AA + B A + B B Si A Silicon-Tethered Reactions B Si Duke M. Fitch Evans' Group Seminar March 15, 1996 Review: Bols, M.; Skrydstrup, T. Chem. Rev. 1995, 95, 1253-1277. I. Cycloadditions A. 5-Atom Tether Ring 1. [4 + 2] 2. [2 + 2] 3. [5 + 2] B. 6-Atom Tether Ring C. 7-Atom Tether Ring 1. Type I and II Diels-Alder D. 8-Atom and Larger Tether Rings 1. Type II Diels-Alder II. Radical Reactions A. 5-Exo- and 6-Endo- Ring Formations 1. Trig-Cyclizations 2. Dig-Cyclizations B. 6-Exo- and 7-Endo- Ring Formations C. Others III. Silicon Addition to Double Bonds A. Addition to C=C Bonds 1. Hydrosilylation 2. Bis-silylation B. Addition to C=O Bonds IV. Nucleophile Delivery 33A-01 3/14/96 11:15 PM OH SiR 2 Cl O Si R R Si O R R Si O R R OH SiR 2 Cl O Si R R ? Increased Reactivity ? High Regioselectivity ? Increased Stereoselectivity ? Functional Group Protection ? Facile Refunctionalization H O Si Why use a silicon tether? - Intramolecularity offers reduced entropic factors - Higher yields - Certain reactions that could not be carried out intermolecularly are possible - Function of tether length - Certain cases offer route to opposite regioisomer obtained from intermolecular variant - Function of tether length and steric bulk of alkyl substituents on silicon - Serves as protecting group before and after reaction - Protodesilylation, Tamao oxidation, allylsilane additions, and transmetallations are possible Et 3 N H O Si 160 - 170 °C + R = Me 2 : 1 R = Ph R = t-Bu 1 : 4 Note: Bulkier substituent favors exo-cyclization Et 3 N 190 °C + R = Me 4 : 1 R = Ph R = t-Bu >20 : 1 R R R 10 : 1 Sieburth, S. M.; Fensterbank, L. J. Org. Chem. 1992, 57, 5279. 1 : 1 R Diels-Alder To Form 5-Atom Tether Ring: 33A-02 3/14/96 11:14 PM O H H Si R R H H O Si R R Si O R R OH OH OH OH SiMe 3 O SiMe 2 exo SiMe 2 O endo Transition States: Me Me OH vs. Further Transformations: TBAF TBAF or KF then H 2 O 2 MeLi R = Me or Ph, 71-85% over 2 steps Occurs with retention of configuration O SiMe 2Ph R = Me, 75% over 2 steps Ph OH Tamao oxidation: Organometallics 1983, 2, 1694. R = Me, 75% over 2 steps Occurs with retention of configuration 60:40 mixture of isomers 160 °C 80% TBAF-DMF, 75 °C 65% O SiMe 2 Stereoselectivity and Regioselectivity: OH 1. 160 °C 75% 2. TBAF-DMF 85% 1. 180 °C 80% 2. TBAF-DMF 85% Ph Stork, G.; Chan, T. Y.; Breault, G. A. J. Am. Chem. Soc. 1992, 114, 7578. Ph 1 isomer 33A-03 3/14/96 5:30 PM O SiMe 2 CO 2 Et SiMe 2 O CO 2 Et SiMe 2 O CO 2 Et O SiMe 2 CO 2 Et OH CO 2 Et OH OH CO 2 Et OH CO 2 Et OH CO 2 Et OH 80 °C 90% O O O SiPh 2 O O H Si Ph Ph O SiPh 2 O H H O OH OH H Stork Delivers More: TBAF-DMF then H 2 O 2 80% TBAF-DMF then H 2 O 2 TBAF-DMF 60 °C 75% O SiMe 2 Note: Selectivity in each case results from endo-addition with respect to the ester, even when the product contains four contigous cis stereocenters. This highly strained compound is epimerized by fluoride ion in the course of desilylation. 190 °C retro-Diels-Alder Bu TBAF-DMF 60 °C ? SiMe 2 O hetero-Diels-Alder 1 isomer Bu KF, H 2 O 2 75%, 2 steps Other Interesting Examples from Sieburth: SiMe 2 O 190 °C 1:1 mixture of diastereomers Bu DDQ 46%, 2 steps 33A-04 3/14/96 11:31 PM H H SiMe 2 (NMe 2 ) HO Ph Si O Ph Ph OMe 2 Si Ph OH OH O CO 2 Me R O Si Ph Ph O O Si CO 2 Me H R Ph Ph O O Si CO 2 Me H R Ph Ph + H-SiMe 2 (NEt 2 ) OO BzO OH 1 mol% Ni(acac) 2 2 mol% DIBAl-H benzene, 50 °C 52% Z:E = 94:6 + Et 2 O, r.t. 10 h OO BzO O 1 isomer KF, H 2 O 2 75%, 3 steps Silicon Connected to Diene: xylene SiMe 2 Tamao, K; Kobayashi, K; Ito, Y. J. Am. Chem.Soc. 1989, 111, 6478. ClMe 2 Si Photochemical [2+2]: Crimmins, M. T.; Guise, L. E. Tet. Lett. 1994, 35, 1657. O O SiMe 2 O + hν, >350 nm 70-80% BzO R = n-C 5 H 11 R = Me R = Ph H 90 : 10 85 : 15 >95 : 5 O OH O170 °C Note: Similar results were obtained with a four atom tether. Also, for the subsequent Tamao oxidation, protection of the ketone was necessary to prevent Baeyer-Villiger oxidation. BzO 1 isomer Formal [5+2]: KF m-CPBA OH Et 3 N 78%, 3 steps Rumbo, A.; Castedo, L.; Mourino, A.; Mascarenas, J. L. J. Org. Chem. 1993, 58, 5585. Note: Intermolecular variant failed to react. 33A-05 3/14/96 5:33 PM O Si R R Si O R R TMS OH OH OH O Si O R t-Bu t-Bu CO 2 Et OR O Si EtO 2 C O O Si EtO 2 C R t-Bu t-Bu O Si O R CO 2 Et t-Bu t-Bu O Si O R CO 2 Et t-Bu t-Bu exception: TMS 72%, 2 steps 75%, 2 steps Shea, K. J.; Zandi, K. S.; Staab, A. J.; Carr. R. Tetrahedron Lett. 1990, 31, 5885. O Si Me Me Si O Me Me OH O Si O CO 2 Me 190 °C R = Me or Ph cis:trans = 1:1 Ph Ph MeLi R = Me KF, H 2 O 2 R = Ph Note: In general, yields are good and regioselectivity is absolute, but stereoselectivity is poor. O Si O Diels-Alder To Form 6-Atom Tether Ring: ? ? Ph Ph CO 2 Me H vs. xylene 160 °C >90% R = Me or H R = H R = Me 90 10 >99 <1 O Si O : : Gillard, J. W.; Fortin, R.; Grimm, E. L.; Maillard, M.; Tjepkema, M.; Bernstein, M. A.; Glasser, R. Tetrahedron Lett. 1991, 32, 1145. Ph Ph Toluene 190 °C MeLi O Si O ratio not determined 25%, 2 steps Note: With monosilyl ether tether, reaction is slow and poor yielding in comparison to shorter tether versions. Ph Ph CO 2 Me H 1 isomer However: Diels-Alder To Form 7-Atom Tether Ring: 175 °C 98% 175 °C 77% 1 isomer CO 2 Me Note: Intermolecular variant gives 1:1 ratio with opposite regiochemistry. Note: Yields are generally high and selectivities good for 5-member silyl acetal tethers. In the case of type II Diels-Alders, regioselectivity and stereoselectivity are absolute. 33A-06 3/14/96 11:22 PM O O Si Me Ph Ph CO 2 Me R O SiO H H R CO 2 Me Me Ph Ph O O Si Me Ph Ph CO 2 Me Me O SiO H H Me CO 2 Me Me Ph Ph Me Me O SiO H H Me CO 2 Me Me Ph Ph Me Si O R 2 R 1 O Me Me Si O O R 1 R 2 Me Me O Si O O O Ph Ph O Si O O O Ph Ph Me CO 2 Me H CO 2 Me O Si O O O Ph Ph 160 - 170 °C R = H 64% R = Me 100% 1 isomer Silyl Acetal 7-Atom Tether Ring: H O Si O O O 170 °C 94% Craig, D.; Reader, J. C. Tetrahedron Lett. 1992, 33, 6165. Craig, D.; Reader, J. C. Tetrahedron Lett. 1990, 31, 6585. Craig, D.; Reader, J. C. Tetrahedron Lett. 1992, 33, 4073. 1:1 mixture of diastereomers Note: Intermolecular variant gives a mixture of 4 diastereomers. 1 : 1 Ph Ph 1 isomer 115 - 200 °C Me + R 1 R 2 Yield H O Si O H Me H H Me CN H H Me Ph Me Pr Longer Tethers: 98% 88% 78% 93% 65% 53% Ph Ph 1 isomer 80 °C 90% Me Shea, K. J.; Staab, A. J.; Zandi, K. S. Tetrahedron Lett. 1991, 32, 2715. O O Type II Diels-Alder To Form 8-Atom Tether Ring: however: + 70 : 30 33A-07 3/14/96 11:27 PM Ph OH Ph O Si Br Me Me Si O Ph Me Me Ph OAc OH Ph OH OH R O Si MeMe Br R Me OH OH R Me OH OH R OH OH Transition States: O R Si Me Me R 1 R 2 1) Ac 2 O, KF 2) H 2 O 2 O Si Me R Me R 1 R 2 BrCH 2 SiMe 2 Cl Me Ph O Si Br Me Me Me O KF, H 2 O 2 Si Br Me Me Note: The rate of 5-exo trig-cyclization is markedly slower when the radical is α to silicon. Thus, 6-endo becomes a competing pathway. In the case of phenyl substitution, the stabilized benzylic radical formed from 5-exo cyclization precludes the formation of the 6-endo product. 1) n-Bu 3 SnH, AIBN 2) KF, H 2 O 2 80%, 3 steps 85%, 3 steps + Ph n-Bu 3 SnH AIBN + R = Me R = i-Pr R = t-Bu R = vinyl R = Ph Me Ph 66% 74% 66% 52% 48% 14% - - 9% 4% OH OH 15% 16% 26% 24% 36% Nishiyama, H.; Kitajima, T.; Matsumoto, K.; Itoh, K. J. Org. Chem. 1984, 49, 2298. Me Ph Radical Cyclizations to Form 1,3-Diols: . OH OH . vs. A 1,3 strain Me Ph Other Examples: 1) n-Bu 3 SnH, AIBN 2) KF, H 2 O 2 85%, 2 steps OH OH 1) n-Bu 3 SnH, AIBN 2) KF, H 2 O 2 94%, 2 steps 1 isomer + 5 : 1 33A-08 3/14/96 11:36 PM O O SiSi BrMe Me Me Me HO OH O O SiSi BrMe Me Me Me HO OH Me Ot-Bu H Me Ot-Bu Me Ot-Bu H HO Me Me Ot-Bu H Me Me Me Me Me O Si Br Me Me Me Me Me Me Me HO Me H Me O Si Br Me Me Me HO Me H 1) n-Bu 3 SnH, AIBN 2) KF, H 2 O 2 65%, 2 steps O SiBr Me Me OH OH H HO HO H H O SiBr Me Me H OH H HO H O SiBr Me Me H OTMS H O SiBr Me Me H OH O O HO H O SiBr Me Me O H O O H O 1) n-Bu 3 SnH, AIBN 2) KOt-Bu, DMSO 75%, 2 steps Cyclic Allylic Alcohols: Si Me Me H O Si Me Me n-Bu 3 SnH AIBN KF, H 2 O 2 75%, 2 steps n-Bu 3 SnH AIBN KF, H 2 O 2 88%, 2 steps KOt-Bu, DMSO 60%, 2 steps 1) n-Bu 3 SnH, AIBN 2) KOt-Bu, DMSO 80%, 2 steps H Note: In all cases a single isomer is obtained, resulting exclusively from 5-exo cyclization. This methodology has been employed in the synthesis of branched sugars. O Si CH 3 CH 3 Stork, G.; Sofia, M. J. J. Am. Chem. Soc. 1986, 108, 6826. 1) n-Bu 3 SnH, AIBN 2) KF, H 2 O 2 91%, 2 steps 3.7 : 1 + n-Bu 3 SnH AIBN (100%) 1) n-Bu 3 SnH, AIBN (100%) 2) KF, H 2 O 2 (45%) H H H O Si CH 3 H 3 C n-Bu 3 SnH, AIBN "Poor Yield" 3 : 2 + Stork, G.; Mah, R. Tetrahedron Lett., 1989, 30, 3609. ? . Introduction of Angular Functionality: . ? Lejeune, J.; Lallemand, J. Y. Tetrahedron Lett. 1992, 33, 2977. 33A-09 3/14/96 5:42 PM Me Me O Me Si Br Me Me Me Si O Me Me Me Me Me OH Me Me Me OH Me Me TMS Me OH Me Me O Me OH Me Me Br Me Me O Me Si Br Me Me Me Si O Me Me Me Me n-C 6 H 13 n-C6H13 Me OH Me Me O n-C 6 H 13 Me OH Me Me n-C 6 H 13 O SiR Me Me H H H O Si Me Me H H H R n-Bu 3 SnH AIBN MeLi 52%, 2 steps KF, H 2 O 2 KOt-Bu, DMSO/H 2 O 62%, 2steps 30%, 2 steps 62%, 2 steps NBS, DMF Selective Hydrovinylation/Hydroacylation: KOt-Bu DMSO/H 2 O 33%, 2 steps KF, H 2 O 2 50%, 2 steps n-Bu 3 SnH AIBN Tamao, K.; Maeda, K.; Yamaguchi, T.; Ito, Y. J. Am. Chem. Soc. 1989, 111, 4984. . E:Z = 1:9 E Only . 1 isomer Dig-Cyclizations: O Me Me Si Br MeMe Si O Me Me Me Me HO Me Me HO O Me Si Br MeMe Si O Me Me Me HO Me HO O Me Me Si Br MeMe Si O Me Me Me Me HO Me Me TMS OTHP OTHP OTHP C 4 H 9 C 4 H 9 C 4 H 9 O Ph Me Me Si Br MeMe HO HO Ph O TMS Me Me E:Z = 95:5 Ph 3 SnH AIBN Ph 3 SnH AIBN Si Br MeMe Ph 3 SnH AIBN MeLi 60%, 2 steps KF, H 2 O 2 65%, 2 steps E Only KF, H 2 O 2 70%, 2 steps 1) Ph 3 SnH, AIBN 2) KF, H 2 O 2 85%, 2 steps HO HO TMS E:Z = 25:75 E Only 1) Ph 3 SnH, AIBN 2) KF, H 2 O 2 84%, 2 steps E:Z = 35:65 Journet, M.; Malacria, M. J. Org. Chem. 1992, 57, 3085. 33A-10 3/11/96 6:00 PM Me O C 5 H 11 Si Br Me Me CN Me O C 5 H 11 Si Me Me Me O Si C 5 H 11 Me Me O Si Me Me Me C 5 H 11 CN O Si Me Me Me C 5 H 11 CN O Si Me C 5 H 11 CN Me Me O Si Me C 5 H 11 CN Me Me HO Me C 5 H 11 CN HO O Si C 5 H 11 H Me Me H Me O Si C 5 H 11 H Me Me H Me H H O Si C 5 H 11 H Me Me Me O Si C 5 H 11 H Me Me Me O BnO BnO BnO O SiMe Me Ph SePh O BnO BnO BnO O Si Me Me Ph O BnO BnO BnO HO Ph O BnO BnO BnO SePh O BnO BnO BnO O Si Ph Me Me Si O Me Me Ph O BnO BnO BnO OH Ph O BnO BnO BnO O SiMe Me R S N O O O BnO BnO BnO HO . . . . Ph 3 SnH, AIBN R . 1 isomer Journet, M.; Malacria, M. J. Org. Chem. 1992, 57, 3085. E:Z >50:1 76% R = Ph 78% R = TMS 1) SmI 2 2) TBAF O BnO BnO BnO KF, H 2 O 2 51%, 2 steps Authors' Explanation: .. O Si Ph Tandem Cyclizations: Syn-Pentane A 1,3 Me Me . Campos' Explanation: O BnO BnO BnO E:Z = 10:1 Synthesis of C-Glycosides: TBAF 83%, 2 steps n-Bu 3 SnH, AIBN OH Note: Similar yields were obtained with the furanose series, however, E/Z selectivity was slightly lower. R n-Bu 3 SnH, AIBN SO O N . E:Z = 10:1 TBAF 69%, 2 steps 1) SmI 2 2) TBAF E:Z = 10:1 64% R = Ph 61% R = TMS Stork, G.; Suh, H. S.; Kim, G. J. Am. Chem. Soc. 1991, 113, 7054. Mazeas, D.; Skrydstrup, T.; Doumeix, O.; Beau, J. M. Angew. Chem., Int. Ed. Engl. 1994, 33, 1383. 33A-11 3/14/96 11:39 PM O Si Br Me Me Si O Me Me OH OH O Si Br Me Me Si O Me Me OHOH Me OMe Me O Me Si Br Me Me R OH OH Me Me OMe Me O Me Si Br Me Me R OH OH Me Si O R R 2 R 1 Me Me Si O R Me Me Si O R H H Me Me R 2 R 1 O O O Me Me TBSO AcHN O O CbzHN BOMO O Si O Me Me O HO OH N NBOC O O SePh O O O Me Me TBSO AcHN O O CbzHN BOMO OH O HO OH N NBOC O O HO H O O O Me Me N H O OTBS O CbzHN BOMO O Si Me O Me O HH N NBOC O O 6-Exo vs. 7-Endo n-Bu 3 SnH AIBN H 2 O 2 77%, 2 steps n-Bu 3 SnH AIBN Me O H 2 O 2 80%, 2 steps OOH 1) n-Bu 3 SnH, AIBN 2) H 2 O 2 83%, 2 steps 1) n-Bu 3 SnH, AIBN 2) H 2 O 2 83%, 2 steps H Note: Substituted olefins give exclusively 6-exo products with complete selectivity for the syn-isomer. Terminal olefins give exclusively 7-endo products. ? vs. Koreeda, M.; Hamann, L. G. J. Am. Chem. Soc. 1990, 112, 8175. . . . Application of 7-Endo Cyclization: 1) n-Bu 3 SnH, Et 3 B 2) KF H H 7.5:1 60% isolated yield of desired diastereomer, 2 steps H Proposed Transition State: (+)-Tunicamycin-V Note: Attempts at cyclization with the highlighted hydroxyl protected as the TBS ether afforded only the undesired isomer at C5'. Also, cyclization of the free hydroxyl substrate in methanol led to an erosion in selectivity (1.6:1). 5' Myers, A. G.; Gin, D. Y.; Rogers, D. H. J. Am. Chem. Soc. 1994, 116, 4697. . 33A-12 3/14/96 5:50 PM Si Br O Me Me CO 2 Et Si O Me Me CO 2 Et H H OSiMe 2 Ph CO 2 Et H OSiMe 2 Ph CO 2 Et Br Si O Me Me Me Me Me Me Me Me HO Me Me Me Me HO Me Me Me Me HO Me Me Me Me HO Me Me Me H Me Me Me OSiMe 2 PhMe Me OSiMe 2 Ph H Me Me Intramolecular Hydrosilylation: Ph O Si H MeMe O Si Ph Me Me Me Ph OH OH R O Si H MeMe Me Me R OH OH n-Pent O Si H MeMe 1) n-Bu 3 SnH, AIBN 2) TBAF 65%, 2 steps n-Bu n-Pent n-Pent OH OH cis:trans = 1:1.1 Curran, D. P.; Kim, D.; Liu, H. T.; Shen, W. J. Am. Chem. Soc. 1988, 110, 5900. n-Bu 3 SnH AIBN 61% . . + + 1 O 3.5 Si H MeMe . : : 4.8 Tandem Cyclizations: Me OH OH ? Schwartz, C. E.; Curran, D. P. J. Am. Chem. Soc. 1990, 112, 9272. H 2 PtCl 6 ?6H 2 O Me Me 1 . Syn-Pentane O 5.7:1 Si H MeMe 1) H 2 PtCl 6 ?6H 2 O 2) H 2 O 2 63-95% 5.3:1 (72% from alcohol) 3.5:1 (33% from alcohol) 3.3:1 (53% from alcohol) R = n-Pent R = i-Pr R = Ph 1) H 2 PtCl 6 ?6H 2 O 2) H 2 O 2 1) H 2 PtCl 6 ?6H 2 O 2) H 2 O 2 67% OH OH 1) H 2 PtCl 6 ?6H 2 O 2) H 2 O 2 40% 1.6:1 6.1:1 Me Me H 2 O 2 71% from alcohol E or Z Me Me Intramolecular 1,5-Hydrogen Transfer: A 1,3 Strain: Me 1:1 Tamao, K.; Nakajima, T.; Sumiya, R.; Arai, H.; Higuchi, N.; Ito, Y. J. Am. Chem. Soc. 1986, 108, 6090. 33A-13 3/14/96 5:52 PM O OBn Me Si H Me Me Me Si O OBn Me Me Me Me Si O Me Me Me Me O N Me OMe N O Me OMeOH OSi HO Me Me Me Me N O Me OMeOMe OSi TrO Me Me Me Me N O Me OMeOMe TrO Me Me OH O Si Me Me O Me H Me H R A 1,2 Strain: R O Me Si H Me Me R OHOH Me Me R O H Si Me Me H OH Me O Si Me Me Me OHHO Me Pt cat. 98% 4:1 OTBSSi O Me Me 1) H 2 , Pd/C (100%) 2) Swern 3) Horner-Emmons (70%, 2 steps) cat. OsO 4 NMO 80% 94:6 1) Tr?pyr + BF 4 - 2) MeI, NaH 88%, 2 steps C27-C33 Segment of Rapamycin Me Me TBAF 88% Proposed "hypervalent" siloxane complex: Me OTBSOH Me δ - Application of A 1,3 Strain Methodology: Hale, M. R.; Hoveyda, A. H. J. Org. Chem. 1992, 57, 1643. 1) H 2 PtCl 6 ?6H 2 O 2) H 2 O 2 HO R = n-Bu R = i-Pr R = t-Bu R = Ph 2.4:1 (73% from alcohol) 24:1 (66% from alcohol) >100:1 (52% from alcohol) 6.7:1 (55% from alcohol) anti M minimizes A 1,2 strain 1) (HMe 2 Si) 2 NH 2) H 2 PtCl 6 ?6H 2 O 78% OH 13:1 Enantioselective variant: Me O Si Me 1) TBSCl 2) (HMe 2 Si) 2 NH 3) H 2 PtCl 6 ?6H 2 O 62% 10:1 KF H 2 O 2 91% KF H 2 O 2 74% Tamao, K.; Nakajima, T.; Sumiya, R.; Arai, H.; Higuchi, N.; Ito, Y. J. Am. Chem. Soc. 1986, 108, 6090. OHHO Me 93% e.e. syn:anti >99:1 Application to Polypropionate Synthesis: 1) (Me 2 Ph) 2 SiHCl, NH 3 2) [RhCl(CH 2 =CH 2 ) 2 ] 2 (R,R)-DIOP KF, H 2 O 2 66%, 3 steps Tamao, K.; Tohma, T.; Inui, N.; Nakayama, O.; Ito, Y. Tetrahedron Lett. 1990, 31, 7333. 33A-14 3/14/96 5:54 PM PhMe 2 Si Si O Me Me Me NC Si O Me PhMe 2 Si Me Me PhMe 2 Si Si O MeO 2 C Me Me NC Si O CO 2 Me PhMe 2 Si Me Me Si O Pd L Si R PhMe 2 Si Si O Me Me NC Si O PhMe 2 Si Me Me PhMe 2 Si Si O Me Me NC Si O PhMe 2 Si Me Me Si O Pd L Si Me i-Pr Me i-Pr R PhMe 2 Si Si O Me Me Me NC Si O Me PhMe 2 Si Me Me PhMe 2 Si Si O Me Me NC Si O PhMe 2 Si Me Me Me Me Me Me Me Me PhMe 2 Si Si O Me Me NC Si O PhMe 2 Si Me Me Me Me Me OH NC OSi PhMe 2 Si Me Me PhMe 2 Si OHPhMe 2 Si NC SiO SiMe 2 PhPhMe 2 Si Me MePhMe2Si OAcAcO OAc OAc OAc O Et Si PhMe 2 Si Me Me Intramolecular Bis-Silylation: cat. Pd(OAc) 2 NC 95% Si O PhMe 2 Si Me Me Et 93:7 cat. Pd(OAc) 2 85% >99:1 cat. Pd(OAc) 2 90% 93:7 cat. Pd(OAc) 2 Si O PhMe 2 Si Me Me Et cat. Pd(OAc) 2 94% 96:4 98% 93:7 cat. Pd(OAc) 2 96% cat. Pd(OAc) 2 96:4 Murakami, M.; Suginome, M.; Fujimoto, K.; Nakamura, H.; Andersson, P. G.; Ito, Y J. Am. Chem. Soc. 1993, 115, 6487. 1) PhMe 2 SiSiMe 2 Cl Et 3 N 2) 1 mol% Pd(OAc) 2 O Et Si PhMe 2 Si Me Me 82:18 97% H 2 , Pd/C Application to Polyacetate Synthesis: NC 94% Si O PhMe 2 Si Me Me Et 92:8 1) PhMe 2 SiSiMe 2 Cl Et 3 N 2) 1 mol% Pd(OAc) 2 85%, 2 steps 83%, 2 steps 93:7 PhLi 89% Pd(OAc) 2 Si O PhMe 2 Si Me Me Et 96% Bis-Silylation of Alkynes: Pd(OAc) 2 1) TFA 2) KF, H 2 O 2 3) Ac 2 O, Et 3 N DMAP 44%, 3 steps Murakami, M.; Suginome, M.; Fujimoto, K.; Nakamura, H.; Andersson, P. G.; Ito, Y J. Am. Chem. Soc. 1993, 115, 6487. 93% Et " HN=NH " Et 97% 89:11 Et 85:15 Murakami, M.; Oike, H.; Sugawara, M.; Suginome, M.; Ito, Y Tetrahedron 1993, 49, 3933. 33A-15 3/14/96 11:44 PM OO Si H OO Si OH OH OO Si H OH OH OO Si H OH OH OO Si H OH OH Me Me OO Si H OH OH Me Me O Si i-Pr R 1 R 2 O i-Pr i-Pr H i-Pr Cl 4 Sn O Si i-Pr R 1 R 2 i-Pr i-Pr i-Pr H O Cl 4 Sn Me O O Si Me Me OH OH Me O O Si Me Me anti:syn OH OH 10 mol% SnCl 4 -80 °C 120:1 HF aq. MeCN Si O Me O Me Me Ti 67%, 2 steps 1) 10 mol% SnCl 4 , -80 °C 2) HF aq., MeCN H 67%, 2 steps 50:1 Intramolecular Reduction of Ketones: 1) 10 mol% SnCl 4 , -80 °C 2) HF aq., MeCN 69%, 2 steps 40:1 Cl Cl Cl Cl Anwar, S.; Davis, A. P. Tetrahedron 1988, 44, 3761. 1) 10 mol% SnCl 4 , -80 °C 2) HF aq., MeCN 90%, 2 steps 250:1 O O Si Me Me Intramolecular Allylation: TiCl 4 70% 58%, 2 steps 300:1 Anwar, S.; Bradley, G.; Davis, A. P. J. Chem. Soc., Perkin Trans. I 1991, 1383. Me 1) 10 mol% SnCl 4 , -80 °C 2) HF aq., MeCN syn:anti 92:8 SnCl 4 70% OH OH anti:syn 92:8 EtAlCl 2 92% 1,2-Asymmetric Induction: Me anti:syn 85:15 Reetz, M. T.; Jung, A.; Bolm, C. Tetrahedron 1988, 44, 3889. For application to the synthesis of C-glycosides see: Martin, O. R.; Rao, S. P.; Kurz, K. G.; El-Shenawy, H. A. J. Am. Chem. Soc. 1988, 110, 8698. 33A-16 3/14/96 5:58 PM O BnO BnO BnO O Si O MeMe Sugar O BnO BnO BnO O Si O Me Me Sugar N O BnO BnO BnO O OH O OBn OMe BnO BnO O AcO AcO AcO SPh OSi Me Me O O OMe BnO BnO BnO O AcO AcO AcO HO O O OMe BnO BnO BnO Intramolecular Anodic Olefin Coupling: O Si Me Me MeO Me Me OSiMe 2 OMe MeO MeO Me Me O Si MeO Me Me Me Me Synthesis of Disaccharides via Intramolecular Nucleophile Delivery: + + Tf 2 O workup 68% Only β-Mannoside O Si Me MeO 1 isomer Stork, G.; Kim, G. J. Am. Chem. Soc. 1992, 114, 1087. Note: Intermolecular variant gives exclusively α-Mannoside. NIS, MeNO 2 74% Me Me RVC anode 0.4N LiClO 4 in 50% MeOH/THF Constant current 2.0 F/mole 2,6-lutidine Bols, M. Tetrahedron 1993, 49, 10049. RVC anode 0.4N LiClO 4 in 50% MeOH/THF Constant current 2.0 F/mole 2,6-lutidine OSiMe 2 OMe MeO MeO Me + . E:Z 3:2 72% 1 isomer 33% Only α-Glucoside E:Z = 50:1 Moeller, K. D.; Hudson, C. M.; Tinao-Wooldridge, L. V. J. Org. Chem. 1993, 58, 3478. O BnO BnO BnO O Si O OMe BnO BnO BnO MeMe SPh O O 33A-17 3/14/96 11:54 PM