Organosilicon Compounds As Water Scavengers in Reactions of Carbonyl Compounds Organosilicondmitriy Compounds As Water Scavengers M

REVIEW 3719

Organosilicon Compounds as Water Scavengers in Reactions of Carbonyl Compounds OrganosiliconDmitriy Compounds as Water Scavengers M. Volochnyuk,*a,b Sergey V. Ryabukhin,a Andrey S. Plaskon,a Oleksandr O. Grygorenkoa,c a Enamine Ltd., Alexandra Matrosova Street 23, Kyiv 01103, Ukraine Fax +38(44)5024832; E-mail: [email protected] b Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Murmanska Street 5, Kyiv 02660, Ukraine c Department of Chemistry, Kyiv National Taras Shevchenko University, Volodymyrska Street 64, Kyiv 01033, Ukraine Received 16 July 2009; revised 6 August 2009

organic acids (e.g., acetic, formic or p-toluenesulfonic) or Abstract: The literature data on the application of organosilicon 2 compounds as water scavengers in reactions of carbonyl com- amines (triethylamine, piperidine, pyridine, etc.). How- pounds is surveyed. The reactions leading to both carbon–carbon ever, the latter lack sufficient dehydrating activity, there- (in particular, aldol-type condensations) and carbon–nitrogen bond fore they can be used only if the reaction equilibrium is formation, the synthesis of iminium salts by elimination reactions shifted towards the products. Otherwise, additional tools and heterocyclizations are considered. should be applied to make the equilibrium state more fa- vorable, such as azeotropic distillation of water and use of 1 Introduction ceolytes or anhydrous inorganic salts. 2 Reactions Leading to Carbon–Carbon Bond Formation 2.1 Aldol-Type Condensations The methods mentioned above still find application; 2.2 Other Reactions nevertheless, they cannot satisfy the growing demands of 3 Reactions Leading to Carbon–Nitrogen Bond Formation organic and medicinal chemistry. Therefore it is not sur- 3.1 Two-Component Condensations prising that water scavengers have evolved drastically 3.2 Three-Component Condensations th 4 Formation of Iminium Salts by Elimination Reactions since the 19 century (Figure 1). Some examples of these 5 Heterocyclizations regents include Al2O3, MgO, TiCl4, cation-exchanged 5.1 Synthesis of O- and O,N-Containing Heterocycles zeolites, SiO2, calcite, fluorite, modified Mg-Al hydro- 5.2 Synthesis of Pyrimidines by Biginelli Reaction talcite, and Lewis acidic ionic liquids.3–7 Several criteria 5.3 Synthesis of Other N-Containing Heterocycles for reagents that can be expected to be efficient as water 5.4 Recyclization of 3-Formylchromones scavengers are formulated from both the literature data 6 Conclusions and our own experience (the most critical are italicized): Key words: carbonyl compounds, condensation, organosilicon compounds, water scavengers, chlorotrimethylsilane – stability to air exposure and long-term storage; – commercial availability and low cost; – wide applicability; – solubility in common organic solvents; 1 Introduction – high activity under normal conditions and the possibility of use at elevated temperatures; The chemistry of carbonyl compounds has always attract- – simple and efficient synthetic protocols; ed the attention of organic chemists because of their great – high selectivity, conversion and yields in the reactions; synthetic potential that has not yet been exhausted despite – simple procedures for the separation of the products Downloaded by: University of Chicago. Copyrighted material. the overwhelming amount of research performed in this formed from the scavenger. area. Most of the reactions of these compounds (e.g., al- Organosilicon compounds satisfy most of the require- dol-type condensations, imine synthesis, heterocycliza- ments cited above. The chemical behavior of these com- tions) result in water formation. Therefore, the successful pounds is determined primarily by the tendency of the outcome of these reactions relies on the use of appropriate silicon atom to expand its valence shell, giving rise to reagents that can act not only as catalysts but also as water five- and six-coordinate intermediates, therefore, they can scavengers. The early examples of the reagents of that be considered as Lewis acids. Unlike many traditional type included concentrated inorganic acids (H2SO4, 1 metal-centered activators, silicon Lewis acids are compat- H3PO4, etc.) and alkalis [e.g., NaOH, KOH, Ba(OH)2]. ible with most synthetically valuable nucleophiles and are Despite the high catalytic and dehydrating activities of not prone to aggregation, thus substantially simplifying these systems, they lack efficiency as most of the sub- the analysis of the reaction mechanisms.8 strates are unstable under the reaction conditions. One way to solve this problem is to use milder reagents such as Most of the organosilicon compounds discussed in this review are halogenosilanes (in particular, chlorotrimethylsilane). Apart from increasing the Lewis acidity of silicon SYNTHESIS 2009, No. 22, pp 3719–3743xx.xx.2009 atom, the intrinsic role of the halogeno substituent is relat- Advanced online publication: 22.10.2009 ed to the high acceptability of Si–X bond towards hydrol- DOI: 10.1055/s-0029-1217066; Art ID: E24909SS ysis which is explained by the strong preference of silicon © Georg Thieme Verlag Stuttgart · New York 3720 D. M. Volochnyuk et al. REVIEW to form silicon–oxygen bonds. In addition, an easily re- scavengers in the reactions of carbonyl compounds. The movable hydrogen halide is formed upon hydrolysis of reactions leading to carbon–carbon and carbon–nitrogen halogenosilanes (Scheme 1), which increases the catalytic bond formations, formation of iminium salts by elimina- activity of the system further. The advantages that halo- tion reactions, and heterocyclizations are all considered. genosilanes have as water scavengers in reactions of car- In some cases, related transformations resulting in elimi- bonyl compounds are summarized in Figure 2. nation of small molecules other than water are also dis-

cussed. It should be noted that the use of polyphosphoric

2 TMSCl + H O (TMS) O + 2 HCl

2 2 acid trimethylsilyl ester (PPSE) and related compounds is beyond the scope of this review, as the properties of this Scheme 1 Hydrolysis of chlorotrimethylsilane water scavenger are defined by the P–O–P fragment and are not related to the silicon atom.9 The main goal of this review is to survey the literature data on the application of organosilicon compounds as water

Biographical Sketches

Dmitriy M. Volochnyuk try, National Academy of ment, senior scientific was born in 1980 in Irpen, Sciences of Ukraine under worker, and Enamine Ltd Kiev region, Ukraine. He the supervision of Dr. A. (Kiev, Ukraine), as Director graduated from Kiev State Kostyuk with research con- of Chemistry. His main in- University, Chemical De- centration in the chemistry terests are fluoroorganic, or- partment in 2002 and was of enamines. At present, he ganophosphorus, hetero- awarded an MS in chemis- divides his time between the cyclic and combinatorial try. He recieved his PhD in Institute of Organic Chem- chemisiry. He is co-author chemistry in 2005 from In- isty, as deputy head of the of 61 papers. stitute of Organic Chemis- Organophosphorus Depart-

Sergey V. Ryabukhin was chev. At present, he works combinatorial chemistry, born in Kirovograd in 1979. in Enamine Ltd. (Kyiv, molecular design, drug dis- He received his MS in Ukraine) as a director of the covery, modern methods in chemistry (2001) and PhD Combinatorial Chemistry organic synthesis, chemistry in organic chemistry (2007) Department and lectures of heterocyclic compounds, from Kyiv National Taras about combinatorial chem- bioorganic and medicinal Shevchenko University un- istry in Kyiv National Taras chemistry. He is co-author der the supervision of Prof. Shevchenko University. His of 30 papers. Dr. Sci. Andrey A. Tolma- scientific interests include

Andrey S. Plaskon was vision of Prof. Dr. Sci. ment at Enamine Ltd (Kyiv, born in 1982 in Kalush, Andrey A. Tolmachev. At Ukraine). His scientific in- Ukraine. He received his present he divides his time terests are focused on chem- Downloaded by: University of Chicago. Copyrighted material. MS in chemistry in 2004 between Kyiv National istry of heterocycles and and PhD in organic chemis- Taras Shevchenko Univer- combinatorial chemistry. try in 2009 from Kyiv sity as scientific worker and He is co-author of 28 pa- National Taras Shevchenko as researcher in the Combi- pers. University under the super- natorial Chemistry Depart-

Oleksandr O. Grygorenko At present, he divides his organic synthesis, molecu- was born in Brody in 1982. time between Kyiv National lar rigidity concept, chemis- He received his MS in Taras Shevchenko Univer- try of amino acids and chemistry (2004) and PhD sity as Assistant Professor, related compounds, bioor- in organic chemistry (2007) and Enamine Ltd. (Kiev, ganic and medicinal chem- from Kyiv National Taras Ukraine) as researcher in the istry. He is co-author of 8 Shevchenko University un- Custom Synthesis Depart- papers. der the supervision of Prof. ment. His scientific interests Dr. Sci. Igov V. Komarov. include modern methods in

Synthesis 2009, No. 22, 3719–3743 © Thieme Stuttgart · New York REVIEW Organosilicon Compounds as Water Scavengers 3721

Figure 1 Evolution of water scavengers

O O O O O TMSCl 2 + R R1 H R2 20 °C, 72 h R1

1 2 1a, R = n-Bu, R = OEt

1 2 1b, R = n-C7H15, R = OEt

1 2 1c, R = Ph, R = OEt

1 2 1d, R = n-Bu, R = Me

Scheme 2

The method was extended to some other carbonyl compounds.10b In particular, Knoevenagel adduct 1d was obtained in condensation of butyraldehyde and acetylacetone. Reaction of benzaldehyde with diethyl ma- lonate or p-bromoacetophenone in the presence of chlorotrimethylsilane required the use of zinc chloride as co- catalyst; compounds 2a,b were obtained from these reac- Figure 2 Advantages of chlorotrimethylsilane as water scavenger tions in 60–70% yields. Reaction of benzaldehyde with acetylacetone, acetophenone and a-bromoacetophenone afforded the b-chloro ketones 3, 4a and 4b, respectively 2 Reactions Leading to Carbon–Carbon Bond (Scheme 3).

Formation Downloaded by: University of Chicago. Copyrighted material. A chlorotrimethylsilane–N,N-dimethylformamide system was applied to the synthesis of 5-(arylmethylene)hexahy- In this section, silicon-promoted reactions of aldehydes dropyrimidine-2,4,6-triones 5 (from barbituric acid and and ketones with carbon nucleophiles such as carbonyl the corresponding aromatic aldehydes) possessing immu- compounds, activated alkenes and aromatic compounds nosuppressive, fungicidal and anti-inflammatory activi- are considered. Most of the reactions discussed include ties (Scheme 4).11 the use of chlorotrimethylsilane itself, or as a reagent component, as water scavengers. Combinations of chlorotrimethylsilane with other Lewis 12–14 13 15 16 acids (e.g., SnCl2, BF3·OEt2, TiCl4 or InCl3 ) were found to be efficient as promoters for the addition reac- 2.1 Aldol-Type Condensations tions of aldehydes, acetals and a,b-unsaturated ketones One of the first literature examples of chlorotrimethylsi- with p-donor alkenes (enol silyl ethers, dihydropyrans, lane-mediated aldol-type condensation was reported by styrenes) as well as for Knoevenagel-type condensations Zav’yalov and co-workers.10a Aliphatic and aromatic al- under very mild conditions.8 For example, adduct 6 was dehydes reacted with ethyl acetoacetate under mild condi- obtained in 64% yield by the reaction of 3-phenyl-1,1- tions to give Knoevenagel adducts 1 in 70–75% yields dimethoxypropane (7) and 3,4-dihydropyran in the pres- (Scheme 2). ence of chlorotrimethylsilane and tin(II) chloride at 0 °C (Scheme 5).12

Synthesis 2009, No. 22, 3719–3743 © Thieme Stuttgart · New York

3722 D. M. Volochnyuk et al. REVIEW

O O O

O O

O Pd/C, TMSCl

TMSCl

OEt Ph

+ Ar Ar +

ZnCl

Ph H DMF, 5 h OEt EtO Ar H

EtO O 79–90%

n n

8a, n = 0 2a

8b, n = 1

O O

O TMSCl

Ph +

ZnCl

2 Ph H

Pd/C, TMSCl

+ Ar

Br Br

Ar H

DMF, 5 h 2b

70–85%

O Cl

O O O

TMSCl

+ Scheme 6

Ph H

(59%)

3 8 in high yields. In the case of cyclooctanone, the 1:1 ad-

O Cl ducts 9 were obtained exclusively (Scheme 6).

O O

TMSCl, ZnCl 2

X Reaction of acetophenones and aromatic aldehydes under

Ph Ph

Ph Ph H the conditions described above allowed for the substituted

X alkylideneacetophenones 10 to be obtained, whereas the 4a, X = H (44%)

, X = Br (92%) 4b analogous transformation in the case of cycloalkanones Scheme 3 and aliphatic aldehydes led to the 2-alkylidenecyclo- alkanones 11 (Scheme 7). These products were also

obtained when a chlorotrimethylsilane–ytterbium(III) tri-

O flate system was used as reaction promoter.18 R O

TMSCl–DMF

HN +

O O O R

H Pd/C, TMSCl

O N O

+ O N O

1 2 1 2 DMF, 5 h Ar H Ar Ar Ar

5 (85–92%)

O O

Scheme 4 O

Pd/C, TMSCl

R H DMF, 5 h

OMe OMe

TMSCl

n n

OMe Ph Cl Ph – TMSOMe 11 R = alkyl

7 Scheme 7

SnCl 2

OMe a,a¢-Bis(benzylidene)cycloalkanones 8 were also ob-

OMe O

– tained, in 70–95% yields, by the reaction of alicyclic ke-

+ SnCl

– SnCl 2

Ph tones and aromatic aldehydes in the presence of

Ph O Cl iodotrimethylsilane, generated in situ from chlorotrimeth- Downloaded by: University of Chicago. Copyrighted material.

ylsilane and sodium iodide in acetonitrile (Scheme 8).19

TMSOMe

– TMSCl

O O

OMe

TMSCl, NaI

Ar Ar

Ar H

n n

Ph O OMe

8 6 Scheme 8 Scheme 5 The chlorotrimethylsilane-induced condensation of 2,5- Recently, a system of chlorotrimethylsilane, N,N-dimeth- dihydro-2,5-dimethoxyfuran (12) and aromatic or het- ylformamide and palladium-on-carbon was shown to be eroaromatic aldehydes led to the formation of the corre- an efficient catalyst in the aldol condensation of aldehydes sponding g-arylidene-a,b-butenolides 13 in 17–62% 20,21 with cycloalkanones and acetophenones.17 In particular, yields (Scheme 9). the reaction of cyclopentanone and cyclohexanone with All of the procedures described above for Knoevenagel- aromatic aldehydes led to the formation of the 2:1 adducts type condensations are limited in scope due to the volatil-

Synthesis 2009, No. 22, 3719–3743 © Thieme Stuttgart · New York

REVIEW Organosilicon Compounds as Water Scavengers 3723

R tic acid derivatives, hetaryl acetonitriles, cycloalkanones OMe

O [in this case, a,a¢-bis(arylidene)cycloalkanones 8 were

TMSCl

O +

O obtained] and cyclic methylene active compounds R

H (Scheme 10). OMe

O The proposed mechanistic scheme for the reaction postu- 12 (17–62%)

13 lates a double function for chlorotrimethylsilane as activa- Scheme 9 tor for both the aldehyde and the methylene reaction

components, owing to the formation of the silyl deriva-

O R

TMSCl, DMF tives 14a–c and 15a–c (Scheme 11). The latter react to

1 2

+ R R

100 °C, 0.5–6 h form intermediates 16a–c. In the next step, extrusion of 2 R

Ar H hexamethyldisiloxane (HMDS) and elimination of hydrogen chloride occur from 16a–c, giving the final products

NHR 17a–c. NC

NC CN NC COOEt The condensation proceeds in a stereoselective manner af-

O fording exclusively alkenes that possess a trans disposi-

3 O

R tion of the aryl substituent and the possible silylation site

NC S

3 (circled in Scheme 11) even if such a product is not the R

O O most thermodynamically stable of the two possibilities (as

in the case of compound 18a).22

3 R

N N The method discussed above was successfully applied to

CN CN

CN less reactive substrates such as aryl methyl ketones and

S methyl derivatives of p-acceptor heterocycles

NMe 22 2

R (Scheme 12).

N Other methylene active compounds were also used as sub- N

O CN

CN strates in chlorotrimethylsilane-mediated Knoevenagel-

N N H N

2 type condensations, including hydroxymethyl, chloro-

methyl and tosyloxymethyl derivatives of heterocycles

(H C)

n 23

O O R (Scheme 13 and Scheme 14). The latter transformations allowed for the preparation of chlorovinyl derivatives 19 that are difficult to obtain by other methods.

When o-dialkylamino aldehydes were used as carbonyl

R N O O components in chlorotrimethylsilane-mediated Knoevenagel-type condensations, the reactions were ac-

complished by way of ring fusion; this is referred to as the

X 24,25

R T-amino effect (Scheme 15). A set of methylene active X

3 3

NH R R

N compounds was successfully applied to this transforma- NN

S tion under optimized reaction conditions O O O

O O

OO [TMSCl (4 equiv), DMF, 100 °C, 12 h]. In the case of py-

3 3 Ph ridine as a solvent, benzylidene derivatives were obtained

Ph Downloaded by: University of Chicago. Copyrighted material.

R R

R NH HN

X as a result of the usual Knoevenagel reaction. Thus, free

N 3

R hydrogen chloride, which is formed in N,N-dimethyl-

O O O

O O formamide and not in pyridine as a solvent, is essential for the T-amino effect. Scheme 10 Selected examples of methylene active compounds When aldehydes processing cyclic dialkylamino moieties R1CH R2 are given 2 were applied to these conditions, tricyclic fused heterocycles 20 were obtained. ity of chlorotrimethylsilane (bp 57 °C). In the case of the substrates possessing low reactivity, a modification of When Meldrum’s acid (21) was used as a substrate in the reaction described above, fused nipecotic acid derivatives the water scavenger is needed; for example, introducing a 26 second Lewis acid as a co-reagent. An alternative 22 were obtained in a one-pot procedure (Scheme 16). approach22 includes performing the reactions in sealed re- In the latter reaction, moderate diastereoselectivity was actors, which allows heating of the reaction mixture to the observed (de ~60%). desired temperature without loss of chlorotrimethylsilane A system comprising chlorotrimethylsilane, sodium io- or hydrogen chloride from the reaction mixture. The opti- dide, and acetonitrile–dichloromethane was successfully mized reaction conditions [TMSCl (3 equiv), DMF, 100 applied to promote a reductive Knoevenagel-type conden- °C, 0.5–6 h] allowed for the execution of Knoevenagel- sation.27,28 The reaction results in C-arylmethylation of type condensations of aromatic aldehydes with cyanoace- the corresponding methylene active compound (e.g.,

Synthesis 2009, No. 22, 3719–3743 © Thieme Stuttgart · New York

3724 D. M. Volochnyuk et al. REVIEW

– Cl

H Cl

TMSCl

Ar O

TMS

O Ar Ar O

O Ar

TMS Cl

14a 14b 14c

TMS

+ TMS

– TMS

O O O

O O

TMSCl 14 – HMDS

1 R

R Ar 18a

– HCl

2 H less stable

2 R

R R R

cis) (aryl groups are

17a 15a 16a

TMS

TMS N N O N N

TMSCl 14 – HMDS

X Ar

X X

– HCl – HCl

2 2 R R R R

17b 15b 16b

TMS

TMS O N

– TMS

O O

TMSCl 14 Ar N

– HMDS

18b Cl

more stable Ar – HCl

2 – HCl

NOT formed

2 R

R :B

17c 15c 16c

Scheme 11 Mechanistic scheme for the chlorotrimethylsilane-promoted Knoevenagel-type condensation

Ar N O

TMSCl R TMSCl, DMF

Ar RMe + +

100 °C, 15–24 h 1

DMF

Ar H Ar H S OH S O

O Scheme 13

O TMSCl

Y Ar DMF Ar H

X = Cl, OTs 19

NN N N

Downloaded by: University of Chicago. Copyrighted material. O

Ar NO N

2 N 2

N N

X N

R Cl N N

N O S

O O O

N H

HN NH NH

O Cl N Cl N

N N

OTs N

Scheme 12 Selected examples of compounds RMe are given; HN Cl

X = O, S, NR1 Cl MeS N

N N

acetylacetone or ethyl acetoacetate) thus leading to the N

OTs

O Cl products 23. The proposed mechanism for this reaction is R N

shown in Scheme 17. The postulate is supported by the Cl isolation of intermediate 24a (68%) in the case where di- Scheme 14 Selected examples of heterocyclic derivatives are given ethyl ether was used as the solvent.27

Synthesis 2009, No. 22, 3719–3743 © Thieme Stuttgart · New York

REVIEW Organosilicon Compounds as Water Scavengers 3725

2 R An example of a heterogeneous catalyst used in R

2 Knoevenagel-type condensations is represented by silica

R TMSCl, DMF 3

1 gel functionalized with amino groups; this catalyst was +

1 NR

R N 100 °C, 12 h

R prepared by the treatment of silica gel with (3-aminopro-

) (CH

2 29 1 R n

R pyl)trimethoxysilane (Scheme 18). 20

OH O

O O

O R

Si(CH ) NH (MeO) N

3 2 3 2

O ) NH Si(CH

N R R N

N 2 3 2

1 N R N

OH O

1 1

R R

O Scheme 18

4 O R

S CN N

O In some cases, the Knoevenagel reactions discussed above O

O 4 R were accomplished by self-condensation of the starting al-

13,17,30,31

O dehydes. Analogous halogenosilane-promoted

R self-condensations of preparative significance were also N

N reported in the literature. Thus, acetone and cyclohex-

X CN

CN N

O anone underwent self-condensation smoothly, in the pre-

OO sense of a chlorotrimethylsilane–sodium bromide system,

N 4

R to give the corresponding b-bromo ketones

4 30

R N

R N (Scheme 19).

X CN

NaBr TMSCl +

Scheme 15 Selected examples of aromatic aldehydes and methyle- +

ne active compounds are given Br

+ NaBr TMSCl + O

O OO Br TMSCl +

R N – HCl

R N

OO Scheme 19

R 21

Aldehydes of the formula RCH2CHO formed self-con-

HCl densation products 26 in 78–89% yields in the presence of

O H

2 iodotrimethylsilane. A mechanistic scheme of the reaction

was suggested. The key step of the transformation was COOH postulated to be the reaction between trimethylsilyl-

COOH iodohydrine 27 (formed by TMSI addition to the starting +

N R N 28 27 R aldehyde) and trimethylsilyl enolate (formed from

by HI elimination) (Scheme 20).13 Downloaded by: University of Chicago. Copyrighted material.

R R

~ 4:1 22a 22b

O MeCN

TMSI R

R OTMS

Scheme 16 R

OTMS + – H I – [MeCNH]

27 28

TMS

O O O

OTMS TMS Cl, NaI

OTMS

TMS R +

MeCN

R Ar H Ar I –

– R

+ R I

R O OTMS OTMS

– HMDS

O I O

– TMSI

R HI

Ar R

O – (TMS)

– I – TMSI

2 O

–

– HI R O R R O +

O(TMS)

2 R OTMS

23a, R = OEt

24a, R = OEt

23b, R = Me 24b, R = Me Scheme 20 Scheme 17

Synthesis 2009, No. 22, 3719–3743 © Thieme Stuttgart · New York

3726 D. M. Volochnyuk et al. REVIEW Complexes of chlorotrimethylsilane with Lewis acids ap- OH

peared to be more efficient as promoters of aldehyde self-

condensations than iodotrimethylsilane. That can be ex- R

OH plained by lower nucleophilicity of complex anion OH

–

[LA·Cl] (where LA is Lewis acid) comparing to iodide TMSCl

R R +

H , C H , 0–4 °C ion. Trimethylsilyl triflate (TMSOTf) appeared to be the C 6 12 6 6

13 2

most efficient among the reagents used for this reaction. 3 R

33 (40–77%) 32

2.2 Other Reactions OH

Apart from the aldol-type condensations discussed above,

the transformations considered in this section include re- OH actions of C-electrophiles with activated alkenes and aro- TMSCl

matic compounds. +

MeO

The reaction of aliphatic aldehydes with 1,1-diarylethyl- MeO (60%)

enes led to the formation of complex mixtures that include 34 35 1,1-bis(2,2-diarylethylenyl)alkanes 29 and cyclic ketals Scheme 22

30 as the main products.13 In contrast, chlorides 31 were

the only products formed, in 80% yield, in the reaction of OH

TMSCl acetals and styrene in the presence of chlorotrimethylsi- O

12 H +

C lane–tin(II) chloride (Scheme 21). O – HCl

OTMS OTMS

–

Ar R

37 Ar

1 O Ar

HCl

1 TMSI

1 R

Ar R H

Ar 29 30

– HCl

C OMe Cl O

OMe

TMSCl

+ Ph

–

H Cl

SnCl (cat.)

2 OMe Ph Ph

36 38 31

Scheme 21 Scheme 23

Chlorotrimethylsilane is a convenient catalyst in Friedel– sations with secondary amines affording iminium salts are Crafts reactions.32,33 In particular, it was applied success- also discussed. fully in the condensation of alcohols 32 and substituted A chlorotrimethylsilane–N,N-dimethylformamide system phenols that led to diarylmethanes 33. In an analogous re- was successfully applied in the reaction of cyclic b-dike- action of o-cresol and secondary alcohol 34, compound 35 tones (cyclohexane-1,3-dione, dimedone) and aromatic 32 was obtained in 60% yield (Scheme 22). amines to give N-arylenamino ketones 39, which are in- Downloaded by: University of Chicago. Copyrighted material. A chlorotrimethylsilane-promoted reaction of salicylic al- termediates in the syntheses of some analgesics dehyde and 1-methylfuran allowed (2-hydroxyphenyl)di- (Scheme 24).34

furylmethane (36) to be obtained in 90% yield

33 NH 2

(Scheme 23). O

TMSCl–DMF

1 R R

N O

3 Reactions Leading to Carbon–Nitrogen 1

R R

H 2

Bond Formation R

39 (70–90%) = Me, H R

= Cl, H, Me, COOEt, COOMe 3.1 Two-Component Condensations R In this section, two-component condensations of alde- Scheme 24 hydes and ketones with various nitrogen-containing compounds (e.g., primary amines, amides, ureas, and Use of chlorotrimethylsilane as the reaction promoter al- hydrazines) leading to the formation of imines or deriva- lowed Schiff bases to be obtained, even from weakly basic tives thereof are under consideration. Analogous conden- amines. An example of this is shown in Scheme 25.35

Synthesis 2009, No. 22, 3719–3743 © Thieme Stuttgart · New York REVIEW Organosilicon Compounds as Water Scavengers 3727

mutation of the final products, pyridine was used as

+ solvent. This transformation was extended to include the

2 use of acetophenones, cyclic ketones and heterocyclic al-

TMSCl

N dehydes as the carbonyl components in the reaction + N

MeCN

–

ClO (Scheme 28). The reaction scope showed its limitations in 4

N the case of electron-rich aldehydes; in this case, dismuta-

–

ClO N 4 tion products were isolated from the reaction mixture. The

T-amino effect was also not observed in the case of o-pi- 70% peridinylanilines as amine components; usual imine formation was observed instead.38

Scheme 25

The condensation of aromatic/heteroaromatic amines N

1 2 N 1

X X with 1-methylparabanic acid was studied extensively. In R

N 3

TMSCl (4 equiv), py

particular, reaction of 1-methylparabanic acid and pre- R

2 100 °C, 2 h NH R

clathridin A (40) in the presence of chlorotrimethylsilane, X 1

triethylamine, imidazole and DMAP afforded alkaloid X (48–75%)

clathridin A (41) regioselectively in 73% yield 44 36

(Scheme 26). Scheme 28

N O O

N The proposed mechanistic scheme suggests silylated am-

NH TMSCl

2 O

+ inal 45 as a key reaction intermediate. A [1,6]-hydride

N O

O shift in 45 accompanied by silicon–oxygen bond forma- Me

Me 40 tion affords iminium salt 46, which undergoes fast cy-

clization into the final product (Scheme 29).38

N O

1 N

1 1 O

H R R

1 2

X X H N

X TMSCl

N R 2

NH R 2

OTMS

Scheme 26 TMS 45

Tetraethylorthosilicate [Si(OEt)4] was proven to be an ef-

1 1 ficient reagent in the synthesis of sterically hindered 1 R R

ketimines 42 and 43 (Scheme 27).37 This water scavenger R

N – HMDS

does not form acidic products upon hydrolysis; thus, an 1 R

excess of the amine is not needed in the reaction. 2 2

1 2

X X

– X

OTMS Si Me

Downloaded by: University of Chicago. Copyrighted material.

Si(OEt) , cat. H

RNH + 2

160 °C, 16 h Scheme 29

O NR

R = Ar, CHMePh, CHPh 42 (72–90%)

2 Carbonyl compounds and amides or ureas were found to

react with chlorotrimethylsilane–N,N-dimethylform-

O NR

Si(OEt) , cat. H

4 amide at room temperature to afford the corresponding

RNH +

2 condensation products in good yields (67–92%). The re- 160 °C, 4–75 h Ph Ph

Ph Ph action of benzaldehyde and benzamides allowed for

arylidenebisbenzamides 47 to be obtained, whereas acetyl-

R = Ar, CH(Ph) , 43 (62–98%)

2 acetone and ethyl acetoacetate led to enamine derivatives 48 (Scheme 30).39 Scheme 27 This method was modified for the synthesis of tosylform- amides 49 – substituted tosylmethylisonitrile precursors. Reactions of o-(dialkylamino)anilines and aromatic alde- It was shown that aromatic, heteroaromatic and aliphatic hydes performed in sealed reactors at 100 °C resulted in aldehydes reacted with formamide (or acetamide) and the T-amino effect, thus leading to the formation of dihy- chlorotrimethylsilane in toluene–acetonitrile (1:1) at 50 drobenzimidazoles 44. To avoid the acid-catalyzed dis- °C to afford the corresponding condensation products. In

Synthesis 2009, No. 22, 3719–3743 © Thieme Stuttgart · New York

3728 D. M. Volochnyuk et al. REVIEW

O O Ph

TMSCl–DMF O O

AcOH +

Ar Ar N

1 Ar

R R HN N

H H R HN NH TMSCl R H 2

47a, Ar = Ph

= H, Alk R

47b, Ar = 2-O NC H 2 6 4

NaBH

4 O O

TMSCl–DMF

1 1 +

R R

R N R NH O 2

R HN N 1 2 48a, R = Ac, R = Ph

1 2 48b, R = COOEt, R = Ph

51 (60–90%)

1 2

48c, R = COOEt, R = NH 2

Scheme 30 Scheme 33

CHO situ reaction of the latter with toluenesulfinic acid allowed S

for compounds 49 to be obtained in excellent yields 1. TMSCl, AcOH

N NHR

40 +

(Scheme 31). H

2. NaBH

R HN NH

1 R

O R

52, R = H (50–65%)

TMSCl, TolSO H

R = t-Bu, OMe

53, R = Ar, Et, OPh (74–93%)

R TolO S N

2 R H

H N R

2 toluene–MeCN

50 °C, 5–6 h Scheme 34 49 (62–93%)

Scheme 31 mycin C (via 55),45,46 the spiroketal polyketide antibiotics spirofungins A and B (via 56),47 the polyether antibiotic Recently, tetraethylorthosilicate was used as a reaction X-206 (via 57)48 and the secondary metabolite ulapualide promoter to obtain aromatic and heteroaromatic N-tosyl- A (via 58)49 (Scheme 35). aldimines 50 from p-toluenesulfonamide and correspond- 41 Reaction of aldehydes with primary or secondary amines, ing aldehydes (Scheme 32). a-amino esters, O-trimethylsilylhydroxylamine and N,N-

dimethylhydrazine in the presence of chlorotrimethylsi-

Si(OEt) lane and lithium perchlorate followed by reduction of the N

p-TsNH + 2

140–160 °C carbon–nitrogen double bond (BH3·NEt3) afforded Ar H

4–12 h amines 59, a-amino esters 60, N-substituted hydroxyl-

(46–85%) 50 amines 61 and hydrazines 62, respectively (Scheme 36).50 Scheme 32 An approach to the synthesis of iminium salts that includes the reaction of carbonyl compounds with dialkyl- Reductive alkylation of unsubstituted and monosubstitut- aminotrimethylsilane and chlorotrimethylsilane has been ed ureas by aromatic aldehydes was achieved using developed. The corresponding products 63 were stable chlorotrimethylsilane in combination with sodium boro- enough to be isolated in 75–93% yields and characterized (Scheme 37, see also Scheme 41). The method was ap- hydride. It should be noted that monoalkylation products Downloaded by: University of Chicago. Copyrighted material. 51 were obtained only when a large excess (up to 20 plied to non-enolizable and a,b-unsaturated aldehydes equiv) of urea was used; otherwise, bis-alkylation oc- and dimethylformamide. The procedure can also be uti- curred (Scheme 33). The reaction was carried out under lized in the case of aldehydes capable of enolization if tri- mild conditions, and the products were easily isolated methylsilyl triflate is used instead of chloro- 51,52 from the reaction mixture. However, the method was not trimethylsilane. successful for enolizable or a,b-unsaturated aldehydes.42 Reaction of the dialkylaminotrimethylsilane–chlorotrime- An analogous reaction of aromatic aldehydes with thio- thylsilane system with 3,3-dichloroacrolein afforded a urea and chlorotrimethylsilane followed by sodium boro- mixture of salts 64 and 65 (Scheme 38). Compound 66 hydride reduction of the intermediate products afforded was isolated in 75% yield as a perchlorate salt from a mix- monosubstituted thioureas 52. When N-monosubstituted ture obtained by the reaction of dimethylaminotrimethyl- thioureas were subjected to these conditions, N,N¢-disub- silane and the precursor dialdehyde in the presence of 51 stituted thiuoreas 53 were formed in good yields chlorotrimethylsilane (Scheme 39). (Scheme 34).43 A modification of the method discussed above relies on The chlorotrimethylsilane-mediated construction of hy- using dialkylamines and in situ generated iodotrimethylsi- 53,54 drazones was used in the syntheses of various complex or- lane. The first step of the reaction was amine silyla- ganic molecules, including the macrolide antibiotics tion, leading to quantitative yield of the rutamycin B (obtained via intermediate 54)44,45 and oligo- dialkylaminotrimethylsilane which then reacted with the

Synthesis 2009, No. 22, 3719–3743 © Thieme Stuttgart · New York

REVIEW Organosilicon Compounds as Water Scavengers 3729

OTBS OBn TBDPSO

TMSCl

-NMe NH

2 2

NMe

O O O O TBDPSO TBDPSO

TMSCl

NMe

O N

NH -NMe 2 2

NMe

MeO MeO

TMSCl O N TBSO TBSO

NH -NMe O O 2 2

O O

MeO

TMSCl

N O

N NMe O 2

NH -NMe

2 2 O Me O Me

OMe OMe

O O

TMSCl

N O

-NMe NH

NMe 2 2 O O 2

PMBO PMBO 58

Scheme 35

H R TMS

–

O 3

NR 2 O

R 2

TMSNR

– (TMS) O

2 3

1 TMSCl

R H R H R

R = Ar, t-Bu, i-Pr

X = Cl or NR 63

2 = H, Et R

= Ph, t-Bu, Et R

59 (80-95%)

NR = NMe , NO N 2 2 ,

NH 2

R NH

O Scheme 37

2 Downloaded by: University of Chicago. Copyrighted material. R

2 R

OMe

– H Cl

– Cl

= Ar, Het, t-Bu R NTMS R Cl

TMSCl

= Ar, MeSCH CH R

2 2

N R

Cl TMSCl

O + Cl NR

60 (85–90%)

BH NEt ⋅ 2 3 3

R H

Et O, r.t., 1 h 64 65 2

N-OTMS H

2 Scheme 38

NH R

1 = Ar, Het, t-Bu R

(65–88%) 61 aldehyde to give the iminium salt. This approach was used

in the synthesis of dialkylamino-9H-pyrrolo[1,2-a]indoles

H N-NMe

H 2

2 68 obtained in 68–84% yields from 2-(pyrrolyl)benz-

1 N R

NMe

2 aldehydes 67 and secondary amine hydrochlorides by ac-

= Ar, t-Bu, Pr R tion of chlorotrimethylsilane in combination with sodium

(65–83%) 62 iodide and triethylamine, followed by intramolecular cy- 54 Scheme 36 clization of the iminium salts thus formed (Scheme 40).

Synthesis 2009, No. 22, 3719–3743 © Thieme Stuttgart · New York

3730 D. M. Volochnyuk et al. REVIEW

O O

TMSCl

NH O

LiClO

NMe

Me N

+ + COOMe BrZnCH

2 2

1. Me NTMS, TMSCl

H H

2 Ph

Ar H Et O, r.t. 2

N NMe Me N

2 2 2. NaClO

Cl N Cl

H H

–

2 ClO OMe N OMe

N 4 Ph

66 (75%)

Ar H HAr O Ph O Ph

(75–90%)

Scheme 39 71

TMSCl

NH O 2

LiClO

+ +

3 + –

NR X

3 + –

Ph Ar H

R N H Cl , TMSCl,

Et O, r.t. N N O N 2 2 2

N or NaI, Et

3 3

NR 2

H R NH, TMSCl, H

Nu N Nu

+ –

NH Cl NaI, Et

1 3

1 +

R R R

MeCN, 0 °C/r.t.

Ar H

2 HAr

2 2 Ph Ph R R R

72 (60–80%)

68 67

1 2 1 2 1 2 3 R = R = H, R = R = OMe, R = Cl, R = H, R = Alk

ZnBr ZnBr Nu =

Scheme 40 , Scheme 42 3.2 Three-Component Condensations a-Aminophosphonates 73 were obtained in an analogous The transformations discussed in this section proceed in manner when trialkylphosphites were used as nucleo- two steps: first, an imine or an iminium salt is formed, and philes (Scheme 43).56 This was a one-pot procedure and this then reacts with a nucleophile to afford the three-com- resulted in high yields and diastereoselectivities of the ponent condensation product. products, even in the case of a,b-unsaturated and some Chlorotrimethylsilane–lithium perchlorate in diethyl enolizable aldehydes.

ether is a mild reagent for Mannich-type three-component

NHR condensations, and has allowed for the corresponding H

TMSCl, LiClO

P(OR )

50,55–57 + + R NH

products to be obtained in high yields. First, it was 2

Et O, r.t. Ar PO(OR ) 2 2 Ar

shown that aromatic and heteroaromatic aldehydes were H

1 2

R = Ph, Bu; R = Me, Et (85–98%) aminoalkylated by trimethylsilylamines in the presence of 73 lithium perchlorate.58–63 Imines or iminium salts formed Scheme 43 in the first step of the reaction were trapped by the corresponding nucleophile to afford corresponding amines 69, 70 (Scheme 41). Later, the approach was modified in or- A system comprising chlorotrimethylsilane, sodium io- der to allow trimethylsilylamines to be generated in situ. dide and triethylamine was used in the synthesis of b-ami- In particular, reaction of aromatic aldehydes and (R)-a- no ketones 74 from secondary amines, aldehydes and phenylethylamine in the precence of chlorotrimethylsi- enamines (Scheme 44). The reaction resulted in high lane–lithium perchlorate led to the formation of chiral yields and diastereoselectivity; however, its use was lim- 53 imines which reacted with organozinc compounds to give ited to non-enolizable aldehydes. Downloaded by: University of Chicago. Copyrighted material.

chiral amino esters 71 or amines 72 (Scheme 42).55 It

should be noted that moderate to high diastereoselectivi- NR

ties were achieved in these transformations (90% de for 3

2 +

71 and 40% de for 72). 4

NaI, TMSCl

1 R

HNR

2 +

2 3

R R

Et N, MeCN, r.t.

2 2

– R R H

R H O

74 (68–98%)

Nu-M

TMSNR

2 1

N R R R H

R Nu

R Scheme 44

69 (60–80%)

3 3 LiO Zn, R MgBr, R Li, Nu-M = Et

2 3-Functionalized indoles 75 were prepared in high yields by the three-component reaction of aliphatic aldehydes,

O-trimethylsilylhydroxylamine and indole by action of

2 chlorotrimethylsilane in 5 M ethereal lithium perchlorate

Nu-M 2 TMSNHR

1 53

R H

1 solution (Scheme 45). a-(Hydroxylamino)alkyl/ 1 R N Nu

R arylphosphonates 76 possessing antibacterial properties

(65–85%)

70 56 Nu-M = R Li, BrZnCH COOEt 2 were obtained in an analogous manner (Scheme 46). Scheme 41

Synthesis 2009, No. 22, 3719–3743 © Thieme Stuttgart · New York

REVIEW Organosilicon Compounds as Water Scavengers 3731

OTMS silane or trichloro(methyl)silane and dialkyl(alkoxy-

TMSCl

R methyl)amines, as well as dichlorodimethylsilane or

LiClO

4 trichloro(methyl)silane and aminals were detected by

+ N-OTMS H +

Et O, r.t., 2 h

2 N

H spectral methods. However, in the case of chlorotrimeth-

N ylsilane and aminals, the iminium ion was not observed. R = Alk

(90–96%) 75 The reaction of chlorotrimethylsilane with aminals and electron-rich aromatic heterocycles (i.e., N-methylpyr- Scheme 45 role, furans) led to the formation of 2,5-disubstituted de-

rivatives 83, with chlorotrimethylsilane thus showing

O catalytic behavior. In the case of dichlorodimethylsilane

TMSCl–LiClO HN

P(OMe)

H N-OTMS + +

2 and trichloro(methyl)silane, monosubstituted heterocy-

Et O, r.t., 1 h

2 R

H 66,67 R P(O)(OMe)

2 cles 81 were isolated as hydrochlorides.

R = Ar, Het, Alk (70–98%)

76 To explain the results obtained, a mechanistic scheme was Scheme 46 proposed for the transformations (Scheme 49). The first step of the reaction is supposed to be reversible aminal silylation. In the case of chlorotrimethylsilane, the concen- 4 Synthesis of Iminium Salts by Elimination tration of the silylammonium salt 79a is not high enough Reactions to generate iminium salt 80 due to the lowered stability of 79a. In the presence of a nucleophile, quaternary salt 79a In the previous section, condensations of carbonyl com- reacts rapidly and irreversibly to give the product 81 and pounds leading to the formation of iminium salts were trimethylsilylamine 82a. The hydrogen chloride formed mentioned. Another approach to the synthesis (or in situ in this step of the reaction then protonates amine 82a, thus generation) of iminium salts relies on the elimination of regenerating chlorotrimethylsilane; in other words, the an alcohol or amine molecule from the corresponding a- latter acts as a catalyst. Compound 81 is a stronger nucleo- amino ethers or aminals. These transformations bear re- phile than the starting heterocycle, and hence reacts with semblance to those discussed in the previous section; quaternary ammonium salt 79 to give the 2,5-disubstituted hence they are considered herein despite their being be- heterocyclic derivatives 83 (Scheme 49).

yond the main goal of this review.

–

NCHCl R R N–SiMe +

2 2 3 The first example of an iminium salt synthesis by elimina- 2

tion reaction involving the use of organosilicon com- 80 pounds was reported in 1986 and included the reaction of

dialkyl(alkoxymethyl)amines and trichloromethylsilane X

+ –

N R Cl

R NCH (Scheme 47). The corresponding iminium salts 77 were +

NCH NR R SiCl Me 2 2 2

2 2 2

64 3

isolated in 85–98% yields and characterized. SiMe 3

79a

2 3

H R

MeCN

X = O, NMe N R O

– MeSiCl N +

3 Cl

r.t., 5 min

3 R R H

77 (85–98%)

79a

N–SiMe R

++HCl 3 2 Downloaded by: University of Chicago. Copyrighted material.

X X

Scheme 47 – HCl

N-SiMe – R

R N NR NR 2 3 2 2 2

83 81 82a

The method was successfully applied to the regioselective

–

R N –SiMe Me SiCl

NH R + + HCl R N–SiMe 2 3 3

3 aminomethylation of ketones. Thus, Mannich bases 78 2 were obtained in the reaction of silyl ethers and pre-gen- Scheme 49

erated iminium salts (Scheme 48).65

4 In the case of dichlorodimethylsilane and trichloro(meth- R OTMS

MeSiCl yl)silane, the chlorine atom(s) present in the correspond-

H 3

5 3

R R

MeCN

1 – 2

NR R O Cl

NR ing silylammonium salts 79b weaken the neighboring R R N 2 2

10 °C

4 5 0 °C

R R

H carbon–nitrogen bond, thus activating the compounds to- 78 wards formation of iminium salts 80. On the other hand, (di)chloromethylsilylamines 82b are not basic enough to Scheme 48 capture the hydrogen chloride formed. The latter protonates amines 81, thus preventing their further reaction The approach was extended to other chlorosilanes with 80, hence monosubstituted heterocycles 81 are ob- 66,67 (Me3SiCl, Me2SiCl2) and aminals. Formations of imi- tained as the final products (Scheme 50). nium salts from chlorotrimethylsilane, dichlorodimethyl-

Synthesis 2009, No. 22, 3719–3743 © Thieme Stuttgart · New York

3732 D. M. Volochnyuk et al. REVIEW

MeSiXCl

R NCH N R

R NCH NR

2 2 2 2

2 2 2 3 2

R R

R N SiMeXCl

TMSCl

+ X = Cl, Me

79b

1 or MeSiCl

3 O R MeN O

3 R OH

– R N-SiMeXCl

1 2 3 1 2 3

87a, R R = H, Me 86a, R = R = H = R = R = H

82b

2 3 1 2 3 86b, R 87b, R = Me, R = Ph = Me, R = R = H

1 2 3

87c, R = R = Me, R = Ph

+ –

HCl +

R N CH Cl 2 2

X = O, NMe Scheme 52

NR 2 81 salt 89 was synthesized preliminarily. That fact could be explained by generation of iminium salt 92 from the secondary amine 90. For example, amine 91a (R = n-Bu) was

obtained from N,N-bis(methoxymethyl)butylamine (88a;

X R=n-Bu), 2-methylfuran and trichloro(methyl)silane in

– 70 Cl NHR 2 87% yield.

Scheme 50

OMe R H OMe

TMSCl

+ RN + N

Reaction of dialkyl(alkoxymethyl)amines with 1-meth- N

–

O OMe Cl

H R

– ylpyrrole, 2-methylfuran and 1-methylindole afforded Cl

88 monosubstituted heterocycles as the main products 89

(Scheme 51).66

OEt

Me R

–

TMSCl Cl

TMSCl N +

O N

48 h

O OMe N

TMS O O

84 (86%)

NR 2

TMSCl

1 2

R N OR

–

2 R Cl

20 h

+ Me N H

Me N O

O O

85a, NR = NEt (89%) 2 2

92 91

(93%) N O 85b, NR = 2 Scheme 53 Scheme 51 This approach was recently extended to cyclic b-keto 1,3-Oxazolidines 86 were also shown to react with nu- esters71–73 and cycloalkanones.74 In the case of cyclic b- cleophilic aromatic substrates in the presence of chloro- keto esters, 3-azabicyclo[3.2.1]octanes 93a and 3-azabi- trimethylsilane, dichlorodimethylsilane or tri- cyclo[3.3.1]nonanes 93b were obtained (Scheme 54);71,72 chloro(methyl)silane. In particular, reaction of 3-methyl- these were then used in the synthesis of the alkaloid meth- Downloaded by: University of Chicago. Copyrighted material. 1,3-oxazolidine (86a), furan and trichloro(methyl)silane yllycaconitine and its analogues. The method was also ap- allowed monosubstitution product 87a to be obtained in plied to the chiral N,N-bis(ethoxymethyl)(1¢-phenyl- 75% yield. Amino alcohol 87b was obtained in 73–87% ethyl)amine. Despite it not being possible to separate the yields from 86a, 2-methylfuran and either trichloro(meth- diastereomers of the amino ketones obtained (93, R1 =1¢- yl)silane or chlorotrimethylsilane. An analogous transfor- phenylethyl), the presence of the chiral auxiliary in the mation of 3,4-dimethyl-5-phenyl-1,3-oxazolidine (86b) molecules was exploited in their further transforma- afforded the expected product 87c in 80% yield tions.73

(Scheme 52).68

N,N-Bis(alkoxymethyl)alkylamines such as 88 reacted R R

CO Et R

CO Et TMSCl

2 N

with chlorosilanes to form a-alkoxymethyleneiminium 3

+ R N

salts 89 which are more reactive than their methylene- MeCN, r.t., 20 h

(CH )

2 2 OEt EtO n

iminium counterparts.69,70 In particular, a mixture of n

93a, n = 1 (75–99%)

amines 90 and 91 was formed from 89 and 2-methylfuran n = 1, 2

93b, n = 2 (56–90%) 1

= Alk, Bn

at ambient temperature (Scheme 53). When the reaction R

= H, -CH -CH=CH R 2

time was increased or when an excess of chlorosilane was 2 used, tertiary amine 91 became the main product even if Scheme 54

Synthesis 2009, No. 22, 3719–3743 © Thieme Stuttgart · New York

REVIEW Organosilicon Compounds as Water Scavengers 3733

The method was also applied to some cycloalkanones, in- O

2 3

R R CO, TMSCl

cluding cyclooctanone, cycloheptanone and substituted R 1 NHR

cyclohexanones. In particular, azabicyclo[4.3.1]de- N

2 R

O OH 3 canones 94 and azabicyclo[5.3.1]undecanone derivatives R

1 2 3

, R = H, R = R = Me (59%)

95 were obtained from the corresponding cyclic ketones 99a

1 2 3

99b, R = H, R = H (90%)

by treatment with chlorotrimethylsilane in acetonitrile at = Me, R

1 2 3 99c, R = H, R = Me (95%)a

ambient temperature (Scheme 55). The scope and limita- = Me, R tions of the approach were established; it was shown that Scheme 57 variation of the substituent at nitrogen in N,N- bis(alkoxymethyl)alkylamine as well as the ring size or alkyl substituents a to the ketone did not affect the reac- An analogous transformation involving salicylic acid tion progress significantly, whereas introduction unsatur- amides or N-methylamides and paraform, paraldehyde or ated substituents or heteroatoms at that position lowered acetone led to the formation of benzo-1,3-oxazine[2H]-4- the yield of the product.74 ones 99 (Scheme 57).75,76

In the case of N-acetyl a-amino acids, the reaction re-

O quired harsher conditions: for example, N-acetylvaline or

) (CH 2

TMSCl, MeCN

OEt N EtO N-acetylleucine reacted with paraform in an acetic acid–

N +

48 h, r.t. R

R chlorotrimethylsilane mixture only under reflux. On the

) (CH

2 other hand, corresponding N-tosyl derivatives easily un- n

n = 1, 2; R = Alk , n = 1

94 derwent cyclization at ambient temperature to give oxazo- , n = 2

95 lidinones 100 (Scheme 58).76

(74–95%)

2 1

Scheme 55 R NHR R

3 4

R R CO, TMSCl N

4 O OH R O

5 Heterocyclizations O

1 2 3 4

100a, R = i-Pr, R = Ac, R = R = H (70%)

2 3 4

In this section, chlorotrimethylsilane-mediated heterocy- 1 100b, R = i-Bu, R = Ac, R = R = H (60%)

1 2 3 4

100c, R = Ts, R = R = H (86%)

clizations are under consideration. Modifications of clas- = Me, R

1 2 3 4

100d, R i-Bu, R = Ts, R = R = Me (89%) sical transformations, such as the Biginelli reaction, = Hantzsch and Friedlander syntheses, are among those dis- Scheme 58 cussed. In a separate section, 3-formylchromone recy- clizations are illustrated. Some of the heterocyclization reactions were also mentioned previously 4-Acetyl-2,2,5-trimethyl-2,3-dihydrofuran (101) was ob- (Schemes 15, 16, 28, 54 and 55). tained in quantitative yield in a one-pot reaction involving acetylacetone, isobutyric aldehyde, a chlorotrimethylsilane–sodium iodide system and a stoichiometric amount 5.1 Synthesis of O- and O,N-Containing Hetero- of water. The overall process was a Knoevenagel conden- cycles sation followed by cyclization (Scheme 59).27 An early example of chlorosilane-mediated heterocycliza-

tion goes back to 1985 when it was shown that hydroxy O Downloaded by: University of Chicago. Copyrighted material. O O

TMSCl, NaI

and amino acid derivatives undergo cyclization upon O

O (1 equiv) H

treatment with chlorotrimethylsilane and a carbonyl com- 2 hexane

pound (e.g., formaldehyde, acetaldehyde or acetone).75 O Thus, heating of paraform, lactic or mandelic acid and an 101 excess of chlorotrimethylsilane afforded dioxolanone de- Scheme 59 rivatives 96.76 Oxazolidines 97 and 98 were obtained from glycolic or lactic acid methylamides and acetone or formaldehyde (Scheme 56).75,76 An analogous transformation of dimedone led to the

formation of 1,8-dioxooctahydroxanthenes 102

OXH (Scheme 60). The reaction steps included a Knoevenagel

2 3 R

R CO, TMSCl

R condensation, a Michael addition and a cyclodehydra-

R 77

1 1 O

R R OH tion.

2 2 3

1 4-Iodo-2,6-disubstituted tetrahydropyrans 103 were ob- X = O, NH, NMe = H, Me 96, R = Me or Ph, R = R = H, X = O R

1 3 1 2 3

97, R = H, Me, Ph = H, Me = Me or H, R = R = H, X = NMe R

R tained at first by Prins cyclization of homoallyl alcohols

1 2 3

98, R = R = Me, X = NMe. = Me or H, R 104 and aromatic aldehydes in the presence of in situ gen- Scheme 56 erated iodotrimethylsilane. The reaction was carried out in acetonitrile at ambient temperature for three to eight min-

Synthesis 2009, No. 22, 3719–3743 © Thieme Stuttgart · New York

3734 D. M. Volochnyuk et al. REVIEW

Ar OO

O In 1992, Zav’yalov and Kulikova showed that using a sys-

TMSCl, MeCN tem of chlorotrimethylsilane and N,N-dimethylform-

reflux, 8–10 h amide allowed for the process to be carried out at ambient Ar H

O O temperature. Products were obtained in 62–80% yields

from aromatic aldehydes and in 32–37% from aliphatic al-

(72–84%) 102 dehydes. The procedure included two steps: first, the b-di- Scheme 60 carbonyl compound and the aldehyde underwent aldol condensation to give an a,b-unsaturated ketone, then urea utes to afford products 103 as mixtures of diastereomers. was introduced into the reaction mixture to react with the product of the previous step. The final products were iso- The all-cis isomer of 103 was the main product of the re- 80 action, presumably due to its greater thermodynamic sta- lated and purified chromatographically. bility. The method appeared to be ineffective in the case It was found that 3,4-dihydropyrimidine-2-(1H)-one de- of aliphatic aldehydes; however, it was successfully ap- rivatives 106 could be obtained in high (76–97%) yields plied in the synthesis of the antibiotic (±)-centrolobine using chlorotrimethylsilane in a mixture of acetonitrile 105 (Scheme 61).78 and N,N-dimethylformamide (2:1). The method was ap-

plied to various aromatic, aliphatic and a,b-unsaturated

I H O aldehydes, ureas and thioureas, acetylacetone and ethyl

acetoacetate. The products were separated from the reac-

TMSCl, NaI tion mixture simply by filtration.81

1 MeCN, r.t., 3–8 min

R O

R The reaction was also extended to N- and N,N¢-(di)substi-

2 R tuted ureas. Thus, N-substituted 3,4-dihydropyrimidine- R

104 (70–96%) 103 2-(1H)-ones 107 were obtained in 77–97% yields using

R = Alk, Ar

SnH AIBN, Bu chlorotrimethylsilane (4 equiv) and N,N-dimethylform- 3

= CH CH (4-HOC H ) (R

2 6 4

2 amide at room temperature for one to three days

= OMe)

R (Scheme 63).82

Ar O

O O

O R N TMSCl

+ +

ArCH O

1 2

DMF, r.t. R OR

N R O

MeO OH

3 R

105 (93%)

107 (77–97%) Scheme 61 Scheme 63

5.2 Synthesis of Pyrimidines by Biginelli Reac- Cycloalkanones can be used in the chlorotrimethylsilane- tion mediated Biginelli reaction in place of the b-dicarbonyl One of the prevalent applications of chlorotrimethylsilane compounds. Depending on the structure of the starting as a water scavenger is related to the Biginelli reaction and compounds, three types of products can be obtained in this involves a three-component condensation of b-dicarbonyl reaction: fused heterobicyclic structures 108, benzylidene Downloaded by: University of Chicago. Copyrighted material. compounds, aldehydes and ureas leading to the formation heterobicyclic compounds 109 or spiroheterotricyclic py- of 3,4-dihydropyrimidine-2-(1H)-one derivatives 106. An rimidines 110 (Scheme 64). In particular, cyclopen- original method included refluxing of a mixture of the tanone, urea and most aromatic aldehydes reacted in the starting matherials in ethanol in the presence of hydro- presence of the chlorotrimethylsilane–acetonitrile–N,N- chloric acid as a catalyst and allowed the condensation dimethylformamide system to afford pyrimidines 109. products to be obtained in 20–60% yields (Scheme 62).79 Under these conditions, p-fluorobenzaldehyde gave a

mixture of 109 and 110 in an 87:13 ratio.83

R H

O Aliphatic aldehydes were less reactive in these transfor-

O O

O mations: the corresponding condensation products were

EtOH

1 formed in satisfactory yields only under reflux. Cyclopen-

+ O

R OR H , reflux H N NH 2

2 tanone reacted with aliphatic aldehydes and ureas or thio-

2 3

R O NH

R ureas to give the products 110, whereas higher

1 cycloalkanones afforded fused heterobicyclic pyrimidines

R N O

H 108.83

(20–60%) 106 Condensation of butyric or valeric aldehydes and urea in a chlorotrimethylsilane–acetonitrile–N,N-dimethylform- Scheme 62 amide system led to the formation of 5,6-dihydropyrimi-

Synthesis 2009, No. 22, 3719–3743 © Thieme Stuttgart · New York

REVIEW Organosilicon Compounds as Water Scavengers 3735 R rivative 114 predominating in the mixture, ortho- and

R meta-substituted benzaldehydes gave only the octahydro-

quinazolines 115 (Scheme 66).84

(CH )

) (CH

2 n

TMSCl N X

+ +

N X

DMF–MeCN

N H NH

1 R H H 2 2

R R

1 109 108 R

H O

1 2 O X = O, S R = H, Me = Alk, Ar R

+ +

H N NH

2 2

) (CH

O R

NH HN

2 2 R R

R OO

N X

H R R R

) (CH

115 2 114 n

HN NH Scheme 66

NH HN

X X 110 In an analogous transformation involving dimedone, aromatic aldehydes and a chlorotrimethylsilane–acetonitrile– Scheme 64 N,N-dimethylformamide system, octahydroquinazolines 115 (R2 = Me) were also obtained.77 din-2-ones 111 in 53% and 62% yields, respectively. b-Ketonitriles were used in a Biginelli-type reaction with Under these conditions, isovaleric aldehyde and urea or aromatic aldehydes and thiourea in the presence of chlo- thiourea afforded 3,4-dihydro-1H-pyrimidin-2-ones 112, rotrimethylsilane–N,N-dimethylformamide at 25 °C to whereas cyclohexanone and thiourea gave spirotricyclic obtain 1:2:1 condensation products 116 (Scheme 67). In 83 product 113 in 78% yield (Scheme 65). the case of cyanoacetamides, one-step fusion of 1,3-thiaz-

ine and pyrimidine cycles occurred to give hydrochlorides

R O

H 117 (Scheme 68). The structure of the latter products was

TMSCl, DMF, MeCN

R 85

R N H NH confirmed by single-crystal X-ray analysis. O

2 2

NH reflux, 4–6 h

N O

111a, R = Et (53%)

Ar O Ar

111b, R = n-Pr (62%) TMSCl

2 ArCHO + +

N H NH DMF, r.t. R NH 2 2

X H

t-Bu, Ph R =

TMSCl, DMF, MeCN

N H NH O 2 2

116 (85–92%)

Downloaded by: University of Chicago. Copyrighted material.

NH reflux, 6 h X = O, S

Scheme 67

N X

112

O Ar

O R

TMSCl

HN N

TMSCl, DMF, MeCN

+ 2 ArCHO HN NH

HN DMF, r.t.

R reflux, 6 h

1 N N Ar S

H N NH 2 2 R

N S

1 3

R = H, Me, Bn, Ar, (CH ) OR 2 n

117 (56–92%)

O 113 (78%)

2 3

= H, Me, Ph, (CH ) OR , R CH 2 n

Scheme 65 2 Scheme 68 Condensation of cyclohexane-1,3-dione and urea or thiourea in the presence of chlorotrimethylsilane–acetoni- When trifluoromethyl-substituted b-dicarbonyl com- trile–N,N-dimethylformamide led to the formation of pounds were used as substrates in the Biginelli reaction, either spiro (114) or heterobicyclic compounds (115) in 4-hydroxyhexahydropyrimidin-2-one derivatives 118a high yields. Whereas benzaldehyde or para-substituted were obtained in 48–82% yields. It should be noted that a aromatic aldehydes afforded both products, with spiro de-

Synthesis 2009, No. 22, 3719–3743 © Thieme Stuttgart · New York 3736 D. M. Volochnyuk et al. REVIEW different diastereoselectivity (compound 118b) was ob- ortho-substituted aldehydes and was efficient in the case served when N,N¢-dimethyl(thio)urea was used instead of of sensitive substrates (e.g., those containing nitro, hy- the unsubstituted or monosubstituted derivatives. The droxy, alkoxy or chloro groups) due to the milder reaction only exception was represented by 1,1,1-trifluoropentane- conditions.89 2,5-dione, which afforded classical dihydropyrimidine

86 products 119 under these conditions (Scheme 69). O

NH OAc, MeCN

1 OR R CHO +

TMSCl–NaI

O Ph

1 r.t., 6–8 h

X R O O

O O O

N R TMSCl

HN NH

OR O R PhCHO

1 +

R F C

DMF, r.t.

3 OH

R R N X

R = OEt, Ph, CF X = O, S H R 3

TMSCl–NaI, MeCN

= H, Me, Ph R

120

+ 118a (56–82%) CHO R

R = H, Me r.t., 2–3 h

(R = H)

H N 2

O Ph

1 Ph O

= Ar, Het, i-Pr R

= Me, Et R Me R

R N CF N 3

Scheme 70 OH

X N X N

2 Me R

119 (48–60%) (41–56%) 118b 5.3.2 Quinolines and Heterofused Pyridines

2 3

= R = Me or (R

= OEt, Ph, CF (R

2 3

= Ph, R = H) R

3 2 Chlorotrimethylsilane was successfully applied in the = R = Me)

R Friedlander quinoline synthesis. In this case, o-aminoace- Scheme 69 tophenones reacted with a set of methylene active compounds [e.g., b-dicarbonyl compounds, acetophenones Other organosilicon compounds have also been used as and other alkyl (het)aryl ketones, tert-butyl methyl ke- water scavengers in Biginelli reactions. For example, io- tone, cycloalkanones, 4-piperidones, ethyl 2-oxobutyrate, dotrimethylsilane generated in situ from chlorotrimethyl- laevulinic acid, 1,3-dichloroacetone, ethyl 4-chloroace- silane and sodium iodide was successfully applied in the toacetate, 2-chlorocyclohexanone] in the presence of condensation of aromatic, heterocyclic, aliphatic or a,b- chlorotrimethylsilane–N,N-dimethylformamide in a pres- unsaturated aldehydes, urea and acetylacetone or ethyl sure tube to give various quinoline derivatives 121 in 76– 90,91 acetoacetate, leading to the formation of dihydropyrimi- 97% yields (Scheme 71). dine-2(1H)-ones 106. The reaction was carried out for 30– Heterofused pyridines were also synthesized by this meth- 50 minutes and afforded compounds 106 in 82–98% od. In particular, thieno[2,3-b]pyridines 122, [1]benzofu- yields.87 ro[3,2-b]pyridines 123, 5H-chromeno[2,3-b]pyridin-5- Trimethylsilyl triflate is another effective catalyst in the ones 124 and pyrido[2,3-d]pyrimidin-2,4(1H,3H)-diones 92 Biginelli reaction. In this case, the reaction was complete 125 were obtained (Scheme 71).

within 15 minutes of the addition of 0.01 equivalent of tri-

methylsilyl triflate to the mixture of starting compounds R 3

R 3

R Downloaded by: University of Chicago. Copyrighted material.

TMSCl (5 equiv)

(i.e., aldehyde, urea and b-dicarbonyl compound) in ace- R

2 2

R R

tonitrile at ambient temperature. The corresponding prod- DMF, 95 °C, 4–10 h

NH R

88 N

ucts 106 were formed in 80–95% yields. 2

R = Me, Ph

121

= H, 5-Cl, 5-NO , 4,5-OCH O R 2

5.3 Synthesis of Other N-Containing Hetero- 2

1 1

R R

cycles R

R 2

5.3.1 Pyridines R

S 4

In situ generated iodotrimethylsilane has been found to be R

an efficient condensing reagent in Hantzsch pyridine syn- 122 123

thesis. The 1,4-dihydropyridines 120 were obtained from O

R Me aromatic aldehydes, ethyl acetoacetate and ammonium 3 R

acetate. An analogous result was obtained under modified N

N O N R

reaction conditions starting from aldehydes and amino- 4

ON R

crotonate (Scheme 70). Unlike the classical Hantzsch pro- R cedure or its newer modifications, the method described 124 125 above afforded better yields of the products in the case of Scheme 71

In an analogous reaction, fused heterocyclic compounds the reaction of acetylacetone and urea that led to the 126 were obtained in 45–98% yields from o-amino- formation of 1,2-dihydropyrimidin-2-ones 129 thiophenecarbaldehydes 127a–c and creatinine in the (Scheme 74).39

presence of bis(trimethylsilyl)acetamide (Scheme 72).93

O O

OTMS TMSCl, DMF

Me + NN

r.t., 6–12 h

N H NHR

N NH 2 N

2 NTMS

NH 2 + 2

N 129a, R = H (76%) O N 140 °C, 2 h

CHO

129b, R = Me (99%)

128 126a (45%) 127

(98%)

126b Scheme 74 Me

126c (98%)

N NH

2 Pyrimidine derivatives 130 were obtained in the reaction

N of azadienes 131 and acyl chlorides in the presence of

S 126a chlorotrimethylsilane and triethylamine. N,N¢-Diacylaza-

dienes 132 were also formed as by-products; nevertheless, Me

S 132 N the use of chlorotrimethylsilane decreased the yield of

N 95

NH significantly (Scheme 75). 2

2 N N

N N

1 1

R R

R 126b 126c

NHC(O)R

TMSCl, Et N 2

R N

NH CHO

+ R

3 NC(O)R

R C(O)Cl

R N 1

CHO NH R 2

CHO S S S

130 (63–97%) 132 (0–13%) 131

127a 127b 127c Scheme 75 Scheme 72 A chlorotrimethylsilane-induced dehydrative cyclization Another approach to quinoline synthesis involved the of diamides 133 in the presence of N,N-dimethylethyl- chlorotrimethylsilane-promoted cyclization addition of amine (DMEA) afforded 3H-quinazolin-4-ones 134 enolizable aldehydes to arylimines, under an air atmo- (Scheme 76). The reaction appeared to be insensitive to sphere in dimethylsulfoxide, that afforded 2-arylquino- the nature of the acyl substituent (R3) and was also effec- lines 128 (Scheme 73). The clean and mild reaction tive in the case of compounds containing OH and NH conditions, high yields of the products and simple work- groups.96

up protocol are attractive features of the procedure de-

scribed above which thus enable a facile preparation of O

the quinoline derivatives.94 O

R HN O

2 TMSCl, DMEA R

MeCN, 30 °C, 70 h HN R

R N

1 Downloaded by: University of Chicago. Copyrighted material.

R R

TMSCl, DMSO 1

4 1

+ R CH CHO R

2 N

90 °C, 3–5 h

134 133

2 R

Scheme 76

4 3

R R

1 R Analogues of an alkaloid vasicinone 135a–c were ob-

N tained in quantitative yields by subsequent reduction of

2 R the corresponding N-(2-azidobenzoyl)lactams 136 and io-

128 dotrimethylsilane-promoted reductive cyclization, with Scheme 73 iodotrimethylsilane acting both as reaction promoter and as reducing reagent (Scheme 77).97 5.3.3 Pyrimidines and Quinazolines In addition to the chlorotrimethylsilane-mediated Biginelli 5.3.4 Azoles reaction discussed in section 5.2, several examples of 2-Substituted 2,3-dihydro-3-phenyl-1,3,4-thiadiazoles other pyrimidine syntheses have been reported. In partic- 137 were obtained in high yields from N¢-phenylthiofor- ular, Zav’yalov and Kulikova successfully applied the mic hydrazide 138 and aldehydes by treatment with chlo- chlorotrimethylsilane–N,N-dimethylformamide system in rotrimethylsilane (Scheme 78).98

3738 D. M. Volochnyuk et al. REVIEW

4 O O R

R O

O O R

1 N

TMSCl, NaI

) (CH +

3 TMSCl

(CH )

2 _

MeCN n

N 2

2 R

O R

R N 3

TMS

136 135a, n = 1

141 143

135b, n = 2

= H, Me R

4 4

135c, n = 3

R R

R = H, Cl

1 3 1 3 N N

R R R R n = 1–3

2 COOH R

Scheme 77 N

2 R COOH

trans cis

142 ( 60–78%)

S N

1 H O trans/cis = 95:5 (R = Ph)

N TMSCl

S R = Ph, Bn +

2 R H

= Me, Ph, Het R

3 R

= Ph, Het, COOEt R

= Bn, Ar, CH COOMe R

2 138 137a, R = Ph (96%) , R = Me (87%)

137b Scheme 80 Scheme 78 N-Aryl diamines, as well as diamines with a bulky substit- Recently, it was shown that some endothiopeptides 139 uent on the nitrogen, behaved poorly in the reaction: the were transformed into thiazoles 140 by treatment with a products were formed in 10–25% yields. Only aldehydes chlorotrimethylsilane–sodium iodide system and micro- that are sufficiently stable under reaction conditions (e.g., wave irradiation (Scheme 79).99 aromatic aldehydes) actually gave the desired products.

The target products (namely, benzoxazoles) were also not

O 102

R O formed in the case of o-aminophenols. H

TMSCl, NaI N

N R

N 2

TMSCl (2 equiv)

1 OMe MeO

1 R + R CHO

DMF, 95 °C, 2 h

140 139

X = S, NR (7–99%)

Scheme 79 R

NH Br

O N NH NH 2 2 2

The chlorotrimethylsilane-initiated [3+2]-cycloaddition R

5 3 3 N NH

R NHR NHR

reaction of imines and oxazolones 141 was shown to be a 2

convenient method of obtaining highly substituted imida- O

NNH H N 2 2

zolines 142. The first step of the reaction was the revers- 2

ible N-silylation of 141 leading to the formation of ylide 3 R NH

2 143 (so-called ‘munchnone’), which acted as a 1,3-dipolar SH compound in the cycloaddition (Scheme 80). The diaste- O reoselectivity of the reaction was determined by steric in- Scheme 81 Selected examples of the substrates are given teractions of the bulky silyl group in 143 and the C- Downloaded by: University of Chicago. Copyrighted material. substituent of the imine, and led to preferential formation 2-(Chloromethyl)indolizine-1-carbonitrile 144 was ob- of the trans-isomer. It should be noted that in the case of tained from pyridin-2-ylacetonitrile and 1,3-dichloroace- R = Me or Bn instead of R = Ph, the stability of cationic tone (Scheme 82). It is interesting to note that other center is lowered, thus resulting in diminished stereo- condensing reagents used did not allow for compound 144 100,101

selectivity. to be obtained.103

CN O

5.3.5 Benzo- and Heterofused Azoles TMSCl

The chlorotrimethylsilane–N,N-dimethylformamide sys- CN N N

Cl Cl

tem has been applied successfully to the synthesis of Cl benzimidazoles, 3H-imidazo[4,5-b]pyridines, purines, 144 xanthines and benzothiazoles from the corresponding Scheme 82 (hetero)aromatic o-diamines or o-aminothiophenols and aldehydes (Scheme 81). The reaction scope and limita- Other examples of chlorotrimethylsilane- and/or hexa- tions were also established. In the case of N-unsubstituted methyldisilazane-promoted dehydrative cyclizations phenylenediamines, diimines were obtained as by-prod- leading to the formation of heterofused azoles are illus- ucts, resulting in lowered yields of the desired products. trated in Scheme 83.104,105

REVIEW Organosilicon Compounds as Water Scavengers 3739

COOH

O H

N H

N HMDS, TMSCl

+ O

N NH

2 H , reflux, 36 h

N COOH

O N H

O CN

) SO HMDS, (NH N 4 2 4

140 °C, 50 h

O CN N NH

O N 2

OMe

HO H

H TMSCl, MeOH

N Me

MeO 10 °C, 1 h

O CN

MeO

H N CN

NHPh N

O S

Scheme 83

5.4 Recyclization of 3-Formylchromones OH

O O

EWG

The condensation of 1,3-dicarbonyl compounds is one of TMSCl +

the most widely used reactions in the synthesis of hetero- HN O DMF, 100 °C

O N

cycles. In many cases, these electrophiles possess several R

1 R

147

non-equivalent reaction centers, thereby presenting a 148

= H, F, Cl, Me, OMe

regioselectivity problem. Hence, one of the major tasks in R 3 , COMe

this area is to find the substrates and the conditions that al- EWG = CN, CONHR low for single regioisomers to be obtained. 3-Formyl- Scheme 85 chromone (145), a molecule which possesses three electrophilic centers, is that type of substrate In the chlorotrimethylsilane-promoted reaction of 3- (Scheme 84). The tendency of the chromone fragment to formylchromone and primary hetarylmethylamines, undergo recyclization reactions allows one to consider (5-hetaryl-1H-pyrrol-3-yl)(2-hydroxyphenyl)methanones 145 as a synthetic equivalent of 2-(2-hydroxybenzoyl)ma- 149 were obtained in 68–91% yields (Scheme 86). With a lonic aldehyde (146). 2:1 ratio of the reagents, fused chromonepyrroles 150

were formed in moderate yields. When secondary hetaryl-

O O methylamines were used as substrates in this reaction,

OH only pyrrole derivatives 149 were isolated in 65–99% O O

yields. Downloaded by: University of Chicago. Copyrighted material.

O An analogous transformation was also observed in the 145 146 case of glycine derivatives 151 (Scheme 86).

Scheme 84 The chlorotrimethylsilane-mediated pyrrole synthesis appeared to be also applicable to the fusion of the pyrrole and the dihydroquinoxaline rings (compounds 152). How- The first expedient method for the preparation of the com- ever, in the case of prolinamide and N,N¢-dimethylgly- 145 106 pound was reported in 1973, and this chromone de- cinamide, imidazolinones 153 and 154 were obtained rivative has been widely applied in heterocycle synthesis (Scheme 87).109 since then.107 Nevertheless, the first example of using chlorotrimethylsilane as a promoter of the recyclization of Unexpected results were obtained in the reaction of 3- 3-formylchromones was reported only in 2004. Specifi- formylchromone with aromatic amines. In many cases, cally, the reaction of 3-formylchromones 147 and elec- the target 3-(2-hydroxybenzoyl)quinolines 155 were syn- tron-withdrawing-group-substituted acetamides, in the thesized in 35–87% yields, indicative of the amine acting presence of a chlorotrimethylsilane–N,N-dimethylform- first as a C-nucleophile. However, in the case of aniline amide system, led to the formation of pyridone derivatives derivatives possessing an electron-withdrawing group in 148 as a result of a Guareschi–Thorpe condensation the meta-position, or any para-substituted anilines, the (Scheme 85).108 fused chromenoquinolines 156 were formed in 39–67%

3740 D. M. Volochnyuk et al. REVIEW

HO OH O O

NHR

TMSCl

Het

R +

DMF, 100 °C

Het

N N

O 149 (68–91%) O 155 (35–87%) O R

145

+ TMSCl R

O OO

DMF, 100 °C NH O

2 TMSCl Het

N 2 DMF, 100 °C

Het

O O

O 150 (54–64%)

O X OO N

X TMSCl 156 (39–67%)

DMF, 100 °C

N Scheme 88

R O

R 151 152

, NEt , N(CH ) X = OH, OMe, NMe 2 2 2 4

OH O O O

Scheme 86 TMSCl +

DMF, 100 °C

N O

157 (35–87%)

N O R

1 R

N N

2 N N

O N

NH NH HN

2 2

O S

1 152

R 153 (84%)

MeO C N NH O R

2 2

NH O

NH EtO C

2 2 S

O N

O H N

2 R

N HN

N O

N NH MeS

NH O 2 2

NMe N Me H

H Scheme 89 Examples of amino heterocycles are given

O Me

1 R

O O

O Downloaded by: University of Chicago. Copyrighted material. N N

1 O TMSCl R

Me 154 (79%) +

DMF, 100 °C N NH

Scheme 87 O

O OH

158 (55–95%) and no traces of 155 were detected, thus the amine was

acting first as an N-nucleophile (Scheme 88). In the case

N N N

of 3,4-disubstituted anilines, the products 155 or 156 were N

obtained, depending on the electronic effects of the sub- 2

NH N

110 H

H stituents. H

EWG 2 R 2

EtO C

An analogous transformation was observed in the case of 2

heteroaromatic amines capable of acting as CCN-binu- N N

N N O N

cleophiles, which thus led to the formation of fused py- N

H H H

ridines 157 (Scheme 89).111 H Heteroaromatic amines lacking a carbon atom at the posi- Scheme 90 Examples of amino heterocycles are given tion a to the amino group showed NCN-binucleophilic behavior in the reaction with 3-formylchromone, thereby transformation was observed in the case of amidines affording pyrimidines 158 (Scheme 90). An analogous (Scheme 91).112

REVIEW Organosilicon Compounds as Water Scavengers 3741

OH O

2 thus prevents any nucleophilic attack from taking place at R

O that site.116

HN NH R 2

TMSCl

2 N R

DMF, 100 °C

O 1

2 6 Conclusions

R = Ph, N(CH ) 2 4

Scheme 91 Organosilane compounds, in particular chlorotrimethylsilane, act as very efficient water scavengers in many com- The reaction of 3-formylchromones 147 and 1-aminoimi- mon reactions of carbonyl compounds, including the dazoles 159 in the presence of chlorotrimethyl- Knoevenagel condensation, imine and enamine syntheses, silane and N,N-dimethylformamide led to the formation the Mannich reaction, and heterocyclizations such as the of imidazo[1,5-b]pyridazines 160 (Scheme 92). However, Biginelli and Friedlander reactions. The procedures de- 1-aminobenzimidazole and 4-amino-1,2,4-triazoles did veloped for these syntheses are applicable to a vast range not undergo an analogous heterocyclization under these of substrate molecules. Taking into account the simplicity conditions; only hydrazone formation was observed.113 and generality of the methods based on organosilane-pro-

moted condensations of carbonyl compounds, one should

1 R expect further progress in this area with regard to other re-

actions for which the outcome depends on the use of a wa-

O O

N ter scavenger.

1 TMSCl R

DMF, 100 °C

O Acknowledgment NH

2 N

147

2 2

159a, R = NH R

2 (81–96%)

160 The authors thank Prof. A. A. Tolmachev for the great encourage-

, R = SH 159b ment and support. Scheme 92 References Finally, in the reaction of 3-formylchromone with com- (1) (a) Claisen, L.; Claparède, A. Chem. Ber. 1881, 14, 2460. 114 pounds 161 (imidazole, benzimidazole, quinazolone (b) Fehnel, E. A. J. Org. Chem. 1966, 31, 2899. (c) Conard, and thieno[2,3-d]pyrimidin-4(3H)-one115 derivatives), C. R.; Dolliver, M. A. Org. Synth. 1932, 12, 22. (d) Noland, fused polycyclic heterocycles 162 were obtained W. E. Org. Synth. 1961, 41, 67. (e) Kyriakides, L. P. J. Am. (Scheme 93). Chem. Soc. 1914, 36, 530. (2) (a) Newkomel, G. R.; Fishe, D. L. Org. Synth. 1970, 50,

102. (b) Cornell, J. H. Jr.; Gollis, M. H. Org. Synth. 1962, OH O

O O 42, 57. (c) Hünig, S.; Lücke, E.; Brenninger, W. Org. Synth.

N 1961 41 Org. Synth. TMSCl , , 65. (d) Buckles, R. E.; Bremer, K.

+ 1953, 33, 70. (e) Billek, G. Org. Synth. 1963, 43, 49. DMF, 100 °C

N (f) Jessup, P. J.; Petty, C. B.; Roos, J.; Overman, L. E. Org.

R 161 (40–98%) 162 Synth. 1980, 59, 1.

(3) (a) Ranu, B. C.; Jana, R. Eur. J. Org. Chem. 2006, 3767.

X = CN, COPh, CO(2-thienyl), CONH , CONHBn, (b) Su, C.; Chen, Z.-C.; Zhen, Q.-G. Synthesis 2003, 555. 2

CON(CH ) O, CSNH , SO Me, SO Ph,

4 2 2 2 2 (c) Khan, F. A.; Dash, J.; Satapathy, R.; Upadhyay, S. K.

2-benzothiazolyl, Ph, SCH CO H, Cl, NHCOPh, N

X 2

2 Tetrahedron Lett. 2004, 45, 3055. (d) Forbes, D. C.; Law, Downloaded by: University of Chicago. Copyrighted material.

H CH NHCOPh, OPh, H

2 A. M.; Morrison, D. W. Tetrahedron Lett. 2006, 47, 1699.

O (4) (a) Deb, M. L.; Bhuyan, P. J. Tetrahedron Lett. 2005, 46,

X = CN, H, Cl, CH CO H, (CH ) CO H, 2 2 2 2 2

NH 6453. (b) Xing, C.; Li, X.; Zhu, S.; Zhao, J.; Zhu, S.

N(CH ) NH, N(CH ) NMe, N(CH ) O 4 2 4 2 4

2 Tetrahedron Lett. 2006, 47, 4951. (c) Bartoli, G.; Beleggia, X

N R.; Giuli, S.; Giuliani, A.; Marcantoni, E.; Massaccesi, M.;

O O

O Paoletti, M. Tetrahedron Lett. 2006, 47, 6501. (d) Lai, G.;

Ph Peng, J.; Li, J.; Qiu, H.; Jiang, J.; Jiang, K.; Shen, Y.

NH Tetrahedron Lett. 2006, 47, 6951.

N SMe

S (5) (a) Yadav, J. S.; Reddy, B. S. S.; Basak, A. K.; Visali, B.; H N

S N Narsaiah, A. V.; Nagaiah, K. Eur. J. Org. Chem. 2004, 546. (b) Ebitani, K.; Motokura, K.; Mori, K.; Mizugaki, T.; Scheme 93 Selected examples of methylene components are given Kaneda, K. J. Org. Chem. 2006, 71, 5440. (6) (a) Das, D. D.; Harlick, P. J. E.; Sayari, A. Catal. Commun. It should be noted that the use of chlorotrimethylsilane in 2007, 8, 829. (b) Komura, K.; Kawamura, T.; Sugi, Y. Catal. Commun. 2007, 8, 644. (c) Dong, F.; Li, Y. Q.; Dai, most of the 3-formylchromone condensations discussed R. F. Chin. Chem. Lett. 2007, 18, 266. (d) Climent, M. J.; above significantly improved the regioselectivity of the Corma, A.; Domínguez, I.; Iborra, S.; Sabater, M. J.; Sastre, reaction. This is presumably due to the preliminary silyla- G. J. Catal. 2007, 246, 136. (e) Seki, T.; Onaka, M. J. Mol. tion of the carbonyl group of the chromone ring, which Catal. A: Chem. 2007, 263, 115. (f) Xin, X.; Guo, X.; Duan, H.; Lin, Y.; Sun, H. Catal. Commun. 2007, 8, 115. (g) Gawande, M. B.; Jayaram, R. V. Catal. Commun. 2006,

7, 931. (h) Martins, L.; Bonagamba, T. J.; Azevedo, E. R.; (35) Bellani, P.; Clavenna, G.; Sosio, A. Farmaco, Ed. Sci. 1984, Bargiela, P.; Cardoso, D. Appl. Catal., A 2006, 312, 77. 39, 846. (7) (a) McNulty, J.; Steere, J. A.; Wolf, S. Tetrahedron Lett. (36) Ohta, S.; Tsuno, N.; Maeda, K.; Nakamura, S.; Taguchi, N.; 1998, 39, 8013. (b) Watson, B. T.; Christiansen, G. E. Yamashita, M.; Kawasaki, I. Tetrahedron Lett. 2000, 41, Tetrahedron Lett. 1998, 39, 6087. (c) Draper, R. W.; Hu, B.; 4623. Iyer, R. V.; Li, X.; Lu, Y.; Rahman, M.; Vater, E. J. (37) Love, B. E.; Ren, J. J. Org. Chem. 1993, 58, 5556. Tetrahedron 2000, 56, 1811. (d) Nakamura, M.; Endo, K.; (38) Ryabukhin, S. V.; Plaskon, A. S.; Volochnyuk, D. M.; Nakamura, E. Org. Lett. 2005, 7, 3279. (e) Yanagisawa, A.; Shivanyuk, A. N.; Tolmachev, A. A. J. Org. Chem. 2007, 72, Goudu, R.; Arai, T. Org. Lett. 2004, 6, 4281. (f) Bandini, 7417. M.; Benaglia, M.; Sinisi, R.; Tommasi, S.; Umani-Ronchi, (39) Zav’yalov, S. I.; Kulikova, L. B. Khim.-Farm. Zh. 1992, 26, A. Org. Lett. 2007, 9, 2151. 88. (8) Dilman, A. D.; Ioffe, S. L. Chem. Rev. 2003, 103, 733. (40) Sisko, J.; Mellinger, M.; Sheldrake, P. W.; Baine, N. H. (9) (a) López, S. E.; Restrepo, J.; Salazar, J. J. Chem. Res. 2007, Tetrahedron Lett. 1996, 37, 8113. 497. (b) Hedrera, M. E.; Perillo, I. A. Trends Heterocycl. (41) Wynne, J. H.; Price, S. E.; Rorer, J. R.; Stalick, W. M. Synth. Chem. 2002, 8, 105. Commun. 2003, 33, 341. (10) (a) Zav’yalov, S. I.; Dorofeeva, O. V.; Taganova, O. K. Izv. (42) Xu, D.; Ciszewski, L.; Li, T.; Repič, O.; Blacklock, T. J. Akad. Nauk SSSR, Ser. Khim. 1985, 495. (b) Zav’yalov, S. Tetrahedron Lett. 1998, 39, 1107. I.; Dorofeeva, O. V.; Rumyantseva, E. E. Izv. Akad. Nauk (43) Ciszewski, L.; Xu, D.; Li, T.; Repič, O.; Blacklock, T. J. SSSR, Ser. Khim. 1989, 2351. Tetrahedron Lett. 2004, 45, 8091. (11) Zav’yalov, S. I.; Zavozin, A. G. Khim.-Farm. Zh. 1994, 28, (44) Jain, N. F.; Panek, J. S. Tetrahedron Lett. 1997, 38, 1349. 49. (45) Panek, J. S.; Jain, N. F. J. Org. Chem. 2001, 66, 2747. (12) Mukaiyama, T.; Wariishi, K.; Saito, Y.; Hayashi, M.; (46) Panek, J. S.; Jain, N. F. J. Org. Chem. 1998, 63, 4572. Kobayashi, S. Chem. Lett. 1988, 17, 1101. (47) Dias, L. C.; Oliveira, L. G. Org. Lett. 2004, 6, 2587. (13) Ishai, E.; Shamai, S.; Feit, B.-A. J. Chem. Soc., Perkin (48) Evans, D. A.; Bender, S. L.; Morris, J. J. Am. Chem. Soc. Trans. 1 2002, 434. 1988, 88, 2506. (14) Iwasaka, N.; Mukaiyama, T. Chem. Lett. 1987, 16, 463. (49) Panek, J. S.; Beresis, R. T.; Celatka, C. A. J. Org. Chem. (15) Bender, A.; Guenther, D.; Wingen, R. Liebigs Ann. Chem. 1996, 61, 6494. 1985, 3, 579. (50) Heydari, A.; Tavakol, H.; Aslanzadeh, S.; Azarnia, J.; (16) Mukaiyama, T.; Ohno, T.; Han, J. S.; Kobayashi, S. Chem. Ahmadi, N. Synthesis 2005, 627. Lett. 1991, 20, 949. (51) Schroth, W.; Jahn, U.; Ströhl, D. Chem. Ber. 1994, 127, (17) Zhu, Y.; Pan, Y. Chem. Lett. 2004, 33, 668. 2013. (18) Kagawa, N.; Toyota, M.; Ihara, M. Aust. J. Chem. 2004, 57, (52) Jahn, U.; Schroth, W. Tetrahedron Lett. 1993, 34, 5863. 655. (53) Arend, M.; Risch, N. Synlett 1997, 974. (19) Sabitha, G.; Reddy, G. S. K. K.; Reddy, K. B.; Yadav, J. S. (54) Kobayashi, K.; Takanohashi, A.; Hashimoto, K.; Morikawa, Synthesis 2004, 263. O.; Konishi, H. Tetrahedron 2006, 62, 3158. (20) Reisch, J.; Mester, Z. Monatsh. Chem. 1983, 114, 635. (55) Saidi, M. R.; Azizi, N. Tetrahedron: Asymmetry 2002, 13, (21) Reisch, J.; Mester, Z. Arch. Pharm. (Weinheim, Ger.) 1985, 2523. 318, 459. (56) Heydari, A.; Mehrdad, M.; Tavakol, H. Synthesis 2003, (22) Ryabukhin, S. V.; Plaskon, A. S.; Volochnyuk, D. M.; 1962. Pipko, S. E.; Shivanyuk, A. N.; Tolmachev, A. A. J. Comb. (57) Saidi, M. R.; Azizi, N. Synthesis 2002, 1347. Chem. 2007, 9, 1073. (58) Saidi, M. R.; Azizi, N. Tetrahedron Lett. 2001, 42, 8111. (23) (a) Ryabukhin, S. V.; Plaskon, A. S.; Tverdokhlebov, A. V.; (59) Azizi, N.; Saidi, M. R. Tetrahedron Lett. 2002, 43, 4305. Tolmachev, A. A. Synth. Commun. 2004, 34, 1483. (60) Saidi, M. R.; Azizi, N.; Zali-Boinee, H. Tetrahedron 2001, (b) Ryabukhin, S. V.; Plaskon, A. S.; Volochnyuk, D. M.; 57, 6829. Tolmachev, A. A. Synthesis 2007, 3163. (61) Naimi-Jamal, M. R.; Ipaktschi, J.; Saidi, M. R. Eur. J. Org. (24) Ryabukhin, S. V.; Plaskon, A. S.; Volochnyuk, D. M.; Chem. 2000, 1735.

Tolmachev, A. A. Synthesis 2007, 2872. (62) Naimi-Jamal, M. R.; Mojtahedi, M. M.; Ipaktschi, J.; Saidi, Downloaded by: University of Chicago. Copyrighted material. (25) Tverdokhlebov, A. V.; Gorulya, A. P.; Tolmachev, A. A.; M. R. J. Chem. Soc., Perkin Trans. 1 1999, 3709. Kostyuk, A. N.; Chernega, A. N.; Rusanov, E. B. Synthesis (63) Saidi, M. R.; Khalaji, M. R.; Ipaktschi, J. J. Chem. Soc., 2005, 2161. Perkin Trans. 1 1997, 1983. (26) Ryabukhin, S. V.; Plaskon, A. S.; Volochnyuk, D. M.; (64) Rochin, C.; Babot, O.; Dunogues, J.; Duboudin, F. Synthesis Pipko, S. E.; Tolmachev, A. A. Synth. Commun. 2008, 38, 1986, 228. 3032. (65) Rochin, C.; Babot, O.; Dunogues, J.; Duboudin, F. Synthesis (27) Sakai, T.; Miyata, K.; Tsuboi, S.; Utaka, M. Bull. Chem. Soc. 1986, 667. Jpn. 1989, 62, 4072. (66) Heaney, H.; Papageorgiou, G.; Wilkins, R. F. J. Chem. Soc., (28) Dräger, G.; Solodenko, W.; Messinger, J.; Schön, U.; Chem. Commun. 1988, 1161. Kirschning, A. Tetrahedron Lett. 2002, 43, 1401. (67) Heaney, H.; Papageorgiou, G.; Wilkins, R. F. Tetrahedron (29) Angeletti, E.; Canepa, C.; Martinetti, G.; Verturello, P. 1997, 53, 2941. Tetrahedron Lett. 1988, 29, 2261. (68) Fairhurst, R. A.; Heaney, H.; Papageorgiou, G.; Wilkins, R. (30) Schmidt, A. H.; Russ, M. Chem. Ber. 1981, 114, 1099. F.; Eyley, S. C. Tetrahedron Lett. 1989, 30, 1433. (31) Esteban, G.; Plumet, J. ARKIVOC 2007, (iv), 182. (69) Earle, M. J.; Fairhurst, R. A.; Heaney, H.; Papageorgiou, G.; (32) Srivastava, N.; Kumar, A.; Dwivedy, I.; Ray, S. Synth. Wilkins, R. F. Tetrahedron Lett. 1990, 31, 4229. Commun. 1997, 27, 2877. (70) Heaney, H.; Papageorgiou, G. Tetrahedron 1996, 52, 3473. (33) Gutnov, A. V.; Abaev, V. T.; Butin, A. V.; Zavodnik, V. E.; (71) Brocke, C.; Brimble, M. A.; Lin, D. S.-H.; McLeod, M. D. Kul’nevich, V. G. Khim. Geterotsikl. Soedin. 1996, 12, 162. Synlett 2004, 2359. (34) Zav’yalov, S. I.; Dorofeeva, O. F.; Rumyantseva, E. E.; (72) Brimble, M. A.; Brocke, C. Eur. J. Org. Chem. 2005, 2385. Zavozin, A. G. Khim.-Farm. Zh. 1995, 29, 58.

(73) Buckley, B. R.; Page, P. C. B.; Heaney, H.; Sampler, E. P.; (97) Kamal, A.; Ramana, K. V.; Rao, M. V. J. Org. Chem. 2001, Carley, S.; Brocke, C.; Brimble, M. A. Tetrahedron 2005, 66, 997. 61, 5876. (98) Yoshio, M.; Kazutada, K.; Akihiro, T.; Masakuni, Y.; (74) Halliday, J. I.; Chebib, M.; Turner, P.; McLeod, M. D. Org. Toshihisa, M. Chem. Pharm. Bull. 1994, 42, 373. Lett. 2006, 8, 3399. (99) Kazmaier, U.; Ackermann, S. Org. Biomol. Chem. 2005, 3, (75) Shipov, A. G.; Orlova, N. A.; Novikova, O. P.; Baukov, Yu. 3184. I. Zh. Obshch. Khim. 1985, 55, 943. (100) Peddibhotla, S.; Jayakumar, S.; Tepe, J. J. Org. Lett. 2002, (76) Shipov, A. G.; Orlova, N. A.; Kobzareva, V. P.; 4, 3533. Mozzhukhin, A. O.; Antipin, M. Yu.; Struchkov, Yu. T.; (101) Peddibhotla, S.; Tepe, J. J. Synthesis 2003, 1433. Baukov, Yu. I. Zh. Obshch. Khim. 1993, 63, 371. (102) Ryabukhin, S. V.; Plaskon, A. S.; Volochnyuk, D. M.; (77) Kantevari, S.; Bantu, R.; Nagarapu, L. ARKIVOC 2006, Tolmachev, A. A. Synthesis 2006, 3715. (xvi), 136. (103) Tereschenko, A. D.; Sysoiev, D. A.; Tverdokhlebov, A. V.; (78) Sabitha, G.; Reddy, K. B.; Reddy, G. S. K. K.; Fatima, N.; Tolmechev, A. A. Synthesis 2006, 349. Yadav, J. S. Synlett 2005, 2347. (104) Hayallah, A. M.; Sandoval-Ramirez, J.; Reith, U.; Schobert, (79) (a) Biginelli, P. Gazz. Chim. Ital. 1893, 23, 360. (b) Kappe, U.; Preiss, B.; Schumacher, B.; Daly, J. W.; Müller, C. C. O. Tetrahedron 1993, 49, 6937. (c) Kappe, C. O. Acc. J. Med. Chem. 2002, 45, 1500. Chem. Res. 2000, 33, 879. (105) Ceballos, P. A.; Pérez, M.; Cuevas, C.; Francesch, A.; (80) Zav’yalov, S. I.; Kulikova, L. B. Khim.-Farm. Zh. 1992, 26, Manzanares, I.; Echvarren, A. Eur. J. Org. Chem. 2006, 116. 1926. (81) Zhu, Y.; Pan, Y.; Huang, S. Synth. Commun. 2004, 34, 3167. (106) Nohara, A.; Umetami, T.; Sanno, Y. Tetrahedron Lett. 1973, (82) Ryabukhin, S. V.; Plaskon, A. S.; Ostapchuk, E. N.; 14, 1995. Volochnyuk, D. M.; Tolmachev, A. A. Synthesis 2007, 417. (107) (a) Ellis, G. P. In Heterocyclic Compounds, Vol. 35; (83) Zhu, Y.; Huang, S.; Pan, Y. Eur. J. Org. Chem. 2005, 2354. Weisberger, A., Ed.; Interscience: New York, 1977, 921. (84) Zhu, Y.; Pan, Y.; Huang, S. Heterocycles 2005, 65, 113. (b) Ghosh, C. K. J. Heterocycl. Chem. 1983, 20, 1437. (85) Ryabukhin, S. V.; Plaskon, A. S.; Ostapchuk, E. N.; (c) Sabitha, G. Aldrichimica Acta 1996, 29, 15. (d) Ghosh, Volochnyuk, D. M.; Shishkin, O. V.; Shivanyuk, A. N.; C. K.; Ghosh, C. Indian J. Chem., Sect. B: Org. Chem. Incl. Tolmachev, A. A. Org. Lett. 2007, 9, 4215. Med. Chem. 1997, 36, 968. (e) Ghosh, C. K. Heterocycles (86) Ryabukhin, S. V.; Plaskon, A. S.; Ostapchuk, E. N.; 2004, 63, 2875. Volochnyuk, D. M.; Shishkin, O. V.; Tolmachev, A. A. (108) Ryabukhin, S. V.; Plaskon, A. S.; Volochnyuk, D. M.; J. Fluorine Chem. 2008, 129, 625. Tolmachev, A. A. Synlett 2004, 2287. (87) Sabitha, G.; Reddy, G. S. K. K.; Reddy, C. S.; Yadav, J. S. (109) Plaskon, A. S.; Ryabukhin, S. V.; Volochnyuk, D. M.; Synlett 2003, 858. Shivanyuk, A. N.; Tolmachev, A. A. Tetrahedron 2008, 64, (88) Bose, D. S.; Kumar, R. K.; Fatima, L. Synlett 2004, 279. 5933. (89) Sabitha, G.; Reddy, G. S. K. K.; Reddy, C. S.; Yadav, J. S. (110) Plaskon, A. S.; Ryabukhin, S. V.; Volochnyuk, D. M.; Tetrahedron Lett. 2003, 44, 4129. Gavrilenko, K. S.; Shivanyuk, A. N.; Tolmachev, A. A. (90) Ryabukhin, S. V.; Volochnyuk, D. M.; Plaskon, A. S.; J. Org. Chem. 2008, 73, 6010. Naumchik, V. S.; Tolmachev, A. A. Synthesis 2007, 1214. (111) Ryabukhin, S. V.; Plaskon, A. S.; Volochnyuk, D. M.; (91) Degtyarenko, A. S.; Tolmachev, A. A.; Volovenko, Yu. M.; Tolmachev, A. A. Synthesis 2007, 1861. Tverdokhlebov, A. V. Synthesis 2007, 3891. (112) Ryabukhin, S. V.; Plaskon, A. S.; Volochnyuk, D. M.; (92) Ryabukhin, S. V.; Volochnyuk, D. M.; Plaskon, A. S.; Pipko, S. E.; Tolmachev, A. A. Heterocycles 2008, 75, 583. Naumchik, V. S.; Pipko, S. E.; Tolmachev, A. A. (113) Plaskon, A. S.; Ryabukhin, S. V.; Volochnyuk, D. M.; Heterocycles 2007, 71, 2397. Shivanyuk, A. N.; Tolmachev, A. A. Heterocycles 2008, 75, (93) Björk, M.; Grivas, S. J. Heterocycl. Chem. 2006, 43, 101. 1765. (94) Geng, X.; Li, S.; Bian, X.; Xie, Z.; Wang, C. ARKIVOC (114) Ryabukhin, S. V.; Plaskon, A. S.; Volochnyuk, D. M.; 2008, (xiv), 50. Tolmachev, A. A. Synthesis 2007, 3155. (95) Barluenga, J.; Pozo, C.; Olano, B. Synthesis 1996, 133. (115) Plaskon, A. S.; Ryabukhin, S. V.; Volochnyuk, D. M.;

(96) O’Mahony, D. J. R.; Krchňák, V. Tetrahedron Lett. 2002, Tolmachev, A. A. Synthesis 2008, 1069. Downloaded by: University of Chicago. Copyrighted material. 43, 939. (116) Iwasaki, H.; Kume, T.; Yamamoto, Y.; Akiba, K. Heterocycles 1988, 27, 1599.