689, TBPA•SbCl6368 | ||
| 2° TBDPS | NaH/HMPA909, TBATB/MeOH355 |
| Deprotection of: | In presence of 2° TMS | In presence of 2° TES | In presence of 2° TIPS | In presence of 2° TBS | In presence of 2° TBDPS |
|---|---|---|---|---|---|
| 2° TMS | TBAF910, SiO2-Cl/ NaI911, [bmim]Cl215, KF/polyether-diol912 | Hf•pyr575,913, TBAF410, KF736, citric acid914, PhCOF915 | Citric Acid916, TBAF/HOAc917,918, FeCl3919, TBAF447, KF411, NaOH462, H2SiF6676, HF•pyr425 | HCl920, TsOH813,815,921,922, HOAc479,923,924, PPTS925,926, HF/Et3N927, Citric Acid/MeOH928,929, Cu(NO3)2221, Ce(NO3)3221, DDQ/wet EtOAc930, K2CO3479,820,931-934, HOAc935,936, CSA937, Hf•pyr425,575,913, HF/Et3N938, BF3-OEt2939,940, KF411,736, TBAF941, TFA942,943, SnCl4944 | TBAF945, Cu(NO3)2221, Ce(NO3)3221, K2CO3479,931,933,934, NaIO4946, HOAc479, K2CO3479,931 |
| 2° TES | HOAc947-950, TBAF402,403,540,951-953, TsOH954, TFA955,956 Hf•pyr575,779, (NH4)HF2957, KF411, NaOH/DMPU736, CSA532, PPTS477, catecholborane/(Ph3)3RhCl62 | TFA453,958,959, HOAc233,949,950,960-962, PPTS16,425,477,480,740,963, MoO5/HMPA929,964, WO5/HMPA964,965, Hf•pyr21,217,966, H2SO4267, TFA967, Zn(OTf)2/EtSH968,969, NH4F967, Amberlyst-15970, CSA303,829,971, TMS-Br/MeOH236, (HF)3•xNEt3499, BF3•OEt2/Et3SiH742 | HOAc514,741,878,949,959,972,97, TFA434,453,955,956,958,959,976, PPTS13,16,242,438,446,546,641,784,831-833,868,885,895,937,977-989, HF990,991, Hf•pyr27,264,395,399,428,575,859,913,990,992-1001,1046, HF-Et3N398,949,1002, TBAF289,402,403,540,952,953,1003-1009, HCl1010,1011, PTSA/MeOH436, CSA241,242,534,830,971, TsOH436,813,835,853,1046, DDQ240,1012, MCM-41/MeOH220, TfOH/H2O-THF1013, WO5/HMPA964,965, MoO5/HMPA964,065, Zn(OTf)2/EtSH968, TiCl3(O-iPr)995, KF411, NaOH/DMPU736, MCM-41220, PdCl2/CuCl/H2O1014, HCO2H244, TES-OTf882, TAS-F1046, PdCl2/CuCl2/O21015, (NH4)6Mo7O24/H2O21016, Et2BOMe/NaBH41017, EtSH/Zn(OTf)2969, Cp2ZrHCl1018 | HCl414,1019, HOAc58,713,1020-1022, CSA1023-1025, PPTS843,987, HF533,990,995,1026,1027, Hf•pyr286, TBAF296,444,1028-1030, K2CO31031,1032, SiF4/CH2Cl2246, DDQ/MeCN/H2O240, NaIO4946, BF3•OEt21033 | |
| 2° TIPS | HF578,1034, PPTS1035 | TBAF1036-1040, PTSA/MeOH482, TsOH481, HF/Et3N21, LiAlH41041 | NaIO4946 | ||
| 2° TBS | HCl1042 | TBAF995 | HCl24,1043-1045, H2SiF6(aq)265, HOAc13,233,961,962, HF515,578,1034, TBAF270,918,1046-1048, CSA480,1049,1050, Et3N-3HF1051, H2SiF6/Et3N1052, PPTS469,1053, TsOH488 | HCl24, CSA403,1054-1056, TsOH1057, HF515,1058-1061, LiAlH4382, KF/H2O1062, TBAF28,541,576,577,659,902,945,980,981,985,1063-1075, H2SO41076, Hf•pyr477,640,1075,1077-1080, HF/Et3N949, HOAc950, P2O5/(MeO)2CH2338, MnO2/AlCl3285, TMS-OTf452, BF3•OEt21081, PPTS896,1082, SnCl4905, TAS-F1079, NaOH380, NaIO4689, salen-Mn(III)/PhIO1083, 2-mercaptobenzothiazine/Ph3P/DIAD833 | TsOH1084-1086, HCO2H/THF/H2O1087, CSA726,1056,1088,1089, PPTS1090-1093, HF/MeCN1094, TBAF651,899,1095,1096, SiF4/CH2Cl2246, Cu(NO3)2221, Ce(NO3)3221, DDQ/MeCN/H2O240, HCl1097,1098, HOAc889,1099-1101, Hf•pyr712,713,1102, TMS-OTf383,725,898, BF3•OEt21103, Sc(OTf)31104, NaIO4946, HCl1105,1106, TiCl41107, NaIO4689, CrO3/H5IO6731 |
| 2° TBDPS | TBAF/THF460 | HF•pyr479, TBAF32, TAS-F1108 | NaBH433 |
| Deprotection of: | In presence of 3° TMS | In presence of 3° TES | In presence of 3° TIPS | In presence of 3° TBS | In presence of 3° TBDPS |
|---|---|---|---|---|---|
| 2° TMS | TsOH922,1109 | HOAc923, CSA1110, KF411,736, TBAF65HF•pyr575,913 | HOAc/HCl1111 | ||
| 2° TES | TsOH1112, HF•pyr27,264,573,575,779,9913,96, HCl1010,1011, PPTS784,885,1113,1114, TBAF65,402,952,1115,1116 | HOAc1117, CSA242,303,650,829,865, HCl404, TfOH1013, Zn(OTf)2/EtSH253,254,865, Cp2ZrHCl1018 | |||
| 2° TIPS | |||||
| 2° TBS | H2SiF6/tBuOH/H2O263 | HOAc1118, CSA1119,1120, TBAF1121,1122, TfOH1013, HF1123 | |||
| 2° TBDPS | TBAF32 |
| Deprotection of: | In presence of 1° TMS | In presence of 1° TES | In presence of 1° TIPS | In presence of 1° TBS | In presence of 1° TBDPS |
|---|---|---|---|---|---|
| 3° TMS | PPTS/MeOH834, PPTS1124, HCl828 | ClCH2CO2H/MeOH276, HCl1126, BH3-SMe21127 | HCl336, HOAc790, BF3-OEt21128-1130, PPTS1131, K2CO3256,1132 | ||
| 3° TES | HF-Et3N834, TBAF1133, PPTS1125 | SiO21134, TBAF/ NH4Cl1133, LiHMDS/CeCl3555 | TBAF1133, HCl847, CSA1135 | ||
| 3° TIPS | |||||
| 3° TBS | LiAlH41119,1136 | ||||
| 3° TBDPS |
| Deprotection of: | In presence of 2° TMS | In presence of 2° TES | In presence of 2° TIPS | In presence of 2° TBS | In presence of 2° TBDPS |
|---|---|---|---|---|---|
| 3° TMS | TBAF/HOAc1137, K2CO31137 | TBAF13,1018 | TBAF/HOAc918,1138 | HCl336,1126,1139, LiAlH41140, TBAF13,1018,1138,1141, FeCl31132, HF1061, HF•pyr1142, K2CO31132, HOAc1142, PPTS229, H2/Pd(OH)2-C1143, BH3•THF1144 | HCl783, H2SiF6720,1145, K2CO3460, TBAF1146 |
| 3° TES | LiAlH996 | TBAF/HOAc1138 | Et3NHF1147,1148, HF-Et3N398,1002, TBAF/HOAc1138, TBAF1149, LiHMDS/CeCl3555 | TBAF1146 | |
| 3° TIPS | |||||
| 3° TBS | TBAF/HOAc1138 | TBAF1117 | TBAF69 | ||
| 3° TBDPS |
| Deprotection of: | In presence of 3° TMS | In presence of 3° TES | In presence of 3° TIPS | In presence of 3° TBS | In presence of 3° TBDPS |
|---|---|---|---|---|---|
| 3° TMS | HCl/THF1150 | ||||
| 3° TES | LiHMDS/CeCl3555 | TBAF1116 | |||
| 3° TIPS | |||||
| 3° TBS | CSA1151 | ||||
| 3° TBDPS |
| Deprotection of: | In presence of 1° TMS | In presence of 1° TES | In presence of 1° TIPS | In presence of 1° TBS | In presence of 1° TBDPS |
|---|---|---|---|---|---|
| ArOTMS | Dowex 1-X8 (HO- form)1152 | TBAF1153,1154, BiCl3905, Bi(O2CCF3)3905, Bi(OTf)3905, PIFA-MK101155 | |||
| ArOTES | DBU1156 | NaOH219 | NaOH219 | ||
| ArOTIPS | LiOAc63 | NaOH219, K2CO31157,1158, TBAF375,1155,1159-1163, KF/18-crown-61163, KF/Al2O3/MeCN1164, KF-Al2O31165, CsF/RX/DMF1166, CsCO31167, Et3NO1168, LiOH1169, NaOH/TBAH1166, KOH1170, LiOH/RX/DMF1171, TMG1172, PIFA-MK101155, DMSO/H2O286, KF/glycol788, SelectFluor1173, DBU1156,1174,1175, CuBr879, LiOAc63 | TBATB/MeOH355, Zn(BH4)2341, TBAF1176,1177, NaOH/TBAH1166, LiOAc63 | ||
| ArOTBS | PIFA-MK101155 | PIFA-MK101155, KF/glycol788 | PIFA-MK101155, KOAc63 | NaOH1178, KF/glycol788, LiOAc63 | |
| ArOTBDPS | NaOH219, PIFA-MK101155 | NaOH219, PIFA-MK101155 | NaOH219, PIFA-MK101155 | TMG1172 |
| Deprotection of: | In presence of 2° TMS | In presence of 2° TBS | In presence of 3° TBDPS | In presence of 3° TBS |
|---|---|---|---|---|
| ArOTMS | ||||
| ArOTES | CsF1179 | |||
| ArOTIPS | KOAc63 | TBAF28, NaOMe1183,1184 | NaOMe1183,1184 | TBAF1185, NaOH1178 |
| ArOTBS | TBAF299, Triton-B982,983 | TBAF518,691,1180,1181, Triton-B982,983, LiOAc63 | 10% HCl1182 | |
| ArOTBDPS | NaOH219, PIFA-MK101155 | TMG1172 |
| Deprotection of: | In presence of ArOTMS | In presence of ArOTES | In presence of ArOTBS | In presence of ArOTIPS | In presence of ArOTBDPS |
|---|---|---|---|---|---|
| ArOTMS | |||||
| ArOTES | |||||
| ArOTBS | SbCl31178, KF-Al2O31226, CCl4/MeOH1227, NaClO2/NaH2PO4/py1228KF/HBr/HOAc1229 | HCl1178, HClO4•SiO21206, LiOAc63 | |||
| ArOTIPS | NaOMe1183,1184 | KOAc1230 | |||
| ArOTBDPS |
| Deprotection of: | In presence of ArOTMS | In presence of ArOTES | In presence of ArOTBS | In presence of ArOTIPS | In presence of ArOTBDPS |
|---|---|---|---|---|---|
| 1° TMS | Dowex CCR-2 (H+ form)1152, Br2/PVPP218 | HCl219 | HCl219, Amberlite IR-120 (H+ form)1186 | HCl219 | |
| 2° TMS | Amberlite IR-120 (H+ form)1186 | ||||
| 1° TES | FeCl3216, Pd/C/MeOH842, MeCClO2CCl234 | ZnBr2/H2O250, FeCl3/Et3SiH/ArCHO96 | ZnBr2/H2O250, HOAc1187 | ZnBr2/H2O250 | |
| 2° TES | PPTS1188, BiBr3/Et3SiH1189, ZnBr2/H2O250, NaHSO4-SiO21190 HOAc1187 | ZnBr2/H2O250, HOAc1187 | ZnBr2/H2O250 | ||
| 1° TBS | FeCl3216 | HCl219,1191, TFA1192, PPTS1157,1193, HF/MeCN1157,1194,1195, BF3OEt21157,1196, SiF4/CH2Cl2246, MeOH/CCl4330, TMS-Cl/H2O/CH3CN1197, Oxone/MeOHaq 685, Nafion-H/NaI1198, LL-ALPS-SO3H339, AcCl/MeOH340, TMS-Cl/H2O1197, TMS-Cl/NaI/H2O1197, Me2SBr21198, TBSOTf/THPOAc101, BiBr3/H2O/MeCN1199, BiCl3/NaI1200, CeCl3•7H2O1169, CuOTf/Ac2O92, Sc(OTf)3/H2O1104, MeCHClO2CCl234, FeCl3/Et3SiH/ArCHO96, ZnBr2/H2O250, InCl3343, ZrCl4/Ac2O1201, decaborane272, Ce(OTf)4/THF/H2O345, CBr4/MeOH449, I2/MeOH1202, CAN/SiO2450, H2/Pd-C1203, HCO2H1204,1205, HClO4-SiO21206, KHSO41207, NaHSO4-SiO2190, TMS-Br236, pyridinium tribromide275, TMS-Cl/KF/MeOH357, FeCl3/Ac2O1208, Fe(OTs)3•6H2O258, CeCl3•7H2O1209, Ce(OTf)3•xH2O1210, sulfated SnO2365, SnCl2•2H2O367, Bi(OTf)3366, NHPI/Co(O2CPh)2/O21211, NIS/MeOH1212, I2/MeOH691,1213,1214, SelectFluor/MeCN1173, MeCOPPh3Br370, TBPA•SbCl6368 | HCl219, Amberlite IR-120 (H+ form)1186, HF•pyr1215, BF3•OEt21216 ZnBr2/H2O250, ZrCl4/Ac2O1201 | HCl219,468, ZnBr2/H2O250, InCl3343, BiOClO41217 TsOH369 | |
| 2° TBS | TFA1218,1219, BF3•OEt21157,1196, HF/MeCN1159, PPTS1157, SiF4/CH2Cl2246, Nafion-H/NaI1198, BiBr3/H2O/ MeCN1199, BiCl3/NaI1200, CeCl3•7H2O1169, ZnBr2/H2O250, InCl3343, Me2SBr21198, MeCOPPh3Br370, (PhO)2PON31220 | TFA1219, ZnBr2/H2O250 | ZnBr2/H2O250 | ||
| 1° TIPS | HCl219, CBr4/MeOH449, I2/MeOH1202, TMS-Br236, SelectFluor/MeCN1173 | HCl219, Sc(OTf)3/H2O712, CBr4/MeOH449, I2/MeOH1202 |
|||
| 1°TBDPS | HCl219 | HCl219, Sc(OTf)3/H2O712, CBr4/MeOH449, I2/MeOH1202, HClO4-SiO21206, TMS-Br236, MeCHClO2CCl234, SelectFluor/MeCN1173 |
| Deprotection of: | In presence of 2° TMS | In presence of 2° TES | In presence of 2° TIPS | In presence of 2° TBS | In presence of 2° TBDPS |
|---|---|---|---|---|---|
| DTBS silylene | HF•pyr43,205,1221,1222, KF/MeOH1062,1223,1224 | ||||
| TIPDS silioxane | HF/MeCN1225 |