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

Other Gelest Synthetic Reagents Gelest offers a number of other organosilane reagents that are of high use in the organic synthetic area. These include, among others, trimethyliodosilane, trimethylbromosilane, trimethylsilyl triflate, cyanotrimethylsilane, a number of silyl enol ethers and silyl ketene acetals, in addition to an extensive variety of organosilanes that are attached to inorganic surfaces for the purpose of final Enabling Synthetic purification of desired products. Gelest also offers several non-silicon-based synthetic reagents that complement and, oftentimes, assist in the reactions of the silicon-based reagents. These Enabling Synthetic Organic Transformations

Enabling Synthetic Organic Transformations Organic 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- Transformations organic reagents for various synthetic transformations.

CH3 CH3 CH3 CH3 CH3 Organosilicon Based H3C Si OTf H3C Si CN H3C Si N3 H3C Si I H3C Si Br CH3 CH3 H3C CH3 CH3 and

SIT8564.0 SIT8430.0 SIT8620.0 SIT8585.0 SIT8580.0 Metal-Organic Synthetic Reagents OSi(CH3)3 H3C OSi(CH3)3 (H3C)3SiO OSi(CH3)3 H3C Gelest, Inc. O OSi(CH3)3 Silicon-Based OCH3 The core manufacturing technology of Gelest is silanes, silicones and metal- Blocking Agents SIC2462.0 SIT8171.2 SIT8571.0 SIT8571.3 SIM6496.0 organics with the capability to handle flammable, corrosive and air sensi- Silicon-Based Ph Cross-Coupling Reagents CH3 CH tive liquids, gases and solids. Headquartered in Morrisville, PA, Gelest is Si 3 Si(CH ) Enabling Your Technology H3C Si CH2Cl 3 3 Cl Si(CH3)3 H3C Si OLI N N recognized worldwide as an innovator, manufacturer and supplier of commer- Me CH3 CH (H3C)3Si Li 3 SIA0433.0 SIC2305.0 cial and research quantities serving advanced technology markets through a SIA0555.0 SIL6469.7 SIL6467.0 Br Cl

Br O OMe N materials science driven approach. The company provides focused technical NEt2 MeO Br O Br O Si(OMe)3 Br Si(OEt)3 CH3CH2 Zn CH2CH3 O O H2N Br O NEt2 3 O Si(OEt) O N 2 NEt OMe H development and application support for: semiconductors, optical materials, Si(OMe)3 I OTf O Si(CH ) NEt2 3 3 O OMZN017 Pd Si Si(OEt)3 Me OH Si(OEt)3 3 Al CF3 CF

3 N H11 Si(OEt)

5 pharmaceutical synthesis, diagnostics and separation science, and specialty n-C (H C) Si K F (CH3)2CHCH2 CH2CH(CH3)3 N 3 3 OMe

Me SiMe3

Me Version 2.0 Reagents For: F SIP6890.0 F OMAL021.2 polymeric materials. -Functional Group Protection -Synthetic Transformation

-Derivatization

F F

F F

F F Oi-Pr B

Cl Offering Selective i-PrO Ti Cl Zn

Al

F F

CH CH Cl Oi-Pr F and 3 2 F

OMZN040

F OMAL033.2 AKT851 F Versatile Reagents for:

OMBO087 For additional information on Gelest’s Silicon and Metal-Organic

PPh2 based products or to inquire how we may assist in Enabling Your • Reductions Fe Oi-Pr OCH3 Technology, please contact: PPh2 B B • Functional Group Protection i-PrO Oi-Pr H3CO OCH3 H3CO Mg OCH3 OMFE022 AKB156.5 AKB157 AKM503 11 East Steel Rd. • Synthetic Organic Transformations Morrisville, PA 19067 Cl CH • Cross-Coupling C-C Bond Formation n-Bu 3 n Sn( Bu)3 Phone: 215-547-1015 Cl Sn Cl n-Bu Sn H H3C Sn CH3 Sn Fax: 215-547-2484 Cl n-Bu CH3 OCH2CH3 www.gelest.com [email protected] SNT7930 SNT8130 SNT7560 SNE4620 SNT7906 © 2014 Gelest, Inc. 1093_Vasanti brochure_Layout 1 10/24/14 9:53 PM Page 2

Organosilane Reducing Agents Organosilane Cross-Coupling Reagents Organosilane Protecting Groups Organosilane reductions are very commonplace in synthetic organic chemistry with the Si-H bond, Cross-coupling reactions are usually associated with the metals of boron (Suzuki-Miyaura), zinc It is very common that in a multi-step synthetic sequence the protection of one or more functional groups being weakly polarized such that the hydrogen is hydridic in nature. Because the Si-H bond is only (Negishi), tin (Stille), and copper (Sonogashira) along with magnesium (Kumada). 1 As a viable will be required. The most common groups that fall into this class are alcohols, amines, weakly hydridic, the silanes have the potential to be highly selective reducing agents, reducing a alternative to these metals the Hiyama-Denmark cross-coupling reactions involve organosilicon thiols, acids, and carbonyls, in particular ketones and aldehydes. For the protection of functional groups number of functionalities with excellent tolerance for other reducible functionalities. Organosilanes reagents as the nucleophilic partner in C-C bond forming cross-coupling protocols. The organosilanes with active hydrogens, such as alcohols and amines, organosilanes have proven to be among the best have further advantages in terms of low toxicity, ease of handling, and ease of final product purifi- 1 have several advantages, including being readily prepared by a variety of approaches, excellent and most favored alternatives. The reasons for this are that the silyl groups can be both introduced and cation. In addition, a number of enantioselective organosilane reductions have been reported. Ionic removed in high-yield, facile processes. In addition, the organosilanes have the ability to be modified both and organometalic-catalyzed organosilane reductions have been extensively reviewed.1,2 storage stability, ease of removal or recycling of the organosilane by-products, good functional group toleration, and low to non-toxicity profiles. The organosilane cross-coupling chemistry has been sterically and electronically, thus giving them excellent selectivity and versatility in their reactivity, stabil- The extensive electronic and steric diversity of organosilanes offers a large range of selectivities in thoroughly reviewed.2 The use of sodium and potassium silanolates as the nucleophilic partner in the ity, and ease of deprotection. Indeed, in many of the more complicated and lengthy synthetic sequences reactivity. For example, the homopolymeric methylhydrogensiloxane, HMS-992, and related silicon-based cross-coupling transformations has been shown to be of practical utility.3 it is common to have a requirement to remove one organosilyl-protected group in the presence of other homopolymers represent a high molecular weight silane reducing agent that can offer significant similar groups. A thorough presentation on the selective deprotection of one organosilyl-protected group product isolation advantages.3 Diphenylsilane, SID4559.0, has been shown to selectively reduce in the present of another has been compiled.2 Gelest offers an extensive range of organosilanes designed Si(OMe) 4 Si(OMe)3 amides to aldehydes. Triisopropylsilane, SIT8385.0, has been shown to offer a steric advantage Si(OMe) H2N Si(OMe)3 Si(OMe)3 for the protection of various functional groups including alcohols, diols, amines, thiols, carboxylic acids 5 and terminal alkynes. Of particular note is the use of the trimethylsilylenol ether of acetone, SII6264.0, leading to a higher degree of the β-aryl glucoside from the hemiketal precursor. H N O 2 MeO for the protection of diols as their acetonides in a very fast and high-yield reaction.3 Gelest is proud to Tetramethyldisiloxane, TMDS, SIT7546.0, has recently been shown to be highly useful in the SIP6822.0 SIA0599.1 SIA0599.0 SIM6492.55 SIT8177.0 offer the E. J. Corey BIBS reagent for the protection of alcohols, amines, and carboxylic acids and the reduction of hemiketals to the corresponding ether. This has been applied to successful syntheses formation of highly stable enol silyl ethers.4 of the pharmaceutically important gliflozin family of diabetes 2 Specific Glucose Transport 2 (SGLT2) F H3C Si(OEt) inhibitor drugs, such as canagliflozin, (Invokana) and dapagliflozin (Farxiga) among F Si(OEt)3 3 H3C Si O CH3 H3C 6 7 Si(OEt)3 SiMe2ONa CH CH3 N others. TMDS has also been shown to very effectively reduce nitroaryls to anilines and is an 3 H C Si N H3C N CH3 H3C Si OTf H C Si N(CH ) 3 F F SiMe ONa H3C Si CI 3 3 2 H3C Si CH3 improvement over triethylsilane in the reduction of a ketone to a methylene in the production of S SiMe2ONa O 2 H C F N CH3 CH 3 a key intermediate in the preparation of ziprasidone.8 CH3 3 CH3 SIP6716.7 SIN6596.8 SIP6934.0 SIS6986.1 SIS6987.0 SIS6980.6 SIT8510.0 SIT8620.0 SID3605.0 SIT8590.0 SIB1846.0 H3C H CH3 CH3CH2 CH3 H3C C H H H3C CH CH CH CH Si H HC Si H Si H3C Si O CH3 3 2 CH CH CH3 3 2 Si H Si H Si Si 3 2 H C O O H3C N CH3 Si Cl CH3CH2 Si Cl Si Cl CH3CH2 CH3 3 CH H H Si CH3CH2 Si OTf H3C CH3 O O F C Si CH SiMe3 3 3 CH CH3CH2 CH SiMe Si H SiMe 3 CH3CH2 3 SIT8330.0 SIP6729.0 SIP6750.0 SID4559.0 Si(OMe)3 3 3 CH3 SIT8385.0 SII6462.0 SIV9220.0 SIP6905.0 SIT7900.0 SIT8606.5 SIE4904.0 SIB1876.0 SIT8250.0 SIT8335.0 SIP6828.0 (CH3)3Si CH OTf CH3CH2O Cl CH3 CH3 CH3 Ph 3 CH3 CH3 H C (CH3)3Si Si H 3 CH t-Bu Si OTf CH3CH2O Si H Cl Si H t-Bu Si Cl Si Si 3 t-Bu C Si Cl t-Bu Si OTf CH3CH2 Si H H C N CH Si H Me3SiO 3 3 Ph CH t-Bu CH3CH2O (CH ) Si Cl CH3 H 3 CH3 CH 3 3 SiMe Me3SiO Me3Si CN HO 3 3 Me3Si-O-K O H SiMe3 SIB1935.0 SIH6110.0 SIB1968.0 SIB1967.0 SID3345.0 SIE4894.0 SIT8185.0 SIT8724.0 SIT8155.0 SIT8623.0 SIP6903.0 SIP6901.0 SIT8579.0 SIT8604.0

H SIT8665.0 H C Si(CH ) t-Bu 3 i OS CH 3 3 Si Cl Si OTf 3 O Br t-Bu Si Cl Si Si CH3 CH3 O Si H O O Si Cl O H H (t-Bu3P)2Pd (2.5 mol%) CH Cl Cl H Si O Si H Si O (CH3)3Si O Si H CH CH SiMe2ONa + OTBS 3 3 2 Si CH3 toluene, 90° H C O Si O SID3255.0 SIT8384.0 SIT8387.0 SIT7273.0 CH3 CH3 3 CH3 H Si H H TBSO H 99% Si(CH3)3 CH3CH2 SIT7546.0 SIT7530.0 SIT8721.0 SID3415.0 SIP6742.0 SIT8645.0

t-Bu O OH O OH References: References: t-Bu Si OTf OH Et3N ( 2 eq.) OBIBS 1. Larson, G. L.; Fry, J. L. “Ionic and Organometallic-Catalyzed Organosilane Reductions”, Organic Reactions, Vol. 71, 2008, 1. a. De Meijre, A.; Diederich, F. Eds. Metal-Catalyzed Cross-Coupling Reactions; Wiley-VCH: Weinheim, 2004. b. Bringmann, G.; Walter, R.; + HO BIBSO Denmark, S. E. Ed. Wiley and Sons, Hoboken, NJ. Weirich, R. Angew. Chem. Int. Ed. 1990, 29, 977. c. Negishi, E. “Handbook of Organopalladium Chemistry for Organic Synthesis” Wiley- CH2Cl2, rt, 12 h OH O OH O 2. Larson, G. L. “Silicon-Based Reducing Agents” Version 2.0, Gelest, Inc. 2008. Interscience: New York, 2002. 94% 3. Chandrasekhar, S.; Reddy, Ch. R.; Ahmed, M. Synlett. 2000, 1655. 2. a. Hiyama, T. in “Metal-Catalyzed Cross-Coupling Reactions” Diederich, F.; Stang, P. J. Eds. Wiley-VCH: Weinheim, 1998; chapter 10. b. Den- 4. Bower, S.; Kreutzer, K. A.; Buchwald, S. L. Angew. Chem. Int. Ed. 1996, 35, 1515. 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, SID3226.0 reference 4 5. Elsworth, B. A. et al. Tetrahedron: Asymmetry 2003, 14, 3243. S. E. “Cross-Coupling with Organosilicon Compounds” Organic Reactions 2011, Vol. 75, pp d. Denmark, S. E. in “Silicon Compounds: Silanes References: 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. and Silicones” Arkles, B. and Larson, G. L. Eds. Gelest, Inc. 2013, pp 63-70. 1. Wuts, P. G. M.; Greene, T. W. “Greene’s Protective Groups in Organic Syntheses” Wiley and Sons, 2007. Med. Chem. 2010, 18, 2178. 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. 2. Larson, G. L. “Silicon-Based Blocking Agents” Gelest, Inc. 2014. 7. Nagashima, H. et al. J. Am. Chem. Soc. 2009, 131, 15032. 2009, 131, 3104. c. Denmark, S. E.; Smith, R. C.; Tymonko, S. A. Tetrahedron 2007, 63, 5730. 3. Larson, G. L.; Hernández, A. J. Org. Chem. 1973, 38, 3935. 8. Nadkarni, D.; Hallissey, J. F. Org. Proc. Res. Dev. 2008, 12, 1142. 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. Org. Lett. 2011 13 III Org. Lett. 2014, 16, 2070. 4. Liang, H.; Hu, L.; Corey, E. J. , , 4120. 1093_Vasanti brochure_Layout 1 10/24/14 9:53 PM Page 1

Other Gelest Synthetic Reagents Gelest offers a number of other organosilane reagents that are of high use in the organic synthetic area. These include, among others, trimethyliodosilane, trimethylbromosilane, trimethylsilyl triflate, cyanotrimethylsilane, a number of silyl enol ethers and silyl ketene acetals, in addition to an extensive variety of organosilanes that are attached to inorganic surfaces for the purpose of final Enabling Synthetic purification of desired products. Gelest also offers several non-silicon-based synthetic reagents that complement and, oftentimes, assist in the reactions of the silicon-based reagents. These Enabling Synthetic Organic Transformations

Enabling Synthetic Organic Transformations Organic 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- Transformations organic reagents for various synthetic transformations.

CH3 CH3 CH3 CH3 CH3 Organosilicon Based H3C Si OTf H3C Si CN H3C Si N3 H3C Si I H3C Si Br CH3 CH3 H3C CH3 CH3 and

SIT8564.0 SIT8430.0 SIT8620.0 SIT8585.0 SIT8580.0 Metal-Organic Synthetic Reagents OSi(CH3)3 H3C OSi(CH3)3 (H3C)3SiO OSi(CH3)3 H3C Gelest, Inc. O OSi(CH3)3 Silicon-Based OCH3 The core manufacturing technology of Gelest is silanes, silicones and metal- Blocking Agents SIC2462.0 SIT8171.2 SIT8571.0 SIT8571.3 SIM6496.0 organics with the capability to handle flammable, corrosive and air sensi- Silicon-Based Ph Cross-Coupling Reagents CH3 CH tive liquids, gases and solids. Headquartered in Morrisville, PA, Gelest is Si 3 Si(CH ) Enabling Your Technology H3C Si CH2Cl 3 3 Cl Si(CH3)3 H3C Si OLI N N recognized worldwide as an innovator, manufacturer and supplier of commer- Me CH3 CH (H3C)3Si Li 3 SIA0433.0 SIC2305.0 cial and research quantities serving advanced technology markets through a SIA0555.0 SIL6469.7 SIL6467.0 Br Cl

Br O OMe N materials science driven approach. The company provides focused technical NEt2 MeO Br O Br O Si(OMe)3 Br Si(OEt)3 CH3CH2 Zn CH2CH3 O O H2N Br O NEt2 3 O Si(OEt) O N 2 NEt OMe H development and application support for: semiconductors, optical materials, Si(OMe)3 I OTf O Si(CH ) NEt2 3 3 O OMZN017 Pd Si Si(OEt)3 Me OH Si(OEt)3 3 Al CF3 CF

3 N H11 Si(OEt)

5 pharmaceutical synthesis, diagnostics and separation science, and specialty n-C (H C) Si K F (CH3)2CHCH2 CH2CH(CH3)3 N 3 3 OMe

Me SiMe3

Me Version 2.0 Reagents For: F SIP6890.0 F OMAL021.2 polymeric materials. -Functional Group Protection -Synthetic Transformation

-Derivatization

F F

F F

F F Oi-Pr B

Cl Offering Selective i-PrO Ti Cl Zn

Al

F F

CH CH Cl Oi-Pr F and 3 2 F

OMZN040

F OMAL033.2 AKT851 F Versatile Reagents for:

OMBO087 For additional information on Gelest’s Silicon and Metal-Organic

PPh2 based products or to inquire how we may assist in Enabling Your • Reductions Fe Oi-Pr OCH3 Technology, please contact: PPh2 B B • Functional Group Protection i-PrO Oi-Pr H3CO OCH3 H3CO Mg OCH3 OMFE022 AKB156.5 AKB157 AKM503 11 East Steel Rd. • Synthetic Organic Transformations Morrisville, PA 19067 Cl CH • Cross-Coupling C-C Bond Formation n-Bu 3 n Sn( Bu)3 Phone: 215-547-1015 Cl Sn Cl n-Bu Sn H H3C Sn CH3 Sn Fax: 215-547-2484 Cl n-Bu CH3 OCH2CH3 www.gelest.com [email protected] SNT7930 SNT8130 SNT7560 SNE4620 SNT7906 © 2014 Gelest, Inc. 1093_Vasanti brochure_Layout 1 10/24/14 9:53 PM Page 2

Organosilane Reducing Agents Organosilane Cross-Coupling Reagents Organosilane Protecting Groups Organosilane reductions are very commonplace in synthetic organic chemistry with the Si-H bond, Cross-coupling reactions are usually associated with the metals of boron (Suzuki-Miyaura), zinc It is very common that in a multi-step synthetic sequence the protection of one or more functional groups being weakly polarized such that the hydrogen is hydridic in nature. Because the Si-H bond is only (Negishi), tin (Stille), and copper (Sonogashira) along with magnesium (Kumada). 1 As a viable will be required. The most common groups that fall into this class are alcohols, amines, weakly hydridic, the silanes have the potential to be highly selective reducing agents, reducing a alternative to these metals the Hiyama-Denmark cross-coupling reactions involve organosilicon thiols, acids, and carbonyls, in particular ketones and aldehydes. For the protection of functional groups number of functionalities with excellent tolerance for other reducible functionalities. Organosilanes reagents as the nucleophilic partner in C-C bond forming cross-coupling protocols. The organosilanes with active hydrogens, such as alcohols and amines, organosilanes have proven to be among the best have further advantages in terms of low toxicity, ease of handling, and ease of final product purifi- 1 have several advantages, including being readily prepared by a variety of approaches, excellent and most favored alternatives. The reasons for this are that the silyl groups can be both introduced and cation. In addition, a number of enantioselective organosilane reductions have been reported. Ionic removed in high-yield, facile processes. In addition, the organosilanes have the ability to be modified both and organometalic-catalyzed organosilane reductions have been extensively reviewed.1,2 storage stability, ease of removal or recycling of the organosilane by-products, good functional group toleration, and low to non-toxicity profiles. The organosilane cross-coupling chemistry has been sterically and electronically, thus giving them excellent selectivity and versatility in their reactivity, stabil- The extensive electronic and steric diversity of organosilanes offers a large range of selectivities in thoroughly reviewed.2 The use of sodium and potassium silanolates as the nucleophilic partner in the ity, and ease of deprotection. Indeed, in many of the more complicated and lengthy synthetic sequences reactivity. For example, the homopolymeric methylhydrogensiloxane, HMS-992, and related silicon-based cross-coupling transformations has been shown to be of practical utility.3 it is common to have a requirement to remove one organosilyl-protected group in the presence of other homopolymers represent a high molecular weight silane reducing agent that can offer significant similar groups. A thorough presentation on the selective deprotection of one organosilyl-protected group product isolation advantages.3 Diphenylsilane, SID4559.0, has been shown to selectively reduce in the present of another has been compiled.2 Gelest offers an extensive range of organosilanes designed Si(OMe) 4 Si(OMe)3 amides to aldehydes. Triisopropylsilane, SIT8385.0, has been shown to offer a steric advantage Si(OMe) H2N Si(OMe)3 Si(OMe)3 for the protection of various functional groups including alcohols, diols, amines, thiols, carboxylic acids 5 and terminal alkynes. Of particular note is the use of the trimethylsilylenol ether of acetone, SII6264.0, leading to a higher degree of the β-aryl glucoside from the hemiketal precursor. H N O 2 MeO for the protection of diols as their acetonides in a very fast and high-yield reaction.3 Gelest is proud to Tetramethyldisiloxane, TMDS, SIT7546.0, has recently been shown to be highly useful in the SIP6822.0 SIA0599.1 SIA0599.0 SIM6492.55 SIT8177.0 offer the E. J. Corey BIBS reagent for the protection of alcohols, amines, and carboxylic acids and the reduction of hemiketals to the corresponding ether. This has been applied to successful syntheses formation of highly stable enol silyl ethers.4 of the pharmaceutically important gliflozin family of diabetes 2 Specific Glucose Transport 2 (SGLT2) F H3C Si(OEt) inhibitor drugs, such as canagliflozin, (Invokana) and dapagliflozin (Farxiga) among F Si(OEt)3 3 H3C Si O CH3 H3C 6 7 Si(OEt)3 SiMe2ONa CH CH3 N others. TMDS has also been shown to very effectively reduce nitroaryls to anilines and is an 3 H C Si N H3C N CH3 H3C Si OTf H C Si N(CH ) 3 F F SiMe ONa H3C Si CI 3 3 2 H3C Si CH3 improvement over triethylsilane in the reduction of a ketone to a methylene in the production of S SiMe2ONa O 2 H C F N CH3 CH 3 a key intermediate in the preparation of ziprasidone.8 CH3 3 CH3 SIP6716.7 SIN6596.8 SIP6934.0 SIS6986.1 SIS6987.0 SIS6980.6 SIT8510.0 SIT8620.0 SID3605.0 SIT8590.0 SIB1846.0 H3C H CH3 CH3CH2 CH3 H3C C H H H3C CH CH CH CH Si H HC Si H Si H3C Si O CH3 3 2 CH CH CH3 3 2 Si H Si H Si Si 3 2 H C O O H3C N CH3 Si Cl CH3CH2 Si Cl Si Cl CH3CH2 CH3 3 CH H H Si CH3CH2 Si OTf H3C CH3 O O F C Si CH SiMe3 3 3 CH CH3CH2 CH SiMe Si H SiMe 3 CH3CH2 3 SIT8330.0 SIP6729.0 SIP6750.0 SID4559.0 Si(OMe)3 3 3 CH3 SIT8385.0 SII6462.0 SIV9220.0 SIP6905.0 SIT7900.0 SIT8606.5 SIE4904.0 SIB1876.0 SIT8250.0 SIT8335.0 SIP6828.0 (CH3)3Si CH OTf CH3CH2O Cl CH3 CH3 CH3 Ph 3 CH3 CH3 H C (CH3)3Si Si H 3 CH t-Bu Si OTf CH3CH2O Si H Cl Si H t-Bu Si Cl Si Si 3 t-Bu C Si Cl t-Bu Si OTf CH3CH2 Si H H C N CH Si H Me3SiO 3 3 Ph CH t-Bu CH3CH2O (CH ) Si Cl CH3 H 3 CH3 CH 3 3 SiMe Me3SiO Me3Si CN HO 3 3 Me3Si-O-K O H SiMe3 SIB1935.0 SIH6110.0 SIB1968.0 SIB1967.0 SID3345.0 SIE4894.0 SIT8185.0 SIT8724.0 SIT8155.0 SIT8623.0 SIP6903.0 SIP6901.0 SIT8579.0 SIT8604.0

H SIT8665.0 H C Si(CH ) t-Bu 3 i OS CH 3 3 Si Cl Si OTf 3 O Br t-Bu Si Cl Si Si CH3 CH3 O Si H O O Si Cl O H H (t-Bu3P)2Pd (2.5 mol%) CH Cl Cl H Si O Si H Si O (CH3)3Si O Si H CH CH SiMe2ONa + OTBS 3 3 2 Si CH3 toluene, 90° H C O Si O SID3255.0 SIT8384.0 SIT8387.0 SIT7273.0 CH3 CH3 3 CH3 H Si H H TBSO H 99% Si(CH3)3 CH3CH2 SIT7546.0 SIT7530.0 SIT8721.0 SID3415.0 SIP6742.0 SIT8645.0

t-Bu O OH O OH References: References: t-Bu Si OTf OH Et3N ( 2 eq.) OBIBS 1. Larson, G. L.; Fry, J. L. “Ionic and Organometallic-Catalyzed Organosilane Reductions”, Organic Reactions, Vol. 71, 2008, 1. a. De Meijre, A.; Diederich, F. Eds. Metal-Catalyzed Cross-Coupling Reactions; Wiley-VCH: Weinheim, 2004. b. Bringmann, G.; Walter, R.; + HO BIBSO Denmark, S. E. Ed. Wiley and Sons, Hoboken, NJ. Weirich, R. Angew. Chem. Int. Ed. 1990, 29, 977. c. Negishi, E. “Handbook of Organopalladium Chemistry for Organic Synthesis” Wiley- CH2Cl2, rt, 12 h OH O OH O 2. Larson, G. L. “Silicon-Based Reducing Agents” Version 2.0, Gelest, Inc. 2008. Interscience: New York, 2002. 94% 3. Chandrasekhar, S.; Reddy, Ch. R.; Ahmed, M. Synlett. 2000, 1655. 2. a. Hiyama, T. in “Metal-Catalyzed Cross-Coupling Reactions” Diederich, F.; Stang, P. J. Eds. Wiley-VCH: Weinheim, 1998; chapter 10. b. Den- 4. Bower, S.; Kreutzer, K. A.; Buchwald, S. L. Angew. Chem. Int. Ed. 1996, 35, 1515. 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, SID3226.0 reference 4 5. Elsworth, B. A. et al. Tetrahedron: Asymmetry 2003, 14, 3243. S. E. “Cross-Coupling with Organosilicon Compounds” Organic Reactions 2011, Vol. 75, pp d. Denmark, S. E. in “Silicon Compounds: Silanes References: 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. and Silicones” Arkles, B. and Larson, G. L. Eds. Gelest, Inc. 2013, pp 63-70. 1. Wuts, P. G. M.; Greene, T. W. “Greene’s Protective Groups in Organic Syntheses” Wiley and Sons, 2007. Med. Chem. 2010, 18, 2178. 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. 2. Larson, G. L. “Silicon-Based Blocking Agents” Gelest, Inc. 2014. 7. Nagashima, H. et al. J. Am. Chem. Soc. 2009, 131, 15032. 2009, 131, 3104. c. Denmark, S. E.; Smith, R. C.; Tymonko, S. A. Tetrahedron 2007, 63, 5730. 3. Larson, G. L.; Hernández, A. J. Org. Chem. 1973, 38, 3935. 8. Nadkarni, D.; Hallissey, J. F. Org. Proc. Res. Dev. 2008, 12, 1142. 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. Org. Lett. 2011 13 III Org. Lett. 2014, 16, 2070. 4. Liang, H.; Hu, L.; Corey, E. J. , , 4120. 1093_Vasanti brochure_Layout 1 10/24/14 9:53 PM Page 2

Organosilane Reducing Agents Organosilane Cross-Coupling Reagents Organosilane Protecting Groups Organosilane reductions are very commonplace in synthetic organic chemistry with the Si-H bond, Cross-coupling reactions are usually associated with the metals of boron (Suzuki-Miyaura), zinc It is very common that in a multi-step synthetic sequence the protection of one or more functional groups being weakly polarized such that the hydrogen is hydridic in nature. Because the Si-H bond is only (Negishi), tin (Stille), and copper (Sonogashira) along with magnesium (Kumada). 1 As a viable will be required. The most common groups that fall into this class are alcohols, amines, weakly hydridic, the silanes have the potential to be highly selective reducing agents, reducing a alternative to these metals the Hiyama-Denmark cross-coupling reactions involve organosilicon thiols, acids, and carbonyls, in particular ketones and aldehydes. For the protection of functional groups number of functionalities with excellent tolerance for other reducible functionalities. Organosilanes reagents as the nucleophilic partner in C-C bond forming cross-coupling protocols. The organosilanes with active hydrogens, such as alcohols and amines, organosilanes have proven to be among the best have further advantages in terms of low toxicity, ease of handling, and ease of final product purifi- 1 have several advantages, including being readily prepared by a variety of approaches, excellent and most favored alternatives. The reasons for this are that the silyl groups can be both introduced and cation. In addition, a number of enantioselective organosilane reductions have been reported. Ionic removed in high-yield, facile processes. In addition, the organosilanes have the ability to be modified both and organometalic-catalyzed organosilane reductions have been extensively reviewed.1,2 storage stability, ease of removal or recycling of the organosilane by-products, good functional group toleration, and low to non-toxicity profiles. The organosilane cross-coupling chemistry has been sterically and electronically, thus giving them excellent selectivity and versatility in their reactivity, stabil- The extensive electronic and steric diversity of organosilanes offers a large range of selectivities in thoroughly reviewed.2 The use of sodium and potassium silanolates as the nucleophilic partner in the ity, and ease of deprotection. Indeed, in many of the more complicated and lengthy synthetic sequences reactivity. For example, the homopolymeric methylhydrogensiloxane, HMS-992, and related silicon-based cross-coupling transformations has been shown to be of practical utility.3 it is common to have a requirement to remove one organosilyl-protected group in the presence of other homopolymers represent a high molecular weight silane reducing agent that can offer significant similar groups. A thorough presentation on the selective deprotection of one organosilyl-protected group product isolation advantages.3 Diphenylsilane, SID4559.0, has been shown to selectively reduce in the present of another has been compiled.2 Gelest offers an extensive range of organosilanes designed Si(OMe) 4 Si(OMe)3 amides to aldehydes. Triisopropylsilane, SIT8385.0, has been shown to offer a steric advantage Si(OMe) H2N Si(OMe)3 Si(OMe)3 for the protection of various functional groups including alcohols, diols, amines, thiols, carboxylic acids 5 and terminal alkynes. Of particular note is the use of the trimethylsilylenol ether of acetone, SII6264.0, leading to a higher degree of the β-aryl glucoside from the hemiketal precursor. H N O 2 MeO for the protection of diols as their acetonides in a very fast and high-yield reaction.3 Gelest is proud to Tetramethyldisiloxane, TMDS, SIT7546.0, has recently been shown to be highly useful in the SIP6822.0 SIA0599.1 SIA0599.0 SIM6492.55 SIT8177.0 offer the E. J. Corey BIBS reagent for the protection of alcohols, amines, and carboxylic acids and the reduction of hemiketals to the corresponding ether. This has been applied to successful syntheses formation of highly stable enol silyl ethers.4 of the pharmaceutically important gliflozin family of diabetes 2 Specific Glucose Transport 2 (SGLT2) F H3C Si(OEt) inhibitor drugs, such as canagliflozin, (Invokana) and dapagliflozin (Farxiga) among F Si(OEt)3 3 H3C Si O CH3 H3C 6 7 Si(OEt)3 SiMe2ONa CH CH3 N others. TMDS has also been shown to very effectively reduce nitroaryls to anilines and is an 3 H C Si N H3C N CH3 H3C Si OTf H C Si N(CH ) 3 F F SiMe ONa H3C Si CI 3 3 2 H3C Si CH3 improvement over triethylsilane in the reduction of a ketone to a methylene in the production of S SiMe2ONa O 2 H C F N CH3 CH 3 a key intermediate in the preparation of ziprasidone.8 CH3 3 CH3 SIP6716.7 SIN6596.8 SIP6934.0 SIS6986.1 SIS6987.0 SIS6980.6 SIT8510.0 SIT8620.0 SID3605.0 SIT8590.0 SIB1846.0 H3C H CH3 CH3CH2 CH3 H3C C H H H3C CH CH CH CH Si H HC Si H Si H3C Si O CH3 3 2 CH CH CH3 3 2 Si H Si H Si Si 3 2 H C O O H3C N CH3 Si Cl CH3CH2 Si Cl Si Cl CH3CH2 CH3 3 CH H H Si CH3CH2 Si OTf H3C CH3 O O F C Si CH SiMe3 3 3 CH CH3CH2 CH SiMe Si H SiMe 3 CH3CH2 3 SIT8330.0 SIP6729.0 SIP6750.0 SID4559.0 Si(OMe)3 3 3 CH3 SIT8385.0 SII6462.0 SIV9220.0 SIP6905.0 SIT7900.0 SIT8606.5 SIE4904.0 SIB1876.0 SIT8250.0 SIT8335.0 SIP6828.0 (CH3)3Si CH OTf CH3CH2O Cl CH3 CH3 CH3 Ph 3 CH3 CH3 H C (CH3)3Si Si H 3 CH t-Bu Si OTf CH3CH2O Si H Cl Si H t-Bu Si Cl Si Si 3 t-Bu C Si Cl t-Bu Si OTf CH3CH2 Si H H C N CH Si H Me3SiO 3 3 Ph CH t-Bu CH3CH2O (CH ) Si Cl CH3 H 3 CH3 CH 3 3 SiMe Me3SiO Me3Si CN HO 3 3 Me3Si-O-K O H SiMe3 SIB1935.0 SIH6110.0 SIB1968.0 SIB1967.0 SID3345.0 SIE4894.0 SIT8185.0 SIT8724.0 SIT8155.0 SIT8623.0 SIP6903.0 SIP6901.0 SIT8579.0 SIT8604.0

H SIT8665.0 H C Si(CH ) t-Bu 3 i OS CH 3 3 Si Cl Si OTf 3 O Br t-Bu Si Cl Si Si CH3 CH3 O Si H O O Si Cl O H H (t-Bu3P)2Pd (2.5 mol%) CH Cl Cl H Si O Si H Si O (CH3)3Si O Si H CH CH SiMe2ONa + OTBS 3 3 2 Si CH3 toluene, 90° H C O Si O SID3255.0 SIT8384.0 SIT8387.0 SIT7273.0 CH3 CH3 3 CH3 H Si H H TBSO H 99% Si(CH3)3 CH3CH2 SIT7546.0 SIT7530.0 SIT8721.0 SID3415.0 SIP6742.0 SIT8645.0

t-Bu O OH O OH References: References: t-Bu Si OTf OH Et3N ( 2 eq.) OBIBS 1. Larson, G. L.; Fry, J. L. “Ionic and Organometallic-Catalyzed Organosilane Reductions”, Organic Reactions, Vol. 71, 2008, 1. a. De Meijre, A.; Diederich, F. Eds. Metal-Catalyzed Cross-Coupling Reactions; Wiley-VCH: Weinheim, 2004. b. Bringmann, G.; Walter, R.; + HO BIBSO Denmark, S. E. Ed. Wiley and Sons, Hoboken, NJ. Weirich, R. Angew. Chem. Int. Ed. 1990, 29, 977. c. Negishi, E. “Handbook of Organopalladium Chemistry for Organic Synthesis” Wiley- CH2Cl2, rt, 12 h OH O OH O 2. Larson, G. L. “Silicon-Based Reducing Agents” Version 2.0, Gelest, Inc. 2008. Interscience: New York, 2002. 94% 3. Chandrasekhar, S.; Reddy, Ch. R.; Ahmed, M. Synlett. 2000, 1655. 2. a. Hiyama, T. in “Metal-Catalyzed Cross-Coupling Reactions” Diederich, F.; Stang, P. J. Eds. Wiley-VCH: Weinheim, 1998; chapter 10. b. Den- 4. Bower, S.; Kreutzer, K. A.; Buchwald, S. L. Angew. Chem. Int. Ed. 1996, 35, 1515. 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, SID3226.0 reference 4 5. Elsworth, B. A. et al. Tetrahedron: Asymmetry 2003, 14, 3243. S. E. “Cross-Coupling with Organosilicon Compounds” Organic Reactions 2011, Vol. 75, pp d. Denmark, S. E. in “Silicon Compounds: Silanes References: 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. and Silicones” Arkles, B. and Larson, G. L. Eds. Gelest, Inc. 2013, pp 63-70. 1. Wuts, P. G. M.; Greene, T. W. “Greene’s Protective Groups in Organic Syntheses” Wiley and Sons, 2007. Med. Chem. 2010, 18, 2178. 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. 2. Larson, G. L. “Silicon-Based Blocking Agents” Gelest, Inc. 2014. 7. Nagashima, H. et al. J. Am. Chem. Soc. 2009, 131, 15032. 2009, 131, 3104. c. Denmark, S. E.; Smith, R. C.; Tymonko, S. A. Tetrahedron 2007, 63, 5730. 3. Larson, G. L.; Hernández, A. J. Org. Chem. 1973, 38, 3935. 8. Nadkarni, D.; Hallissey, J. F. Org. Proc. Res. Dev. 2008, 12, 1142. 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. Org. Lett. 2011 13 III Org. Lett. 2014, 16, 2070. 4. Liang, H.; Hu, L.; Corey, E. J. , , 4120. 1093_Vasanti brochure_Layout 1 10/24/14 9:53 PM Page 1

Other Gelest Synthetic Reagents Gelest offers a number of other organosilane reagents that are of high use in the organic synthetic area. These include, among others, trimethyliodosilane, trimethylbromosilane, trimethylsilyl triflate, cyanotrimethylsilane, a number of silyl enol ethers and silyl ketene acetals, in addition to an extensive variety of organosilanes that are attached to inorganic surfaces for the purpose of final Enabling Synthetic purification of desired products. Gelest also offers several non-silicon-based synthetic reagents that complement and, oftentimes, assist in the reactions of the silicon-based reagents. These Enabling Synthetic Organic Transformations

Enabling Synthetic Organic Transformations Organic 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- Transformations organic reagents for various synthetic transformations.

CH3 CH3 CH3 CH3 CH3 Organosilicon Based H3C Si OTf H3C Si CN H3C Si N3 H3C Si I H3C Si Br CH3 CH3 H3C CH3 CH3 and

SIT8564.0 SIT8430.0 SIT8620.0 SIT8585.0 SIT8580.0 Metal-Organic Synthetic Reagents OSi(CH3)3 H3C OSi(CH3)3 (H3C)3SiO OSi(CH3)3 H3C Gelest, Inc. O OSi(CH3)3 Silicon-Based OCH3 The core manufacturing technology of Gelest is silanes, silicones and metal- Blocking Agents SIC2462.0 SIT8171.2 SIT8571.0 SIT8571.3 SIM6496.0 organics with the capability to handle flammable, corrosive and air sensi- Silicon-Based Ph Cross-Coupling Reagents CH3 CH tive liquids, gases and solids. Headquartered in Morrisville, PA, Gelest is Si 3 Si(CH ) Enabling Your Technology H3C Si CH2Cl 3 3 Cl Si(CH3)3 H3C Si OLI N N recognized worldwide as an innovator, manufacturer and supplier of commer- Me CH3 CH (H3C)3Si Li 3 SIA0433.0 SIC2305.0 cial and research quantities serving advanced technology markets through a SIA0555.0 SIL6469.7 SIL6467.0 Br Cl

Br O OMe N materials science driven approach. The company provides focused technical NEt2 MeO Br O Br O Si(OMe)3 Br Si(OEt)3 CH3CH2 Zn CH2CH3 O O H2N Br O NEt2 3 O Si(OEt) O N 2 NEt OMe H development and application support for: semiconductors, optical materials, Si(OMe)3 I OTf O Si(CH ) NEt2 3 3 O OMZN017 Pd Si Si(OEt)3 Me OH Si(OEt)3 3 Al CF3 CF

3 N H11 Si(OEt)

5 pharmaceutical synthesis, diagnostics and separation science, and specialty n-C (H C) Si K F (CH3)2CHCH2 CH2CH(CH3)3 N 3 3 OMe

Me SiMe3

Me Version 2.0 Reagents For: F SIP6890.0 F OMAL021.2 polymeric materials. -Functional Group Protection -Synthetic Transformation

-Derivatization

F F

F F

F F Oi-Pr B

Cl Offering Selective i-PrO Ti Cl Zn

Al

F F

CH CH Cl Oi-Pr F and 3 2 F

OMZN040

F OMAL033.2 AKT851 F Versatile Reagents for:

OMBO087 For additional information on Gelest’s Silicon and Metal-Organic

PPh2 based products or to inquire how we may assist in Enabling Your • Reductions Fe Oi-Pr OCH3 Technology, please contact: PPh2 B B • Functional Group Protection i-PrO Oi-Pr H3CO OCH3 H3CO Mg OCH3 OMFE022 AKB156.5 AKB157 AKM503 11 East Steel Rd. • Synthetic Organic Transformations Morrisville, PA 19067 Cl CH • Cross-Coupling C-C Bond Formation n-Bu 3 n Sn( Bu)3 Phone: 215-547-1015 Cl Sn Cl n-Bu Sn H H3C Sn CH3 Sn Fax: 215-547-2484 Cl n-Bu CH3 OCH2CH3 www.gelest.com [email protected] SNT7930 SNT8130 SNT7560 SNE4620 SNT7906 © 2014 Gelest, Inc.