enabling synthetic organic transformations...the most common groups that fall into this class are...

11 East Steel Rd.Morrisville, PA 19067Phone: 215-547-1015Fax: [email protected]

Gelest, Inc.The core manufacturing technology of Gelest is silanes, silicones and metal-organics with the capability to handle flammable, corrosive and air sensi-tive liquids, gases and solids. Headquartered in Morrisville, PA, Gelest isrecognized worldwide as an innovator, manufacturer and supplier of commer-cial and research quantities serving advanced technology markets through amaterials science driven approach. The company provides focused technicaldevelopment and application support for: semiconductors, optical materials,pharmaceutical synthesis, diagnostics and separation science, and specialtypolymeric materials.

Offering Selective and

Versatile Reagents for:

Enabling Synthetic Organic

Transformations

For additional information on Gelest’s Silicon and Metal-Organic based products or to inquire how we may assist in Enabling Your Technology, please contact:

Enabling Synthetic Organic Transformations

© 2014 Gelest, Inc.

• Reductions• Functional Group Protection

• Synthetic Organic Transformations• Cross-Coupling C-C Bond Formation

www.gelest.com

Organosilicon Basedand

Metal-Organic Synthetic Reagents

Gelest offers a number of other organosilane reagents that are of high use in the organic syntheticarea. These include, among others, trimethyliodosilane, trimethylbromosilane, trimethylsilyl triflate, cyanotrimethylsilane, a number of silyl enol ethers and silyl ketene acetals, in addition to anextensive variety of organosilanes that are attached to inorganic surfaces for the purpose of finalpurification of desired products. Gelest also offers several non-silicon-based synthetic reagentsthat complement and, oftentimes, assist in the reactions of the silicon-based reagents. These include a number of Lewis acid catalysts such as tin tetrachloride, tetraisopropyltitanate, tris(penta-fluorophenyl)boron, and a variety of metal diketonates. In addition Gelest offers several metal-organic reagents for various synthetic transformations.

Other Gelest Synthetic Reagents

H3C Si ICH3

CH3

SIT8564.0

H3C Si BrCH3

CH3

SIT8430.0

H3C Si OTfCH3

CH3

SIT8620.0

H3C Si CNCH3

CH3

SIT8585.0 SIT8580.0

H3C Si N3

CH3

H3C

OSi(CH3)3

SIC2462.0

OSi(CH3)3

SIT8571.0

(H3C)3SiO

SIT8171.2

O OSi(CH3)3

SIT8571.3

H3COSi(CH3)3

H3C

OCH3

SIM6496.0

NMe

Si

Ph

Cl

SIA0433.0

Si(CH3)3

SIA0555.0

H3C Si CH2ClCH3

CH3

SIC2305.0

H3C Si OLICH3

CH3SIL6469.7

(H3C)3SiN

Li

Si(CH3)3

SIL6467.0

(H3C)3SiN

K

Si(CH3)3

SIP6890.0

CH3CH2 Zn CH2CH3

OMZN017(CH3)2CHCH2

AlCH2CH(CH3)3

H

OMAL021.2

CH3CH2Al

Cl

Cl

OMAL033.2

i-PrO Ti ClOi-Pr

Oi-Pr

AKT851

BF

FF

F

F FF

F

F

FF

F

F

FF

OMBO087

Zn

OMZN040

FePPh2

PPh2

OMFE022

i-PrOB

Oi-Pr

Oi-Pr

AKB156.5

H3COB

OCH3

OCH3

AKB157

H3CO Mg OCH3

AKM503

SNT7930

Cl Sn ClCl

Cln-Bu Sn H

n-Bu

n-Bu

SNT8130

H3C Sn CH3

CH3

CH3

SNT7560

OCH2CH3

Sn(nBu)3

SNE4620 SNT7906

Sn


Silicon-BasedBlocking Agents


Reagents For:-Functional Group Protection

-Synthetic Transformation-Derivatization

Enabling Your Technology

Silicon-Based

Cross-Coupling Reagents

Pd

Si(OEt)3

ONEt2

O

Si(OEt)3

ONEt2

O

H2N

Si(OMe)3

SiOH

n-C5H11

OMe

Si(OEt)3

Si(OEt)3

Me

MeSiMe3

N

Si(OEt)3

N

Br

N

Br

OTf

CF3

Cl

MeO

OMe

O

O

Br

OMe

Br

I

Me

Br

ONEt2

O

Br

ONEt2

O

Si(OMe)3

CF3

Version 2.0

1093_Vasanti brochure_Layout 1 10/24/14 9:53 PM

Organosilane reductions are very commonplace in synthetic organic chemistry with the Si-H bond,being weakly polarized such that the hydrogen is hydridic in nature. Because the Si-H bond is onlyweakly hydridic, the silanes have the potential to be highly selective reducing agents, reducing anumber of functionalities with excellent tolerance for other reducible functionalities. Organosilaneshave further advantages in terms of low toxicity, ease of handling, and ease of final product purifi-cation. In addition, a number of enantioselective organosilane reductions have been reported. Ionicand organometalic-catalyzed organosilane reductions have been extensively reviewed.1,2

The extensive electronic and steric diversity of organosilanes offers a large range of selectivities in reactivity. For example, the homopolymeric methylhydrogensiloxane, HMS-992, and related homopolymers represent a high molecular weight silane reducing agent that can offer significantproduct isolation advantages.3 Diphenylsilane, SID4559.0, has been shown to selectively reduceamides to aldehydes.4 Triisopropylsilane, SIT8385.0, has been shown to offer a steric advantageleading to a higher degree of the β-aryl glucoside from the hemiketal precursor.5

Tetramethyldisiloxane, TMDS, SIT7546.0, has recently been shown to be highly useful in the reduction of hemiketals to the corresponding ether. This has been applied to successful synthesesof the pharmaceutically important gliflozin family of diabetes 2 Specific Glucose Transport 2 (SGLT2)inhibitor drugs, such as canagliflozin, (Invokana) and dapagliflozin (Farxiga) among others.6 TMDS has also been shown to very effectively reduce nitroaryls to anilines7 and is an improvement over triethylsilane in the reduction of a ketone to a methylene in the production of a key intermediate in the preparation of ziprasidone.8

Organosilane Reducing Agents

CH3CH2 Si HCH3CH2

CH3CH2

SIT8330.0

SiCH3

CH3

H

SIP6729.0

HC Si H

HC

CH

CH3H3CH3C

H3CH3C CH3

SIT8385.0

Si HH

H

SIP6750.0

SiH

H

SID4559.0

CH3CH2 Si HCH3

CH3

SIE4894.0

CH3CH2O Si HCH3CH2O

CH3CH2O

SIT8185.0

Si H

SIT8665.0

(CH3)3Si Si H

(CH3)3Si

(CH3)3Si

SIT8724.0

Cl Si HCl

Cl

SIT8155.0

H Si OCH3

CH3

Si HCH3

CH3

SIT7546.0

SiO Si

OSi

OSiO

H3CH

CH3

H

CH3H

H

H3C

SIT7530.0

O Si HO

O

Si(CH3)3

(CH3)3Si

Si(CH3)3

SIT8721.0

H Si HCH3CH2

CH3CH2

SID3415.0

Si CH3

H

H

SIP6742.0

References:1. Larson, G. L.; Fry, J. L. “Ionic and Organometallic-Catalyzed Organosilane Reductions”, Organic Reactions, Vol. 71, 2008,

Denmark, S. E. Ed. Wiley and Sons, Hoboken, NJ.2. Larson, G. L. “Silicon-Based Reducing Agents” Version 2.0, Gelest, Inc. 2008.3. Chandrasekhar, S.; Reddy, Ch. R.; Ahmed, M. Synlett. 2000, 1655.4. Bower, S.; Kreutzer, K. A.; Buchwald, S. L. Angew. Chem. Int. Ed. 1996, 35, 1515.5. Elsworth, B. A. et al. Tetrahedron: Asymmetry 2003, 14, 3243.6. a. Lemaire, S. et al. Org. Lett. 2102, 14, 1480. b. Nomura, S. et al. J. Med. Chem. 2010, 53, 6355. c. Lee, J. et al. Bioorg.

Med. Chem. 2010, 18, 2178.7. Nagashima, H. et al. J. Am. Chem. Soc. 2009, 131, 15032.8. Nadkarni, D.; Hallissey, J. F. Org. Proc. Res. Dev. 2008, 12, 1142.

Cross-coupling reactions are usually associated with the metals of boron (Suzuki-Miyaura), zinc(Negishi), tin (Stille), and copper (Sonogashira) along with magnesium (Kumada).1 As a viable alternative to these metals the Hiyama-Denmark cross-coupling reactions involve organosiliconreagents as the nucleophilic partner in C-C bond forming cross-coupling protocols. The organosilaneshave several advantages, including being readily prepared by a variety of approaches, excellent storage stability, ease of removal or recycling of the organosilane by-products, good functional grouptoleration, and low to non-toxicity profiles. The organosilane cross-coupling chemistry has been thoroughly reviewed.2 The use of sodium and potassium silanolates as the nucleophilic partner in thesilicon-based cross-coupling transformations has been shown to be of practical utility.3

Organosilane Cross-Coupling Reagents Organosilane Protecting Groups

Si(OMe)

SIP6822.0

Si(OMe)

H2N

SIA0599.1

Si(OMe)3H2N

SIA0599.0

Si(OMe)3

MeO

SIM6492.55

Si(OMe)3

O

SIT8177.0

FF

FF

F

Si(OEt)3

SIP6716.7

Si(OEt)3

SIN6596.8

N

Si(OEt)3

SIP6934.0

SiMe2ONa

SIS6986.1

S SiMe2ONa

SIS6987.0

O SiMe2ONa

SIS6980.6

Si(OMe)3

SIV9220.0 SIP6905.0

SiMe3

OO

SiSi

OO

Si

Si

SIT7900.0

SiMe3

SIT8606.5

H SiMe3

SIE4904.0

SIT8604.0

SiMe3

HOSiMe3

Me3SiO

OSIT8623.0 SIP6903.0

HMe3SiO Me3Si-O-K

SIP6901.0

Me3Si CN

SIT8579.0

OSiMe2ONa +

TBSO

Br(t-Bu3P)2Pd (2.5 mol%)

toluene, 90°

99%

OOTBS

References:1. a. De Meijre, A.; Diederich, F. Eds. Metal-Catalyzed Cross-Coupling Reactions; Wiley-VCH: Weinheim, 2004. b. Bringmann, G.; Walter, R.;

Weirich, R. Angew. Chem. Int. Ed. 1990, 29, 977. c. Negishi, E. “Handbook of Organopalladium Chemistry for Organic Synthesis” Wiley-Interscience: New York, 2002.

2. a. Hiyama, T. in “Metal-Catalyzed Cross-Coupling Reactions” Diederich, F.; Stang, P. J. Eds. Wiley-VCH: Weinheim, 1998; chapter 10. b. Den-mark, S. E. Sweis, R. F. Acct. Chem. Res. 2002, 35, 835. c. Chang, W-T. T.; Smith, R. C.; Regens, C. S.; Bailey, A. D.; Werner, N. S.; Denmark,S. E. “Cross-Coupling with Organosilicon Compounds” Organic Reactions 2011, Vol. 75, pp d. Denmark, S. E. in “Silicon Compounds: Silanesand Silicones” Arkles, B. and Larson, G. L. Eds. Gelest, Inc. 2013, pp 63-70.

3. a. Denmark, S. E.; Baird, J. D. Chem. Eur. J. 2006, 8, 793. b. Denmark, S. E.; Smith, R. C.; Chang, W-T. T.; Muhuhi, J. M. J. Am. Chem. Soc.2009, 131, 3104. c. Denmark, S. E.; Smith, R. C.; Tymonko, S. A. Tetrahedron 2007, 63, 5730.

4. a. Smith, A. B. III; Hoye, A. T.; Martinez-Solorio, D.; Kim, W.-S.; Tong, R. J. Am. Chem. Soc. 2012, 134, 4533. b. Nguyen, M. H.; Smith, A. B.III Org. Lett. 2014, 16, 2070.

It is very common that in a multi-step synthetic sequence the protection of one or more functional groupswill be required. The most common groups that fall into this class are alcohols, amines, thiols, acids, and carbonyls, in particular ketones and aldehydes. For the protection of functional groupswith active hydrogens, such as alcohols and amines, organosilanes have proven to be among the bestand most favored alternatives.1 The reasons for this are that the silyl groups can be both introduced and removed in high-yield, facile processes. In addition, the organosilanes have the ability to be modified bothsterically and electronically, thus giving them excellent selectivity and versatility in their reactivity, stabil-ity, and ease of deprotection. Indeed, in many of the more complicated and lengthy synthetic sequencesit is common to have a requirement to remove one organosilyl-protected group in the presence of othersimilar groups. A thorough presentation on the selective deprotection of one organosilyl-protected groupin the present of another has been compiled.2 Gelest offers an extensive range of organosilanes designedfor the protection of various functional groups including alcohols, diols, amines, thiols, carboxylic acidsand terminal alkynes. Of particular note is the use of the trimethylsilylenol ether of acetone, SII6264.0,for the protection of diols as their acetonides in a very fast and high-yield reaction.3 Gelest is proud tooffer the E. J. Corey BIBS reagent for the protection of alcohols, amines, and carboxylic acids and the formation of highly stable enol silyl ethers.4

H3C Si CICH3

CH3

SIT8510.0

H3C Si OTfCH3

CH3

SIT8620.0 SID3605.0

H3C Si N(CH3)2

CH3

CH3

Si NN

H3CH3C

H3C

SIT8590.0

NH3C

O

Si

SiH3C

H3CH3C

CH3

CH3

CH3

SIB1846.0

NF3C

O

Si

SiH3C

H3CH3C

CH3

CH3

CH3SIB1876.0

Si ClCH3

CH3

SII6462.0

CH3CH2 Si ClCH3CH2

CH3CH2

SIT8250.0

CH3CH2 Si OTfCH3CH2

CH3CH2

SIT8335.0

SiCH3

CH3

Cl

SIP6828.0

t-Bu Si ClCH3

CH3

SIB1935.0

H3CSi

NH

SiCH3

CH3H3CCH3

CH3

SIH6110.0

C Si ClCH3

CH3

Pht-Bu

Ph

SIB1968.0

t-Bu Si OTfCH3

CH3

SIB1967.0

t-Bu Si OTfOTf

t-Bu

SID3345.0

Si Cl

SIT8645.0

t-Bu Si Clt-Bu

CH3

SID3255.0

Si Cl

SIT8384.0

Si OTf

SIT8387.0

SiO

SiCl Cl

SIT7273.0

Et3N ( 2 eq.)

CH2Cl2, rt, 12 h

94%

reference SID3226.0 4

t-Bu Si OTft-Bu

+ HOOH

O

OOH

OH

BIBSOOBIBS

O

OOH

OH

References:1. Wuts, P. G. M.; Greene, T. W. “Greene’s Protective Groups in Organic Syntheses” Wiley and Sons, 2007.2. Larson, G. L. “Silicon-Based Blocking Agents” Gelest, Inc. 2014.3. Larson, G. L.; Hernández, A. J. Org. Chem. 1973, 38, 3935.4. Liang, H.; Hu, L.; Corey, E. J. Org. Lett. 2011, 13, 4120.

1093_Vasanti brochure_Layout 1 10/24/14 9:53 PM






Transformations






www.gelest.com





H3C Si ICH3

CH3

SIT8564.0

H3C Si BrCH3

CH3

SIT8430.0

H3C Si OTfCH3

CH3

SIT8620.0

H3C Si CNCH3

CH3

SIT8585.0 SIT8580.0

H3C Si N3

CH3

H3C

OSi(CH3)3

SIC2462.0

OSi(CH3)3

SIT8571.0

(H3C)3SiO

SIT8171.2

O OSi(CH3)3

SIT8571.3

H3COSi(CH3)3

H3C

OCH3

SIM6496.0

NMe

Si

Ph

Cl

SIA0433.0

Si(CH3)3

SIA0555.0

H3C Si CH2ClCH3

CH3

SIC2305.0

H3C Si OLICH3

CH3SIL6469.7

(H3C)3SiN

Li

Si(CH3)3

SIL6467.0

(H3C)3SiN

K

Si(CH3)3

SIP6890.0

CH3CH2 Zn CH2CH3

OMZN017(CH3)2CHCH2

AlCH2CH(CH3)3

H

OMAL021.2

CH3CH2Al

Cl

Cl

OMAL033.2

i-PrO Ti ClOi-Pr

Oi-Pr

AKT851

BF

FF

F

F FF

FF

FF

FF

FF

OMBO087

Zn

OMZN040

FePPh2

PPh2

OMFE022

i-PrOB

Oi-Pr

Oi-Pr

AKB156.5

H3COB

OCH3

OCH3

AKB157

H3CO Mg OCH3

AKM503

SNT7930

Cl Sn ClCl

Cln-Bu Sn H

n-Bu

n-Bu

SNT8130

H3C Sn CH3

CH3

CH3

SNT7560

OCH2CH3

Sn(nBu)3

SNE4620 SNT7906

Sn







Silicon-Based


Pd

Si(OEt)3

ONEt2

O

Si(OEt)3

ONEt2

O

H2N

Si(OMe)3

SiOH

n-C5H11

OMe

Si(OEt)3

Si(OEt)3

Me

MeSiMe3

N

Si(OEt)3

N

Br

N

Br

OTf

CF3

Cl

MeO

OMe

O

O

Br

OMe

Br

I

Me

Br

ONEt2

O

Br

ONEt2

O

Si(OMe)3

CF3

Version 2.0

1093_Vasanti brochure_Layout 1 10/24/14 9:53 PM Page 1

Organosilane reductions are very commonplace in synthetic organic chemistry with the Si-H bond,being weakly polarized such that the hydrogen is hydridic in nature. Because the Si-H bond is onlyweakly hydridic, the silanes have the potential to be highly selective reducing agents, reducing anumber of functionalities with excellent tolerance for other reducible functionalities. Organosilaneshave further advantages in terms of low toxicity, ease of handling, and ease of final product purifi-cation. In addition, a number of enantioselective organosilane reductions have been reported. Ionicand organometalic-catalyzed organosilane reductions have been extensively reviewed.1,2

The extensive electronic and steric diversity of organosilanes offers a large range of selectivities in reactivity. For example, the homopolymeric methylhydrogensiloxane, HMS-992, and related homopolymers represent a high molecular weight silane reducing agent that can offer significantproduct isolation advantages.3 Diphenylsilane, SID4559.0, has been shown to selectively reduceamides to aldehydes.4 Triisopropylsilane, SIT8385.0, has been shown to offer a steric advantageleading to a higher degree of the β-aryl glucoside from the hemiketal precursor.5

Tetramethyldisiloxane, TMDS, SIT7546.0, has recently been shown to be highly useful in the reduction of hemiketals to the corresponding ether. This has been applied to successful synthesesof the pharmaceutically important gliflozin family of diabetes 2 Specific Glucose Transport 2 (SGLT2)inhibitor drugs, such as canagliflozin, (Invokana) and dapagliflozin (Farxiga) among others.6 TMDS has also been shown to very effectively reduce nitroaryls to anilines7 and is an improvement over triethylsilane in the reduction of a ketone to a methylene in the production of a key intermediate in the preparation of ziprasidone.8

Organosilane Reducing Agents

CH3CH2 Si HCH3CH2

CH3CH2

SIT8330.0

SiCH3

CH3

H

SIP6729.0

HC Si H

HC

CH

CH3H3CH3C

H3CH3C CH3

SIT8385.0

Si HH

H

SIP6750.0

SiH

H

SID4559.0

CH3CH2 Si HCH3

CH3

SIE4894.0

CH3CH2O Si HCH3CH2O

CH3CH2O

SIT8185.0

Si H

SIT8665.0

(CH3)3Si Si H

(CH3)3Si

(CH3)3Si

SIT8724.0

Cl Si HCl

Cl

SIT8155.0

H Si OCH3

CH3

Si HCH3

CH3

SIT7546.0

SiO Si

OSi

OSiO

H3CH

CH3

H

CH3H

H

H3C

SIT7530.0

O Si HO

O

Si(CH3)3

(CH3)3Si

Si(CH3)3

SIT8721.0

H Si HCH3CH2

CH3CH2

SID3415.0

Si CH3

H

H

SIP6742.0

References:1. Larson, G. L.; Fry, J. L. “Ionic and Organometallic-Catalyzed Organosilane Reductions”, Organic Reactions, Vol. 71, 2008,

Denmark, S. E. Ed. Wiley and Sons, Hoboken, NJ.2. Larson, G. L. “Silicon-Based Reducing Agents” Version 2.0, Gelest, Inc. 2008.3. Chandrasekhar, S.; Reddy, Ch. R.; Ahmed, M. Synlett. 2000, 1655.4. Bower, S.; Kreutzer, K. A.; Buchwald, S. L. Angew. Chem. Int. Ed. 1996, 35, 1515.5. Elsworth, B. A. et al. Tetrahedron: Asymmetry 2003, 14, 3243.6. a. Lemaire, S. et al. Org. Lett. 2102, 14, 1480. b. Nomura, S. et al. J. Med. Chem. 2010, 53, 6355. c. Lee, J. et al. Bioorg.

Med. Chem. 2010, 18, 2178.7. Nagashima, H. et al. J. Am. Chem. Soc. 2009, 131, 15032.8. Nadkarni, D.; Hallissey, J. F. Org. Proc. Res. Dev. 2008, 12, 1142.

Cross-coupling reactions are usually associated with the metals of boron (Suzuki-Miyaura), zinc(Negishi), tin (Stille), and copper (Sonogashira) along with magnesium (Kumada).1 As a viable alternative to these metals the Hiyama-Denmark cross-coupling reactions involve organosiliconreagents as the nucleophilic partner in C-C bond forming cross-coupling protocols. The organosilaneshave several advantages, including being readily prepared by a variety of approaches, excellent storage stability, ease of removal or recycling of the organosilane by-products, good functional grouptoleration, and low to non-toxicity profiles. The organosilane cross-coupling chemistry has been thoroughly reviewed.2 The use of sodium and potassium silanolates as the nucleophilic partner in thesilicon-based cross-coupling transformations has been shown to be of practical utility.3

Organosilane Cross-Coupling Reagents Organosilane Protecting Groups

Si(OMe)

SIP6822.0

Si(OMe)

H2N

SIA0599.1

Si(OMe)3H2N

SIA0599.0

Si(OMe)3

MeO

SIM6492.55

Si(OMe)3

O

SIT8177.0

FF

FF

F

Si(OEt)3

SIP6716.7

Si(OEt)3

SIN6596.8

N

Si(OEt)3

SIP6934.0

SiMe2ONa

SIS6986.1

S SiMe2ONa

SIS6987.0

O SiMe2ONa

SIS6980.6

Si(OMe)3

SIV9220.0 SIP6905.0

SiMe3

OO

SiSi

OO

Si

Si

SIT7900.0

SiMe3

SIT8606.5

H SiMe3

SIE4904.0

SIT8604.0

SiMe3

HOSiMe3

Me3SiO

OSIT8623.0 SIP6903.0

HMe3SiO Me3Si-O-K

SIP6901.0

Me3Si CN

SIT8579.0

OSiMe2ONa +

TBSO

Br(t-Bu3P)2Pd (2.5 mol%)

toluene, 90°

99%

OOTBS

References:1. a. De Meijre, A.; Diederich, F. Eds. Metal-Catalyzed Cross-Coupling Reactions; Wiley-VCH: Weinheim, 2004. b. Bringmann, G.; Walter, R.;

Weirich, R. Angew. Chem. Int. Ed. 1990, 29, 977. c. Negishi, E. “Handbook of Organopalladium Chemistry for Organic Synthesis” Wiley-Interscience: New York, 2002.

2. a. Hiyama, T. in “Metal-Catalyzed Cross-Coupling Reactions” Diederich, F.; Stang, P. J. Eds. Wiley-VCH: Weinheim, 1998; chapter 10. b. Den-mark, S. E. Sweis, R. F. Acct. Chem. Res. 2002, 35, 835. c. Chang, W-T. T.; Smith, R. C.; Regens, C. S.; Bailey, A. D.; Werner, N. S.; Denmark,S. E. “Cross-Coupling with Organosilicon Compounds” Organic Reactions 2011, Vol. 75, pp d. Denmark, S. E. in “Silicon Compounds: Silanesand Silicones” Arkles, B. and Larson, G. L. Eds. Gelest, Inc. 2013, pp 63-70.

3. a. Denmark, S. E.; Baird, J. D. Chem. Eur. J. 2006, 8, 793. b. Denmark, S. E.; Smith, R. C.; Chang, W-T. T.; Muhuhi, J. M. J. Am. Chem. Soc.2009, 131, 3104. c. Denmark, S. E.; Smith, R. C.; Tymonko, S. A. Tetrahedron 2007, 63, 5730.

4. a. Smith, A. B. III; Hoye, A. T.; Martinez-Solorio, D.; Kim, W.-S.; Tong, R. J. Am. Chem. Soc. 2012, 134, 4533. b. Nguyen, M. H.; Smith, A. B.III Org. Lett. 2014, 16, 2070.

It is very common that in a multi-step synthetic sequence the protection of one or more functional groupswill be required. The most common groups that fall into this class are alcohols, amines, thiols, acids, and carbonyls, in particular ketones and aldehydes. For the protection of functional groupswith active hydrogens, such as alcohols and amines, organosilanes have proven to be among the bestand most favored alternatives.1 The reasons for this are that the silyl groups can be both introduced and removed in high-yield, facile processes. In addition, the organosilanes have the ability to be modified bothsterically and electronically, thus giving them excellent selectivity and versatility in their reactivity, stabil-ity, and ease of deprotection. Indeed, in many of the more complicated and lengthy synthetic sequencesit is common to have a requirement to remove one organosilyl-protected group in the presence of othersimilar groups. A thorough presentation on the selective deprotection of one organosilyl-protected groupin the present of another has been compiled.2 Gelest offers an extensive range of organosilanes designedfor the protection of various functional groups including alcohols, diols, amines, thiols, carboxylic acidsand terminal alkynes. Of particular note is the use of the trimethylsilylenol ether of acetone, SII6264.0,for the protection of diols as their acetonides in a very fast and high-yield reaction.3 Gelest is proud tooffer the E. J. Corey BIBS reagent for the protection of alcohols, amines, and carboxylic acids and the formation of highly stable enol silyl ethers.4

H3C Si CICH3

CH3

SIT8510.0

H3C Si OTfCH3

CH3

SIT8620.0 SID3605.0

H3C Si N(CH3)2

CH3

CH3

Si NN

H3CH3C

H3C

SIT8590.0

NH3C

O

Si

SiH3C

H3CH3C

CH3

CH3

CH3

SIB1846.0

NF3C

O

Si

SiH3C

H3CH3C

CH3

CH3

CH3SIB1876.0

Si ClCH3

CH3

SII6462.0

CH3CH2 Si ClCH3CH2

CH3CH2

SIT8250.0

CH3CH2 Si OTfCH3CH2

CH3CH2

SIT8335.0

SiCH3

CH3

Cl

SIP6828.0

t-Bu Si ClCH3

CH3

SIB1935.0

H3CSi

NH

SiCH3

CH3H3CCH3

CH3

SIH6110.0

C Si ClCH3

CH3

Pht-Bu

Ph

SIB1968.0

t-Bu Si OTfCH3

CH3

SIB1967.0

t-Bu Si OTfOTf

t-Bu

SID3345.0

Si Cl

SIT8645.0

t-Bu Si Clt-Bu

CH3

SID3255.0

Si Cl

SIT8384.0

Si OTf

SIT8387.0

SiO

SiCl Cl

SIT7273.0

Et3N ( 2 eq.)

CH2Cl2, rt, 12 h

94%

reference SID3226.0 4

t-Bu Si OTft-Bu

+ HOOH

O

OOH

OH

BIBSOOBIBS

O

OOH

OH

References:1. Wuts, P. G. M.; Greene, T. W. “Greene’s Protective Groups in Organic Syntheses” Wiley and Sons, 2007.2. Larson, G. L. “Silicon-Based Blocking Agents” Gelest, Inc. 2014.3. Larson, G. L.; Hernández, A. J. Org. Chem. 1973, 38, 3935.4. Liang, H.; Hu, L.; Corey, E. J. Org. Lett. 2011, 13, 4120.







Transformations






www.gelest.com





H3C Si ICH3

CH3

SIT8564.0

H3C Si BrCH3

CH3

SIT8430.0

H3C Si OTfCH3

CH3

SIT8620.0

H3C Si CNCH3

CH3

SIT8585.0 SIT8580.0

H3C Si N3

CH3

H3C

OSi(CH3)3

SIC2462.0

OSi(CH3)3

SIT8571.0

(H3C)3SiO

SIT8171.2

O OSi(CH3)3

SIT8571.3

H3COSi(CH3)3

H3C

OCH3

SIM6496.0

NMe

Si

Ph

Cl

SIA0433.0

Si(CH3)3

SIA0555.0

H3C Si CH2ClCH3

CH3

SIC2305.0

H3C Si OLICH3

CH3SIL6469.7

(H3C)3SiN

Li

Si(CH3)3

SIL6467.0

(H3C)3SiN

K

Si(CH3)3

SIP6890.0

CH3CH2 Zn CH2CH3

OMZN017(CH3)2CHCH2

AlCH2CH(CH3)3

H

OMAL021.2

CH3CH2Al

Cl

Cl

OMAL033.2

i-PrO Ti ClOi-Pr

Oi-Pr

AKT851

BF

FF

F

F FF

F

F

FF

F

F

FF

OMBO087

Zn

OMZN040

FePPh2

PPh2

OMFE022

i-PrOB

Oi-Pr

Oi-Pr

AKB156.5

H3COB

OCH3

OCH3

AKB157

H3CO Mg OCH3

AKM503

SNT7930

Cl Sn ClCl

Cln-Bu Sn H

n-Bu

n-Bu

SNT8130

H3C Sn CH3

CH3

CH3

SNT7560

OCH2CH3

Sn(nBu)3

SNE4620 SNT7906

Sn







Silicon-Based


Pd

Si(OEt)3

ONEt2

O

Si(OEt)3

ONEt2

O

H2N

Si(OMe)3

SiOH

n-C5H11

OMe

Si(OEt)3

Si(OEt)3

Me

MeSiMe3

N

Si(OEt)3

N

Br

N

Br

OTf

CF3

Cl

MeO

OMe

O

O

Br

OMe

Br

I

Me

Br

ONEt2

O

Br

ONEt2

O

Si(OMe)3

CF3

Version 2.0


enabling synthetic organic transformations...the most common groups that fall into this class are...

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