J. Braz. Chem. Soc., Vol. 12, No. 1, 7-31, 2001. c 2001 Soc. Bras. Química Printed in Brazil 0103 - 5053 $6.00+0.00

Review

Acylsilanes and Their Applications in Organic Chemistry

Amauri F. Patrocínio and Paulo J. S. Moran*

Instituto de Química, Universidade Estadual de Campinas, CP 6154, 13083-970 Campinas - SP, Brazil

Estudos sobre o emprego de acilsilanos em rotas sintéticas e as novas metodologias de preparação desenvolvidas nos últimos anos, tornaram estes organo-silanos importantes reagentes para síntese de compostos orgânicos. Esta revisão apresenta algumas aplicações recentes e vários métodos desenvolvidos para síntese de acilsilanos.

Current studies concerning the use of acylsilanes in a variety of organic synthetic routes and the improved methodologies of their preparation have turned organosilanes into important reagents for organic chemistry. This review discusses the recent employment of acylsilanes in organic synthesis and also effective methods for their preparation.

Keywords: organosilicon compounds, Brook rearrangement, carbonyl compounds, stereocontrol

Introduction are compounds that present particular physical and chemical properties. The spectral data of acylsilanes are well described ´ 2 3 Acylsilanes (RCOSiR 3) are compounds that have the in the reviews by Brook and Page and co-workers . The silicon directly attached to the carbonyl group, exhibiting inductive effect of the silicon favors the polarization of the unique chemical properties. The use of acylsilanes in organic carbonyl group, which absorbs at a lower frequency than synthesis has increased significantly over the last few years due simple ketones in the infrared and ultraviolet spectra. In 13C to the discovery of valuable new reactions and the improvement NMR spectroscopy, the signals for the carbonyl carbon are of acylsilane synthesis methods. The substantial effect of the quite different from the corresponding ketones, appearing at electronic properties and the bulk of trimethylsilyl group may higher δ values. The anisotropy effect and electronegativity be used to control the stereochemistry of reactions1. One of the differences also lead to higher δ values in the 1H NMR spectra well-established uses of acylsilanes in organic synthesis is as an for hydrogens attached to the α-carbon of acylsilanes (except equivalent, in which a stereoselective nucleophilic for α,β-unsaturated). Table 1 shows some examples of IR and attack on the carbonyl group, α to a chiral center, is followed by NMR spectral data for acylsilanes. Another interesting stereospecific replacement of the silyl group by hydrogen. characteristic of acylsilanes is the abnormally long Si-CO Moreover, acylsilanes can be used as ester equivalents for bond (1.926 Å), first observed by Trotter8 based on X-ray chirality induction, since acylsilanes can be smoothly oxidized analysis, which can be compared to the analogous bond to esters. The enantioselective reduction and the cyclization length in C-CO (1.51 Å)2 compounds. The same authors reaction of acylsilanes appear to have substantial synthetic determined that the carbonyl bond length is essentially potential. In the first part of this review we present some physical normal, despite the low vibrational frequency. properties of acylsilanes as well as some classical reactions involving organosilicon compounds. In the second part, we Table 1. Infrared C=O absorption and NMR data of some acylsilanes2,3. 13 1 present some new work in this area as a complement to the Acylsilane IR C NMR H NMR ν (cm-)a δ C=Oa δ CHCOa previous reviews2-7 and finally, in the third part, useful methods C=O MeCOSiMe 1645 (1710) 247.6 (215) 2.20 (2.08) of acylsilane synthesis. 3 PhCOSiMe3 1618 (1675) 233.6 (207) — MeCOSiPh3 1645 240.1 2.30 (2.01) Physical properties and classical reactions of PhCOSiPh3 1618 (1692) — — the acylsilanes t-BuCOSiMe3 1636 249.0 (215) — Me3SiCOSiMe3 1570 318.2 — PhCH COSiMe 1635 — 3.77 (3.55) In the organosilicon compounds class, the acylsilanes 2 3 CH2=CHCOSiMe3 1641 237.0 6.28 (6.88) aValues in parenthesis are for analogues in which the silicon atom has e-mail: [email protected] been replaced by carbon. 8 Patrocínio & Moran J. Braz. Chem. Soc.

Studies have shown that acylsilanes in general behave towards nucleophilic addition9,10. His work is historically as ordinary ketones. However, in some cases, these important because it led to a better knowledge of the reaction compounds have abnormal chemical behavior. Due to the pathway. A nucleophilic attack of alkoxide ion on the silicon intrinsic properties already mentioned, these compounds atom of acylsilane 7 was initially proposed for the formation should undergo many unusual reactions. For example, in of aldehyde 8 (Scheme 3, pathway a). Later, Brook proposed reactions of aroylsilanes with nucleophiles, the Brook another competitive pathway, which involves a nucleophilic rearrangement9 is very common. An example is the known attack by the alkoxide ion at the carbonyl group of 7 hydrolysis of aroylsilanes 1 to the corresponding (Scheme 3, pathway b). Using the optically active acylsilane 5, promoted by traces of OH- (Scheme 1). (-)-9 in reactions with different alkoxide ions, 10 was reduced The Brook rearrangement, after carbonyl addition of a by LiAlH4 to give (-)-11 (Scheme 4). Although the optical nucleophilic reagent, is commonly observed in aroylsilanes purities of (-)-11 were observed to be dependent on the bulk due to the relative stabilization of the of the alkoxide ion (EtO- 22% vs. t-BuO- 65%), in all intermediate 3 by the aromatic ring. Two classical reactions with chiral acylsilane (-)-9 the enantiomer (-)-11 examples in this context are presented in Scheme 2, where was predominant, showing the retention of configuration at the silyloxyalkene 6 is formed only when an anion- silicon. Therefore the bulkier alkoxides find it more difficult stabilizing group is attached to the carbonyl group2. to attack at silicon and, consequently, the attack at the Brook investigated the great reactivity of acylsilanes carbonyl group becomes relatively easier11.

Brook rearrangment Ar Ar O O R3SiOH OH- H O R Si Ar R3SiO C 2 R3SiO C H R3Si Ar 3 OH OH OH ArCHO 1 2 3 45 Scheme 1.

O O R3SiO CH2N2 -N R3Si C Ar 2 C R3Si Ar H2C Ar CH2 N2 1 6

O CH PPh 2 3 -PPh3 R3Si C Ar

CH2 PPh3

Scheme 2.

O Ph O Ph O Ph pathway a RO cleavage - Ph Si Ph Ph Si OR Ph Si Ph RO ROH H Ph Ph Ph Ph 8 7

- pathway b RO

Brook O OSiPh3 O rearrangement - RO ROSiPh Ph3Si C Ph HC Ph H 3 ROH Ph OR OR 8

Scheme 3. Vol. 12 No. 1, 2001 Acylsilanes and Their Applications in Organic Chemistry 9

Schemes 5 and 6 show recent examples of acylsilane optically active Grignard reagent to reduce benzoyl- reactions involving the Brook rearrangement. The triphenylsilane and benzoyltrimethylsilane in low acylsilane 12 reacts with amines to form the imine 13 or enantiomeric excess. Due to the relative facility that the silyl aminals 1412. The acylsilane 15 reacts with cyanide anion moiety can be removed and replaced by hydrogen, generally under liquid-liquid (CH2Cl2-H2O) phase-transfer catalytic by the action of fluoride ion, acylsilanes can be considered as conditions to form O-silylated cyanohydrin 1713. aldehyde equivalents in nucleophilic additions. Addition of nucleophiles can occur with a high Cram selectivity when Novel work involving acylsilane chemistry the chiral center in the acylsilane is on the α-carbon, as in 18 (Scheme 7), and even in some cases where the chiral center is β 1 Herein some of the most important synthetic on the -carbon , as in 19 (Scheme 8). applications of acylsilanes will be presented, focusing In general, the protiodesilylation (replacement of the especially on reports of the last ten years. R3Si moiety by H) occurs with a high level of stereoselectivity through the Brook rearrangement15. Two a. Stereocontrolled nucleophilic additions recent examples are shown in the Schemes 8 and 9 in which high stereocontrol was obtained in asymmetric induction The first study involving enantioselective addition to in the syntheses of calcitriol lactone derivatives 2016 and acylsilanes was reported by Mosher14 in which he used an β-aminoalcohols 21 and 2217. Scheme 10 illustrates a key

Me O O Me RO /ROH Me O Si Np LiAlH Me Me Si 4 H Si Me Si Np Me H Ph Np Np OR Ph Ph Ph OR

(-)-9 10 (-)-11

Np: Naphthyl

Scheme 4.

O O H H2NCH2CH(CH3)2 Ph3Si C Ph Ph3SiO C Ph Ph3Si Ph "dark" 12 NH2CH2CH(CH3)2 NHCH2CH(CH3)2 H N "dark" PhCH NCH2CH(CH3)2 Ph3SiOH 13

H H O N H Ph Si C Ph Ph3SiO C Ph 3 NCPh H N Ph3SiOH N N

14 Scheme 5.

Brook O rearrangem ent t-BuMe2SiO KCN t-BuMe2Si O PTC t-BuMe Si R CN R CN 2 R CH2Cl2-H2O 15 (1:1) 16 17 (74-96%

R = Me, CH2CH2OMe, Ph, R'

PTC: n-Bu4PBr (20 mol%)

Scheme 6. 10 Patrocínio & Moran J. Braz. Chem. Soc. step of Corey’s total synthesis of pentacyclic triterpene 24 rearrangement and coupling with allylic bromide, resulted of the β-Amyrin family18. The addition of 2-propenyl- in the Z-olefin in an overall yield of 82% with excellent lithium to acylsilane 23, followed by a Brook stereoselectivity (> 95%).

Me Me Me BuLi Bu TBAF Bu SiMe3 Ph Ph Ph SiMe3 H HO O HO 18 (99:1) Scheme 7.

SiMe3 Nu Nu

SiMe3 H O Nu-M OH TBAF OH

CH2 Cl2 iv Ti OBn OBn OBn 19 (93-95% d.e., 90% yield) syn-20 (93-95% d.e., 52-96% yield)d

Nu-M = Allyl-SiMe3 , Methallyl-SiMe3 Scheme 8.

O HO SiMe2Ph HO H Allyl brom ide/In TB AF SiMe2Ph THF/1 5 h/rt NHBoc NHBoc NHBoc

(98% d.e., 96% yield) 21 (9 2 %)

OSiMe2t-Bu HO SiMe2Ph HO O OEt O H TB AF OEt OEt BF3 Et2 O, CH2 Cl2 -7 8 o C, 48 h NHBoc NHBoc

(98% d.e., 67% yield) 22 (98% d.e., 67% yield)

Scheme 9.

1. Li o OSiMe2Ph O , Et2O, -78 C, 1h o 2. BaI2, THF, -78 C, 1h SiMe2Ph

3. , -78 to 0 oC, O Br 15 min O Br Br 23 (82%)

Me Me

H Me HO H 24 S h 10 Scheme 10. Vol. 12 No. 1, 2001 Acylsilanes and Their Applications in Organic Chemistry 11

Syn-α-alkoxy-(β-silyloxy)acylsilanes 25 undergo retention of configuration15,22. The B-allyl(diisopino- chelation-controlled addition reactions with vinyl and campheyl)-borane has been also used for asymmetric phenyl Grignard reagents affording all-syn triols 26 with allylation of acylsilanes 32 (Scheme 13)23. diastereoselectivities up to >98:2 (Scheme 11)19,20. The addition of alkyl and phenyl lithium24,25 or Grignard The allylation reaction of acylsilane 27 has been reagents (Scheme 14)26 to acylsilanes 33 having a chiral applied to a stereoselective synthesis of allyl myrtanols center at silicon is also diastereoselective. High diastereo- 29 and 31 (Scheme 12)21. In this case, the reaction of 27 selective excesses are obtained with Grignard reagents by with tetraallyltin/Sc(OTf)3 provides an asymmetric means of a chelate-controlled reaction pathway involving induction opposite to that observed by using intermediate 34 (Scheme 15)24. Cyclopropanediol monosilyl allyltrimethylsilane/TiCl4. The configurations of 28 and ethers 36 and 37 are obtained with good diastereoselectivity 30 were tentatively assigned taking into account that the from reaction of benzoylsilane 35 with lithium enolates protiodesilylation generally proceeds with complete derived from methylketones (Scheme 16)27.

OR OR R Si R Si Nu-M 3 3 Nu

OOTBS OH OTBS

25 26 (48-96% d.e.; 86-96% yield)d

Nu-M: Allyl-Sn(Bu)3/ZnCl2; Vinyl-MgBr; Ph-MgBr R = MOM; BOM Scheme 11.

(CH2=CHCH2)4Sn Sc(OTf)3 TBAF o CH2Cl2, 10 C H THF, r.t. H

PhMe2Si OH H OH

H 28 (69% d.e.; 53% yield) 29

O SiMe2Ph CH =CHCH SiMe 27 2 2 3 TBAF TiCl4 o H THF, r.t. H CH2Cl2, -70 C

PhMe2Si H HO HO 30 (80% d.e.; 51% yield) 31 Scheme 12.

O (+)-[Ipc]2BAllyl HO 2 3 SiR R 2 1 2 3 R SiR 1 R 2 R 32 (02-92% e.e.)

1 R = 4-CF3-C6H4, 4-Me-C6H4, cyclopentyl R2, R3 = Me, Et, Ph

(+)-[Ipc]2BAllyl: (+)-B-allyldiisopinocam pheylborane Scheme 13. 12 Patrocínio & Moran J. Braz. Chem. Soc.

Ethynyl triphenylsilyl ketone 38 undergo stereospecific b. Stereocontrolled aldol reactions Michael addition with silylated nucleophiles28, dialkyl- cuprates29 and tributylstannyl-cuprate30 to afford only one Lithium enolates of propanoyl silanes 41 react with double bond isomer of β-functionalized propenoylsilanes aryl and alkyl aldehydes to afford mainly syn-β- depending on the type of nucleophile used. An interesting hydroxyacylsilanes 42, which can be converted into 43 as application of these reactions is the preparation of a variety the major product (Scheme 18) in 31-68% overall yields32. of α,β-unsaturated acylsilanes 40 by reaction of 38 with While benzaldehyde gives a modest syn/anti ratio, trimethylsilyl iodide yielding 39, which undergoes isobutyraldehyde gives good diastereoselectivity (syn/anti stereospecific palladium-catalyzed coupling with tin > 20). Adehydes having a chiral center on the α-carbon compounds (Scheme 17)31. react with 41, giving 44 in good diastereoselectivity.

O 1 R 3 3 R MgX/Et2O HO R 1 NH4Cl sat. R R2 Si Me -80 oC o 2 Si Me Ph -80 C R 33 Ph (9-79% d.e.; 63-98% yield)d R1 = n-Bu, t-Bu, α−Np; R2 = Me, Ph; R3 = Me, Ph Scheme 14.

2 1 2 R R R 2 R3 R1 R 1 t-Bu t-Bu R3 MgBr t-Bu R O MgBr 3 Si O Si O Si R O Et2 O o r T HF O OH Me Me Me

34 (46-99% d.e.; 42-98% yield) 1 2 3 R = MeOCH2 CH2 , PhCH2 ; R = Me, Ph; R = Me, Bu, Ph Scheme 15.

OLi O Me SiO O Me SiO O Me3Si O O 3 3 R Ph SiMe3 THF Ph R Ph R Ph R o 35 -80 to -30 C R = Et, n-Pr, i-Pr, t-Bu

Me3SiO OH HO OSiMe3

Ph R Ph R 36 (64-75%) 37 (7-21%)

Scheme 16.

O SiPh3 O O O RSnBu , PdCl (MeCN) Me 3 SiNu Me 3 SiI 3 2 2 Nu SiPh3 I SiPh3 R SiPh3 H 39 40 (64-86%) H 38

Nu = H2 N, MeNH, SPh ≡ R =R Me= Me3 SiC3SiC CC, CH2 =C(OE t), CH2 CH, 2-furyl, BOCNHCH2 CH=CH, Ph3 SiCOCH=CH Scheme 17. Vol. 12 No. 1, 2001 Acylsilanes and Their Applications in Organic Chemistry 13

Stereoselective intramolecular aldol reaction was production of acetylene derivatives 46, which are probably performed with bis-acylsilanes under Lewis acid activation formed by the addition of a silyl-radical 45 to another to give cis-β-hydroxyacylsilanes33. acylsilane molecule and involve two consecutive Brook rearrangements34. Other reactions such as intramolecular c. Acylsilanes in radical reactions radical cyclization reactions of acylsilanes (Scheme 20), aldol reactions (Scheme 21) and pinacol couplings 35 Lanthanoids, especially ytterbium and samarium, (Scheme 22) take place mediated by SmI2 . The example promote several kinds of reactions with alkanoyl and presented in Scheme 20 shows an interesting cis- aroylsilanes. The mechanism of these reactions is always stereoselectivity observed for the cyclization of the dependent on the metal and on the group attached to the acyltrimethylsilyl group (giving 47), while the diphenyl- carbonyl group (Scheme 19). An interesting point is the methylsilyl group gave poor (48:49) stereoselectivity.

O 1. LDA -78 oC OH O OH O 2. R2CHO 3. H2O2 1 2 1 2 SiR 3 R OSiR 3 R OH

41 42 43 (60 to >90% d.e.; 31-68% yield)

1. LDA, -78 oC

3 1 2. R CHO SiR3 R3 OH O 44 (72 to >90% d.e.; 44-48% yield)

1 1 2 3 R = Et or R 3 = t-BuMe2; R = Ph, i-Pr; R = Ph, (CH3)2C=CH Scheme 18.

RCH SiMe3

R = alkyl,alkyl aryland Ln = SmI2 OH Ln = SmI R = aryl 2and Ln = SmI2

O Yb O OLn O Ln R = aryl Yb R SiMe3 OO RC RC R SiMe3 THF CC R SiMe3 Ln = Yb SiMe3 SiMe3 Me3Si R 45 Me SiOYbO SiMe3 Yb(OSiMe ) 3 3 2 RCCR CC 46 R R Scheme 19.

SmI2/HMPA/t-BuOH SiMe3 O OH R = Me 47 (26%) SiMeR2

R = Ph OH SiMePh2

SiMePh2 OH 48 49 (49/48: 70/30 to 40/60; 32% yield)

Scheme 20. 14 Patrocínio & Moran J. Braz. Chem. Soc.

Trialkyltin radicals can promote intramolecular cyclization synthesis of endo bicyclic alcohol 60 from acylsilane 59 of acylsilanes 53-55 with alkyl, aryl and vinyl radicals, affording (Scheme 25)36a. On the other hand, bicyclic spiro-lactones 62 cyclopentyl silyl ethers 56 and 57 and enol silyl ether 58 and 63 are obtained in the reaction of 61 with methyl acrylate 36 (Scheme 23) by a mechanism involving a radical Brook and tributyltin hydride or CH2=C(CO2Et)CH2SnBu3 (Scheme rearrangement, as shown in the example outlined in the Scheme 26)37. For other examples see Tsai38, including tandem 2436c. An interesting application of the tandem cyclization- cyclizations with acylsilanes containing C=C or CºC groups addition reaction of acylsilanes is the diastereoselective attached at the silicon atom.

O

O O SmI2 OH THF, 22 oC SiMe3 SiMe3 50 51 (5 6 %) Scheme 21.

Sm O O O O

SmI2 SiMe3 HMPA SiMe3 SiMe3

52 (30%) Scheme 22.

OSiMe3 O

Bu3SnH/benzene Me3Si Br AIBN, reflux 53 56 (60%)

Br O OSiMe2Ph Bu 3SnH/benzene SiMe2Ph 80 o C, 2h

54 57 (83%)

OSiMePh2 O Br Bu3SnH/benzene AIBN, 80 o C, hv Ph2MeSi 55 58 (62%) Scheme 23.

O H OSiMe O SiMe3 OSiMe3 3 Bu SnH SiMe 53 3 3 AIBN CH2 56 Scheme 24.

O OH Me 1. n-Bu3SnH, AIBN SiMe3 2. TBAF

Br H 59 60 (81%) Scheme 25. Vol. 12 No. 1, 2001 Acylsilanes and Their Applications in Organic Chemistry 15 d. Cyclization reactions of acylsilanes contribution of the polarized resonance form II (Scheme 27)39. Scheme 28 presents examples of syntheses of In addition to the examples cited above, many other disilylhydropyranes 68 and disilylfurans 69 through a cyclization reactions involving acylsilanes can be found similar cyclization of 1,5-bis-acylsilanes 6640 and 1,4- in the literature. Carbonyl acylsilanes 64 provide furans bis-acylsilanes 6741 respectively, catalyzed by p-toluene- 65 under milder conditions and in higher yields than the sulfonic acid (TsOH). The nucleophilicity of the carbonylic common cyclization reactions of dicarbonyl compounds. oxygen in acylsilane is also observed in the cyclization of This advantage is derived from the high nucleophilicity γ- and δ-haloacylsilanes 70 affording 71 in reasonable to of the carbonylic oxygen in acylsilanes, due to the good yield (Scheme 29)42.

1. CH =CHCO Me, Bu SnH, AIBN 2 2 3 O O 2. TBAF O

SiMe3 62 (64%) 1. CH =C(CO Et)CH SnBu , AIBN I 2 2 2 3 O O 61 2. TBAF

63 (3 9 %) Scheme 26.

2 3 2 O R O 2 R R 1 R + 1 H 1 R R R Ph2MeSi 3 Ph2MeSi Ph2MeSi R 3 O O R O OH I II + 64 -H3O R3 R2 R1 = H, Me; R2 = H, Me; R3 = H, Me, Ph

Ph MeSi 1 2 O R 65 (57-87%) Scheme 27.

3 O O R TsOH R1 R2Si SiR4 R5 2 2 ∆ 1 2 4 5 3 R R Si O SiR R R 2 2 66 68 (50 - 94%)

O 12 34 3 4 R2RSi OSiR2R SiR R TsOH 1 2 2 R 2R Si ∆ 67 O 69 (68-71%) R1 = R2 = R3 = R4 = Me R1 = R3 = Me; R2 = R4 = t-Bu Scheme 28.

X X O O O NMP -HX

1 2 n 1 2 n 1 2 n R 2R Si R 2R Si R 2R Si 70 71 (49 - 97%) R 1 = Ph or Me; R2 = Me; n =1 or 2 NMP: N-methylpyrrolidone Scheme 29. 16 Patrocínio & Moran J. Braz. Chem. Soc.

α,β-Unsaturated acylsilanes 72 combine with anion13,45 to acylsilane 81 (or phenyllithium in an analogous 46 allenylsilanes 73 in presence of TiCl4 to produce [3+2] or reaction) produces a cyanohydrin which undergoes a [3+3] annulation products 74 and 75 in good yield. The course Brook rearrangement, followed by an intramolecular of the annulation reactions can be controlled to produce either alkylation to give cyclopropane 82 (Scheme 32). five- or six-membered rings by controlling the reaction e. Thioacylsilanes: preparation and synthetic applications temperature or by using an appropriate trialkylsilyl group in 72 (Scheme 30)43, since the initially produced cyclopentene The replacement of the C=O with the C=S functionality undergoes rearrangement at higher temperatures. in acylsilanes is possible by reacting acylsilanes such as α β On the other hand, , -unsaturated acylsilanes 76 and 83 with H2S/HCl or by treatment with (Me3Si)2S under α β 47 lithium enolates of , -unsaturated methyl ketones 77 afford CoCl2 catalysis . These highly reactive compounds are interesting [3+4]-annulation products 78 (Scheme 31)44. employed as unstable thioaldehyde equivalents and also These stereospecific reactions were proposed to occur by a to afford molecules containing the Si-C-S unit or to prepare concerted anionic oxy-Cope rearrangement through sulfur heterocycles. Contrary to the thiocarbonyl cyclopropanediolate intermediate 80. The addition of cyanide analogues, the thioacylsilanes as 84 having an α-hydrogen

O -78 oC, 1h t-BuMe2Si O R = t-Bu SiMe3 SiMe3 TiCl /CH Cl 74 (78%) SiMe2R 4 2 2 O 72 73 -50 oC, 2h

R = Me

SiMe3 75 (56%) Scheme 30.

O O O OLi R1 R1 R1 1.NBS TBS R2 2.TBAF R2 TBSO or mCPBAO X R2 X 76 77 78(67-84%, X = TMS) 79 (75-89%, from 78 X = TMS) (26-72%, X = SnBu3) (57-89%, from 78 X = SnBu) TBS: t-BuMe2Si TBAF: tetra-n-butylammonium fluoride mCPBA: m-chloroperbenzoic acid

O t t LiO SiMe2Bu OSiMe2Bu t mechanism: mecha nis m: SiMe2Bu Brook Li rearrangement OLi X X O X O R R

R

t t OSiMe2Bu OSiMe2Bu

oxy-Cope rearrangement OLi X X OLi R R 80

Scheme 31. Vol. 12 No. 1, 2001 Acylsilanes and Their Applications in Organic Chemistry 17 bonded to the C=S group exist in the thioenol tautomeric or tricyclic 91 structures depending upon the nature of the form affording compounds Z-α-silyl vinyl mercaptans48, alkyl chloride (Scheme 34)50. Scheme 35 presents some such as 85. These are interesting molecules because two reactions of thioacylsilanes 92 containing the ferrocene functional groups with opposite polarization are bonded moiety attached to the thiocarbonyl group51. Unlike to a single double bond. An example of these reactions is ketones and common acylsilanes, which need long reaction concisely outlined in Scheme 33 where halothioacylsilanes periods and high temperatures for replacement of the C=O 84 are cyclized in the presence of a base to provide 2-silyl- with the C=S functionality, acylsilanes containing thiocycloalkyl-2-enes 86 in good yields49. These ferrocene are converted readily into thioacylsilanes by compounds react with acid chlorides, such as 88 and 90, Lawesson’s52 reagent in high yields in a few minutes at in presence of a Lewis acid to give interesting bicyclic 89 room temperature.

O t-BuMe2Si O t-BuMe2SiO KCN (1.1 eq) CN CN t-BuMe2Si 18-crown-6 CH2 Cl2 Br Br Br 81

OSiMe2t-Bu CN 82 (75%) S 32 Scheme 32.

SH ( )n SiMe2Ph

NaHCO3 X 85 (87-100%) O S ( )n ( )n H2S/HCl NaOH SiMe2Ph SiMe2Ph Et2O ( )n X X 83 84 NaOH PhMe Si R 2 S n = 2-5, 9, 11; X = Cl, Br 86 (63-100%) Scheme 33.

O S SSiMe3 n AgBF4 n Cl CH2Cl2, (ClCH2)2 O 87 88 89 (n = 2-5, 83-91%)%

O

Cl

90 H S

n = 3 AgBF4 CH2Cl2 H O 91 (45%)

Scheme 34. 18 Patrocínio & Moran J. Braz. Chem. Soc. f. Acylsilanes derived from natural products difluorosilyl enol ether 95, formed by the reaction of acylsilane with trifluoromethylsilane, followed by Brook rearrangement We have already described the application of acylsilanes and the subsequent loss of fluoride ion, as outlined in Scheme 54 for the synthesis of a pentacyclic triterpene, vitamin D3 37 . The reaction of acylsilanes with trifluoromethyl- metabolites and in aminoalcohol synthesis. However, the use trimethylsilane has been utilized to afford alicyclic 2-fluoro- of acylsilane moiety in natural product synthesis is still very 1,3-diketone55, 2,2-difluoro-1,5-diketone56 and “difluoro-ar- restricted and few examples are found in the literature. Scheme tumerone” 9757, a sesquiterpene derivative with antitumor 36 shows an “acylsilane-sugar” 93 as the starting material to activity, as shown in Scheme 38. The stereoselective synthesis prepare C-difluorosaccharide 94. Sugar chemistry may be a of β- and γ-amino alcohols 100 and 101, starting from a natural good option for the preparation of optically active silanes, aminoacid and proceeding through the homochiral little explored to date53. The proposed mechanism of this aminoacylsilanes 98 and 99, reveals the great potential of these condensation of the saccharides is based on the highly reactive compounds as chiral building blocks (Scheme 39)58.

O

3 Fc SiMe2R R1 Lawesson`s Fc PPh3 CC reagent 3 2 ∆ R Me Si R C6H6, 2 S 1 2 1 (59 - 84%) R R CN2 Fc S R 3 3 Fc SiMe R Et O R Me Si 2 1 2 2 2 R Fc R 92 (55 - 94%) TBAF CC THF, r.t. H R2 ( 89 - 90 %)

S S TBAF S Fc Fc Fc 3 SiMe R3 H SiMe2R 2 3 (80 - 82%) (84 - 97%) (93% when R = Me)

1 2 3 R = H or Ph; R = CO2Et or Ph; R = Me or Ph; Fc = ferrocenyl Scheme 35.

OAc O O O Ac O Me3 Si . CF SiMe /CH Cl /cat./O oC O 1 3 3 2 2 F O F OBn OBn OAc O 2. O O AcO /BF3Et2O/CH2Cl2 O AcO -40 o C O 93 94 (α/β: 80/20; 75% yield)

+ - cat.: Bu4N Ph3SnF2 Scheme 36.

mechanism: O O Brook OSiMe3 rearrangement Me3Si CF3SiMe3 Me3Si

R CH2Cl2/cat. F3C F2C R R OBn 93 F O - R = O -F O OAc OAc O cat. Bu N+ Ph SnF - O AcO 4 3 2 O OSiMe AcO AcO F 3 F F F BF3Et2O R R 94 95 Scheme 37. Vol. 12 No. 1, 2001 Acylsilanes and Their Applications in Organic Chemistry 19

O F 1. CF SiMe /CH Cl /cat. 3 3 2 2 F SiMe , ZnBr 3 2. Br 2 O 96

cat.: Bu N+ Ph SnF - 4 3 2 97 (53%) Scheme 38.

NPht NPht (P hMe 2 Si)2 Cu(CN)(ZnCl)2 Me3Si Ph Cl Ph SiMe2Ph o THF, -20 C TiCl4 , CH2 Cl2 , O O -78 o C

98 (65% )

NPht TBAF, THF NPht Ph Ph r.t. HO SiMe Ph NPhtO HO 2 Ph 100 (>98%d.e., 60% yield) (>98% d.e., 75% yield) SiMe2Ph 99

NPht NPht OH Me Si OH TB AF , T HF 3 Ph Ph TiCl4 , CH2 Cl2 , r.t. -78 o C SiMe2Ph (>98% d.e., 80% yield) 101 (>98% d.e., 72% yield) Scheme 39. g. Reactions of α-haloacylsilanes triethylborane to α-iodoacylsilane provides boron enolate that reacts with aldehydes to give aldol types adducts with α In spite of -haloacylsilanes being little known, their good diastereoselectivity in reasonable yields61. reactions are very interesting due to a variety of products that they provide. Ketone enolates usually react with h. Acylsilane oxidation α-chloroacyltrimethylsilane under mild reaction conditions to give the corresponding 1,3-dicarbonyl compounds59. The acylsilanes have a much smaller oxidation Titanium tetrachloride promotes coupling reactions of α- potential than aldehydes and ketones due to the large chloroacylsilanes 102 to afford α-silyl ketones 103, β,γ- interaction of the C-Si bond with the lone electron pair of unsaturated ketones 106 and Friedel-Crafts type products the carbonyl oxygen62. This characteristic allows the 104 and 105 (Scheme 40). The intermediate acyl cation acylsilanes to suffer oxidation to the corresponding equivalent 109 was proposed to be responsible for the carboxylic acids mediated by peroxides63, ozone64 and formation of 103 (Scheme 41). An interesting observation electrochemistry65. The oxidation of acylsilanes has been in these reactions is the migration of silyl group and showing of great importance in organic synthesis, for subsequent loss of this moiety, which happens when R’ = example in chain homologation66 and as a precursor for Me or Ph, but not t-butyl. Apparently, the formation of the chiral esters (Scheme 43)67. The most common method for intermediate 107 is difficult when the silyl oxidation of acylsilanes utilizes peroxides but the group is very bulky (R’ = t-Bu). The presence of intermediate electrochemical method, although seldom applied, appears 107 was inferred from the aldol type products 10860 isolated to be advantageous because it permits the direct preparation upon addition of acetaldehyde to the reaction mixture. of acids, esters or derivatives, depending upon the Another example involving these α-haloacylsilanes is additive present during electrolysis. Recently, we introduced presented in Scheme 42, where α-bromoacylsilane 110 a new method for direct esterification of alkyl and reacts with zinc in a Reformatsky type reaction giving 111 aroylsilanes by means of iron (III) ion or nitric acid oxidation with high diastereoselectivity61. The addition of in dilute alcohol solution (Scheme 44)68. 20 Patrocínio & Moran J. Braz. Chem. Soc.

O H (OMe) R R' = Me OMe H (OMe) O O 104 (77-84%)

R SiMe3 R OMe SiMe2R' TiCl , CH Cl TiCl4, CH2Cl2 H (OMe) t-BuMe2Si 4 2 2 Cl O 103 (7 8 %) R'= t-B u R 102 R' = t-B u t-BuMe Si R = n-C3 H7 , n-C6 H13 2 R'= Me,Ph OMe SiMe3 TiCl4, CH2Cl2 105 (66-87%) O R O OSiMe2R' work-up CH3 CHO R R H OH CH3 106 (76-98%) 107 108 (70%) Scheme 40.

mechanism: SiMe3 Cl4Ti O TiCl4 O 102 R 103 R' = t-Bu Cl SiMe2t-Bu SiMe2t-Bu R 109

Scheme 41.

OZnBr O OZnBr BrZnO O Ph C O O Zn PhCHO PhCHO Br SiMe H SiMe3 3 Ph SiMe3 Ph SiMe3 R R R R 110

R = n-C H 6 13 O O O Ph C OH O Ph BrZnO O Ph O OZnBr H Ph SiMe3 Ph SiMe3 Ph SiMe3 R R R 111 (single diastereomer; 80% yield)

Scheme 42.

OH OH O O Et2 Zn/CH2 I2 1 . [O]-S we rn CH N C H 3 2 C4H9 4 9 C4H9 C4H9 MeO Me3Si Me3Si HO 2. H2O2, NaOH (9 7 %) (8 4 %) (8 6 %)

Scheme 43. Vol. 12 No. 1, 2001 Acylsilanes and Their Applications in Organic Chemistry 21

In this context, an important property of the acylsilanes are important substrates for bioreductions, from which is their oxidation through photoprocesses, affording the corresponding α-hydroxysilanes can be obtained with compounds such as carboxylic acids (promoted by room high enantiomeric excesses by using a variety of isolated light)69,70 or silylesters 112 and viniloxysilanes 114 as enzymes or microorganisms76. Scheme 48 shows one of principal products (Scheme 45)71. Also see Brook72 for other the first reports of this methodology, the acylsilane 119 examples of classical photolyses reactions of acylsilanes. being reduced by Trigonopsis variabilis 20 times faster than the analogue dimethylphenylpropanone77. Although i. Enantioselective reduction of acylsilanes Saccharomyces cerevisiae is one of the most commonly used micro-organisms in enantioselective reductions of Chiral boranes have been used for enantioselective ketones, it is usually inert toward substrates possessing reduction of acylsilanes affording optically active alcohols steric hindrance78 or having electron-donating groups (Scheme 46)73,74. Compound 115 was used as homochiral attached to the aromatic ring of the aroyl ketone79. On building block in the synthesis of (+)-sesbanimide A20. the other hand, aroylsilanes such as 121 were reduced by Scheme 47 shows an interesting reduction of α,β- this microorganism, affording the corresponding α- unsaturated acylsilanes 116, which is mediated by the hydroxy-silanes 120 and 122 with enantiomeric excesses chiral lithium amide 117 affording alcohols 118 in varying from 43 to 88%, Scheme 4980. The disadvantage excellent enantiomeric excesses75. in using acylsilane bioreductions is the required lengthy Because of the higher reactivity of the carbonyl group period of reaction, which generally leads to the formation of acylsilanes compared to the analogous ketones, of by-products such as primary alcohols and carboxylic attributed mainly to the high polarization of the acids from C-Si bond cleavage. A radical oxidation of acylsilane carbonyl group, these compounds can react acylsilanes seems to be responsible for the formation of with weak nucleophiles. Therefore, these organosilanes carboxylic acids81.

O O O HNO3 R'OH R'OSiMe R OR' 3 R SiMe3 r.t. R SiMe3 (88-100%)

R = Ph, p-MeOC6H4, C5H11; R`OH = H2O, MeOH, EtOH, n-PrOH, n-BuOH, n-C6H13OH

Scheme 44.

O O λ > 345 nm Me3Si OCH3 CH OSiMe CH3 SiMe3 O2 3 3 112

λ > 280 nm Ar, 10 K

CH3 Me3Si O CH 3 Me3Si O

s-E-113 s-Z-113

CH2 Ar, 45 K Me3Si Me3Si OCH2 O

s-E-114 s-Z-114

Scheme 45. 22 Patrocínio & Moran J. Braz. Chem. Soc.

O H OH (-)-[Ipc]2BCl a) R SiR'3 R SiR'3 (80-98% e.e.; 11-93% yield)

R' = Me, Et, n-Bu, i-Pr, t-Bu, Ph ; R = Me ; Et ; i-Pr, H2C=CH, (CH3)2C=CH,, , , O Me

Me 2 PhSi (-)-[Ipc]2BCl Me 2 PhSi b) OBn OBn O H OH (R)-(+)-115 (87-92% e.e.; 76% yieldd)

(-)-[Ipc]2BCl: (-)-B-chlorodiisopinocampheylborane Scheme 46.

Ph H t N Bu N Li O HO H N R2 3 R2 3 117 SiMe2R SiMe2R 30 min,THF R1 R1 116 118 (ee > 99%; 31 - 68% yield) 1 2 3 R = Me, i-Pr, -(CH2)3-; R = H; R = t-Bu or Ph Scheme 47.

Me O Me OH Trigonopsis variabilis H Ph Si C Ph Si C Me Me Me Me 119 (86% e.e.; 70% yield)d Scheme 48.

OH H H OH O

S.c S.c SiMe3 SiMe3 SiMe3 G G G

R-(+)-120 (79% e.e.; 20% yield) 121 S-(-)-122 (43-88% e.e.; 45-70% yield)

G = 2-MeO G = H; 4-MeO; 3,4-(OMe)2; 3,4-(OCH2 ) S.c. = Saccharomyces cerevisiae Scheme 49.

In Scheme 50 there is an interesting example of the Chiral secondary silyl alcohols may also suffer thermal bioreduction of a racemic acylsilane (±)-123 containing rearrangements through their acylated derivatives followed asymmetric silicon that was applied to afford chiral silyl by oxidative cleavage74,82 that occurs with high compounds. Thus, acylsilane (-)-123, prepared by stereocontrol83, giving optically active alcohols. oxidation of (+)-124, was treated with phenyllithium, the asymmetric silyl group being a chiral inductor. After the Synthesis of acylsilanes Brook rearrangement promoted by KH, the silyl group was removed by tetrabutylammonium fluoride (TBAF), giving In 1957, Brook reported the first synthesis of an acylsilane, the enantiomerically enriched alcohol (R)-(+)-12725. benzoyltriphenylsilane, which was accomplished by the Vol. 12 No. 1, 2001 Acylsilanes and Their Applications in Organic Chemistry 23 reaction of triphenylsilylpotassium with benzoyl chloride conditions which may lead to C-Si bond cleavage. In this in only 6% yield. The same compound was prepared in review, some of the methodologies developed for much better yield by hydrolysis of dihalide compound acylsilanes synthesis will be introduced concisely. A useful 128 (Scheme 51)84. summary is presented in the Chart, showing that some of The biggest problem in the synthesis of acylsilanes is the common organic functional groups may be used for the instability of these compounds under many reaction the preparation of acylsilanes.

BnO BnO O Trigonopsis BnO variabilis OH OH Si Si Si t-Bu t-Bu H Me H Me Me Me Me t-Bu Me

( )-123 (+)-124 (96% e.e.) (+)-125 (96%e.e.)

(COCl)2, Et3N, DMSO

BnO BnO O PhLi OH KH BnO TBAF O H HO H t-Bu Si Si t-Bu Me Si Me Me Me Me t-Bu Me Ph Me Ph Ph ( )-123 (95%) 126 (86%) (R)-(+)-127 (88%e.e; 70% yield) Scheme 50.

Ph Ph Ph O AgOAc Ph Si CH2Ph 2 NBS Ph Si CBr2Ph Ph Si C H2O Ph Ph Ph Ph (78% yield) NBS: N-bromosuccinimide 128 Scheme 51.

Br Br OH 1 C 1 R R R C Si 2 R Si 2 3 R R R R3

O O R1 O C C C R Si RH RSN R2 R3

O O C C ROMe RCl O C RNMe2

Chart. 24 Patrocínio & Moran J. Braz. Chem. Soc. a. From α-silyl alcohols2,4 136 in good to excellent overall yields (Scheme 55)88. Recently, we have found that potassium permanganate α -Silyl alcohols can be prepared by several methods, supported onto alumina transforms silylalcohols to such as the condensation of trialkylsilyl anions with aroylsilanes in good yields, without significant Si-C bond 85 aldehydes and the transmetalation of trialkylstannanes cleavage or over-oxidation to carboxylic acid89. followed by a reverse Brook rearrangement86. The oxidation of a-silyl alcohol 129 with ordinary oxidizing b. From masked aldehydes reagents like permanganate and chromic acid leads to acylsilanes 130 (Scheme 52). However, this route has The addition of silyllithium reagents to aldehydes gives several limitations since Si-C bond cleavage may compete α-silyl alcohols, which may be oxidised to acylsilanes as (Scheme 53)2, and the products may suffer over-oxidation commented above. However, aldehydes 137 are more to carboxylic acids (Schemes 43 and 44). Very mild commonly converted into acylsilanes 139 by the dithiane conditions, such as those present in Swern oxidation, are route (the methodology90, Scheme 56). The the most indicated options. In the example showed in hydrolysis of 2-silyl-1,3-dithianes 138 was first investigated Scheme 5487,3, the “reverse Brook rearrangement” in simultaneous work by Brook91 and Corey92, and it is (131→132), followed by a mild oxidation, is employed one of the most useful methodologies for acylsilanes for the synthesis of α,β-unsaturated acylsilanes 133. synthesis. The great advantage of this method is the variety Silylalcohol 135, prepared by nucleophilic opening of of compounds that can be prepared, including aroylsilanes, epoxide 134, was oxidized under extremely mild condition alkanoylsilanes, and functionalized acylsilanes. In general, by the use of the Dess-Martin reagent, giving acylsilanes the first and second steps (Scheme 56) afford products in

OH O [O] R3Si CH R' R3Si C R' 129 130 Scheme 52.

O Cr OH R HO R O O R -H2CrO3 H C OH HOHC O Cr HCO R3SiOH -H2O SiR'3 SiR'3 O H2O Scheme 53 Scheme 53.

n-BuLi t-BuLi Li R R OH OSiMe3 R OSiMe Me3SiCl 3 R' R' R' R = H, n-C7H15; R' = H, CH3 131

O OH OLi

[O]-Swern H3O R R R SiMe3 SiMe3 SiMe3 R' R' R' 133 (64-79% overall yield) 132 Scheme 54.

O - Nu Si(i-Pr)3 [O]-De s s -Ma rtin Si(i-Pr)3 Nu Nu Si(i-Pr)3 OH O 134 135 (71-91%) 136 (72-87%) Scheme 55. Vol. 12 No. 1, 2001 Acylsilanes and Their Applications in Organic Chemistry 25 high yields, but the hydrolysis step may be problematic. is well known and proceeds by the reaction of esters with Although there are many procedures for the regeneration of silyl-Grignard derivatives, forming silylacetals 143 the masked carbonyl group in dithianyl compounds93, the (Scheme 58)98. This method generally gives poor yields most frequently applied reagents for 2-silyldithianes 138 and hence has been seldom employed. One-pot synthesis are mercury salts, the oldest methodology for hydrolysis. of aroylsilanes based on reductive silylation of Generally, the hydrolysis with mercuric chloride is very slow, methylbenzoates using Mg/I2/chlorosilane/NMP thus the product aroylsilanes may suffer degradation, as (1-methyl-2-pyrrolidinone) affords aroylsilanes in mentioned earlier. Other methods have been applied for the moderate yields99. regeneration of the masked carbonyl group, giving Compounds containing lithium attached to the silicon acylsilanes in good yields. Among these, we may mention are extremely important reagents in organosilane treatment with methyl iodide41, chloroamine-T33, chemistry. Dimethylphenylsilyllithium (144) is probably 94 95 I2/CaCO3 , anodic oxidation and oxidative hydrolysis the most useful silyllithium for synthesis, due to the aryl mediated by N-bromosuccinimide (NBS)96. group that gives good anion stability and to the fact that The benzotriazole derivatives 140 present a similar this reagent can be readily prepared from the approach to the dithiane methodology, offering advantage corresponding chlorodimethylphenylsilane by its in the hydrolysis step. The hydrolysis of intermediate 141 reaction with lithium in THF100. On the other hand, occurs in situ and under mild conditions, giving the desired trimethylsilyllithium is readily obtained by the reaction aroyl, heteroaroyl, alkenoyl and alkynoylsilanes 142 in of hexamethyldisilane with methyllithium101. These excellent yields (Scheme 57)97. compounds react with esters or amides to afford acylsilanes (Scheme 59)102. Amides appear to be more c. From esters and amides useful, giving better yields than the traditional reaction The synthesis of acylsilanes by reductive silylation with esters, which require much lower temperatures.

O O HS(CH2)3SH S S 1. n-BuLi S S hydrolysis C C C C R BF OEt ' RSiR'3 H 3 2 RH2. R 3SiCl RSiR'3 137 138 139 Scheme 56.

N N 1. BuLi BtH, HC(OEt)3, ' N O O N 2. R 3SiCl EtOH, THF N N HCl/H2O THF, -78 oC SiR'3 R H r.t. r.t. R SiR'3 R OEt R OEt

140 141 142 (57 - 97%)

R = aryl and heteroaryl ; substituted alkenyl and akynyl Scheme 57.

O OMe O Me3SiCl H2O/HCl Ar C OSiMe3 MeOSiMe3 Ar OMe Mg/HMPT Ar SiMe SiMe 3 3 (05 - 75%) 143 Scheme 58.

O O O O R NMe R OMe 2 PhMe SiLi R SiMe Ph o 2 o R SiMe Ph 2 -7 8 C -1 1 0 C 2 (69-91%) 144 (70-76%)

R = Me, C2H5 , t-Bu R = Me, Ph Scheme 59. 26 Patrocínio & Moran J. Braz. Chem. Soc.

In general, the reaction of silyllithium with esters affords acylsilanes. However, this procedure is not general due to the disilylalcohols as undesirable by-products due to double complex reaction mixtures that it provides. On the other hand, nucleophilic attack at the carbonyl group. However, these lithium silylcuprates like 148 react with a variety of acid alcohols, such as 145, have been oxidized by PDC chlorides, giving acylsilanes with good yields, offering (pyridinium dichromate)102, tert-butyl hypochlorite103 advantages over the silyllithium methodology since fewer and lead tetraacetate104 (Scheme 60) to the corresponding by-products are formed106. These cuprates are traditionally acylsilanes. This latter method was recently reported, and obtained from the reaction of an alkylsilyllithium with CuCN involves a “radical Brook rearrangement” providing or CuI107. A limitation of this methodology is that high order acylsilanes in good yield after treatment with silica gel. cuprates are very reactive towards a variety of functional groups. The mixed Cu-Zn complex 147 is less reactive than d. From S-2-pyridyl esters ordinary cuprates, and therefore this type of complex has been applied to the synthesis of acylsilanes containing cyano, S-2-Pyridyl esters 146 react very smoothly with halo, ester and other groups (Scheme 62)6,108. Al(SiMe ) in the presence of CuCN to afford acylsilanes 3 3 Yamamoto and co-workers109 prepared aroylsilanes by in good to excellent yields (Scheme 61). This method may reaction of disilanes (compounds with Si-Si bond) with be applied to substrates having various groups such as benzoyl chloride under palladium catalysis. However this alkoxyl, acetal, ester, or an isolated double bond. Chiral method is not suitable for aliphatic acylsilanes, giving centers α to the carbonyl group are not epimerized under low yields of products. The methodology presented in the reaction conditions105. Scheme 63 is a good alternative, providing both aroyl and alkanoylsilanes by reacting the acid chlorides 149 with e. From acid chloride the polarised Si-Sn bond of 150 (weaker than the Si-Si Treatment of silyllithium with acid chloride gives bond in the disilanes)110.

1. Ph Me SiLi 2 O O THF Pb(OAc) SiO2 PhMe2Si OH 4 PhMe2SiO OAc Ph SiMe Ph Ph OR 2. H2O Ph SiMe2Ph Ph SiMe2Ph 2 145 (94%) Scheme 60.

O O Al(SiMe3)3 R SN CuCN, THF, 0 oC to RTr.t. R SiMe3 146 (61-98%)

R = C9H19; Ph; PhCH=CH; TBDMSO(CH3)CH; BOMOCH2(CH3)CH; Ph(CH3)CH Scheme 61.

O (Me2PhSi)2CuCN(ZnCl)2 O (Me3Si)2CuCNLi2 O 147 148

R SiMe2Ph R Cl R SiMe3 (50 - 95%) (40 - 87%) Scheme 62.

O O η3 5% [( C3H5)PdCl]2 Me3SiSnBu3 SnBu3Cl R Cl R SiMe3 10% (EtO)3P 149 150 (30-74%)

R = n-C4H9, n-C7H15, C4H9(Et)CH, c-C6H11, Ph, o-ClC6H4, p-CH3OC6H4 Scheme 63. Vol. 12 No. 1, 2001 Acylsilanes and Their Applications in Organic Chemistry 27 f. From other organic functionalities which is obtained from an ethereal solution of t- BuMe2SiCHBr2 and lithium diisopropylamide, provides The application of α,β-unsaturated acylsilanes as silyloxiranes 157 which undergo rearrangement, yielding building blocks for organic synthesis is well known in α-bromoacylsilanes 158 in reasonable yields (Scheme such important reactions as the Diels-Alder one111, thermal 66)117. This method is a recent example of an α- rearrangements and cyclizations, as commented above. A bromoacylsilane preparation, where the formation of 2- common method for alkenoylsilane synthesis goes through silyloxiranes 157 is proposed by the authors, based on a the allenylsilanes 151 and is known as Reich’s procedure known method for synthesis of α-iodo, α-fluoro, α-bromo (Scheme 64)113. Scheme 65 summarizes another method and α-chloroacylsilanes 160 from silyloxiranes 159 for the preparation of α-substituted-α,β-unsaturated (Scheme 67)61. acylsilanes 155 from silylpropargyl derivative 152 in a Acylsilane 164 could be prepared in a one-pot methodology involving silyloxy allene formation, a procedure from vinyl ether 161 by the reaction of “reverse Brook rearrangement” (153→154) followed by intermediate 162 with trialkyl silyl chloride in pentane the addition of an aldehyde. at –78 oC, followed by mild acid hydrolysis of 163 Several methods for the preparation of haloacylsilanes (Scheme 68)32,118. Starting with allylic alcohol 165, are reported in the literature, such as bromination of silyl acylsilane 23 was prepared in a one pot procedure enol ethers115 and halogenation of alkyl enol ethers116 (Scheme 69)18. This acylsilane was used in the Corey’s with N-bromosuccinimide (NBS) or N-chlorosuccinimide total synthesis of triterpenes as presented earlier in (NCS). The reaction of ketones with silyl carbanion 156, Scheme 10.

OO Me2RSi OEE O 1.n-B uLi H2SO4 2. Me RSiCl SiMe R 2 H2O 2 R = Me, t-B u 151 (8 1 -8 6 %) (6 5 -8 4 %) Scheme 64.

OOH RSiO LiO 1. t-BuOK R'CHO RSiOCH2 H CC CH2 CCCH2 RSi R' 2. t-BuLi Li RSi

152 153 154 155 (27-92%)

R = TBDM (t-BuMe2) or TIP (triisopropyl) Scheme 65.

Br Br R t-BuMe Si R R2CO TME DA 2 t-BuMe2Si C Li t-BuMe2Si C C OLi Et 2O Br Br Br R O R 156 157

R = Ph, Et or -(CH2 )5 -

O R t-BuMe2Si Br R 158 (5 0 - 7 2 %) Scheme 66. 28 Patrocínio & Moran J. Braz. Chem. Soc.

O n-C H 6 13 SiMe2R Y Metal salt H SiMe2R H X Et2O or acetone O n-C6H13 159 160 (4 9 -9 6 %) R = Ph, Me, t-Bu X = Cl or Br Y = Cl, Br, I or F

Metal salts: ZnCl2, ZnBr2, NaI, AgBF4 Scheme 67.

Li SiR3 O t-BuLi/TMEDA ClSiR3 HCl/MeOH OCH3 o o o SiR -7 8 C OCH3 -78 C OCH3 0 C 3 161 162 163 164

R = t-BuMe2, Et, n-Pr Scheme 68.

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