The Beginnings of Silacyclopropane Chemistry

Transcription

1 The Beginnings of lacyclopropane Chemistry! The first simple silacyclopropane was synthesized in C 2 Br C 2 Br Mg, TF 76% yield Seyferth, D.; Annarelli, D.C. JACS 1975, 97, 2273.! Synthesis of only simple silacyclopropanes (un-, mono-, and di-substituted) was known. 2 X 2 Li Li % yield X Boudjouk, P.;... ACIEE, 1988, 27, C C C 85% yield Boudjouk, P.; Black, E.; Kumarathasan,. rganometallics, 1991, 10,

2 The Beginnings of lacyclopropane Chemistry! lacyclopropanes can be opened by a variety of nucleophiles. X X X =,, 2, 2, Sn 3! lacyclopropanes ring expand on reaction with aldehydes. Seyferth, D.;... J. rganometallic Chem., 1982, 225, 177. yield (%) (required UV irradiation) Seyferth, D.; Duncan, D.P.; Shannon, M.L. rganometallics, 1984, 3, 579. Carbenoid Insertions into lacyclobutanes! Lithium carbenoids (C 2 LiBr and C 2 LiI) will insert into silacyclobutanes. Cl = or 1 alkyl!73% yield C 2 LiBr Br!41% yield! 1-Bromosilacyclopentanes (and 1-Iodosilacyclopentanes) will undergo radical intramolecular exo-cyclizations. Br Bu 3 Sn 20 mol% Et 3 B 6-2 : 1 d.r. (Z-alkenes give poorest d.r.)! Products can be oxidatively opened to the corresponding triols. 2 2, KF, KC 3 then Ac 2, pyr Ac Ac Ac 32-72% yield (2 steps) (lowest yield from terminal olefin)... ; Utimoto, K. Tetrahedron, 1993, 49, : Utimoto, K. Bull. Chem. Soc. Jpn., 1995, 68,

3 ! nly non-enolizable aldehydes insert. Et Aldehyde Insertions into lacyclopropanes C 25 mol% K 25 mol% 18-crown-6 or Lewis Base! eaction is believed to procede through a pentacooordinate silcon intermediate. 54% yield, 86 : 14 d.r. (73% yield, 70 : 30 for cis-silacyclosilane) no insertion products Et Ar Ar -! Product shows 1,3-syn for both cis- and trans-silacyclopropanes! Selectivity independent of Lewis base catalyst... Woerpel K.A. JC 1997, 62, Takeyama, Y.; shima, K.; Utimoto, K. TL, 1990, 31, Amide Carbonyl Insertions into lacyclopropanes! Formamides do not insert into cis-silacyclopropanes. 120 C 93% yield one diastereomer! eaction is believed to procede through a pentacooordinate silcon intermediate.! Amides are more reactive than other carbonyls due to their increased Lewis basicity. 110 C favored = 60 : 40, 63% yield = 94 : 6, 79% yield disfavored Shaw, J.T.; Woerpel, K.A. JC 1997, 62,

4 Isocyanide Insertions into lacyclopropanes! Isocyanides perform similar chemistry to formamides, but with higher reactivity and selectivity.! eaction is believed to procede through the intermediates proposed for formamide insertion. C 85 C 99% yield >20 : 1 d.r. C 85 C 98% yield >20 : 1 d.r. C C n-bu yield 94% 98% 97% regioselectivity >95 : 5 92 : 8 86 : 14! Decrease in selectivity with increasing steric bulk is believed to be due to unfavorable interactions between the group and the coordinated isocyanide. guyen, P.T.; Palmer, W.S.; Woerpel, K.A. JC 1999, 64, tal-catalyzed Insertions into lacyclopropanes! eactions occur at significantly lower temperatures. =,, crotyl X = I, Br 2 10 mol% CuI -78 C to 10 mol% CuI -78 C to 10 mol% CuX -78 C to 72% yield 93 : 7 selectivity 74% yield >95 : 5 selectivity! The copper-catalyzed insertion of formamides and stabilized aldehydes is believed to go through a transmetalation % yield 91 : 9 d.r. or better! Zinc is believed to catalyze the insertion of alkyl aldehydes through cooridination/activation. n-bu 10 mol% ZnBr 2-78 C to n-bu 70% yield 55 : 45 d.r. >99 : 1 regioselectivity guyen, P.T.; Palmer, W.S.; Woerpel, K.A. JC 1999, 64, Franz, A.K.; Woerpel, K.A. Chem. ev. 2000, 33, 813. X Zn Br Br Cu n-bu 4

5 Elaboration of ing-expanded lacyclopropanes! These oxidation conditions work for hindered silanes., Cs 2 TBAF 64% yield 1) Ac, 2 2) Ac 2 Ac 86% yield over 2 steps Ac 1) CuS 4, 2 2) Ac 2 TMS TMS SnBr 4 Ac 66% yield Smitrovich, J..; Woerpel, K.A. JC, 1996, 61, Shaw, J.T.; Woerpel, K.A. JC, 1997, 67, 442. guyen, P.T.; Palmer, W.S.; Woerpel, K.A. JC, 1999, 64, Franz, A.K.; Woerpel, K.A. Acc. Chem. es. 2000, 33, 813. Bear, T.J.; Shaw, J.T.; Woerpel, K.A. JC, 2002, 67, % yield 99 : 1 d.r. 79% yield 94 : 5 : 1 d.r. A ew synthesis of lacyclopropanes! lver-catalyzed silyl transfer is a mild way to form mono- and disubstituted silacyclopropanes. = 1, 2, 3 alkyl 5-10 mol% AgTf 61-99% conversion = 1, 2 alkyl cis, trans, and!,!-disubstituted 5-10 mol% AgTf! lyl transfer is highly diastereoselectiveand allows access to more complex substrates. Et P " Et P 72-99% conversion complete transfer of double bond geometry P = TIPS: 97% yield, 96 ; 4 d.r. P = B: 93% yield, 88 : 12 d.r.! ne-pot silacyclopropanation-insertion is possible 1), 5 mol% AgTf 2) 20 mol% ZnBr 2, C 2 C % yield d.r. no better than 76 : 24 Driver, T.G.; Franz, A.K.; Woerpel, K.A. JACS, 2002, 124, Cirakovic, J.; Driver, T.G.; Woerpel, K.A. JACS, 2002, 124,

6 Strained Cyclosilanes are Stronger educing Agents than Typical lanes! Unstrained silanes do not perform this reduction. reducing agent 95% yield 85% yield 96% yield 98% yield 0% yield! The reducing agent was formed in situ. Li TF 2 Cl 3 Li reducing agent Kira, M.; Sato, K.; Sakurai,. JC, 1987, 52, 948. Increasing Coordination of licon Increases eactivity! Allylations of aldehydes by strained cyclosilanes are believed to go through a cyclic transition state.! Pentacoordinate silicon is formally negatively charged, but the charge is delocalized into electronegative ligands, thereby increasing the Lewis acidity of the silicon. X X X X X X - X X X u X X X u increasing!"# conjugation! Coordination of electron rich ligands to the silicon increases the!"# conjugation. ( 13 C M evidence) Sakurai,. Synlett, 1989, 1. 6

7 Ligand Bond Angle is Directly elated to eactivity! Activation energies calculated for the addition of allylsilane to formaldehyde show a strong relationship to C--C bond angle.!, (C 2 ) 3,,,,,! 78 (actual) 70 (fixed) 80 (fixed) 90 (fixed) 100 (fixed) (actual) activation energy (kcal/mol) ! As the ligand bond angle decreases, the 3p x orbital becomes less occupied and more available for attack by the incoming nucleophile. This reduces the activation energy of the reaction. z x y! The attack of the nucleophile on the allyl silacyclobutane relieves ring strain on forming the pentacoordinate intermediate. moto, K.; Sawada, Y.; Fujimoto,. JACS, 1996, 118, Catechol-Derived Allyl Cyclosilanes eact Without eed for a Catalyst! Transfer of stereochemistry from crotylsilane to product supports a cyclic transition state. 1 Li 2 TF 65 C (88 : 12) (79 : 21) yield (%) (anti 88 : 12) 91 (syn 78 : 22)! Lack of reactivity of a hexacoordinate allyl silane indicates that the aldehyde must coordinate to the silicon to react. 13 C M indicates the!-carbon is more nucleophilic than the pentacoordinate allyl silane. F 3 C CF3 Li TF 65 C no reaction F 3 C CF 3 Kira, M.; Sato, K.; akurai,. JACS, 1988, 110,

8 lacyclobutane Sakurai Chemistry! Allylic silacyclobutane will add to aldehydes at elevated temperatures C n-pr (E) n-pr (E) n-pr (E) n-pr (Z) n-pr (Z) (E) (E) (E) 2 n-hex c-hex n-hex n-hex c-hex yield (%) anti : syn 95 : 5 90 : 10 >99 : 1 5 : : : 8 97 : 3 >99 : 1! Transfer of allyl stereochemistry indicates a cyclic transition state. n-pr n-pr n-pr n-pr Matsumoto, K.; shima, K.; Utimoto, K. JC, 1994, 59, Enantioselective Sakurai! Substitution of the chloride with an alkyl group reduces enantioselectivity. Cl C 2 C 2 40 h : 93% yield, 47% ee -40 C: 73% yield, 60% ee Cl C 2 C h 7-40 C: 76% yield, 80% ee! eaction of the E- and Z-crotylsilanes proceeded with high diastereoselectivity (anti and syn products, respectively), supporting the cyclic transition state. C disfavored favored Cl C 2 2 C Cl! Favored reaction path is proposed to aviod steric interaction with the free ester of the ligand. Zhang, L.C.; Sakurai,.; Kria, M. Chem. Let. 1997,

9 Another Enantioselective Sakurai! Wang proposes the necessity of base activation. Cl C 2 C 2 Lewis base C 2 Cl 2, 24 h B Cl C 2 C 2 Base Et 3 Et 3 DMF DMF MPA MPA n-octyl n-octyl n-octyl yield (%) ee (%) ! Evidence from crotylations supports a closed chair transition state with a hexcoordinate silicon. C 2 Cl C 2 4 : 1 ( E : Z) C DMF 72% yield, 4 : 1 d.r. Cl C 2 C 2 C DMF 76% yield, one diastereomer 100% Z Wang, D.;... Tetrahedron: Asymmetry, 1999, 10, 327. The Most ecent Enantioselective Sakurai eaction! Activation of the silicon by a Lewis base (leading to a hexacoordinate transition state) is not necessary for reactivity. Cl 52% yield (unoptimized) Cl no reaction Cl no reaction Cl no reaction! ing strain activates the allyl silane for addition to the aldehyde....; Leighton, J.L. JACS, 2002, 124,

10 The Most ecent Enantioselective Sakurai eaction! Pseudoephedrine-derived allyl silane will add to aldehydes with good selectivity. Cl 3 Cl -10 C, 2 h yield (%) ee (%) Et Cl 88% yield 2 : 1 d.r. reagent used as 2 : 1 mixture ! Chiral allyl silane is easily prepared and can be stored for months without ill efects. TBS ; Leighton, J.L. JACS, 2002, 124, The Most ecent Enantioselective Sakurai eaction! Diamino auxiliaries allylate with greater selectivity. Cl 3 DBU Cl >95% yield! nly these preliminary reactions have been published. Cl 72 h 46% yield 90% ee Cl 72 h 58% yield 95% ee...; Leighton, J.L. JACS, 2002, 124,

11 lyl ing Strain Accelerates Aldol Chemistry! lacyclobutane ketene acetals show good syn selectivity.! lacyclobutane ketene acetals show increased reactivity. quantitative yield 19 : 1 d.r. 100 C = : no reaction = (C 2 ) 3 : 84% yield (34 h), 7 : 1 d.r. = : 150 C, 24 h, <25% yield = (C 2 ) 3 : 27 C, 4 h, quantitative yield Myers, A.G.; Kephart, S.E.; Chen,. JACS, 1992, 114, Enoxysilacyclobutane Syn-Aldol eaction! The aldol reaction of ester, thioester, and amide silacyclobutane enolates proceeds uncatylized and with high diastereoselectivity. CDCl 3!85% yield!93 : 7 syn : anti =, cinnamyl, 1 and 2 alkyl S CDCl 3 or neat S!68% 1 M conversion!70 : 30 syn : anti =, cinnamyl, 1 alkyl 2 CDCl 3 84% yield 9 : 91 syn : anti! Enoxysilacyclobutanes are not competent Mukiayama-Michael nucleophiles, favoring 1,2-addition over 1,4-addition. Denmark, S.E.; Griedel, B.D.; Coe, D.M. JC, 1993, 58, 988. Denmark, S.E.;... JACS, 1994, 116,

12 Enoxysilacyclobutane Syn-Aldol eaction! igh diastereoselectivity suggests a closed transition state.! Syn aldol product suggests a boat transition state.! Boat transition state is supported by computational studies.! Deuterium-labelling crossover experiments indicate intramolecular silyl transfer, supporting a closed, cyclic transition state. 1 equiv. 3 C C 3 3 C C 3 C 3 2 equiv. 3 C 3 C C % silyl crossover product detected by MS 1 equiv. D 3 C CD 3 D 3 C C 3 D 3 C C 3 3 C C 3 Denmark, S.E.;... JACS, 1994, 116, Uncatalyzed, Syn-Selective Enoxysilacyclobutane Asymmetric Aldol! Ester-derived enoxysilacyclobutanes reacted with high diastereo- and enantioselectivity, but suffered from poor yields due to C-silylation of the enolate and low E : Z ratios. * 60 : 40 : C silyl 80 : 20 E : Z -60 C >99 : 1 syn : anti * (-)-menthol ()-2,2-diphenylcyclopentanol ()-endo-borneol ()-trans-2-phenylcyclohexanol (-)-8-phenylmenthol (-)-trans-2-cumylcyclohexanol ee (%) ! Thioester-derived enoxysilacyclobutanes are preferred due to higher yields, lack of C-silylation in preparation, and high E : Z ratios. S (-)-trans-2-cumylcyclohexanol enoxysilacyclobutane Aryl -35 C, 7 d S (1S, 2S) Aryl Aryl cinamyl p-methoxy 2-furyl 1-naphthyl trifuloro-p-tolyl yield (%) ee (%) Denmark, S.E.; Griedel, B.D. JC, 1994, 59,

13 lacyclobutanes Increase the Enantioselectivity of Ti-BIL-Catalyzed Aldol! The use of silacyclobutyl versus trimethylsilyl enolate increases reactivity and selectivity. C 6 F 5 Ti TMS S 5 mol%, 0 C 4-8 h S = n-c 8 17 : 60% yield, 91% ee = C 2 : 80% yield, 96% ee C 6 F 5 Ti S 5 mol%, 0 C 2 h S = n-c 8 17 : 83% yield, 97% ee = C 2 : 95% yield, 98% ee Matsukawa, S.; Mikami, K. Tet.: Asym., 1995, 6, hodium-catalyzed Intramolecular lylformylation! Isolated yields are over three steps due to the difficulty of purifying the aldehyde product ) 1 mol% h(acac)(c) PSI C 1 2 2) LiBEt 3 3) Ac 2, pyr SI 2 Ac SI SI SI Ac Ac Ac 67% yield 4.5 : 1 d.r. 64% yield 4 : 1 d.r. 79% yield 6 : 1 d.r. TBS SI Ac SI Ac SI Ac SI Ac 60% yield 4 : 1 d.r. 54% yield 7 : 1 d.r. 10% yield 11 : 1 d.r. (rest hydrosilylation) 71% yield 10 : 1 d.r.! This methodology provides access to syn polyol fragments after oxidative removal of the silicon. Leighton, J.L.; Chapman, E. JACS, 1997, 119,

14 Tandem Intramolecular lylformylation-allylation! This is the first use of oxasilacyclopentanes in an uncatalyzed bond-forming process. 3 mol% h(acac)(c) PSI C =, 2 = 1, 2 alkyl, crotyl 3 = b a, ac allylation by 45-65% yield group a favored!69 : 31 d.r.! Deuterium labeling experiments indicate an intramolecular allylation. Leighton, J.L.; Zacuto, M.J. JACS, 2000, 122, Tandem Intramolecular lylformylation-allylation shows 1,5-Asymmetric Induction! lylformylation of alkynes is possible under these tandem reaction conditions. 0.1 mol% h(acac)(c) psi C 1) TBAF 2) Ac 2, pyr Ac Ac n-pr C 2 C C C 2 C 2 TBS yield (%) d.r. 4 : 1 4 : 1 5 : 1 8 : 1 7 : 1 10 : 1! xidative work-up provides access to 1,3,5-oxygenated systems. 1) 0.1 mol% h(acac)(c) psi C 2) 2 2, ac 3 71% yield b a! Transfer of allyl group b is favored due to a's unfavorable steric interaction with. 'Malley, S.J.; Leighton, J.L. ACIEE, 2001, 40,

15 Tandem Intramolecular Aldol-Allylation! The Lewis-acidity of ring-strained cyclosilanes is sufficient to undergo this reaction. Cl3! The stereochemistry of the aldol reaction indicates that it proceeds through a boat transition state. Cy Cy DBU 60% yield 11 : 1 d.r. 59% yield 12 : 1 d.r. Cl 72% yield 1 (Z) (E) (Z) (Z) (E) TMS Li 2 (E) (Z) (Z) (E) (E) 2 Cy 70% yield Wang, X.; ng, Q.; ation, A.J.; Leighton, J.L. JACS, 2002, ASAP. Cy 1 1 yield (%) (Z) stereochemistry yields anti (E) stereochemistry yields syn 2 d.r. (major : others) 8 : 1 10 : 1 65 : 35 2 : 1 66 : : : 14 Some Interesting Lewis-Base-Catalyzed Epoxide pening Chemistry Denmark, S.E.;... JC, 1998, 63, ; Buono, G. ACIEE, 2000, 39, (not available online) eymond, S.; Brunel, J.M.; Buono, G. Tetrahedron: Asymmetry, 2000, 11, ; Buono, G. Eur. J. rg. Chem., 2001, Denmark, S.E.; Wynn, T.; Jellerichs, B.G. ACIEE, 2001, 40, Buono, G. ACIEE, 2001, 40, Buono, G. Eur. J. rg. Chem., 2002,