Properties of Silicon

Properties of Silicon afensteiner Si vs. C - Si is less electronegative than C - More facile nucleophilic addition at Si center Average BDE (kcal/mol) C C C Si Si Si C F Si F 83 76 53 116 135 C Si C Si 86 108 83 76 Average Bond Lengths (Å) C C C Si C Si 1.54 1.87 1.43 1.66 Siliconium Ion - ot believed to exist in any reaction in solution J. Y. Corey, J. Am. Chem. Soc. 1975, 97, 3237 - Pentacoordinate Si compounds have been observed SiF 4 Et 4 3 SiF 2 4 - Lack of cation justified by high rate of bimolecular reactivity at Si chanism of Deprotection Workup Silicon forms weak p-bonds Si F Bu 4 Si F p - C C = 65 kcal/mol p - C Si = 36 kcal/mol Pentavalent Silicon

Properties of Silicon afensteiner ucleophilic addition to Si F Si 3 F Si 3 b-silicon effect and Solvolysis Si 3 Si 3 Li Li -Si 3 3 C A CCF 3 vs. 3 C k A / k B = 2.4 x 10 12 B CCF 3 Duhamel et al. J. rg. Chem. 1996, 61, 2232 b-silicon Effect 3 C Si 3 vs. 3 C - Silicon stabalizes b-carbocations - Stabalization is a result of hyperconjugation CCF 3 k A / k B = 4 x 10 4 CCF 3 Si 3 C 3 Evidence for Stepwise mechanism vs. 3 Si Si 2 Si 2 A B *A is more stable than B by 38 kcal/mol * Jorgensen, JACS, 1986,107, 1496 3 Si Si 2 3 Si Si 2 3 Si Product ratios are equal from either starting material suggesting common intermediate cation

Properties of Silicon afensteiner Evidence for apid ucleophilic Attack Extraordinary tallation Si 3 Sn 4 Si 3 3 Si t-buli Li 2 Si Si vs. 2 Si Gornowicz et al., J. Am. Chem. Soc. 1968, 90, 4478 Si 3 Sn 4 Fleming et al., JCS Chem. Com. 1976, 182 rganosilanes Stabilize C M Bonds - tallation occurs a to silicon - yperconjugation gives stability Cation-Anion armony - Stabalization of a-anion and b-cation exemplified in regioselectivity of the hydroboration of alkynlsilanes Si 3 2 B Si 3 d - d + B 2 d + d - Si 3 B 2 Si M Zweifel et al., J. Am. Chem. Soc. 1977, 99, 3184

Allylic and Vinylsilanes afensteiner Silicon Migration - Conjugate addition can be followed by Si migration - Migration aptitude enhanced when Si has bulky groups (i-pr) 3 Si Ti 4 Ti 4 C 2 2 (i-pr) 3 Si Ti 4 Vinylsilane eactivity - eact with electrophiles - egioselectivity governed by creation of b-carbocation - Elimination of Si 3 occurs with retention of initial double bond geometry due to principle of least motion - Limited rotation also prevents eclipsing interactions between silyl group and olefin substituents Vinylsilane Examples Et Et Si 3 C() 2 Ti 4 Et Et Si(i-Pr) 3 A. I. yers, J. rg. Chem. 1998, 63, 5517 Si(i-Pr) 3 Si3 (C 2 ) n Ts 2 C Ar C 2 = i-pr, (i-pr) 2 Si Zr 4 C 2 2 2 C 2 C Ar Si 3 Grieco et al. J. Chem. Soc. Chem. Comm., 1987, 185 diasteromeric ratio 96:4, ~ 70% yeild

eactions with Silicon Sakurai eaction - Lewis acid catalzed addition of allysilanes to aldehydes and acetals 3 Si 3 Si n-c 4 9 n-c 4 9 Ti 4 80% Ti 4 83% n-c 4 9 n-c 4 9 Examples of Addition to Carbonyls 3 Si 3 Si yashi, Tett. Lett. 1983, 2865. Ti 4 C 2 2 Ti 4 C 2 2 >95:5 syn:anti ~65 : 35 Intramolecular Sakurai eaction BF 3 Et 2 cat. LA C ene reaction Conjugate Addition 3 Si 3 Si Ti 4 Fleming, rg. eactions 1989, 37, 127-133 75 % 3 Si 17 % Si 3 EtAl 2 C 2 2 78% Markó et al. Tett. Lett.,1992, 33, 1799 Majetich, Tetrahedron 1987, 43, 5621

Brook earrangement afensteiner Pioneering Work By A. G. Brook - earrangement of organosilyl alcohols under base catalysis - etention at silicon and inversion at carbon 3 Si Et 2 DMS Si 3 - Brook rearrangement can be used to access homoallylic enolate anions Si 3 Li (C 2 ) 4 I eich, J. Am. Chem. Soc. 1980, 102, 1423 Et 2 3 Si Brook, Accts. Chem. es. 1974, 7, 77-84 Examples of Brook earrangement Si 3 Li 1 Li 3 Si Moser, Tet. 2001, 57, 2065-2084 El 3 Si 3 Si E S Li Si 3 Si 3 S Li [1,2] Takeda, J. Am. Chem. Soc. 1993, 115, 9351 Takeda, Synlett. 1994, 178 Takeda, Synlett. 1997, 255 S Si 3 Li Moser, Tett. 2001, 57, 2065-2084 S Si 3 Li Si 3 S S Si 3 Li

Peterson lefination afensteiner Pioneering Work By Peterson - Investigation aimed at finding a silicon analog to phosphorous ylides - Same cyclic four-membered transition state can be envisioned 3 Si M 1 3 Si M 1 1. Li 2. Si 2, benzene 3 Si M 1 3 Si 1 1. 2 h-al 2 3 2. BF 3 Et 2 Peterson, J. rg. Chem. 1968, 33, 780-784 LA - Mg alkoxides are stable and do not breakdown to give olefin product - Li, a, and K alkoxides are reactive and breakdown to give olefin product - b-silyl-alcohols can be converted to olefins with dilute acid BF 3 Et 2, 3 Si 10% 2 S 4 T 3 Si Si 3 Whitmore et al., J. Am. Chem. Soc. 1947, 69, 1551 Ager, rg. eactions 1990, 38, 1.

Tamao xidation Tamao xidation - Conversion of organosilanes to corresponding alcohols - Pioneered by Tamao in 1984 (Tett. Lett. 1984, 25, 4249) epresentative Silanes C 2 MgBr 2 Si 2 Si 2 Si 2 Si S CuI cat. Si 2 KF 2 TFA 2 Si 2 Si S 2 Si S 30% 2 2 ac 3 F Si 2 Si 2 Tol-p Si 3 Yoshida et al. J. rg. Chem. 1999, 64, 8709 68% overall - ther substrates used and in all cases no Bayer-Villager seen Synthetic Example 2 Si 1. BF 3 Ac 2. 35% 2 2 ac 3 95% Weinreb et al. J. rg. Chem. 2002, 67, 4339

Silicon in Synthesis afensteiner Brook earrangement Cyanthin Tricyclic Core 2 Si Si 2 Li dysidiolide i-pr 0 C to rt 47% i-pr 13 Steps TBS Li 2 Si i-pr 2 Si i-pr TBDPS 1. BF 3, 78 C 2. PPTS, Et Li TBS TBS 6 steps Product i-pr 80 C to 0 C 60% Si 3 i-pr TBDPS Corey, oberts, J. Am. Chem. Soc. 1997, 119, 12425-12431 Takeda et al. rg Lett. 2000, 2, 1907

Silicon in Synthesis afensteiner Brook earrangement (+)-onocerin Tf C 2 ZnBr Tf Pd(P 3 ) 4 TBS Li -78 C Li TBS 1. Al 2 15 min 2. TBAF 0.5 equiv I 2 Tf CsF TBS Mi, Schreiber, Corey, J. Am. Chem. Soc. 2002, 124, 11290-11291 Tf Tf 2 TBS - Properties of silicon exploited - b-carbocation stabalization - a-anion stability

(+)-Tetronomycin Silicon in Synthesis - Stabalization of b-cation afensteiner - Key coupling step in convergent synthesis uses allysilane coupling reaction + TBDPS TBDPS 1 1 Si 3 Piv TBDPS Piv TBDPS BF 3 Et 2, 92% Piv TBDPS Yoshi et al. J. rg. Chem. 1992, 57, 2888

Silicon in Synthesis afensteiner (±)-irsutene 5% K 40% D C 2 Et 97% C 2 Et 1. LiAl 4 2. PDC 72%, 2 steps Sarkar et al. Tett. Lett., 1990, 31, 3461 1. 2 / Pt / C 2. 3 SI, a (±)-Sarain A Core Scaffold 1. Ti 4 2. PCC 53% DMS 60% Pd 2, Cu Sarain A 2 76%

Silicon in Synthesis (±)-Sarain A Core Scaffold Bn TP 65% Bn Bn Bn TP 1. o-dcb, 320 C 2. Ts, 70%, 2 steps (+)-Pumiliotoxin A C 4 9 1. ( )-pinene, 9-BB 2. Li; ; 3. C 2 4. MgBr; CuI 35%, 4 steps Dibal-; Li C 4 9 C4 9 Bn Ts Bn 1. Swern [] 2. MgBr 3. Ac 2, TEA, DMAP 4. () 2 CLi 2 Cu 27%, 4 steps 1. a, 3, t-bu 2. LMDS, Ts, DMAP 3. Dibal- 62%, 3 steps Bn Bn Ts Bn Bn C 2 Bn C4 9 Li Al(i-Bu) 2 C4 9 (C 2 ) n CSA 38% Li Al(i-Bu) 2 C 4 9 C 4 9 K, 2 80% Weinreb et al., J. rg. Chem., 1991, 56, 3210 verman et al., J. rg. Chem., 1985, 50, 3670

Silicon in Synthesis afensteiner Prostoglandins - Fleming contributed greatly to the field of organosilicon chemistry 0 5 C 70% 2 C Ac 1. 3 2. 2 S 47%, 2 steps C 2 Ac Loganin 2 C 1. 2 2 Ac 2. Zn Ac 2 62%, 2 steps 1. a 2, Ac 2 Ac 2. aac 3. C 2 2 2 S 61%, 4 steps C 2 Sn 4 78% Ac S 2 C Ac Fleming, J. Chem. Soc. Chem. Comm., 1977, 79-80 Fleming, J. Chem. Soc. Chem. Comm., 1977, 81 (±)-Linaridial Ti 4 C 2 S 77% 1. K(C 2 ) 3 2 2. ydroboration/ [] S 1. aney i 2. C 2 Br 2, Zn, Ti 4

Silicon in Synthesis afensteiner (±)-Linaridial 1. Swern [] 2. a C (Et) 2 P C C C 1. Dibal- 2. 1M, TF 1. 3 ; Zn / 3 P 2. Wittig 50% EtAl 2 53% 2 : 1 : 2 Tokoroyama et al. Tett. Lett., 1987, 28, 6645 (±)-a-acoradiene Li P() 2 61% Yamamoto et al. J. rg. Chem., 1990, 55, 3971

ydrosilation afensteiner ydrosilation - tal and radical catalyzed addition to alkenes and alkynes - tal catalysis is done at room temperature and best yields obtained with trichloro and methyldichlorosilanes - Addition of methyl grignard converts chlorosilanes to 3 Si Si 3 2 Pt 6 3 Si 3 Si 2 Pt 6 Chalk; arrod; J. Am. Chem. Soc. 1965, 87, 16 -Cr(C) 6 with light gives 1,4 reduction of dienes Germanes and Dehalogenation - rganohalides can also be reduced with various organogermanes - Can be used catalytically with P 3 for reduction of C X bond - eactivity of halide I > Br > > F - Solid support methods can be used - Similar reactivity to silanes - Furanylgermane reduces C X bond under mild conditions eduction with Silanes - Catalysis needed for convenient rates - Catalysts include TBAF, protic and Lewis acids, Wilkinson's cat, silatrane Si Attar-Bashi et al. rganometallic Chem. 1976, 117, C87 Silanes and Dehalogenation - rganohalides can be reduced with various organosilanes - adical mechanism of hydrodehalogenation - eactivity of halide I > Br > > F - eactions are fast and clean often giving quantitative yields -Common Silanes (i-pr)s S(i-Pr) Si S(i-Pr) - Common adical Intiators S S Si S Et Et Si Et -"Common" Germanes AIB Dibenzoylperoxide Ge 2 P 3 Ge 3 P (C 2 ) n Et 2 Ge - enylsilane is also used - eactions with phenylsilane are refluxed neat with a radical initiator