Six-Membered Ring Systems

CHAPTER

6.2

Six-Membered Ring Systems: Diazines and Benzo Derivatives Larry Yet University of South Alabama, Mobile, Alabama 36688 USA [email protected]

6.2.1. INTRODUCTION The literature of the three diazine systems—pyridazine, pyrimidine, and pyrazine— and their respective benzo analogs (cinnoline, phthalazine, quinazoline, quinoxaline, and phenazine) are described in this chapter. Diazines are an important class of compounds and can be found in many areas such as biological, pharmaceutical, polymer, and material sciences. Numerous reports on the synthesis, reactions, and applications of diazines were reported in 2011, and no attempt was made to incorporate all the exciting chemistry and biological applications that were published. N

N N

N

N

N Pyridazine

Cinnoline N N Pyrazine

Phthalazine N N Quinoxaline

N

N

N

N Pyrimidine

Quinazoline

N N Phenazine

6.2.2. PYRIDAZINES AND BENZO DERIVATIVES A review titled “Are Pyridazines Privileged Structures?” <11MCC935> was published. Few papers were published in 2011 for the preparation of pyridazines and their benzo derivatives. Enaminones 1 were treated with hydrazine followed by oxidation with lead(II) acetate in acetic acid to give pyridazines 2 in moderate yields <11SC1119>. Trifluoromethyl-substituted diazoketone 3 underwent Staudingerdiaza-Wittig reactions to give 4-trifluoromethylpyridazine 4 <11TL341>. Condensations of a-keto-a-formylarylhdrazones 5 with ethyl cyanoacetate <11TL202> and 2-arylhydrazono-1-phenylethanones 7 with benzylidenemalononitriles or with ethyl 2-cyanocinnamate <11ARK310> afforded pyridazinones 6 and 8, respectively. Progress in Heterocyclic Chemistry, Volume 24 ISSN 0959-6380, http://dx.doi.org/10.1016/B978-0-08-096807-0.00013-0

#

2012 Elsevier Ltd. All rights reserved.

393

394

L. Yet

O

O

CN

Ar

CN NMe2

1. NH2 NH 2, EtOH

CN NH 2

Ar

2. HOAc, Pb(OAc) 2 N

63–67%

1

MeO2C F3C

N

PPh3 or

O

Me PhH, 80 °C N2

2

F3C

P(NMe2 )3

OMe N

MeOC

43–45%

N

4

3

X NCCH2 CO 2Et

O X

R N

NH4 OAc, HOAc 110 °C

NHPh

O

Ph

O X

R N

73–89%

5 X = CO2Et, CHO

N Ph 6

H

Ph N

O

7

O

CN

1. EtOH, 80 °C

Ph X

Ph

2. HOAc, HCl

N

NHAr X = CO Et, CN 2 8

55–58%

N Ar

O

Several fused pyridazine ring systems were reported. 6-Chloro-[1,2,4]triazolo[4,3-b] pyridazines 11 were obtained from the reaction of 3-chloro-6-hydrazinopyridazine 10, prepared from hydrazinolysis of 3,6-dichloropyridazine 9, with diethyl ethoxymethylenemalonate or with triethyl orthoformate <11ARK309>. 5,6-Fused pyridazines 12 were synthesized from 1,2-diacylcyclopentadienes with hydrazine <11SC1357>. 4-Aryl-6,8-dimethylpyrimido[4,5-c]pyridazine-5,7-diones 13 were prepared from a three-component reaction of 1,3-dimethylbarbituric acid with arylglyoxals in the presence of hydrazinium dihydrochloride <11BKCS2428>. Cl

NHNH 2 N N

NH2NH2×H2O

N N

PhH, 80 °C

EtOCH=C(CO 2Et)2 , CH 3 CN 80 °C (gives R = H) CH 3C(OEt)3 , ref lux

Cl

Cl 10

9

R

H N

N

or (gives R = Me)

Cl

N

N 11

N R

Me N

N

N

N N

R Ar 12

O Me

O 13

Palladium-catalyzed annulation of 2-iodophenyltriazenes 14 with alkynes afforded 3,4-disubstituted cinnolines 15 <11T4933>. Richter cyclization of 2-aryl/alkylethynyl anilines 16 with sodium nitrite and dilute hydrochloric acid delivered 3-aryl/alkyl-4(1H)-cinnolinones 17, which after tin reduction and further treatment with sodium nitrite and potassium iodide on the alkyl intermediates afforded 3-alkylcinnolines 18 <11T8918>.

395

Six-Membered Ring Systems

R1

R2

PdCl2 (7.5 mol%), P(o-Tolyl) 3 N

N

N

(10 mol%), n-Bu 3N (2 equiv.)

NEt 2

N

DMF, 90 °C I 14

R2 R

NH 2 16

1

R 15

35 –82%

O

NaNO 2, HCl

R2

H 2O, 0 °C

1

R2

R 1 = R2 = Ar, CO 2Et, Me

1

R

80–92%

N H 17

R1 = H, Cl, CN R2 = aryl, alkyl

N

1. Sn, HCl 2. NaNO2 , HCl

R2 R

1

KI

N

R2 = alkyl

N

18

70–76%

Several cinnoline-fused ring systems were reported. Bergman cyclization of cinnoline-fused cyclic enediyne 19 under mild thermal conditions provided tetracyclic cinnoline-fused ring 20 <11JOC6937>. Thermal cyclization of phenanthrenofused azo-ene-yne 21 afforded dibenzo[f,h]cinnoline 22 <11JOC8483>. N

i-PrOH OH 75 °C

N N

N

NEt2 1,2-dichlorobenzene

OH

N

200 °C

N N

19

N

58% 20

21

22

Xanthones were employed in the regioselective multistep synthesis of phthalazines <11H(83)1291>. Bidentate Lewis acid 24 was applied as a catalyst for the inverseelectron-demand Diels–Alder reaction of phthalazine 23 with dienophiles to give naphthalenes 25 <11EJO3238>. Palladium-catalyzed cross-coupling reactions of 3-methylthiopyridazine 26 with organozinc reagents in the presence of S-Phos ligand afforded good yields of functionalized pyridazines 27 in good yields <11CEJ2948>. The authors also reported in the same paper that the Ni(acac)2/DPE-Phos combination also worked in these systems. Me B RZnI LiCl (1.4 equiv.) •

N N 23

B Me

OMe 24

R

dienophile, diglyme 120 °C, 2.5 days 10–100%

25

N N

R

SMe 26

Pd(OAc)2 (2.5 mol%) S-Phos (5 mol%) THF, 25 °C R = 4-CNPh (76%), 3-CNC6 H 4CH2 (71%)

OMe N N R 27

Bis-cinchona alkaloid 28 was a highly bifunctional organocatalyst for the asymmetric conjugate addition of malonates to nitroalkenes at room temperature, providing enantioselectivities up to 97% ee <11T10186>. Chiral dinuclear phthalazinebridged bisoxazoline ligand 29 provided excellent yields and enantioselectivities in the copper-catalyzed conjugate addition of ZnEt2 to enones <11TL2375>.

396

L. Yet

N N N

Et

OH

N O

Me Me

O

O

N

HO

N N N

Et N

Me Me O N

Ph

28

Ph

29

Interesting phthalazine-fused derivatives have appeared in 2011. Three independent research groups prepared 2H-indazolo[2,1-b]phthalazine-triones 30 from a onepot, four-component reaction of aryl or alkyl aldehydes and dimedone, and either with phthalhydrazide in the presence of N-halosulfonamides or with phthalic anhydride and hydrazine hydrate <11T1930, 11TL488, 11TL7195>. 1H-Pyrazolo[1,2-b] phthalazine-5,10-diones 31 were prepared by a one-pot cyclocondensation reaction of phthalhydrazide, aromatic aldehydes, and malononitrile or ethyl cyanoacetate under microwave irradiation <11TL5702>. The spiro version 32 of 31 was synthesized by the same reaction above except that isatin was used in place of the aromatic aldehydes <11T7426>. Chiral pyrrolophthalazines 33 were prepared from the organocatalytic enantioselective [3 þ 2] cycloaddition between enals and phthalizinium methylides <11CC12313>. Bicyclic phthalazine ring 34 was obtained from the Diels–Alder reaction between diethyl 1-phosphono-1,3-butadiene and N¼¼N dienophiles <11TL5140>. 1H-3,7-Difurylcyclopenta[3,4-d]pyridazine 35 was prepared from a manganese or rhenium complex <11H(83)1275>. O

O

R O

N

Me

Me

Ar N N

N O

O

N N

R NH2

O

H N

O

R NH2

O

30

31

32

R = aryl, alkyl

R = CN, CO2 Et

R = CN, CO2 Et

(OEt)2 (O)P

N N

CN

H

CN

OHC

O N N

R

O N

X

NH O

O

33

34

R = aryl, alkyl

X = NMe, NPh

35

Pyrimidinonopyridazines <11BMCL6348>, imidazopyridazines <11BMCL904, 11BMCL4160, 11BMCL4550>, and pyrazolopyridazines <11BMCL259> were reported to have potent activities in various medicinal chemistry programs.

397

Six-Membered Ring Systems

6.2.3. PYRIMIDINES AND BENZO DERIVATIVES Pyrimidines can be prepared from 1,3-difunctional groups with amidine precursors. Polysubstitued 5-aminopyrimidines 37 were prepared from a-azidovinyl ketones 36 and amidines at ambient temperatures <11T2676>. Inverse demand Diels–Alder reaction of 1,2,3-triazine 38 with amidines afforded 2-substituted pyrimidines 39 in excellent yields under mild conditions <11OL2492>. 2,4,6-Trisubstituted pyrimidines 41 were synthesized from progargylic ketones 40 with benzamidine in the presence of catalytic copper(II) triflate <11SL1179>. The [5 þ 1] annulation of enamidines 42 with orthoesters in the presence of zinc(II) bromide afforded fully substituted pyrimidines 43 in good to excellent yields <11CEJ9385>. Reaction of ethyl 5-acetyl-3,4-dihydropyridine-1(2H)-carboxylate 44 with benzamidine or guanidine gave the corresponding pyrimidines 45 in good yields <11S1465>. 4-Difluorochloromethylpyrimidines 47 were obtained from the cyclization of benzamidine 46 with 1,3-difunctional reagents <11T5663>. b-Ketoester 48 and amidines participated in three-component coupling reactions to give highly functionalized alkoxy tetrahydropyridopyrimidines 49 <11TL3849>. NH

NH R

O Ar 1

R NH 2 K2 CO 3, DMF

Ar2

25 °C

N3 36

R

N

N

1

Ar

Ar

56–96%

N N

2

N

CH3 CN, 60 °C

N N 90–99% 38 39 R = (Het)Ar, cyclopyropyl

NH 2 37

R = H, Me, Ph

NH 2

1,4-dioxane or

R

NH R 4C(OEt) 3

NH 2

Ph

R1

Cu(OTf) 2 (20 mol%)

O

R1

air, PhCl, 80 °C

R1 R2 40

N

68–91%

R2

R 1 = Het(Ar), Me

N

2

N

R

Ph

R1

PhMe, 110 °C

NH 2

40–99%

3

R

42

41

R 2 = H, TMS, Ph, n-Bu

R4

ZnBr 2 (10 mol%)

R2

R1 = 5-(3-methylisoxazolyl);

N R3

N 43

R2 = R 3 = Het(Ar); R4 = H, OEt, Me

NH O

1. Me

80 °C N

ClF 2C

NH 2 R HOCH 2CH 2OH,

Me N

H2 N

2. c. HCl

CO 2Et 44

NH

N

R = NH2 (84%)

Ph R

O

NH2 46

Me (R = Me)

ClF2 C

NH R2 OEt N

O

R1

NH 2

48

N

DMF, 70 °C 28–81%

O

Oi-Pr

R 2-X, K2CO3

R1 = alkyl R2 = aryl, alkyl, NMe2

R2

N N 49

R1

CF2 Cl N

OEt

O (R = H) NaOAc, xylenes ref lux

45

Ph (96%)

or

O

Ph

N

R

47 R = H (73%) R = Me (71%)

398

L. Yet

Reaction of tertiary enamides 50 with nitriles in the presence of triflic anhydride and 2-chloropyridine afforded saturated fused-pyrimidines 51 in good yields <11SL2387>. Aerobic oxidative dehydrogenation of dihydropyrimidinones 52 with N-hydroxyphthalimide (NHPI) in the presence of oxygen afforded highly substituted pyrimidines 53 <11T5615>. R2 -CN, Tf2 O 2-chloropyridine O

R 1 = Het(Ar)

PMB

N

R 2 = c-Hex,

50

R

1

MeS

51

CH2 -c-Pr

CO2 Et

N

N

78–91%

R1

N

NHPI (10 mol%)

R1

R2

CH2 Cl2 , 25 °C

N H

R

R1

Co(OAc)2 (50 mol%) 1,2-dichloroethane O2 (1 atm.), 80 °C

2

35–97% R1

52

CO2 Et

N MeS

N

R2

53

= Ar, alkyl

R 2 = Me, Ph

Dihydropyrimidinones 57 can be prepared by the Biginelli reaction of ethyl acetoacetate 54, aryl aldehydes 55, and urea 56 in the presence of catalytic urea ligands or other acidic reagents. O O

O

O +

Ar-CHO

OEt 55

54

+

Conditions H 2N

NH 2

Me

56

Conditions

EtO

Ar * NH N H 57

O

Yields (%)

References

80–98

11TL809

72–93 44–99 ee

11OBC3050

Cyclodextrin–SO3H, solvent free, 100  C

73–93

11CCL127

p-Dodecylbenzenesulfonic acid (20 mol%), H2O, 50  C

69–90

11CCL903

Cl

Cl

O

Cl

Cl

N N Cl Cl Cl Cl (30 mol%), EtOH, 80 °C OAc AcO AcO

O

O

NH 2 N OAc N H H (15 mol%), TfOH (15 mol%),

t -NH2 (10 mol%), brine, 25 °C

399

Six-Membered Ring Systems

Ferric chloride immobilized on Al-MCM-41 was an efficient catalyst system for the Biginelli synthesis of 3,4-dihydropyrimidinone derivatives 58 <11SC826>. A one-pot iodine-mediated three-component reaction of acetophenones 59, aryl aldehydes 60, and urea 56 under neat conditions afforded 4,6-diarylpyrimidin-2 (1H)-ones 61 <11SC1875>. O

Ar

O O

O +

Ar-CHO

OEt 54

+ H 2N

NH 2

CH 3 CN, 80 °C

NH

Me

N H

68–90%

56

55

EtO

FeCl3 /Al-MCM-41

58 Ar 1 O

O Ar 1

Me

+

Ar2 -CHO +

H2 N

60

59

N

I 2 , neat, 80 °C NH2

90–96%

Ar

56

2

N H

O

61

A library of pyrimidine-isoxazoline hybrids prepared in ionic liquid [(bmim)] [PF6] was reported <11S2644>. The coupling reaction between electron-rich 2-morpholino-4(3H)-pyrimidinone and nucleophilic side chains of several natural a-amino acids promoted by phosphonium salts afforded optically active pyrimidin4-yl amino acids <11OBC5967>. 2-Arylquinazolines 64 were synthesized by oxidative cyclization of 2-aminoarylketones 63 with arylmethanamines 62 under various conditions. R2

O R1

R NH 2 62

2

+ Ar

NH 2

Conditions

N

R1 N

63

Ar

64

Conditions

Yields (%)

References

4-Hydroxy-TEMPO (15–20 mol%), O2 (1 atm.), o-xylene, 120  C

65–90

11CC7818

60–99

11CC9513

75–91

11SL1089

l2 (0.5 equiv.), TBHP (2 equiv.), DMA, 80  C 

CAN (10 mol%), TBHP (7 equiv.), CH3CN, 80 C

4-Amino-substituted quinazolines 66, 68, and 70 could be prepared, respectively, from the palladium-catalyzed intramolecular CH amidation of 65 with isonitriles <11OL4604> or from the direct amination of quinazolin-4(3H)-ones 67 with hexachlorocyclotriphosphazene (HCCP) in the presence of amines <11T1665> or from the microwave-assisted thermal decomposition of formamide of 2-aminobenzonitriles 69 <11T4852>. 2-Aminoquinazolines 72 were prepared from 2-(aminomethyl)aniline 71 and carbodiimides catalyzed by a titanacarborane

400

L. Yet

monoamide catalyst <11OL4562>. Treatment of 2-(acylamino)benzonitriles 73 with phosphorus pentachloride triggered a novel chlorimidate cyclization to give 4-chloroquinazolines 74 in good yields <11OPRD918>. R2 -NC, Pd(OAc) 2 NHR2

(5 mol%), Cs 2CO3 NH

R1 N H

(1.5 equiv.), O2

Ph

PhMe, 110 °C

N

R1 N

42–99%

Ph

NR 1R 2

R 1R 2NH

N

HCCP

NH

DIPEA

N

N

MeCN 67

66

2

R = t-Bu, i-Pr, Ar

65

O

68

41–92%

titanacarborane monamide NH 2

R 2C(OMe)2 NMe2

CN

NH 2CHO

R1 NH2 69

microwave

NH2

N

R1 N

200 °C

R

N

RN=C=NR

NH 2

2

PhMe, 115 °C

N

90–95%

71

70

50–94%

catalyst (10 mol%)

NHR

72

R = c-C 6H 13 , 4-MePhSO2 , i-Pr

N H 73

Cl

PCl5 (1.75 equiv.)

CN O

N

sulfolane, 110 °C R

R = Ph (91%), CF3 (80%),

N 74

3-pyridyl (84%)

R

A facile one-pot synthesis of quinazoline-2,4-diones 76 from isatoic anhydride 75 was reported <11BKCS2121>. Condensation of 2-aminobenzamides 77 with orthoformates afforded 2-substituted-quinazolin-4(3H)-ones 78 <11CCL951>. O

1. RNH 2 , THF, 25 °C O

2. triphosgene, K2CO3 , THF, 25 °C

N H 75

O

O

44–71%

N N H 76

O

O R O

OH R 2C(OEt) 3, EtOH R1

NH2 77

90 °C 61–97%

NH R1

N

R2

78

A myriad of cross-coupling reactions of halogenated pyrimidines have appeared in the literature. Palladium-catalyzed cross-coupling of 2-chloropyrimidine 79 with amides 80 gave the corresponding 2-(N-acylamino)pyrimidines 81 <11TL1020>. 2,4Dichloro-5-methylpyrimidine 82 underwent double Stille cross-coupling with 2-(tributylstannyl)pyridine to give highly substituted pyrimidine 83, followed by Aldol condensation with aromatic aldehydes to give a series of 4-arylvinyl-2,6-di(pyridin-2-yl) pyrimidines 84 for study of their optical properties <11JOC3837>. The first tetraalkynyl-pyrimidines 86 were prepared from Sonogashira reactions of 2,4,5,6tetrachloropyrimidine 85 for their photophysical property studies <11EJO2089>. 1,1,1,3,3,3-Hexamethyldisilazane was found to be an efficient solvent for the Sonogashira reaction of ethynyldeoxyriboside with halogenated pyrimidine derivatives <11H(82)1137>.

401

Six-Membered Ring Systems

N

Pd2 (dba) 3 (5 mol%), Xantphos (15 mol%) Cs2CO3 (1.4 equiv.),1,4-dioxane,100 °C

O

N

+ Cl

R1

79

NHR2

N

27–94%

N

R 1 = Ar, Me, t-Bu

80

R 2 = H, Me

Cl

N

Me

N Ar-CHO, Aliquat

(2 equiv.), Pd(PPh3)4 (19 mol%)

336 (10 mol%)

N

N

NaOH, reflux

PhMe, 110 °C

Cl

R1

N R2 81

N

2-(tributylstannyl)pyridine N

O

Me

81% 82

N 83

Ar

33–73%

N

N 84

N

Ar Ar (6 equiv.)

Cl Cl

Ar

Pd(PPh 3) 2Cl2 (10 mol%)

N

N

DIPEA, 1,4-dioxane Cl

N

Cl

110 °C

85

N Ar

73–79%

86

Ar

Suzuki–Miyaura cross-coupling of 4-methoxy-5-iodopyrimidines 87 with b-allenyl-9-BBN afforded 5-allenylpyrimidines 88 in good yields <11CL950>. 5-Bromo-6-methylpyrimidine 89 participated in Suzuki–Miyaura cross-coupling reactions with arylboronic acids to give biheterocycles 90 <11S3496>.

B OMe I

N R

N

NaOMe (1.8 equiv.)

Me Br

N

N

DMF, 25 °C R = Cl (50%),

87

OMe

Pd(PPh3 )4 (5 mol%)

OMe (73%)

R

N

N 88

89

ArB(OH)2 Pd(OAc)2 (3 mol%) S-Phos (6 mol%) K3PO4 (3 equiv.) PhMe, 90 °C 75–92%

Me Ar

N N 90

Palladium-catalyzed cross-coupling reactions of 2-methylthiopyrimidine 91 and 4-methylthioquinazoline 93 with organozinc reagents in the presence of S-Phos ligand afforded good yields of functionalized pyrimidines 92 and quinazolines 94, respectively <11CEJ2948>. The authors also reported in the same paper that the Ni(acac)2/DPEPhos combination also worked on these systems. 2-Arylpyrimidine acyclic nucleoside phosphonates 96 were obtained from Liebeskind–Srogl cross-coupling reaction of 2-thiomethylpyrimidines 95 with arylboronic acids <11T7379>. Heating 2-thiomethyldihydropyrimidines 97 with aliphatic and arylamines in methylene chloride afforded 2-aminopyrimidines 98 in excellent yields <11T2661>. The ring cleavage reactions of substrates such as 97 <11TL7185> and the substitution reactions of 4(6)-chlorodihydropyrimidines <11H(83)1807> were reported by the same authors.

402

L. Yet

RZnI• LiCl (1.4 equiv.)

RZnI• LiCl (1.4 equiv.) SMe

Pd(OAc)2 (2.5 mol%) N

THF, 25 °C SMe R = 1-naphthyl (75%),

N 91

MeO

N

S-Phos (5 mol%)

R

N

93

94

4-CO2 EtC 6H 4 CH 2 (78%)

OH

OH

ArB(OH)2 , Pd(PPh3 )4 (5 mol%)

N

N

CuMeSal (2.2 equiv.), THF, 60 °C R

O

N

N

MeO R = 3-cyanopropyl (74%),

3-CF3Ph (59%)

MeS

N

THF, 25 °C

N

92

MeO

S-Phos (5 mol%)

N

MeO

R

Pd(OAc)2 (2.5 mol%)

41–89%

OCH 2P(O)(Oi-Pr) 2

95

Boc

CO2 Et

N N

MeS

Ar

96

RNH 2, CH 2Cl2

Boc

40 °C 76–97%

Me

OCH 2P(O)(Oi-Pr) 2

CO2 Et

N N

RHN

R

O

N

R = H, (R)-CH 2OH

Me

R = aryl, alkyl

97

98

2-Chloropyrimidine 79 was aminated to 2-(arylamino)pyrimidines 99 in the presence of o-tolylzinc bromide as a base <11SL2325>. Mitsunobu coupling reaction of highly functionalized 2-hydroxypyrimidines 100 with amines, alcohols, or acids afforded 2-substituted pyrimidines 101 <11T3267>. Greener thiocyanation of highly substituted pyrimidines 102 was achieved with ammonium thiocyanate and iodine in methanol at ambient temperature to give 5-thiocyanatopyrimidines 103 <11TL2652>. 6-Aminopyrimidines 104 underwent diazotization/alkyl(aryl)thionation to give pyrimidines 105, which then participated in nucleophilic substitutions with arylamines to give 6-arylamino-2,4-dialkyl(aryl)thiopyrimidines 106 <11T5156>. ArNH 2 o-tolylzinc bromide N N

O

(2 equiv.),CH 3CN 25 °C

Cl

N 99

42–90%

79

N

3 OH

R

N

EtO NHAr

R 1 R2 NH or

Ar

Me

N 100

or ArCO2 H

DIAD, PPh 3, THF OH 63–96%

O

Ar N

EtO N

Me

X

101 X= NR1 R 2, OR3 , OCOAr

R2

NH 4SCN, I2 , MeOH, 25 °C R1 = R2 = R 3 = SMe,

N R1

N

R3

NH2 , OMe, Cl

R1

70–92%

H2 N

N 104

SR1

R 1 = Me, n-Pr; R2 = Ph, n-Pr, Bn

R3

R 3NH2 , Et 3N

Cl

CuCl (5 mol%), CH 3 CN, 60 °C 52–82%

N 103

Isoamyl nitrite, R2 SSR2 N

SCN

N

102

Cl

R2

R 2S

EtOH, 80 °C

N N 105

NHR3

SR1

N

73–86% R3 = Ar, ArCH 2

R2 S

N 106

SR 1

403

Six-Membered Ring Systems

Pyrimidine 107 underwent selected C-5 olefination with ethyl acrylate to give 108 with 1,10-phenanthroline as the ligand <11JA6964>. Imidazopyrimidines 109 participated in copper(I)-catalyzed sulfenylation and selenylation to give products 110 in good yields <11T3690>. CO2Et Pd(OAc) 2 (10 mol%) N

PhXXPh

(13 mol%), Ag 2CO3

N 107

N

CO2 Et

1,10-phenanthroline N

108

N

CuI (10 mol%)

Ar

N

N

(0.5 equiv.), air, DMF

N

66–76%

109

N Ar

N

DMSO, 110 °C

110

XPh

X = S, Se

140 °C (30%)

2-Pyrimidinyl-substituted pyrazoles 113 were obtained by the thermal cycloaddition of sydnone 111 with 2-ethynylpyrimidine 112 <11TL1506>. 2-Arylpyrimidines 114 were obtained from the domino [4 þ 2]/retro [4 þ 2] cycloadditions of 2-alkynylpyrimidine 112 with electron-rich dienes <11OBC2185>.

1,2-Cl2C 6 H4

O O N

N PNP 111

N

N

N

ref lux + N i-Pr

N 85% (3:1 ratio of C-3/C-4) 112

N

i-Pr N PNP 113

N

dienes N

N

MeOH 140 °C 48–69%

112

Y

X 114 X = H, OH Y = H, OMe, OEt

Many methods for the synthesis and biological studies of pyrimidine-fused ring systems were published. The different structural types are listed in Table 1. The first example of a SNAr reaction using tetrakis(dimethylamino)ethylene (TDAE)-initiated carbanions of o-nitrobenzyl chloride 116 with 4chloroquinazolines 115 afforded quinazolines 117 <11TL3810>. The preparation of isomeric 6- and 7-propargyloxy derivatives of 4-(3-fluoroanilino)quinazolines was achieved using a six-step process <11TL1053>. 2- and 4-Quinoxalinyl nitrenes were studied for their rearrangements to cyclic and acyclic carbodiimides and ring openings to nitrile ylides <11JA5413>. Hydrogen-bond-donor catalysts such as 118 bearing a 2-aminoquinazolin-4-(1H)-one skeleton were useful in the highly enantioselective hydrazination of 1,3-dicarbonyl compounds with enantiomeric excesses to 96% <11CEJ10470>. A convergent synthesis of structurally diverse quinazolines was reported <11OBC351>. The superacid-promoted additions involving vinyl-substituted pyrimidines, quinoxalines, and quinazolines were reported <11JA8467>. The synthesis of macrobi- and macrotricyclic compounds comprising of pyrimidyl substituted cyclen and cyclam units was published <11H(82)1447>.

404

L. Yet

Table 1 Pyrimidine-Fused Ring Systems Pyrimidine-Fused Ring Types References

Pyrrolopyrimidines

11BMC910, 11BMC4355, 11BMCL2365, 11BMCL6770, 11JMC3368, 11JMC7150, 11JMC8030, 11S1213, 11SL1705, 11T2803, 11TL4140

(Benz)Imidazopyrimidines

11JMC7705, 11S109, 11S1465, 11SC3590, 11T8321, 11TL228, 11TL5521

Thienopyrimidines

11BMC3906, 11BMCL5620, 11BMCL5952, 11BMCL5992, 11BJOC338, 11S3323, 11SC2811

Pyrazolopyrimidines

11ACSCS45, 11BMCL2641, 11BMC5432, 11BMC5955, 11BMC7221, 11BMCL467, 11BMCL471, 11BMCL1342, 11BMCL3134, 11BMCL3452, 11BMCL4233, 11BMCL4736, 11BMCL5633, 11CCL1036, 11JHC279, 11JMC2980, 11MO5182, 11MO6549, 11MO10387, 11S1465, 11T2279, 11TL5761

Triazolo- or tetrazolopyrimidines

11BMC5955, 11BMCL2497, 11BMCL2740, 11BMCL2887, 11BMCL5266, 11H(83)1873, 11JHC1085, 11JMC5660, 11MO7081, 11S316, 11SC3635

Thia(dia)zolopyrimidines

11BMC702, 11JHC776, 11JHC1308, 11JHC1404, 11JMC655, 11OPRD382, 11TL3814

Pyrrolidinopyrimidines

11T5700

Pyridopyrimidines

11ACSCS45, 11BMCL1687, 11BMCL2832, 11BMCL5975, 11CCL1183, 11CEJ9385, 11EJO6909, 11JMC7729, 11JOC1767, 11S1132, 11T3226, 11T5935

Pyrimidopyrimidines

11JMC1847

Pyranopyrimidines

11JOC982, 11T8484

Spiropyrimidines

11CL747, 11SL2657

Pyrimidoazepines

11BMCL2715

Dioxinopyrimidines

11BMCL6122

Benzofuranopyrimidines

11BMCL6577

(Benzo)Imidazoquinazolines

11BMCL524, 11H(83)1831

Indoloquinazolines

11CC5010, 11OBC1429, 11OBC6741

405

Six-Membered Ring Systems

Table 1 Pyrimidine-Fused Ring Systems—cont'd Pyrimidine-Fused Ring Types References

Pyranoquinazolines

11ARK72

Pyrazoloquinazolines

11BMCL4507

Pyridoquinazolines

11S2754

Pyrroloquinazolines

11JHC634

Quinolinoquinazolines

11SC426

Benzo(oxo)-fused quinazolines

11JOC7157, 11T8564, 11TL3033 NO2

O Me2N

Cl N N

O

NO 2

O

Cl

+ R

Me2N

O N

DMF, N 2, 50 °C

N 117

R = CCl3 (72%),

116

115

NMe2 (TDAE) NMe2

R

CF3 (95%) O N

R N H

N H 118

NMe2

6.2.4. PYRAZINES AND BENZO DERIVATIVES Two reviews titled “Synthetic Utilities of o-Phenylenediamines: Synthetic Approaches for Benzimidazoles, Quinoxalines, and Benzo[1,5]diazepines” <11H (83)2689> and “Putting the ‘N’ in ACENE: Pyrazinacenes and Their Structural Relatives” <11OBC5005> were published <11H(83)2689>. The most common preparation of quinoxalines 121 is the condensation of 1,2-phenylenediamines 119 with 1,2-diketones 120. Various conditions have been employed for this preparation and are shown in the table below. 1,2-Diketones 120 could be replaced by other reagents such as a-bromo ketones, a-hydroxy ketones, a-oximino ketones, a-diazo ketones, and unsubstituted ketones in their reactions with 119 to give quinoxalines 121, and these are also shown in the table below: NH 2 1

R

NH 2 119

O

R2

O

R3 120

+

Conditions

R

N

R2

N

R3

1

121

406

L. Yet

Conditions

Yields (%)

References

Oxalic acid (20 mol%), EtOH, H2O, 80 C

90–97

11BJOC860

Nano-TiO2 (2.5 mol%), 1,2-dichloroethane, 25  C

80–99

11BKCS3720

Citric acid (3 mol%), EtOH, 25 C

75–94

11CCL389

Nano-TiO2 (12 mol%), solvent free, 25  C

85–96

11CCL753

75–93

11EJO399

87–100

11JHC403

80–94

11SC417

90–95

11SC2053

, MeOH, H2O, 25 C

84–89

11TL69

Co-grinding, solvent free, 25  C

48–99

11TL4686

Glycerol, H2O, 90 C

83–91

11TL5697

KF, alumina, 25  C

70–92

11TL6597







HOAc, 60 C Al2O3, grinding, solvent free, 25  C 

Silica gel, grinding, 100 C PEG-400 (15 mol%), microwave, 120  C K10-Zn

2þ





NH2 R

1

1,2-Diketone Replacements

NH2

N

R2

N

R3

1

R

Conditions

119

121

Conditions

Yields (%)

References

a-Diazoketones, Cu(OTf)2, 1,2-dichloroethane, PS-scavengers, flow chemistry, 80  C

21–96

11OL320

Benzyl ketones, DABCO, air, DMF, 90  C

73–99

11S387

Cyclic ketones, NBS, HOAC, 110 C

52–90

11S3143

a-Hydroxyketones, silica sulfuric acid (SSA), PEG-400, 120  C

51–85

11SC3334

a-Hydroxylimino ketones, neat or PEG-400 or HOAc, microwave, 140  C

77–96

11TL544

1,3-Diketones, NBS, H2O, 70  C

70–88

11TL2862

82–94

11TL6597





a-Bromoketones, KF, alumina, 25 C

Microwave-assisted Petasis reaction of Boc-protected-1,2-phenylenediamines 122 with glyoxals and boronic acids afforded 123, which were then cyclized to

407

Six-Membered Ring Systems

quinoxalines 124 under acidic conditions <11TL4821>. Copper-catalyzed cyclization of o-phenylenediamine 125 with terminal alkynes afforded quinoxalines 126 in moderate to good yields <11OL4514>. Benzofurazan-N-oxide 127 reacted with ketones in the presence of b-cyclodextrin in water at ambient temperature to give quinoxaline di-N-oxides 128 <11SC3097>. Quinoxaline derivatives (amino, alkoxy, and thiol) 130 were obtained from different reaction sequences from 2-hydroxyquinoxaline 129 <11SC3532>. O R NH2

O H

2

R3 -B(OH)

R1

R3

O 2 , microwave 1

R

120 °C NHBoc

R2 NH

20% TFA

1,2-dichloroethane

24–71%

122

35–98%

123

NH 2

N

DMAP, Cs2 CO 3 PhMe, 70 °C

NH 2

N 126

30–99%

125

O N O N

R

R

N

R2

124

O R2 R1 β-cyclodextrin

R Cu(OAc) 2×H2 O (10 mol%)

R3

R

25 °C

NHBoc

N 1

O N

NaOH, H 2 O

N O 128

61–75%

127

R1 R2

POCl3 ; RNH 2 (X = NHR)

N

N

or RX, K2CO3 , DMF (X = OR)

N H 129

O

or P4 S10 , pyridine; RX, TBAB (X = SR)

N

X

130

N-Aryl-2-nitrosoanilines 131 underwent cyclization under three available reaction conditions to give substituted phenazines 132 in good to excellent yields <11TL6484>. Heating benzofuroxan 133 and dihydroxybenzene derivatives 134 adsorbed on molecular sieves under solvent-free conditions afforded phenazine 5,10-dioxides 135 <11H(83)531>. NO

K2 CO 3, MeOH, 25 °C

H N

R1

R2

133

or N,O-bis(trimethylsilyl)

N R1

R2 N

acetamide, DMF, 60 °C

131

O N O N

or HOAc, 110 °C

132

67–99%

OH R + OH 134

O N

R

N

OH

4A MS, microwave

O 135

408

L. Yet

Quinoxalines 136 underwent asymmetric hydrogenations with a ruthenium metal/ BINAP Brnsted acid 138 <11JA6126>, chiral cationic ruthenium diamine catalyst 139 <11OL6568>, and iridium-diamine catalyst 140 <11T6206> to give tetrahydroquinoxalines 137 in good enantioselectivities or diastereomeric ratios. Alternatively, ring opening of chiral activated aziridines with 2-bromoanilines followed by intramolecular palladium-catalyzed CN bond formation provided a route to chiral tetrahydroquinoxalines <11OL5972>. Furthermore, quinoxalines 141 were reduced to 5,6,7,8tetrahydroquinoxalines 143 with high regioselectivity and in good enantiomeric ratios in the presence of N-heterocyclic carbene complex 142 <11AG(E)3803>. H N

N R

1

R

2

N

Chiral reductions

R1

H2 or sodium formate

136

N 137 H

Ar O O P O OH

* R2 *

140 Ms N

Ru

[Cp*IrCl2]2 BArF

NH

H 2N

NHSO 2(4-CF3 Ph)

Ph Ph

Ar 138

139 2

Ar = 9-anthryl

R = aryl, alkyl, H

[Ru(p-cymene)2 ]2

up to 99% ee, 86:14 dr

R 1 = H, R 2 = Ar, 82–98%, 83–96%ee

N R N 141

Ph

[Ru(cod)(2-methylallyl) 2] (10 mol%) 142 (20 mol%), H2 (10 bar)

Ph KOt-Bu (15 mol%), n-hexane, 25 °C 99% (58:42 to 94:6 e.r.)

N

Ph

N 143

Ph

N

R

N

BF4 142

An SNAr reaction of chloropyrazine 144 with sodium p-toluenesulfinate in the presence of tetrabutylammonium chloride (TBAC) gave sulfonylated pyrazine 145 in excellent yield <11OL102>. 2-Quinoxalinecarbaldehyde 146 was converted to its corresponding esters 147 in a sodium cyanoborohydride-mediated reaction in alcoholic solvents <11SC2505>. Pyrazine imide 148 underwent smooth alkylations with cesium carbonate under microwave irradiation to give alkylated imides 149 <11S571>. The thermal reactions of fluoroalkanesulfonyl azides with pyrazines and its derivatives were studied in detail <11T2232>. An efficient three-step one-pot preparation of novel 1000-membered library of 2,3,5-trisubstituted pyrazines 151 from bromopyrazine 150 was synthesized by parallel chemistry <11ACSCS449>. A one-pot, three-component synthesis of quinoxaline,

Six-Membered Ring Systems

409

quinazoline, and phenazine ring systems using Fischer carbene complexes was reported <11S1419>. A series of rod-like conjugated molecules with a pyrazine or a bipyrazine core with light-emitting properties were published <11T2287>. Palladium-catalyzed asymmetric allylic alkylation reaction of pyrazine derivatives 152 with mesityl ester 153 delivered alkylated product 155 in high enantiomeric ratios with ligand 154 <11JA12439>. Other aromatic heterocycles such as pyrimidines, pyridazines, quinoxalines, and benzimidazoles were also employed as substrates. ROH TolSO2Na MeO 2C

N N

MeO2 C

TBAC Cl

144

DMAC

N 145

90%

O

N

SO2 Tol

NH

N 147

CO2R

O N

NaI, 4A MS, DMF

N R

microwave, 60 °C

N

72–78%

O

65–80% R = Me, Et, i-Pr

CHO

146

RX, Cs2 CO 3

N

148

N

MeOH, 50 °C

100 °C

N

NaCNBH 3

N

N

149

O

OH

OR 1. PS-TPP, ROH, DTAD, CH 2Cl2, 25 °C 2. ArB(OH) 2, Pd(dppf )Cl2,

N Br

NH

N O 150

N

MeOH, CsF, microwave,

OMe

NH

120 °C 3. NH 3 in MeOH, microwave,

Ar

120 °C

NH 2

N 151

O

43–67%

O O

Mes

N R N 152

[(η3-C3 H5 )PdCl] 2 (2.5 mol%) (R,R)-L-154 (5 mol%), LiHMDS

+ Me

(3 equiv.), THF, 25 °C 153

66–83%, 97–99% ee R = H, Me

O

O

N

NH

R N 155

H

HN

PPh 2Ph2 P (R,R)-L-154

Pyrazine 156 and quinoxaline 158 were converted to iodo compounds 157 and 159, respectively, using lithium zincate complex followed by quenching with iodine <11TL4590>. 2-Methylthiopyrazine 160 was converted to its anion with lithium tetramethylpiperidide and allowed to react with dimethyldisulfide to give either bis- or monothiomethylpyrazines 161 or 162, respectively, depending on the temperature of the system <11OBC1839>. Palladium-catalyzed cross-coupling reactions of 2-methylthiopyrazine 163 with a palladium-catalyzed organozinc reagent in the presence of S-Phos ligand or with a nickel-catalyzed reaction with DPE-Phos as the ligand afforded good yields of functionalized pyrazines 164 <11CEJ2948>.

410

L. Yet

N

I2 , THF, 25 °C

N

68%

I

N

N

N

156

N

I

N

Li(TMP)Zn(t-Bu) 2

60 min

162

159 1. LiTMP (1.2 equiv.), THF,

N

2. MeSSMe (3 equiv.), –78 °C,

N

Cl

2. MeSSMe (2 equiv.), warm to 25 °C, 3 h

RZnI×LiCl (1.4 equiv.) S-Phos (5 mol%) N 164

N

SMe

161

RZnI×LiCl (1.4 equiv.) Ni(acac) 2 (2.5 mol%)

N

N

DPE-Phos (5 mol%)

THF, 25 °C

R

SMe

91%

90%

N

N

–78 °C, 30 min

160

Pd(OAc)2 (2.5 mol%)

I

N

50%

158

SMe 1. LiTMP (1.2 equiv.), THF, –78 °C, 30 min Cl

I2 , THF, 25 °C

N

157

N

Li(TMP)Zn(t-Bu) 2

R = 1-naphthyl (83%)

N

THF, 25 °C

SMe

N

R = 4-OMeC6 H4 CH 2

163

R

164

(84%)

Cross-coupling reactions of pyrazines and quinoxalines have been reported. 2-Aryland 2,3-diarylquinoxalines 165 underwent smooth acetoxylation in the presence of palladium(II) acetate and PhI(OAc)2 via CH activation to produce the corresponding acetoxy-substituted quinoxaline derivatives 166 in good yields with high regioselectivity <11SL169>. Pyrazine N-oxide 167 participated in a palladium-catalyzed oxidative cross-coupling reaction with N-benzylindole 168 to give bis-heterocycle 169 with high selectivity using silver carbonate as an oxidant <11OL1766>. AcO Pd(OAc)2 (5 mol%) N

N

PhI(OAc)2

R

1,2-dichloroethane

N

R N

90 °C 78–95%

165

AcO 166

Pd(OAc) 2 (10 mol%) Ag2 CO3 (2.3 equiv.)

N

TBAB (20 mol%)

+ N O 167

168

N Bn

pyridine (4 equiv.) DMF, 135 °C 62%

N N O

N 169

Bn

Pyrazine triflate 170 participated in smooth Suzuki–Miyaura cross-coupling reactions to give 6-arylpyrazines 171 in good yields as part of studies directed toward coelenterazines <11T1150>. Quinoxaline 158 was bis-alkylated with potassium cyclobutyltrifluoroborate to give 2,3-dicyclobutylquinoxaline 172 with manganese(III) acetate in acidic media <11OL1852>. Tetrahydrophthalazine derivatives were synthesized by palladium-catalyzed carbonylation of iodohydrazinoarenes <11T9122>.

Six-Membered Ring Systems

411

Liebeskind–Srogl cross-couplings of chloropyrazines 173 with arylboronic acids afforded highly substituted pyrazines 174 under microwave irradiation <11JOC846>.

N TfO

N

NH 2

ArB(OH)2

BF3 K

Pd(PPh3 )4

Mn(OAc)3

N

(10 mol%) K3 PO4 , 1,4-

Bn

dioxane, 80 °C

170

Ar

70–85%

NH 2

N

N Bn 171

N 158

(3.5 equiv.)

N

TFA (1 equiv.) HOAc, H 2O 50 °C

N 172

59%

R1 Cl

N

SPMB

N

R2

173

ArB(OH)2 (3 equiv.)

R1

Pd(PPh3 )4 (10 mol%) CuTc (2.5 equiv.) THF, microwave, 120 °C

Cl

69–93%

N

Ar

N

R2

R 1 = H, Me, i-Bu, Bn R 2 = OMe, OEt, Me

174

Many methods for the preparation of pyrazine-fused ring systems were reported. The different structural types are listed in Table 2. A review titled “Thieno[3,4-b] pyrazines and Their Applications to Low Band Gap Organic Materials” was published <11CC11394>. Table 2 Pyrazine-Fused Ring Systems Pyrazine-Fused Ring Types References

Thienopyrazines

11CL417, 11JOC6383, 11T2035

Heterothienopyrazines

11S943, 11OL5484

Imidazopyrazines

11BMCL592, 11BMCL1248, 11BMCL2092, 11JMC201, 11T9063

Pyrrolopyrazines

11CC12092, 11OL4490, 11T5219

Pyridopyrazines

11BMC5639, 11S794, 11T5219

Pyrazinoquinoxalines

11OL46, 11TL2725

Imidazoquinoxalines

11BMCL1176, 11BMCL6258

(Thia)Oxa(dia)zolopyrazines

11ARK69, 11ARK217, 11JMC2738, 11OL46

Indolo- or indolizinoquinoxalines

11ACSCS391, 11CCL567, 11JOC4571, 11SC1650, 11T9368

Triazolo- or tetrazoloquinoxalines

11BKCS2260, 11H(83)339, 11JHC1216

Large fused-pyrazines or quinoxalines (tetracyclic or larger)

11ARK252, 11H(83)1527, 11JOC6389, 11JOC8421, 11OL4588, 11SC3325, 11T236, 11T8360, 11TL2496

(Dibenzo)Phenazine-fused

11ACSCS135, 11JOC939, 11JOC6134, 11MO6985, 11OL3304, 11T1633, 11TL2415

412

L. Yet

A series of 3-substituted pyrazinium tetrafluoroborates 175 were utilized as efficient organocatalysts for the oxidation of sulfides with hydrogen peroxide to their respective sulfoxides <11ASC865>. Novel pyrazine–boron complexes 176 bearing a b-iminoketone ligand exhibited fluorescence in solution and in the solid state <11OL6544>. N

R

Ar

N N BF4 Et

Me

N R1

B

R2

175

176

R = Me, CN, CO2 Et,

R 1 = H, CO2 Me, NMe 2

CONH 2, C(Me)=NOH

R 2 = F, Ph

Quinoxalines linked to heterocycles such as benzoxazoles <11T114>, carbazoles <11TL6942>, 3-indoles <11ARK94>, 2-benzimidazoles <11T2110>, triphenylamines/thiophenes <11OL3880>, and pyrazines linked to bis(indol-3-ylmethyls) <11SL2339> were disclosed. Quinoxalines attached to various amino acids or dipeptides were reported <11EJO730>.

REFERENCES 11ACSCS45 11ACSCS135 11ACSCS391 11ACSCS449 11AG(E)3803 11ARK69 11ARK72 11ARK94 11ARK217 11ARK252 11ARK309 11ARK310 11ASC865 11BJOC338 11BJOC860 11BKCS2121 11BKCS2260 11BKCS2428 11BKCS3720 11BMC702

Z. Huang, Y. Hu, Y. Zhou, D. Shi, ACS Comb. Sci. 2011, 13, 45. S.-L. Wang, F.-Y. Wu, C. Cheng, G. Zhang, Y.-P. Liu, B. Jiang, F. Shi, S.-J. Tu, ACS Comb. Sci. 2011, 13, 135. L.-H. Chen, C.-M. Chang, D.B. Salunke, C.-M. Sun, ACS Comb. Sci. 2011, 13, 391. C. Delvare, C.S. Harris, L. Hennequin, P. Koza, C.L. Brempt, J. Pelleter, O. Willerval, ACS Comb. Sci. 2011, 13, 449. S. Urban, N. Ortega, F. Glorius, Angew. Chem. Int. Ed. Engl. 2011, 50, 3803. L.S. Konstantinova, V.V. Popov, N.V. Obruchnikova, K.A. Lyssenko, I.V. Ananyev, O.A. Rakitin, Arkivoc 2011, xi, 69. P. Cledera, M. Villacampa, C. Avendano, J.C. Menendez, Arkivoc 2011, iii, 72. S. Kamila, H. Ankati, E.R. Biehl, Arkivoc 2011, ix, 94. A.A. Caleb, D. Ballo, B. Rachid, H. Amina, B. Mostapha, Z. Abdelfettah, E.A. Rajae, E.E. Mokhtar, Arkivoc 2011, ii, 217. M. Shamsi, M.M. Baradarani, A. Afghan, J.A. Joule, Arkivoc 2011, ix, 252. M. Ilic, J. Ilas, S. Liekens, P. Matyus, D. Kikelj, Arkivoc 2011, x, 309. N.A. Al-Awadi, M.R. Ibrahim, A.M. Al-Etaibi, M.H. Elnagdi, Arkivoc 2011, ii, 310. P. Menova, F. Kafka, H. Dvorakova, S. Gunnoo, M. Sanda, R. Cibulka, Adv. Synth. Catal. 2011, 353, 865. D.R. Gorja, K.S. Kumar, K. Mukkanti, M. Pal, Beilstein J. Org. Chem. 2011, 7, 338. D.-M. Cui, D.-W. Zhuang, Y. Chen, C. Zhang, Beilstein J. Org. Chem. 2011, 7, 860. X. Li, Y.R. Lee, Bull. Korean Chem. Soc. 2011, 32, 2121. S. Kumar, S.A. Khan, O. Zlam, R. Azim, A. Khurana, M. Shaquiquzzaman, N. Siddiqul, W. Ashan, Bull. Korean Chem. Soc. 2011, 32, 2260. J. Khalafy, M. Rimaz, L. Panahi, H. Rabiei, Bull. Korean Chem. Soc. 2011, 32, 2428. H. Alinezhad, M. Tajbakash, F. Salehian, P. Biparva, Bull. Korean Chem. Soc. 2011, 32, 3720. M.-Y. Jang, S.D. Jonghe, K. Segers, J. Anne, P. Herdewijn, Bioorg. Med. Chem. 2011, 19, 702.

Six-Membered Ring Systems

11BMC910 11BMC3906 11BMC4355 11BMC5432 11BMC5639 11BMC5955 11BMC7221 11BMCL259 11BMCL467 11BMCL471 11BMCL524 11BMCL592 11BMCL904 11BMCL1176

11BMCL1248

11BMCL1342 11BMCL1687 11BMCL2092

11BMCL2365 11BMCL2497 11BMCL2641

413

A. Gangjee, S. Kurup, M.A. Ihnat, J.E. Thorpe, B. Disch, Bioorg. Med. Chem. 2011, 19, 910. A. Zhao, X. Gao, Y. Wang, J. Ai, Y. Wang, Y. Chen, M. Geng, A. Zhang, Bioorg. Med. Chem. 2011, 19, 3906. A. Gangjee, O.A. Namjoshi, S.N. Keller, C.D. Smith, Bioorg. Med. Chem. 2011, 19, 4355. T. Saito, T. Obitsu, T. Kondo, T. Matsui, Y. Nagao, K. Kusumi, N. Matsumura, S. Ueno, A. Kishi, S. Katsumata, Y. Kagamiishi, H. Nakai, M. Toda, Bioorg. Med. Chem. 2011, 19, 5432. Y.-D. Gong, M.-S. Dong, S.-B. Lee, N. Kim, M.-S. Bae, N.-S. Kang, Bioorg. Med. Chem. 2011, 19, 5639. T. Saito, T. Obitsu, C. Minamoto, T. Sugiura, N. Matsumra, S. Ueno, A. Kishi, S. Katsumata, H. Nakai, M. Toda, Bioorg. Med. Chem. 2011, 19, 5955. N. Kato, M. Oka, T. Murase, M. Yoshida, M. Sakairi, S. Yamashita, Y. Yasuda, A. Yoshikawa, Y. Hayashi, M. Makino, M. Takeda, Y. Mirensha, T. Kakigami, Bioorg. Med. Chem. 2011, 19, 7221. V.P. Ghidu, M.C. Ilies, T. Cullen, R. Pollet, M. Abou-Gharbia, Bioorg. Med. Chem. Lett. 2011, 21, 259. M.P. Dwyer, K. Paruch, M. Labroli, C. Alvarez, K.M. Keertikar, C. Poker, R. Rossman, T.O. Fischmann, J.S. Duca, V. Madison, D. Parry, N. Davis, W. Seghezzi, D. Wiswell, T.J. Guzi, Bioorg. Med. Chem. Lett. 2011, 21, 467. M. Labroli, K. Paruch, M.P. Dwyer, C. Alvarez, K. Keertikar, C. Poker, R. Rossman, J.S. Duca, T.O. Fischmann, V. Madison, D. Parry, N. Davis, W. Seghezzi, D. Wiswell, T.J. Guzi, Bioorg. Med. Chem. Lett. 2011, 21, 471. B.S. Kuarm, Y.T. Reddy, J.V. Madhav, P.A. Crooks, B. Rajitha, Bioorg. Med. Chem. Lett. 2011, 21, 524. Z. Meng, B.A. Kulkarni, A.D. Kerekes, A.K. Mandal, S.J. Esposite, D.B. Belanger, P.A. Reddy, A.D. Basso, S. Tevar, K. Gray, J. Jones, E.B. Smith, R.J. Doll, M.A. Siddiqui, Bioorg. Med. Chem. Lett. 2011, 21, 592. H. Shimizu, I. Yasumatsu, T. Hamada, Y. Yoneda, T. Yamasaki, S. Tanaka, T. Toki, M. Yokoyama, K. Morishita, S. Iimura, Bioorg. Med. Chem. Lett. 2011, 21, 904. M. Jin, A. Kleinberg, A. Cooke, P.C. Gokhale, K. Foreman, H. Dong, K.W. Siu, M.A. Bittner, K.M. Mulvihill, Y. Yao, D. Landfair, M. O’Connor, G. Mak, J.A. Pachter, R. Wild, M. Rosenfeld-Franklin, Q. Ji, M.J. Mulvihill, Bioorg. Med. Chem. Lett. 2011, 21, 1176. A.J. Buckmelter, L. Ren, E.R. Laird, B. Rast, G. Miknis, S. Wenglowsky, S. Schlachter, M. Welch, E. Tarlton, J. Grina, J. Lyssikatos, B.J. Brandhuber, T. Morales, N. Randolph, G. Vigers, M. Martinson, M. Callejo, Bioorg. Med. Chem. Lett. 2011, 21, 1248. A. Kumar, I. Ahmad, B.S. Chhikara, R. Tiwari, D. Mandal, K. Parang, Bioorg. Med. Chem. Lett. 2011, 21, 1342. F. Pierre, S.E. O’Brien, M. Haddach, P. Bourbon, M.K. Schwaebe, E. Stefan, L. Darjania, R. Stansfield, C. Ho, A. Siddiaui-Jain, N. Streiner, W.G. Rice, K. Anderes, D.M. Ryckman, Bioorg. Med. Chem. Lett. 2011, 21, 1687. A.P. Crew, S.V. Bhagwat, H. Dong, M.A. Bittner, A. Chan, X. Chen, H. Coate, A. Cooke, P.C. Gokhale, A. Honda, M. Jin, J. Kahler, C. Mantis, M.J. Mulvihill, P.A. Tavares-Greco, B. Volk, J. Wang, D.S. Werner, L.D. Arnold, J.A. Pachter, R. Wild, N.W. Gibson, Bioorg. Med. Chem. Lett. 2011, 21, 2092. K. Aso, K. Kobayashi, M. Mochizuki, N. Kanzaki, Y. Sako, T. Yano, Bioorg. Med. Chem. Lett. 2011, 21, 2365. J.M. Harris, B.R. Neustadt, H. Zhang, J. Lachowicz, M. Cohen-Williams, G. Varty, J. Hao, A.W. Stamford, Bioorg. Med. Chem. Lett. 2011, 21, 2497. D.A. Griffith, D.M. Hargrove, T.S. Maurer, C.A. Blum, S.D. Lombaert, J.K. Inthavongsay, L.E. Klade, C.M. Mack, C.R. Rose, M.J. Sanders, P.A. Carpino, Bioorg. Med. Chem. Lett. 2011, 21, 2641.

414

L. Yet

11BMCL2715

11BMCL2740 11BMCL2832

11BMCL2887 11BMCL3134

11BMCL3452

11BMCL4160 11BMCL4233 11BMCL4507 11BMCL4550 11BMCL4736 11BMCL5266 11BMCL5620 11BMCL5633

11BMCL5952 11BMCL5975 11BMCL5992 11BMCL6122 11BMCL6258

M.D. Andrews, P.V. Fish, J. Blagg, F.K. Brabham, P.E. Brennan, A. Bridgeland, A.D. Brown, P.J. Bungay, K.M. Conlon, N.J. Edmunds, K. Forselles, C.P. Gibbons, M.P. Green, G. Hanton, M. Holbrook, A.S. Jessiman, K. McIntosh, G. McMurray, C.L. Nichols, J.A. Root, R.I. Storer, M.R. Sutton, R.V. Ward, D. Westbrook, G.A. Whitlock, Bioorg. Med. Chem. Lett. 2011, 21, 2715. T.S. Kumar, S. Mishra, F. Deflorian, L.S. Yoo, K. Phan, M. Kecskes, A. Szabo, B. Shinkre, Z.-G. Gao, W. Trenkle, K.A. Jacobson, Bioorg. Med. Chem. Lett. 2011, 21, 2740. D. Guay, C. Beaulieu, M. Belley, S.N. Crane, J. DeLuca, Y. Gareau, M. Hamel, M. Henault, H. Hyjazie, S. Kargman, C.C. Chan, L. Xu, R. Gordon, L. Li, Y. Mamane, N. Morin, J. Mancini, M. Therien, G. Tranmer, V.L. Truong, Z. Wang, W.C. Black, Bioorg. Med. Chem. Lett. 2011, 21, 2832. M.K. Khera, I.A. Cliffe, T. Mathur, O. Prakash, Bioorg. Med. Chem. Lett. 2011, 21, 2887. G. Semple, A. Ren, B. Fioravanti, G. Pereira, I. Calderon, K. Choi, Y. Xiong, Y.-J. Shin, T. Gharbaoui, C.R. Sage, M. Morgan, C. Xing, Z.-L. Chu, J.N. Leonard, A.J. Grottick, H. Al-shamma, Y. Liang, K.T. Demarest, R.M. Jones, Bioorg. Med. Chem. Lett. 2011, 21, 3134. M. Soth, S. Abbot, A. Abubakari, N. Arora, H. Arzeno, R. Billedeau, N. Dewdney, K. Durkin, S. Frauchiger, M. Ghate, D.M. Goldstein, R.J. Hill, A. Kuglstatter, F. Li, B. Loe, K. McCaleb, J. McIntosh, E. Papp, J. Park, M. Stahl, M.-L. Sung, R. Suttman, D.C. Swinney, P. Weller, B. Wong, H. Zecic, T. Gabriel, Bioorg. Med. Chem. Lett. 2011, 21, 3452. A. Ali, T. Cablewski, C.L. Francis, A.K. Ganguly, R.M. Sargent, D.G. Sawutz, K.N. Winzenberg, Bioorg. Med. Chem. Lett. 2011, 21, 4160. R. Jorda, N. Sacerdoti-Sierra, J. Voller, L. Havlicek, K. Kracalikova, M.W. Nowicki, A. Nasereddin, V. Krystof, M. Strnad, M.D. Walkinshaw, C.L. Jaffe, Bioorg. Med. Chem. Lett. 2011, 21, 4233. M. Caldarelli, M. Angiolini, T. Disingrini, D. Donati, M. Guanci, S. Nuvoloni, H. Posteri, F. Quartieri, M. Silvagni, R. Colombo, Bioorg. Med. Chem. Lett. 2011, 21, 4507. H. Shimizu, T. Yamasaki, Y. Yoneda, F. Muro, T. Hamada, T. Yasukochi, S. Tanaka, T. Toki, M. Yokoyama, K. Morishita, S. Iimura, Bioorg. Med. Chem. Lett. 2011, 21, 4550. J. Xu, H. Liu, G. Li, Y. He, R. Ding, X. Wang, M. Feng, S. Zhang, Y. Chen, S. Li, M. Zhao, C. Qi, Y. Dang, Bioorg. Med. Chem. Lett. 2011, 21, 4736. M.K. Khera, I.A. Cliffe, O. Prakash, Bioorg. Med. Chem. Lett. 2011, 21, 5266. W.J. McCleelan, Y. Dai, C. Abad-Zapatero, D.H. Albert, J.J. Bouska, K.B. Glaser, T.J. Magoc, P.A. Marcotte, D.J. Osterling, K.D. Stewart, S.K. Davidsen, M.R. Michaelides, Bioorg. Med. Chem. Lett. 2011, 21, 5620. L. Zhang, J. Fan, J.-H. Chong, A. Cesena, B.Y.Y. Tam, C. Gilson, C. Boykin, D. Wang, D. Aivazian, D. Marcotte, G. Xiao, J.-Y. Le Brazidec, J. Piao, K. Lundgren, K. Hong, K. Vu, K. Nguyen, L.-S. Gan, L. Silvian, L. Ling, M. Teng, M. Reff, N. Takeda, N. Timple, Q. Wang, R. Morena, S. Khan, S. Zhao, T. Li, W.-C. Lee, A.G. Taveras, J. Chao, Bioorg. Med. Chem. Lett. 2011, 21, 5633. Y. Ni, A. Gopalsamy, D. Cole, Y. Hu, R. Denny, M. Ipek, J. Liu, J. Lee, J.P. Hall, M. Luong, J.-B. Telliez, L.-L. Lin, Bioorg. Med. Chem. Lett. 2011, 21, 5952. W.-Y. Mo, Y.-J. Liang, Y.-C. Gu, L.-W. Fu, H.-W. He, Bioorg. Med. Chem. Lett. 2011, 21, 5975. B.E. Sleebs, G. Nikolakopoulos, I.P. Street, H. Falk, J.B. Baell, Bioorg. Med. Chem. Lett. 2011, 21, 5992. R.L. Dow, M. Andrews, G.E. Aspnes, G. Balan, E.M. Gibbs, A. Guzman-Perez, K. Karki, J.L. LaPerle, J.-C. Li, J. Litchfield, M.J. Munchhof, C. Perreault, L. Patel, Bioorg. Med. Chem. Lett. 2011, 21, 6122. K.-H. Kim, A. Maderna, M.E. Schnute, M. Hegen, S. Mohan, J. Miyashiro, L. Lin, E. Li, S. Keegan, J. Lussier, C. Wrocklage, C.L. Nickerson-Nutter, A.J. Wittwer, H. Soutter, N. Caspers, S. Han, R. Kurumbail, K. Dunussi-Joannopoulos, J. Douhan, III, A. Wissner, Bioorg. Med. Chem. Lett. 2011, 21, 6258.

Six-Membered Ring Systems

11BMCL6348 11BMCL6577 11BMCL6770 11CC5010 11CC7818 11CC9513 11CC11394 11CC12092 11CC12313 11CCL127 11CCL389 11CCL567 11CCL753 11CCL903 11CCL951 11CCL1036 11CCL1183 11CEJ2948 11CEJ9385 11CEJ10470 11CL417 11CL747 11CL950 11EJO399 11EJO730 11EJO2089 11EJO3238 11EJO6909 11H(82)1137 11H(82)1447 11H(83)339 11H(83)531 11H(83)1275 11H(83)1291 11H(83)1527 11H(83)1807 11H(83)1831

415

R.O. Hughes, T. Maddux, D.J. Rogier, S. Lu, J.K. Walker, E.J. Jacobsen, J.M. Rumsey, Y. Zheng, A. MacInnes, B.R. Bond, S. Han, Bioorg. Med. Chem. Lett. 2011, 21, 6348. B.M. Savall, L. Gomez, F. Chavez, M. Curtis, S.P. Meduna, A. Kearney, P. Dunfold, J. Cowden, R.L. Thurmond, C. Grice, J.P. Edwards, Bioorg. Med. Chem. Lett. 2011, 21, 6577. X. Guo, Y. Li, L. Tao, Q. Wang, S. Wang, W. Hu, Z. Pan, Q. Yang, Y. Cui, Z. Ge, L. Dong, X. Yu, H. An, C. Song, J. Chang, Bioorg. Med. Chem. Lett. 2011, 21, 6770. K.S. Kumar, P.M. Kumar, K.A. Kumar, M. Screenivasulu, A.A. Jafar, D. Rambabu, G.R. Krishna, C.M. Reddy, R. Kapavarapu, K. Shivakumar, K.K. Priya, K.V.L. Parsa, M. Pal, Chem. Commun. 2011, 47, 5010. B. Han, C. Wang, R.-F. Han, W. Yu, X.-Y. Duan, R. Fang, X.-L. Yang, Chem. Commun. 2011, 47, 7818. Y. Yan, Z. Wang, Chem. Commun. 2011, 47, 9513. S.C. Rasmussen, R.L. Schwiderski, M.E. Mulholland, Chem. Commun. 2011, 47, 11394. H. Liu, J. Mack, Q. Guo, H. Lu, N. Kobayashi, Z. Shen, Chem. Commun. 2011, 47, 12092. N. Fernandez, L. Carillo, J.L. Vicario, D. Badia, E. Reyes, Chem. Commun. 2011, 47, 12313. S. Asghari, M. Tajbakhsh, B.J. Kenari, S. Khaksar, Chin. Chem. Lett. 2011, 22, 127. R. Mahesh, A.K. Dhar, T.V.N.V.T. Sasank, S. Thirunavukkarasu, T. Devadoss, Chin. Chem. Lett. 2011, 22, 389. Y.L.N. Murthy, N. Karthikeyan, G. Boddeti, B.S. Diwakar, E.R. Singh, Chin. Chem. Lett. 2011, 22, 567. B.B.F. Mirjalili, A. Akbari, Chin. Chem. Lett. 2011, 22, 753. M.A. Bigdeli, G. Gholami, E. Sheikhosseini, Chin. Chem. Lett. 2011, 22, 903. B. Wang, Z. Li, X.N. Wang, J.H. Tan, L.Q. Gu, Z.S. Huang, Chin. Chem. Lett. 2011, 22, 951. X.J. Song, Y. Shao, X.G. Dong, Chin. Chem. Lett. 2011, 22, 1036. R. Baharfar, R. Azimi, Chin. Chem. Lett. 2011, 22, 1183. L. Melzig, A. Metzger, P. Knochel, Chem. Eur. J. 2011, 17, 2948. T. Sasada, Y. Aoki, R. Ikeda, N. Sakai, T. Konakahara, Chem. Eur. J. 2011, 17, 9385. T. Inokuma, M. Furukawa, T. Uno, Y. Suzuki, K. Yoshida, Y. Yano, K. Matsuzaki, Y. Takemoto, Chem. Eur. J. 2011, 17, 10470. Q. Li, J. Li, L. Deng, Q. Wang, Z. Gao, D. Liu, Chem. Lett. 2011, 40, 417. K.C. Majumdar, K. Ray, S. Ganai, Chem. Lett. 2011, 40, 747. K. Radkowski, G. Seidel, A. Furstner, Chem. Lett. 2011, 40, 950. M. Tingoli, M. Mazzella, B. Panunzi, A. Tuzi, Eur. J. Org. Chem. 2011, 399. A. El-Dahshan, S. Nazir, F.L. Ansari, J. Rademann, Eur. J. Org. Chem. 2011, 730. I. Malik, Z. Ahmed, S. Reimann, I. Ali, A. Villinger, P. Langer, Eur. J. Org. Chem. 2011, 2089. S.N. Kessler, M. Neuburger, H.A. Wegner, Eur. J. Org. Chem. 2011, 3238. K.C. Majumdar, S. Ponra, R.K. Nandi, Eur. J. Org. Chem. 2011, 6909. M. Inouye, Y. Doi, J. Azuchi, W. Shirato, J. Chiba, H. Abe, Heterocycles 2011, 82, 1137. S.M. Kobelev, A.D. Averin, A.K. Buryak, F. Denat, R. Guilard, I.P. Beletskaya, Heterocycles 2011, 82, 1447. K.F.M. Atta, M.G. Marei, F.A.M. Mohamed, Heterocycles 2011, 83, 339. S. Takeuchi, H. Saito, S. Miyairi, T. Takabatake, Heterocycles 2011, 83, 531. C.A. Snyder, N.C. Tice, J.B. Maddox, S. Parkin, A.W. Daniel, J.M. Thomas, Heterocycles 2011, 83, 1275. Y. Gardikis, P.G. Tsoungas, C. Potamitis, G. Pairas, M. Zervou, P. Cordopatis, Heterocycles 2011, 83, 1291. C. Jia, J. Zhang, L. Zhang, X. Yao, Heterocycles 2011, 83, 1527. H. Cho, Y. Yasui, S. Kobayashi, E. Kwon, M. Arisawa, M. Yamaguchi, Heterocycles 2011, 83, 1807. M. Saeedi, Y.S. Beheshtiha, M.M. Heravi, H.A. Oskooie, Heterocycles 2011, 83, 1831.

416

L. Yet

11H(83)1873 11H(83)2689 11JA5413 11JA6126 11JA6964 11JA8467 11JA12439 11JHC279 11JHC403 11JHC634 11JHC776 11JHC1085 11JHC1216 11JHC1308 11JHC1404 11JMC201 11JMC655 11JMC1847 11JMC2738 11JMC2980 11JMC3368

11JMC5660 11JMC7150 11JMC7705 11JMC7729 11JMC8030 11JOC846 11JOC939 11JOC982 11JOC1767

K.F.M. Atta, M.G. Marei, S.M.A. El-Magiad, F.H.A. El-Nashar, Heterocycles 2011, 83, 1873. M.A. Ibrahim, Heterocycles 2011, 83, 2689. D. Kvaskoff, M. Vosswinkel, C. Wentrup, J. Am. Chem. Soc. 2011, 133, 5413. Q.-A. Chen, D.-S. Wang, Y.-G. Zhou, Y. Duan, H.-J. Fan, Y. Yang, Z. Zhang, J. Am. Chem. Soc. 2011, 133, 6126. M. Ye, G.-L. Gao, J.-Q. Yu, J. Am. Chem. Soc. 2011, 133, 6964. Y. Zhang, M.R. Sheets, E.K. Raja, K.N. Boblak, D.A. Klumpp, J. Am. Chem. Soc. 2011, 133, 8467. B.M. Trost, D.A. Thaisrivongs, J. Hartwig, J. Am. Chem. Soc. 2011, 133, 12439. Z.-T. Zhang, Y.-Q. Ma, Y. Liang, D. Xue, Q. He, J. Heterocycl. Chem. 2011, 48, 279. J. Li, D.-N. Jiang, J.-X. Chen, M.-C. Liu, J.-C. Ding, H.-Y. Wu, J. Heterocycl. Chem. 2011, 48, 403. X. Zhao, D.-Q. Shi, J. Heterocycl. Chem. 2011, 48, 634. X. Li, A. Zheng, B. Liu, G. Li, X. Yu, P. Yi, J. Heterocycl. Chem. 2011, 48, 776. N. Zanatta, S.S. Amaral, J.M. dos Santos, L.S. Ferandes, H.G. Bonacorso, M.A.P.Martins, J. Heterocycl. Chem. 2011, 48, 1085. K.F.M. Atta, E.S.H.E. Ashry, J. Heterocycl. Chem. 2011, 48, 1216. M.A. Kukamiev, C. Parkanyi, J. Heterocycl. Chem. 2011, 48, 1308. M.A. Kukamiev, C. Parkanyi, J. Heterocycl. Chem. 2011, 48, 1404. A.D. Kerekes, S.J. Esposite, R.J. Doll, J.R. Tagat, T. Yu, Y. Xiao, Y. Zhang, D.B. Prelusky, S. Tevar, K. Gray, G.A. Terracina, S. Lee, J. Jones, M. Liu, A.D. Basso, E.B. Smith, J. Med. Chem. 2011, 54, 201. M.-Y. Jang, Y. Lin, S. Jonghe, L.-J. Gao, B. Vanderhoydonck, M. Froeyen, J. Rozenski, J. Herman, T. Louat, K.V. Belle, M. Waer, P. Herdewijn, J. Med. Chem. 2011, 54, 655. K. Saravanan, H.C. Barlow, M. Barton, A.H. Calvert, B.T. Golding, D.R. Newell, J.S. Northerm, N.J. Curtin, H.D. Thomas, R.J. Griffin, J. Med. Chem. 2011, 54, 1847. C. Trapella, M. Pela, L.D. Zoppo, G. Calo, V. Camarda, C. Ruzza, A. Cavazzini, V. Costa, V. Bertolasi, R.K. Reinscheid, S. Salvador, R. Guerrini, J. Med. Chem. 2011, 54, 2738. R. Jorda, L. Havlicek, I.W. McNae, M.D. Walkinshaw, J. Voller, A. Sturc, J. Navratilova, M. Kuzma, M. Mistrik, J. Bartek, M. Strnad, V. Krystof, J. Med. Chem. 2011, 54, 2980. L. Zehnder, M. Bennett, J. Meng, B. Huang, S. Ninkovic, F. Wang, J. Braganza, J. Tatlock, T. Jewell, J.Z. Zhou, B. Burke, J. Wang, K. Maegley, P.P. Mehta, M.-J. Yin, K.S. Gajiwala, M.J. Hickey, S. Yamazaki, E. Smith, P. Kang, A. Sistla, E. Dovalsantos, M.R. Gehring, R. Kania, M. Wythes, P.-P. Kung, J. Med. Chem. 2011, 54, 3368. W. Yu, C. Goddard, E. Clearfield, C. Mills, T. Xiao, H. Guo, J.D. Morrey, N.E. Motter, K. Zhao, T.M. Block, A. Cuconati, X. Xu, J. Med. Chem. 2011, 54, 5660. L. Wang, S.K. Desmoulin, C. Cherian, L. Polin, K. White, J. Kushner, A. Fulterer, M.-H. Chang, S. Mitchell-Ryan, M. Stout, M.F. Romero, Z. Hou, L.H. Matherly, A. Gangjee, J. Med. Chem. 2011, 54, 7150. A. Linton, P. Kang, M. Ornelas, S. Kephart, Q. Hu, M. Pairish, Y. Jiang, C. Guo, J. Med. Chem. 2011, 54, 7705. L. Peng, X. Gao, L. Duan, X. Ren, D. Wu, K. Ding, J. Med. Chem. 2011, 54, 7729. T. Ishikawa, M. Seto, H. Banno, Y. Kawakita, M. Oorui, T. Taniguchi, Y. Ohta, T. Tamura, A. Nakayama, H. Miki, H. Kamiguchi, T. Tanaka, N. Habuka, S. Sogabe, J. Yano, K. Aertgeerts, K. Kamiyama, J. Med. Chem. 2011, 54, 8030. S.G. Modha, J.C. Trivedi, V.P. Mehta, D.S. Ermolat’ev, E.V.V. der Eycken, J. Org. Chem. 2011, 76, 846. M. Alfonso, A. Tarraga, P. Molina, J. Org. Chem. 2011, 76, 939. X. Fan, Y. Wang, Y. Qu, H. Xu, Y. He, X. Zhang, J. Wang, J. Org. Chem. 2011, 76, 982. J. Chan, B.J. Burke, K. Baucom, K. Hansen, M.M. Bio, E. DiVirgilio, M. Faul, J. Murry, J. Org. Chem. 2011, 76, 1767.

Six-Membered Ring Systems

11JOC3837 11JOC4571 11JOC6134 11JOC6383 11JOC6389 11JOC6937 11JOC7157 11JOC8421 11JOC8483 11MCC935 11MO5182 11MO6549 11MO6985 11MO7081 11MO10387 11OBC351 11OBC1429 11OBC1839 11OBC2185 11OBC3050 11OBC5005 11OBC5967 11OBC6741 11OL46 11OL102 11OL320 11OL1766 11OL1852 11OL2492 11OL3304 11OL3880 11OL4490 11OL4514 11OL4562 11OL4588 11OL4604 11OL5484 11OL5972 11OL6544 11OL6568 11OPRD382 11OPRD918 11S109 11S387 11S571

417

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418

L. Yet

11S794 11S943 11S1132 11S1213 11S1419 11S1465 11S2644 11S2754 11S3143 11S3323 11S3496 11SC417 11SC426 11SC826 11SC1119 11SC1357 11SC1650 11SC1875 11SC2053 11SC2505 11SC2811 11SC3097 11SC3325 11SC3334 11SC3532 11SC3590 11SC3635 11SL169 11SL1089 11SL1179 11SL1705 11SL2325 11SL2339 11SL2387 11SL2657 11T114 11T236 11T1150 11T1633 11T1665 11T1930 11T2035 11T2110

M. Antoine, M. Czech, M. Gerlach, E. Gunther, T. Schuster, P. Marchand, Synthesis 2011, 794. A. Fernandez-Mato, C. Peinador, J.M. Quintela, Synthesis 2011, 943. K.C. Majumdar, S. Ponra, D. Ghosh, Synthesis 2011, 1132. Y. Song, R. Yang, H. Ding, Q. Sun, Q. Xiao, Y. Ju, Synthesis 2011, 1213. S. Mukherjee, P. Roy, B.K. Ghorai, Synthesis 2011, 1419. N.B. Maximov, P.V. Mykhailiuk, A.I. Kisel, Z.V. Voitenko, A.A. Tolmachev, Synthesis 2011, 1465. K. Lanjewar, A. Rahatgaonkar, M. Chorghade, B. Saraf, Synthesis 2011, 2644. M. Hinoshita, D. Shibata, M. Hatakenaka, E. Okada, Synthesis 2011, 2754. M.-Y. Chang, T.-W. Lee, R.-T. Hsu, T.-L. Yen, Synthesis 2011, 3143. A. Fernandez-Mato, C. Peinador, J.M. Quintela, Synthesis 2011, 3323. D. Blachut, J. Szawkalo, Z. Czarnocki, Synthesis 2011, 3496. G.C. Nandi, S. Samai, R. Kumar, M.S. Singh, Synth. Commun. 2011, 41, 417. S.J. Ahmadi, M. Hosseinpour, S. Sadjadi, Synth. Commun. 2011, 41, 426. H.A. Oskooje, M.M. Heravi, N. Karimi, M.H. Monjezy, Synth. Commun. 2011, 41, 826. F.M. Abdelrazek, A.A. Fadda, A.N. Elsayed, Synth. Commun. 2011, 41, 1119. C.A. Snyder, N.C. Tice, P.G. Sriramula, J.L. Neathery, J.K. Mobley, C.L. Phillips, A.Z. Preston, J.M. Strain, E.S. Vanover, M.P. Starling, N.V. Sahi, Synth. Commun. 2011, 41, 1357. R. Dowlatabadi, A. Khalaj, S. Rahimian, M. Montazeri, M. Amini, A. Shahverdi, E. Mahjub, Synth. Commun. 2011, 41, 1650. M.B.M. Reddy, M.A. Pasha, Synth. Commun. 2011, 41, 1875. X.-Z. Zhang, J.-X. Wang, L. Bai, Synth. Commun. 2011, 41, 2053. S. Goswami, A. Hazra, J.H. Goh, H.-K. Fun, Synth. Commun. 2011, 41, 2505. A.A. Abdalha, M.K.A. El-Regal, M.A. El-Kassaby, A.T. Ali, Synth. Commun. 2011, 41, 2811. T. Sun, W.-J. Zhao, A.-Y. Hao, L.-Z. Sun, Synth. Commun. 2011, 41, 3097. Q. I, J. Li, H. Ren, Z. Gao, D. Liu, Synth. Commun. 2011, 41, 3325. T. Huang, D. Jiang, J. Chen, W. Gao, J. Ding, H. Wu, Synth. Commun. 2011, 41, 3334. A. Makhlouti, M. Baitiche, M. Merbah, D. Benachour, Synth. Commun. 2011, 41, 3532. W.-Y. Han, Z.-T. Zhang, L. Qiu, G. Li, Synth. Commun. 2011, 41, 3590. L.-Y. Zeng, Y.-M. Ren, C. Cai, Synth. Commun. 2011, 41, 3635. B.V.S. Reddy, K. Ramesh, J.S. Yadav, Synlett 2011, 169. K. Karnakar, J. Shankar, S.N. Murthy, K. Ramesh, Y.V.D. Nageswar, Synlett 2011, 1089. M. Lin, Z.-Z. Chen, Y. Zhu, X.-I. Chen, J.-J. Cai, Y.-M. Pan, Z.-P. Zhan, Synlett 2011, 1179. S. Tumkevicius, J. Dodonova, Synlett 2011, 1705. L.B. Delvos, J.-M. Begouin, C. Gosmini, Synlett 2011, 2325. S. Badrinarayanan, J. Sperry, Synlett 2011, 2339. A.A. Estrad, J.P. Lyssikatos, F. St-Jean, P. Bergeron, Synlett 2011, 2387. K.C. Majumdar, T. Ghosh, P.K. Shyam, Synlett 2011, 2657. C.-J. Chen, Y.-C. Wu, H.-S. Sheu, G.-H. Lee, C.K. Lai, Tetrahedron 2011, 67, 114. T.-C. Chou, K.-C. Liao, Tetrahedron 2011, 67, 236. W. Phakhodee, M. Toyoda, C.-M. Chou, N. Khunnawutmanotham, M. Isobe, Tetrahedron 2011, 67, 1150. L. Gavara, E. Saugues, F. Anizon, P. Moreau, Tetrahedron 2011, 67, 1633. Z. Shen, X. He, J. Dai, W. Mo, B. Hu, N. Sun, X. Hu, Tetrahedron 2011, 67, 1665. R. Ghorbani-Vaghei, R. Karimi-Nami, Z. Toghraei-Semiromi, M. Amiri, M. Ghavidel, Tetrahedron 2011, 67, 1930. A. Fernandez-Mato, J.M. Quintela, C. Peinador, C. Platas-Iglesias, Tetrahedron 2011, 67, 2035. C.-T. Chou, G.S. Yellol, W.-J. Chang, M.-L. Sun, C.-M. Sun, Tetrahedron 2011, 67, 2110.

Six-Membered Ring Systems

11T2232 11T2279 11T2287 11T2661 11T2676 11T2803 11T3226 11T3267 11T3690 11T4852 11T4933 11T5156 11T5219 11T5615 11T5663 11T5700 11T5935 11T6206 11T7379 11T7426 11T8321 11T8360 11T8484 11T8564 11T8918 11T9063 11T9122 11T9368 11T10186 11TL69 11TL202 11TL228 11TL341 11TL488 11TL544 11TL809 11TL1020

419

W. Xiong, H. Zhang, Y. Xin, S. Zhu, Tetrahedron 2011, 67, 2232. I. Bassoude, S. Berteina-Raboin, J.-M. Leger, C. Jarry, E.M. Essassi, G. Guillaumet, Tetrahedron 2011, 67, 2279. N. Hebbar, C. Fiol-Petit, Y. Ramondenc, G. Ple, N. Ple, Tetrahedron 2011, 67, 2287. H. Cho, Y. Nishimura, Y. Yasui, S. Kobayashi, S.-I. Yoshida, E. Kwon, M. Yamguchi, Tetrahedron 2011, 67, 2661. M. Hu, J. Wu, Y. Zhang, F. Qiu, Y. Yu, Tetrahedron 2011, 67, 2676. L. Zhao, K. Tao, H. Li, J. Zhang, Tetrahedron 2011, 67, 2803. J. Adcock, C.L. Gibson, J.K. Huggan, C.J. Suckling, Tetrahedron 2011, 67, 3226. X.-C. Wang, G.-J. Yang, X.-D. Jia, Z. Zhang, Y.-X. Da, Z.-J. Quan, Tetrahedron 2011, 67, 3267. Z. Li, J. Hong, X. Zhou, Tetrahedron 2011, 67, 3690. Y. Loidreau, T. Besson, Tetrahedron 2011, 67, 4852. C. Zhu, M. Yamane, Tetrahedron 2011, 67, 4933. G. Liu, J. Xu, K.C. Park, N. Chen, S. Zhang, Z. Ding, F. Wang, D. Du, Tetrahedron 2011, 67, 5156. K. Ostrowska, K. Szymoniak, M. Szczurek, K. Jamrozy, M. Rapala-Kozik, Tetrahedron 2011, 67, 5219. B. Han, R.-F. Han, Y.-W. Ren, X.-Y. Duan, Y.-C. Xu, W. Zhang, Tetrahedron 2011, 67, 5615. V.O. Iaroshenko, V. Specowius, K. Vlach, M. Vilches-Herrera, D. Ostrovskyi, S. Mkrtchyan, A. Villinger, P. Langer, Tetrahedron 2011, 67, 5663. E.E. Elboray, R. Grigg, C.W.G. Fishwick, C. Kilner, M.A.B. Sarker, M.F. Aly, H.H. Abbas-Temirek, Tetrahedron 2011, 67, 5700. S. Samai, G.C. Nandi, S. Chowdhury, M.S. Singh, Tetrahedron 2011, 67, 5935. J. Tan, W. Tang, Y. Sun, Z. Jiang, F. Chen, L. Xu, Q. Fan, J. Xiao, Tetrahedron 2011, 67, 6206. P. Brehova, M. Cesnek, M. Dracinsky, A. Holy, Z. Janeba, Tetrahedron 2011, 67, 7379. X.-N. Zhang, Y.-X. Li, Z.-H. Zhang, Tetrahedron 2011, 67, 7426. V.O. Iaroshenko, A. Maalik, D. Ostrovskyi, A. Villinger, A. Spannenberg, P. Langer, Tetrahedron 2011, 67, 8321. A. Shaabani, F. Jajishaabanha, M. Mahyari, H. Mofakham, S.W. Ng, Tetrahedron 2011, 67, 8360. M. Ghandi, E. Mohammadimehr, M. Sadeghzadeh, A.H. Bozcheloei, Tetrahedron 2011, 67, 8484. R. Csutortoki, I. Szatmari, A. Koch, M. Heydenreich, E. Kleinpeter, F. Fulop, Tetrahedron 2011, 67, 8564. R. Dey, B.C. Ranu, Tetrahedron 2011, 67, 8918. A.R. Harris, D.M. Nason, E.M. Collantes, W. Xu, Y. Chi, Z. Wang, B. Zhang, Q. Zhang, D.L. Gray, J.E. Davoren, Tetrahedron 2011, 67, 9063. D. Marosvolgyi-Hasko, A. Petz, A. Takacs, L. Kollar, Tetrahedron 2011, 67, 9122. W.M. Bloch, S.M. Derwent-Smith, F. Issa, J.C. Morris, L.M. Rendina, C.J. Sumby, Tetrahedron 2011, 67, 9368. F. Li, Y.-Z. Li, Z.-S. Jia, M.-H. Xu, P. Tian, G.-Q. Lin, Tetrahedron 2011, 67, 10186. A. Dhakshinamoorthy, K. Kanagaraj, K. Pitchumani, Tetrahedron Lett. 2011, 52, 69. S.M. Al-Mousawi, M.S. Moustafa, I.A. Abdelhamid, M.H. Elnagdi, Tetrahedron Lett. 2011, 52, 202. M. Bakherad, A. Keivanloo, Z. Kalantar, S. Jajarmi, Tetrahedron Lett. 2011, 52, 228. M.B. Supurgibekov, V.M. Zakharova, J. Sieler, V.A. Nikolaev, Tetrahedron Lett. 2011, 52, 341. E. Mosaddegh, A. Hassankhani, Tetrahedron Lett. 2011, 52, 488. K. Padmavathy, G. Nagendrappa, K.V. Geetha, Tetrahedron Lett. 2011, 52, 544. G.B.D. Rao, B.N. Archarya, S.K. Verma, M.P. Kaushik, Tetrahedron Lett. 2011, 52, 809. M. Vimolratan, J.L. Simard, S.P. Brown, Tetrahedron Lett. 2011, 52, 1020.

420

L. Yet

11TL1053 11TL1506 11TL2375 11TL2415 11TL2496 11TL2652 11TL2725 11TL2862 11TL3033 11TL3810 11TL3814 11TL3849 11TL4140 11TL4590 11TL4686 11TL4821 11TL5140 11TL5521 11TL5697 11TL5702 11TL5761 11TL6484 11TL6597 11TL6942 11TL7185 11TL7195

H.T. Pham, R.N. Hanson, S.L. Olmsted, A. Kozhushnyan, A. Visentin, P.J. Welinsky, C. Massero, K. Bailey, Tetrahedron Lett. 2011, 52, 1053. R.S. Foster, H. Jakobi, J.P.A. Harrity, Tetrahedron Lett. 2011, 52, 1506. L. Zhang, G. Yang, C. Shen, S. Arghib, W. Zhang, Tetrahedron Lett. 2011, 52, 2375. M.J. da Silva, M.C.F.R. Pinto, C.A. de Simone, J.G. Soares, J.R.M. Reys, J.D.S.Filho, W.T. Harrison, C.E.M. Carvalho, M.O.F. Goulart, E.N.S. Junior, A.V. Pinto, Tetrahedron Lett. 2011, 52, 2415. R. Bolligarla, S.K. Das, Tetrahedron Lett. 2011, 52, 2496. R. Rodriguez, P. Camargo, C.A. Siera, C.Y. Soto, J. Cobo, M. Nogueras, Tetrahedron Lett. 2011, 52, 2652. E.K. Unver, S. Tarkuc, D. Baran, C. Tanyeli, L. Toppare, Tetrahedron Lett. 2011, 52, 2725. B.S.P.A. Kumar, B. Madhav, K.H.V. Reddy, Y.V.D. Nageswar, Tetrahedron Lett. 2011, 52, 2862. A. Maity, S. Mondal, R. Paira, A. Hazra, S. Naskar, K.B. Sahu, P. Saha, S. Banerjee, N.B. Mondal, Tetrahedron Lett. 2011, 52, 3033. M. Since, O. Khoumeri, P. Verhaeghe, M. Maillard-Boyer, T. Terme, P. Vanelle, Tetrahedron Lett. 2011, 52, 3810. S. Singh, A. Schober, M. Gebinoga, G.A. Grob, Tetrahedron Lett. 2011, 52, 3814. I.T. Raheem, J.D. Schreier, M.J. Breslin, Tetrahedron Lett. 2011, 52, 3849. N.M. Sekhar, P.V.R. Acharyulu, Y. Anjaneyulu, Tetrahedron Lett. 2011, 52, 4140. V.L. Blair, D.C. Blakemore, D. Hay, E. Hevia, D.C. Pryde, Tetrahedron Lett. 2011, 52, 4590. L. Carlier, M. Baron, A. Chamayou, G. Couarraze, Tetrahedron Lett. 2011, 52, 4686. M. Ayaz, J. Dietrich, C. Hulme, Tetrahedron Lett. 2011, 52, 4821. E. Villemin, B. Elias, R. Robiette, K. Robeyns, M.-F. Herent, J.-L. Habib-Jiwan, J. Marchand-Brynaert, Tetrahedron Lett. 2011, 52, 5140. P. Sadanandam, V. Jyothi, M.A. Chari, P. Das, K. Mukkanti, Tetrahedron Lett. 2011, 52, 5521. H.M. Bachlav, S.B. Bhagat, V.N. Telvekar, Tetrahedron Lett. 2011, 52, 5697. D.S. Raghuvanshi, K.N. Singh, Tetrahedron Lett. 2011, 52, 5702. N. Todorovic, E. Awuah, T. Shakya, G.D. Wright, A. Capretta, Tetrahedron Lett. 2011, 52, 5761. A. Kwast, K. Stachowska, A. Trawczynski, Z. Wrobel, Tetrahedron Lett. 2011, 52, 6484. S. Paul, B. Basu, Tetrahedron Lett. 2011, 52, 6597. M.A. Reddy, A. Thomas, G. Mallesham, B. Sridhar, V.J. Rao, K. Bhanuprakash, Tetrahedron Lett. 2011, 52, 6942. H. Cho, E. Kwon, Y. Yasui, S. Kobayashi, S.-i. Yoshida, Y. Nishimura, M. Yamaguchi, Tetrahedron Lett. 2011, 52, 7185. G. Shukla, R.K. Verma, G.K. Verma, M.S. Singh, Tetrahedron Lett. 2011, 52, 7195.