An unexpected reaction of phosphorous tribromide on chromanone, thiochromanone, 3,4-dihydro-2H-benzo[b]thiepin-5-one, 3,4-dihydro-2H-benzo[b]oxepin-5-one and tetralone derived allylic alcohols: a case study

Tetrahedron 64 (2008) 9962–9976

Contents lists available at ScienceDirect

Tetrahedron

journal homepage: w ww.elsevier.com/locate/tet

An unexpected reaction of phosphorous tribromide on chromanone,

thiochromanone, 3,4-dihydro-2H-benzo[b]thiepin-5-one, 3,4-dihydro-2H-

benzo[b]oxepin-5-one and tetralone derived allylic alcohols: a case study^q

a

b

*

Maloy K. Parai , Shagufta , Ajay K. Srivastava , Matthias Kassack , Gautam Panda

^aMedicinal and Process Chemistry Division, Central Drug Research Institute, Lucknow 226001, Uttar Pradesh, India

^bInstitute of Pharmaceutical and Medicinal Chemistry, Heinrich Heine University Duesseldorf, 40225 Duesseldorf, Germany

a r t i c l e i n f o

a b s t r a c t

Article history:

Treatment of chromanone, thiochromanone, tetralone and benzo[b]thiepinone derived allylic alcohols

with phosphorous tribromide furnished unexpected products instead of desired bromo derivatives.

Reaction of 7-methoxy-2,2-dimethylchromenyl-aryl-methanols and 7-methoxy-2,2-dimethylthio-

chromenyl-aryl-methanols with PBr₃gave saturated carbonyls and exocyclic oleﬁns depending on the

substituents at R⁴, whereas allylic alcohols without 7-methoxy substituent furnished rearranged pro-

ducts. Several related analogs varying in ring size, heteroatom in the ring and substituents at various

positions were synthesized and studied. Reactions of other phosphorous-based reagents like PPh₃, PPh₃/I₂

and PPh₃Br₂on allylic alcohols were also attempted. A case study is presented here.

Received 28 March 2008

Received in revised form 29 July 2008

Accepted 30 July 2008

Available online 5 August 2008

R⁴

Br

R⁴

1. Introduction

HO

PBr_3,0 °C

The reaction of allylic alcohols with phosphorus tribromide to

furnish bromo derivatives is an important transformation in or-

ganic synthesis.¹In this reaction, the hydroxy of allylic alcohol is

replaced by bromide through stereo- and regioselective manner

leading to the formation of corresponding bromo derivatives or the

allylic alcohol rearranges into the terminal bromides involving

migration of the double bond.²Recently in an effort towards

accessing chromene containing bioactive agents,³we needed ad-

vanced intermediates 2a–c, which could be obtained from carbi-

nols 1a–c on treatment with PBr₃. But instead of furnishing bromo

derivatives 2a–c, to our surprise, carbinols 1a–c underwent isom-

erization to give saturated carbonyls 3, 4 and exocyclic oleﬁns 5, 6

(Schemes 1 and 2). From close analysis of the structures of allylic

alcohols 1a–c and the ratio of their products, it was apparent that

reaction was dependent on the substituents of allylic alcohols as 1a

containing para ﬂuoro-phenyl group (ꢀR effect) furnished satu-

rated ketone 3 (77%) whereas 1b containing para methoxyphenyl

group (þR effect) gave saturated ketone 4 (67%) and exocyclic oleﬁn

5 (15%) while 1c furnished exocyclic oleﬁn 6 (32%).

H₃CO

O

H₃CO

O

1a, R⁴= C₆H₄-(4-F)

2a, R⁴= C₆H₄-(4-F)

2b, R⁴= C₆H₄-(4-OCH₃)

2c, R⁴= C₈H₅N-CH₂C₆H₅

1b, R⁴= C₆H₄-(4-OCH₃)

1c, R⁴= C₈H₅N-CH₂C₆H₅

Scheme 1.

2. Results and discussion

This unusual transformation of allylic alcohols to saturated

carbonyls and exocyclic oleﬁns encouraged us to study the reaction

of PBr₃on a set of allylic alcohols as this type of disproportionation

reactions are highly important in organic synthesis⁴and very few

one-step synthetic methods are reported in the literature for such

transformations.⁵

Thus, a series of substituted allylic alcohols were treated with

PBr₃and saturated carbonyls and exocyclic oleﬁns were isolated

from the reactions, Table 1. As stated above, allylic alcohols pos-

sessing R⁴groups with þR resonance effects gave good yields of

exocyclic oleﬁns while R⁴group with ꢀR resonance effects gave

good yields of saturated ketones. Increasing the number of OCH₃

groups and incorporation of N(CH₃)₂group on R⁴(high þR effect)

improved the yield of the exocyclic oleﬁns^6awhile incorporation of

q

CDRI communication number 6996.

* Corresponding author. Tel.: þ91 5222612411–18x4385, 4469; fax: þ91

5222623405.

E-mail addresses: gautam.panda@gmail.com, gautam_panda@cdri.res.in

(G. Panda).

doi:10.1016/j.tet.2008.07.106

M.K. Parai et al. / Tetrahedron 64 (2008) 9962–9976

9963

F

hindrance present in double bond having four substituents. To

explore the possibility of this reaction, tetrasubstituted allylic

alcohols were synthesized from 3-methyl substituted chromanone

13⁸and were treated with PBr₃. To our delight, the saturated

ketones 15a–e and exocyclic oleﬁns 16, 17 were isolated in good

yields, Scheme 3 and Table 2.

F

HO

O

PBr₃

0 °C

H₃CO

O

H₃CO

O

1a

3

HO

R⁴

O

NBn

PBr₃

NBn

HO

H₃CO

O

14a-g

H₃CO

0 °C

13

H₃CO

O

1c

H₃CO

O

R⁴

O

R⁴

6

PBr₃

0 °C

H₃CO

+

OCH₃

H₃CO

O

16-17

O

HO

O

15a-e

PBr₃

0 °C

H₃CO

+

Scheme 3.

O

H₃CO

O

1b

O

H₃CO

Table 2

5

4

Transformation of tetrasubstituted allylic alcohols 14a–g to saturated ketones 15a–e

and exocyclic oleﬁns 16, 17

Scheme 2.

Entry

Alcohol

R⁴

Ketone

Yield (%)

Oleﬁn

Yield (%)

1

2

3

4

5

6

7

14a

14b

14c

14d

14e

14f

C₆H₅

15a

15b

15c

15d

15e

d

84

79

83

75

87

d

16

17

d

71

73

C₆H₄-(3-OCH₃)

C₆H₄-(4-F)

C₃H₇

C₆H₄-(4-Cl)

C₆H₄-(4-OCH₃)

C₆H₄-{4-N(CH₃)₂}

Table 1

Transformation of allylic alcohols into saturated carbonyls and exocyclic oleﬁns

using PBr₃

14g

d

Entry Allylic alcohol R⁴

Ketone Yield (%) Oleﬁn Yield (%)

1

2

3

4

5

6

7

8

1d

1e

1f

1g

1h

1i

1j

1k

1l

1m

1n

1o

1p

1q

1r

1s

1t

C₆H₅

2d

2e

2f

73

65

78

20

d

7

d

19

d

56

65

18

d

25

67

d

C₆H₄-(2-OCH₃)

C₆H₄-(3-OCH₃)

C₆H₃-(2,4-OCH₃)

C₆H₂-(2,4,6-OCH₃) 2h

(2-Thienyl)

(2-Furyl)

CH]CH–C₆H₅

C₆H₄-{4-N(CH₃)₂}

C₆H₄-(2-Cl)

(3-NO₂)

C₆H₄-(4-CN)

C₆H₄-{4-CH(CH₃)₂} 2p

2.2. Reaction of PBr₃on chromanone and 2-isopropyl-

chromanone and 2,2-dimethylchromanone derived allylic

alcohols

d

2g

8

9

2i

2j

58

67

d

10

d

11

12

d

In continuation of our study, PBr₃was reacted with chromene

containing allylic alcohols 18 without dimethyl and 20a,b with

2-isopropyl substituents. While minor amount of saturated car-

bonyls 19 and 21a,b, respectively, were obtained, the reaction gave

mostly inseparable mixture of non-polar products. The allylic

alcohols were also not much stable perhaps due to the presence of

a proton adjacent to oxygen. On the contrary, on treatment of PBr₃

the allylic alcohol 22 without 7-methoxy substituent and proton

adjacent to oxygen, furnished saturated carbonyl 23, Scheme 4 and

Table 3.

2k

2l

2m

2n

2o

9

d

10

11

12

13

14

15

16

17

18

60

82

74

69

75

61

63

69

60

C

₁₀H₇

2q

2r

2s

2t

C₂H₅

C₃H₇

CH]CHCH₃

C₆H₄-(4-Cl)

1u

2u

R⁴

O

HO

CN, F, NO₂, Cl group (high ꢀR effect) increases the yield of saturated

ketones,^6bScheme 2.

Inseperable mixture

of nonpolar products

PBr₃

0 °C

R²

R³

Scheme 4.

R²

R³

+

2.1. Reaction of PBr₃on tetrasubstituted allylic alcohols

O

Further to elaborate this methodology, we were interested to

explore the reaction of PBr₃on tetrasubstituted allylic alcohols.

From the literature reports it was observed that the isomerization

of allylic alcohols using known methods depends largely upon the

substitution on the double bond.^5aThe reaction becomes more

difﬁcult as the number of substituents on double bond increases. A

handful of examples are known for the transposition of tri-

substituted and conjugated allylic alcohols into saturated car-

bonyls.⁷Not a single example of conversion of tetrasubstituted

allylic alcohols into saturated carbonyls by using metal catalyst or

any other regents in one step is known; perhaps due to steric

Table 3

Transformation of allylic alcohols 18, 20a,b, 22 to saturated ketones 19, 21a,b, 23

using PBr₃

Entry

Alcohol

R², R³, R⁴

Ketone

Yield (%)

1

2

3

4

18

R²¼R³¼H, R⁴¼C₆H₄-(3-OCH₃)

R²¼H, R³¼Isopropyl, R⁴¼C₆H₅

R²¼H, R³¼Isopropyl, R⁴¼C₆H₄-(3-OCH₃)

R²¼R³¼Me, R⁴¼C₆H₄-(4-Cl)

19

20

15

26

30

20a

20b

22

21a

21b

23

9964

M.K. Parai et al. / Tetrahedron 64 (2008) 9962–9976

one observed in chroman containing allylic alcohols.^6a,bThus it was

observed that donating effect of OCH₃in 26a–c plays a role in

retaining the polarization of double bond, which eventually fur-

nished the saturated ketones 27a–c (Scheme 7). Further to ascertain

the role of 7-OCH₃at benzene ring on polarization of double bond,

Table 4

List of ﬁnal products 27a–c and 29a–h during treatment of PBr₃on allylic alcohols

26a–c, 28a–h containing thiochromene ring

Entry Alcohol R¹, R⁴

Ketone Yield (%) Rearranged Yield (%)

product

1

2

3

4

5

6

7

8

26a

26b

26c

28a

28b

28c

28d

28e

28f

OCH₃, C₆H₄-(4-Cl)

OCH₃, C₆H₅

27a

27b

50

51

60

d

OCH₃, C₆H₄-(3-NO₂) 27c

d

H, C₆H₄-(3-NO₂)

H, C₆H₄-(4-OCH₃)

H, C₆H₄-{4-N(CH₃)₂}

H, C₆H₅

H, C₆H₄-(4-Cl)

H, C₆H₄-(4-CN)

H, C₆H₃-(2,4-Cl)

H, C₆H₄-(4-CH₃)

d

29a

29b

29c

29d

29e

29f

29g

29h

63

53

59

52

62

65

61

57

R⁴

S

36

S

Not isolated

R⁴

9

10

11

28g

28h

+

R⁴

S

2.3. Reaction of PBr₃on 2,2-dimethyl-thiochromanone and

thiochromanone derived allylic alcohols

Path c

HO

δ−

R⁴

Br₂PO

δ−

R⁴

Br^-

a

We further wanted to observe the role of heteroatom in this

transformation reaction of allylic alcohols and thus 7-methoxy-2,

2-dimethyl-thiochroman-4-one 24a was converted into bromo

derivative 25a, which on subsequent reaction with n-BuLi and

R⁴CHO afforded allylic alcohols 26a–c following reported pro-

cedures.^4,9The resulting compounds 26a–c with 7-methoxy sub-

stituent on reaction with PBr₃at 0 ^ꢁC furnished saturated ketones

27a–c in good yields (Table 4). On the contrary, on treatment with

PBr₃, the allylic alcohols without 7-methoxy substituent 28a–h,

furnished rearranged products 29a–h instead of giving saturated

carbonyls. On the other hand, thiochromanone derived bromo de-

rivative 31 was not stable and further reaction was not performed

on it, Scheme 5.

δ+

CH₃

b

CH₃

δ+

CH₃

PBr₃

S

Br₂PO

S

28a-h

R⁴

32

Path a : migration of

one of the gem-dimethyl

groups

H

+

Path b : Nucleophilic

addition of bromide

Path c: Through epi-

sulfonium intermediate

R⁴

S

H

CH₃

+

CH

³)(

H

33

H₃C

A^1,3

34

R⁴

H

S

R⁴

S

H

CH₃

HO

R⁴

H₂C

29a-h

Br

H₂C

O

PBr₃

35

PBr₃

n-BuLi,-78 °C

R⁴CHO

65 °C

R¹

Scheme 6.

R¹

S

R¹

24a;

S

25a; R¹

= OCH₃

¹= OCH₃

26a-c; R¹= OCH₃

R

25b; R¹= H

24b; R¹= H

28a-h; R¹= H

Ha

R⁴

HO

δ+

Br₂P

O

PBr₃

δ-

H

Br

O

R⁴

MeO

X

MeO

X

38

37

X = O, S

Br₂P

Ha

R⁴

R¹

S

R¹

S

R⁴

O

Br

Br₂P

O

29a-h; R¹= H

27a-c; R¹= OCH₃

H

MeO

Ha: more acidic

X

MeO

X

HO

R⁴

O

Br

43

39

Ha: less acidic

δ+

-POBr₃

R⁴

PBr_3,65 °C

4 days

(R⁴:with -R effect) (R⁴:with +R effect)

δ−

S

H₃CO

S

Br

30

31

Ha

R⁴

26a-c

Highly unstable

Br₂P

O

H

Scheme 5.

H

MeO

X

44

MeO

X

40

2.4. Plausible reaction mechanism for the formation of

rearranged products

-HaBr

O

R⁴

O

R⁴

Br₂P

The sulfur of 26a–c having vacant 3d orbital might induce inverse

polarization on double bond through attracting the electron cloud of

benzene ring. On the other hand, the electron-donating effect of

OCH₃at benzene nucleus nulliﬁes the effect of sulfur and causes the

polarization of double bond of 26a–c (Schemes 5–7) similar to the

H

MeO

Scheme 7.

X

MeO

X

42

41

M.K. Parai et al. / Tetrahedron 64 (2008) 9962–9976

9965

PBr₃reaction was performed on allylic alcohols 28a–h without

2.6. Reaction of PBr₃on benzo[b]thiepinone and 8-methoxy-

7-OCH₃substituent.

benzo[b]thiepinone derived allylic alcohols

This reaction can be thought to proceed via an intermediate 32

formed during the reaction of 28a–h with PBr₃followed by elimi-

nation of HBr. The double bond in 28a–h is not similarly polarized

owing to absence of 7-OCH₃as it was observed in 26a–c (Scheme 7).

Moreover, the tendency of leaving group ability of OPBr₂and the

ability of accommodating electron cloud in vacant 3d orbital of

sulfur atom in 32 caused the inverse polarization of double bond in

32. This resulted into an additional þve charge on trisubstituted

carbon atom of double bond where nucleophilic addition of bro-

mide anion (path b) can take place or one of the gem-dimethyl

groups can migrate (path a) or the reaction may follow through epi-

sulfonium intermediate^11d–fto furnish 36 (path c) (Scheme 6). Close

inspection of six membered half-chair like transition state⁵of 32

revealed that the nucleophilic approach of bromide ion was

obstructed due to the steric hindrance of one of the gem-dimethyl

groups at pseudoaxial (a´) position. Thus the reaction followed path

We became interested in executing the reaction of PBr₃on

benzo[b]thiepinone¹²derived allylic alcohols without gem-di-

methyl substituents. On treatment with PBr₃, 45–47 furnished

bromo derivative 48–50. Reaction of 45 with PBr₃gave a twist-

chair¹³like intermediate 51 with elimination of HBr. Nucleophilic

addition of bromide anion and migration of double bond gave 49.

R⁴

Br

R⁴

HO

R¹

S

48; R¹=H, R⁴=C₆H₄-(4-F)

PBr₃

0 °C

R⁴

R¹

S

Br

´

a and migratory aptitude of a-methyl prevailed over nucleophilic

45; R¹=H, R⁴=C₆H₄-(4-F)

attack of bromide ion and afforded 33. Moreover, the driving force

of migration of one of the gem-dimethyl groups is the formation of

sulfonium ion due to the lone pair participation of sulfur atom in

the stabilization of an intermediate positive charge on carbon

atom bearing methyl group in 34. Further, 33 with methyl at

equatorial rearranged to 34 with methyl at axial due to the exis-

46; R¹=OCH₃, R⁴=C₆H₄-(3-OCH₃)

47; R¹=OCH₃, R⁴=C₆H₅

R¹

S

49; R¹=OCH₃, R⁴=C₆H₄-(3-OCH₃)

50; R¹=OCH₃, R⁴=C₆H₅

Scheme 8.

tence of severe 1,3-allylic strain (A^{1,3 10,11}

between equatorial-

)

methyl and R⁴in 33. Compound 34 got deprotonated to furnish 35,

which again rearranged for an extended double bond de-

localization in presence of acidic medium (PBr₃/benzene) to furnish

29a–h. The possibility of formation of 36 has been ruled out from

the incisive analysis of COSY, NOESY and HMBC spectra of the

rearranged product (Fig. 1).

F

Br^-

F

b

PBr₃

-HBr

HO

S

Br₂PO

δ-

δ+

51

S

F

45

Path b: Nucleophilic addition

45

of bromide anion

7'

5'

O

4'

-POBr₂

H

6'

8'

H

S

3'

H

9'

1'

H

2'

H

5

8

4

H

10

9

3

S

6

7

10'

S

H

2

) (

H

Br

S

A1,3

11'

F

1

Br

F

H

52

48

Figure 1. HMBC correlation of compound 29b.

F

2.5. Plausible reaction mechanism for the formation of

saturated carbonyls and exocyclic oleﬁns from allylic alcohols

containing 7-methoxy and 2,2-dimethyl substituents

Br

S

Based on the preliminary published results,⁶a probable mech-

anism was proposed where addition of HBr was shown on the

double bond. It has been now observed from the detailed results

furnished above that 7-methoxy substituent plays an important

role towards the transformation of allylic alcohols to saturated

carbonyls or exocyclic oleﬁns or other rearranged products. Thus

a revised mechanism is discussed where role of 7-methoxy is

explained.

Treatment of 37 with PBr₃furnished 38 with formation of HBr.

The double bond in 38 got protonated due to the extended conju-

gation of 7-methoxy in aromatic ring giving rise to a quinonoid

structure like 39. In the presence of electronegative substituents in

R₄, H_aproton is more acidic and thus bromide anion in the solution

abstracts it giving rise to 40, which on hydrolysis furnished satu-

rated carbonyl 41. On the other hand, in presence of electron-

donating substituents in R₄, acidity of proton H_ais reduced and thus

bromide anion attacks POBr₂group resulting into formation of

POBr₃and exocyclic oleﬁn 44.

48

R

HO

Br₂PO

Br^-

PBr₃

-HBr

H₃CO

S

H₃CO

S

R=H, 46

R=OMe, 47

53

R

Br

H₃CO

S

H₃CO

S

R=H, 49

R=OMe,50

54

Scheme 9.

9966

M.K. Parai et al. / Tetrahedron 64 (2008) 9962–9976

H_a

Table 5

H_a

HO

δ⁺

R⁴

δ^-

Ph₃P

O

Formation of bromo derivatives 48–50 from alcohols 45–47

PPh₃/I₂

Entry

Alcohol

R¹, R⁴

Product

Yield (%)

H

I

1

2

3

45

46

47

H, C₆H₄-(4-F)

OCH₃, C₆H₄-(3-OCH₃)

OCH₃, C₆H₅

48

49

50

51

53

57

MeO

O

MeO

O

56

1u

R⁴= C₆H₅-(4-Cl)

more acidic

On the other hand, allylic alcohols 46 and 47 with 7-methoxy

substituent afforded bromide 54 through migration of double bond

and elimination of POBr₂. Isomerization of exocyclic double bond to

endocyclic leads to 49 and 50 perhaps due to A^1,3strain^10,11and

increased electron density on R⁴from þR effect of 8-methoxy of 54

(Schemes 8 and 9 and Table 5).

I

H_a

R⁴

H_a

Ph₃P

O

R⁴

Ph₃P

O

H

-H_aI

R⁴

MeO

O

MeO

O

57

( R⁴:with -R effect)

58

2.7. Plausible reaction mechanism

O

R⁴

O

Ph₃P

H

See Scheme 9.

Hydrolysis

MeO

O

MeO

O

2.8. Reaction of PBr₃on benzo[b]oxepinone derived

2u

59

allylic alcohols

Scheme 12.

Similar reaction of PBr₃on allylic alcohols 54 derived from

benzo[b]oxepinone¹²gave non-characterizable products and allylic

alcohols 55 was also unstable, Scheme 10.

2.10. Reaction of PBr₃on tetralone and 6-methoxytetralone

derived allylic alcohols

R

HO

Further to elaborate the reaction of PBr₃on allylic alcohols, we

became interested to decrease the polarizability of the un-

symmetrically substituted double bond by replacing the hetero-

atom of the ring with the carbon atom. Surprisingly the allylic

alcohols 60a–g rearranged to the 1-arylmethylnaphthalenes 62a–g

via aromatization of ring B (Scheme 13).¹⁴

PBr₃

Non-characterizable

products

O

55

Unstable

Scheme 10.

R⁴

2.9. Reaction of allylic alcohols with other reagents based

on phosphorous

HO

R⁴

PBr₃

0 °C

R¹

The allylic alcohols were also treated with other phosphorous

derived reagents to study their properties. Towards this objective,

alcohols 1u and 22 was reacted with triphenyl phosphine, combi-

nation of triphenyl phosphine and iodine and triphenylphosphi-

nedibromide in THF as solvent. On treatment with PPh₃/I₂and

PPh₃Br₂1u containing 7-methoxy gave saturated carbonyl 2u. On

reaction with PPh₃/I₂and PPh₃Br₂alcohol 22 without 7-methoxy

gave inseparable mixture of products. The alcohols 1u and 22 were

intact on treatment of PPh₃on them, Scheme 11.

R¹

62a-g, R¹= OCH₃

63, R¹= H

60a-g, R¹= OCH₃

61 R¹= H

Scheme 13.

In conclusion, we have demonstrated the effect of R¹and R⁴and

heteroatom substituent on polarization of the double bond in allylic

alcohols A (abstract) leading to the formation of saturated ketones,

exocyclic oleﬁns, methyl migrated products 29a–h, bromo de-

rivatives 48–50 and 1-arylmethylnaphthalenes 62a–g and 63. The

chromene containing allylic alcohols having high electron-donating

substituent at R¹and R⁴furnished exocyclic oleﬁns. While saturated

carbonyls are obtained when high electron-withdrawing sub-

stituent at R¹and R⁴are present in the allylic alcohols containing

chromene ring. The thiochromene containing allylic alcohols 26a–c

having OCH₃at R¹and electron-withdrawing substituent at R⁴

furnished saturated carbonyls 27a–c. When electron-donating

group (OCH₃) is absent at R¹like in 28a–h, the reaction involves

a sequence of rearrangement reactions.

PPh₃

No reaction (R¹=OCH₃, H)

Cl

O

HO

PPh₃,I₂

R¹

+ Inseparable

mixtures (R¹=H)

R¹

O

2u;R¹=OCH₃, 63%

1u;R¹=OCH₃

22;R¹=H

PPh₃Br₂

1

Inseparable

+

2u;R =OCH₃,75%

mixtures (R¹=H)

3. Experimental section

3.1. General

Scheme 11.

Reaction may be thought to proceed via an intermediate 56

formed from the reaction of 1u with PPh₃/I₂. The double bond in

56 gets protonated due to the presence of 7-methoxy to furnish 57.

Finally abstraction of proton by iodide and followed by hydrolysis

furnished saturated carbonyl 2u, Scheme 12.

All melting points were recorded in open capillaries on Remi

MP-1, 4/98 melting point apparatus and were uncorrected. IR

spectra were recorded on a Perkin–Elmer RX₁and FTIR 8201 PC

Shimadzu spectrophotometers and values are expressed in cm^ꢀ1

.

M.K. Parai et al. / Tetrahedron 64 (2008) 9962–9976

9967

Solid samples were recorded as KBr wafers and liquid samples as

their ﬁlm between NaCl plates. Proton nuclear magnetic resonance

(¹H NMR) and carbon nuclear magnetic resonance (¹³C NMR)

spectra were generally recorded on Advance DPX200 Bruker

200 MHz and Advance DRX200 Bruker 300 MHz spectrometer

unless otherwise mentioned. NMR samples were generally made in

NMR (200 MHz, CDCl₃):

d

7.33–7.22 (m, 5H, ArH), 6.82 (d, 1H,

J¼8.5 Hz, ArH), 6.29 (d, 1H, J¼2.5 Hz, ArH), 6.17 (dd, 1H, J₁¼8.5 Hz,

J₂¼2.6 Hz, ArH), 5.55 (s, 1H, 3-H), 5.48 (s, 1H, CHOH), 3.58 (s, 3H,

–OCH₃), 2.29 (br s, 1H, CHOH), 1.35 (s, 6H, 2-CH₃). ¹³C NMR (50 MHz,

CDCl₃):

d 160.8, 155.0, 142.0, 133.5, 129.0, 128.4, 127.4, 125.7, 125.2,

113.8, 106.8, 102.6, 73.4, 55.6, 28.2. MS (FAB): m/z (%): 296 (40,

chloroform-d solvent and chemical shifts were reported in d scale in

[M^þ]), 281 (100, [M^þꢀCH₃]), 279 (40, [M^þꢀOH]). Anal. Calcd for

parts per million (ppm) using tetramethylsilane (TMS, Me₄Si) as the

internal standard. FABMS spectra are recorded on JEOL SX 102 Mass

Spectrometer using Argon/Xenon (6 kV, 10 mA) as the FAB gas.

Elemental analyses were performed on Vario EL III and Carlo Erba

1108 CHN Analyzer. All the compounds were dried in abderhalden.

Analytical thin layer chromatography (TLC) was carried out on

(10 cmꢂ5 cm) glass plates coated with Merck’s silica gel G or GF₂₅₄

(containing 13% calcium sulfate as binder) or Merck’s aluminium

oxide 60 GF₂₅₄neutral or 60 HF₂₅₄basic.

C₁₉H₂₀O₃: C, 77.00; H, 6.80. Found C, 77.11; H, 6.86.

3.2.5. (7-Methoxy-2,2-dimethyl-2H-chromen-4-yl)-(2-methoxy-

phenyl)-methanol 1e

Yield¼64% as a yellowoil; R_f¼0.5 (15% ethyl acetate in hexane). IR

(Neat): 3473, 2972, 1612, 1499, 1282, 1245, 1146, 759 cm^ꢀ1. ¹H NMR

(200 MHz, CDCl₃): d 7.16–7.11 (m, 2H, ArH), 6.83–6.75 (m, 3H, ArH),

6.31 (d, 1H, J¼2.5 Hz, ArH), 6.20 (dd, 1H, J₁¼8.5 Hz, J₂¼2.5 Hz, ArH),

5.91 (s, 1H, 3-H), 5.59 (s, 1H, CHOH), 3.80 (s, 3H, OCH₃), 3.62 (s, 3H,

OCH₃), 2.85 (br s, 1H, CHOH), 1.37 (s, 6H, 2-CH₃). ¹³C NMR (50 MHz,

3.2. General procedure to prepare allylic alcohols

CDCl₃): d 160.7, 157.4, 154.7, 132.6, 130.0, 129.6, 128.4, 125.1, 121.3,

114.4,111.0,106.8,102.5, 76.8, 67.3, 55.9, 55.6, 28.2. MS(FAB): m/z (%):

326 (30, [M^þ]), 311 (100, [M^þꢀCH₃]), 309 (40, [M^þꢀOH]). Anal. Calcd

for C₂₀H₂₂O₄: C, 73.60; H, 6.79. Found: C, 73.67; H, 6.74.

The alcohols were prepared from their corresponding chroma-

none, thiochromanone, benzo[b]thiepinone and tetralone de-

rivatives via a two-step reaction sequence as reported earlier.⁶

3.2.6. (7-Methoxy-2,2-dimethyl-2H-chromen-4-yl)-(3-methoxy-

phenyl)-methanol 1f

3.2.1. (4-Fluoro-phenyl)-(7-methoxy-2,2-dimethyl-2H-chromen-

4-yl)-methanol 1a

Yield¼65% as a yellow oil; R_f¼0.5 (15% ethyl acetate in hexane).

Yield¼51% as yellow semi solid. IR (Neat): 3420, 1612, 1506,

IR (Neat): 3434, 2970, 1610, 1270, 1147, 1040, 768 cm^ꢀ^{1 1}H NMR

.

1277, 1223, 1147, 836, 758 cm^ꢀ1. ¹H NMR (200 MHz, CDCl₃):

d

7.34–

(200 MHz, CDCl₃):

d

7.13 (t, 1H, J¼8.4 Hz, ArH), 7.08–6.80 (m, 3H,

7.27 (m, 2H, ArH), 6.93–6.89 (m, 2H, ArH), 6.80 (d, 1H, J¼8.5 Hz,

ArH), 6.31 (d, 1H, J¼2.5 Hz, ArH), 6.20 (dd, 1H, J₁¼8.5 Hz, J₂¼2.5 Hz,

ArH), 5.57 (s, 1H, 3-H), 5.52 (s, 1H, CHOH), 3.63 (s, 3H, OCH₃), 2.24

(br s, 1H, CHOH), 1.37 (s, 6H, 2-CH₃). ¹³C NMR (50 MHz, CDCl₃):

ArH), 6.71–6.67 (m, 1H, ArH), 6.27 (d, 1H, J¼2.5 Hz, ArH), 6.16 (dd,

1H, J₁¼8.5 Hz, J₂¼2.5 Hz, ArH), 5.54 (s, 1H, 3-H), 5.42 (s, 1H, CHOH),

3.65 (s, 3H, OCH₃), 3.57 (s, 3H, OCH₃), 2.62 (br s, 1H, CHOH), 1.34 (s,

6H, 2-CH₃). ¹³C NMR (50 MHz, CDCl₃):

d 160.8, 160.2, 154.9, 143.8,

d

160.9, 155.0, 137.8, 133.5, 129.2, 125.8, 125.2, 116.1, 115.7, 113.6,

133.9, 133.5, 130.0, 125.7, 125.4, 119.8, 113.7, 113.0, 106.8, 102.7, 76.6,

73.2, 55.5, 28.2. MS (FAB): m/z (%): 326 (20, [M^þ]), 311 (100,

[M^þꢀCH₃]), 309 (35, [M^þꢀOH]). Anal. Calcd for C₂₀H₂₂O₄: C, 73.60;

H, 6.79. Found: C, 73.47; H, 6.69.

106.0, 102.8, 76.6, 72.7, 55.6, 28.2. MS (FAB): m/z (%): 314 (40, [M^þ]),

299 (100, [M^þꢀCH₃]), 297 (30, [M^þꢀOH]). Anal. Calcd for

C

₁₉H₁₉FO₃: C, 72.60; H, 6.09. Found: C, 72.69; H, 6.17.

3.2.2. (7-Methoxy-2,2-dimethyl-2H-chromen-4-yl)-(4-methoxy-

phenyl)-methanol 1b

3.2.7. (2,4-Dimethoxy-phenyl)-(7-methoxy-2,2-dimethyl-2H-

chromene-4-yl)-methanol 1g

Yield¼70% as yellow oil; R_f¼0.5 (15% ethyl acetate in hexane). IR

Yield¼64% as a light yellow semi-solid, R_f¼0.4 (15% ethyl acetate

(Neat): 3420, 2974, 1612, 1507, 1249, 1169, 1146, 1030, 754 cm^ꢀ1. ¹H

in hexane). IR (Neat): 3422, 2929,1611,1151,1043, 792 cm^ꢀ1.¹H NMR

NMR (200 MHz, CDCl₃):

d

7.32 (d, 2H, J¼8.6 Hz, ArH), 6.89–6.83 (m,

(200 MHz, CDCl₃):

d

7.09 (d,1H, J¼8.5 Hz, ArH), 6.84 (d,1H, J¼8.5 Hz,

3H, ArH), 6.38 (d, 1H, J¼2.5 Hz, ArH), 6.27 (dd, 1H, J₁¼8.5 Hz,

J₂¼2.5 Hz, ArH), 5.70 (s, 1H, 3-H), 5.56 (s, 1H, CHOH), 3.76 (s, 3H,

ArH), 6.49–6.29 (m, 4H, ArH), 5.93 (s, 1H, 3-H), 5.74 (s, 1H, CHOH),

3.87 (s, 3H, OCH₃), 3.74 (s, 3H, OCH₃), 3.71 (s, 3H, OCH₃), 2.59 (br s,1H,

OCH₃), 3.70(s, 3H, OCH₃), 2.35(brs,1H, CHOH),1.46(s, 6H, 2-CH₃).¹³

C

CHOH), 1.46 (s, 6H, 2-CH₃). ¹³C NMR (50 MHz, CDCl₃):

d 161.0, 160.6,

NMR (50 MHz, CDCl₃):

d

160.7,159.6,154.9,134.5,133.7,128.8,125.3,

158.5,154.7,132.8,129.1,125.1,124.8,122.9,144.4,106.8,104.8,102.5,

99.0, 76.8, 66.7, 55.9, 55.7, 55.5, 28.5, 28.3. MS (FAB): m/z (%): 356 (25,

[M^þ]), 341 (100, [M^þꢀCH₃]), 339 (90, [M^þꢀOH]). Anal. Calcd for

125.2,114.4,114.1,106.8,102.7, 76.7, 72.6, 55.5, 28.2. MASS (FAB): m/z

(%): 326 (50, [M^þ]), 311 (100, [M^þꢀCH₃]), 309 (55, [M^þꢀOH]). Anal.

Calcd for C₂₀H₂₂O₄: C, 73.60; H, 6.79. Found: C, 73.75; H, 6.67.

C

₂₁H₂₄O₅: C, 70.77; H, 6.79. Found: C, 70.89; H, 6.84.

3.2.3. (1-Benzyl-1H-indol-3-yl)-(7-methoxy-2,2-dimethyl-2H-

chromen-4-yl)-methanol 1c

3.2.8. (7-Methoxy-2,2-dimethyl-2H-chromene-4-yl)-(2,4,6-

trimethoxy-phenyl)-methanol 1h

Yield¼50% as yellow oil; R_f¼0.4 (15% ethyl acetate in hexane). IR

Yield¼63% as light yellow semi solid; R_f¼0.4 (20% ethyl acetate

(Neat): 3435, 1619, 1507, 1267, 1229, 1143, 757 cm^ꢀ^{1 1}H NMR

.

in hexane). IR (Neat): 3551, 3013, 1611, 1217, 1147, 761 cm^ꢀ1. ¹H NMR

(200 MHz, CDCl₃):

d

7.58 (d,1H, J¼7.9 Hz, ArH), 7.49 (d,1H, J¼8.8 Hz,

(200 MHz, CDCl₃):

d

7.48 (d, 1H, J¼8.4 Hz, ArH), 6.46–6.37 (m, 2H,

ArH), 7.24–6.84 (m, 7H, ArH), 6.94–5.77 (m, 4H, ArH, CHOH, 3-H),

5.20 (s, 2H, CH₂C₆H₅), 3.68 (s, 3H, OCH₃), 2.19 (br s, 1H, CHOH), 1.39

ArH), 6.15 (s, 2H, ArH), 6.05 (s, 1H, 3-H), 5.15 (s, 1H, CHOH), 3.81 (s,

3H, OCH₃), 3.79 (s, 3H, OCH₃), 3.76 (s, 3H, OCH₃), 3.73 (s, 3H, OCH₃),

(s, 6H, 2-CH₃). ¹³C NMR (50 MHz, CDCl₃):

d

160.6, 155.0, 137.8, 137.3,

1.35 (d, 6H, J¼5.6 Hz, 2-CH₃). ¹³C NMR (50 MHz, CDCl₃):

d 161.1,

131.5,129.1,128.6,127.6,126.5,125.6,125.5,122.1,120.6,119.9,115.4,

110.2,106.7,102.4, 76.8, 73.1, 71.6, 55.5, 50.4, 28.3. MS (FAB): m/z (%):

425 (70, [M^þ]), 408 (100, [M^þꢀOH]). Anal. Calcd for C₂₈H₂₇NO₃: C,

79.03; H, 6.40; N, 3.29. Found: C, 78.96; H, 6.38; N, 3.36.

160.5, 159.2, 154.8, 133.0, 125.8, 124.4, 115.2, 110.5, 106.7, 102.4, 91.7,

76.5, 65.9, 56.1, 55.7, 28.2. MS (FAB): m/z (%): 386 (50, [M^þ]), 371

(100, [M^þꢀCH₃]), 369 (40, [M^þꢀOH]). Anal. Calcd for C₂₂H₂₆O₆: C,

68.38; H, 6.78. Found: C, 68.29; H, 6.85.

3.2.4. (7-Methoxy-2,2-dimethyl-2H-chromen-4-yl)-phenyl-

methanol 1d

3.2.9. (7-Methoxy-2,2-dimethyl-2H-chromen-4-yl)-

thiophen-2-yl-methanol 1i

Yield¼70% as yellow semi solid; R_f¼0.6 (15% ethyl acetate in

Yield¼54% as a dark yellow oil; R_f¼0.5 (15% ethyl acetate in

hexane). IR (Neat): 3429, 2973, 1614, 1502, 1277, 1146, 758 cm^ꢀ1. ¹H

hexane). IR (Neat): 3439, 2975, 1614, 1503, 1276, 1196, 1069,

9968

M.K. Parai et al. / Tetrahedron 64 (2008) 9962–9976

762 cm^ꢀ1

.

¹H NMR (200 MHz, CDCl₃):

d

7.25 (dd, 1H, J₁¼4.7 Hz,

(200 MHz, CDCl₃):

d

8.34 (s, 1H, ArH), 8.10 (d, 1H, J¼1 Hz, ArH), 7.75

J₂¼1.0 Hz, ArH), 7.02–6.91 (m, 3H, ArH), 6.39 (d, 1H, J¼2.5 Hz, ArH),

6.31 (dd, 1H, J₁¼8.5 Hz, J₂¼2.5 Hz, ArH), 5.82 (s, 1H, 3-H), 5.78 (s, 1H,

CHOH), 3.71 (s, 3H, OCH₃), 2.35 (br s, 1H, CHOH), 1.46 (s, 6H, 2-CH₃).

(d,1H, J¼7.6 Hz, ArH), 7.51 (t,1H, J¼7.9 Hz, ArH), 6.95 (d,1H, J¼8.5 Hz,

ArH), 6.39 (d, 1H, J¼2.5 Hz, ArH), 6.30 (dd, 1H, J₁¼8.5 Hz, J₂¼2.5 Hz,

ArH), 5.70 (s,1H, 3-H), 5.62 (s,1H, CHOH), 3.72 (s, 3H, OCH₃), 2.42 (br

¹³C NMR (50 MHz, CDCl₃):

d

160.9, 154.9, 146.6, 133.7, 127.3, 126.0,

s, 1H, CHOH), 1.46 (s, 6H, 2-CH₃). ¹³C NMR (50 MHz, CDCl₃):

d 161.2,

125.0, 113.6, 107.0, 102.7, 76.7, 71.2, 69.0, 55.6, 28.2. MS (FAB): m/z

(%): 302 (40, [M^þ]), 287 (100, [M^þꢀCH₃]), 285 (60, [M^þꢀOH]). Anal.

Calcd for C₁₇H₁₈O₃S: C, 67.52; H, 6.00. Found: C, 67.46; H, 6.09.

155.2, 148.8, 144.2, 133.2, 129.8, 127.1, 125.2, 123.1, 122.2,113.0, 107.1,

103.0, 76.5, 73.0, 55.6, 28.1. MS (FAB): m/z (%): 341 (45, [M^þ]), 326

(100, [M^þꢀCH₃]), 324 (20, [M^þꢀOH]). Anal. Calcd for C₁₉H₁₉NO₅: C,

66.85; H, 5.61; N, 4.10. Found: C, 66.81; H, 5.68; N, 4.07.

3.2.10. Furan-2-yl-(7-methoxy-2,2-dimethyl-2H-chromen-4-yl)-

methanol 1j

3.2.15. 4-[Hydroxy-(7-methoxy-2,2-dimethyl-2H-chromen-4-yl)-

methyl]-benzonitrile 1o

Yield¼58% as a dark yellow oil; R_f¼0.5 (15% ethyl acetate in

hexane). IR (Neat): 3434, 2974, 1614, 1503, 1276, 1145, 746 cm^ꢀ1. ¹H

Yield¼55% as a yellowoil; R_f¼0.5 (20% ethyl acetate in hexane). IR

NMR (200 MHz, CDCl₃):

d

7.30 (s, 1H, ArH), 6.87 (d, 1H, J¼8.4 Hz,

(Neat): 3450, 2969, 1613, 1503, 1277, 1199, 1146, 760 cm^ꢀ1. ¹H NMR

ArH), 6.33–6.20 (m, 3H, ArH), 6.12 (d, 1H, J¼3.2 Hz, ArH), 5.63 (s, 1H,

3-H), 5.59 (s, 1H, CHOH), 3.65 (s, 3H, OCH₃), 2.48 (br s, 1H, CHOH),

(200 MHz, CDCl₃):

d

7.52 (d, 2H, J¼8.2 Hz, ArH), 7.46 (d, 2H, J¼8.2 Hz,

ArH), 6.84 (d,1H, J¼8.5 Hz, ArH), 6.30 (d,1H, J¼2.4 Hz, ArH), 6.21 (dd,

1H, J₁¼8.5 Hz, J₂¼2.5 Hz, ArH), 5.54 (s, 1H, 3-H), 5.46 (s, 1H, CHOH),

3.63 (s, 3H, OCH₃), 1.35 (s, 6H, 2-CH₃). ¹³C NMR (50 MHz, CDCl₃):

1.36 (s, 6H, 2-CH₃). ¹³C NMR (50 MHz, CDCl₃):

d 160.9, 155.1, 154.8,

142.8, 131.1, 125.5, 124.7, 113.8, 110.8, 108.2, 106.9, 102.7, 76.6, 66.9,

55.6, 28.1. MS (FAB): m/z (%): 286 (50, [M^þ]), 271 (100, [M^þꢀCH₃]),

269 (70, [M^þꢀOH]). Anal. Calcd for C₁₇H₁₈O₄: C, 71.31; H, 6.34.

Found: C, 71.40; H, 6.31.

d

161.1, 155.1, 147.5, 133.2, 132.7, 127.8, 127.1, 125.3, 119.1, 113.2, 111.7,

107.0, 102.9, 76.5, 73.2, 55.6, 28.0. MS (FAB): m/z (%): 321 (50, [M^þ]),

306 (100, [M^þꢀCH₃]), 304 (20, [M^þꢀOH]). Anal. Calcd for

C

₂₀H₁₉NO₃:C, 74.75;H, 5.96;N, 4.36. Found:C, 74.81;H, 5.93;N, 4.42.

3.2.11. 1-(7-Methoxy-2,2-dimethyl-2H-chromen-4-yl)-3-phenyl-

prop-2-en-1-ol 1k

3.2.16. (4-Isopropyl-phenyl)-(7-methoxy-2,2-dimethyl-2H-

chromen-4-yl)-methanol 1p

Yield¼52% as a yellow oil; R_f¼0.6 (15% ethyl acetate in hexane).

IR (Neat): 3430, 2928, 1612, 1277, 1146, 758 cm^ꢀ1

.

¹H NMR

Yield¼65% as a yellow oil; R_f¼0.6 (15% ethyl acetate in hexane).

(200 MHz, CDCl₃):

d

7.40–7.24 (m, 6H, ArH), 6.72 (d, 1H, J¼15.9 Hz,

IR (Neat): 3436, 2964, 1614, 1504, 1277, 1198, 1146, 1069, 758 cm^ꢀ1

.

CH]CHC₆H₅), 6.44–6.37 (m, 3H, ArH, CH]CHC₆H₅), 5.64 (s, 1H,

3-H), 5.23 (d, 1H, J¼5.9 Hz, CHOH), 3.74 (s, 3H, OCH₃), 2.19 (br s, 1H,

¹H NMR (200 MHz, CDCl₃):

d

7.35 (d, 2H, J¼8.1 Hz, ArH), 7.25–7.15

(m, 2H, ArH), 6.92 (d, 1H, J¼8.5 Hz, ArH), 6.39 (d, 1H, J¼2.5 Hz, ArH),

6.29 (dd,1H, J₁¼8.5 Hz, J₂¼2.5 Hz, ArH), 5.72 (s, 1H, 3-H), 5.60 (s, 1H,

CHOH), 3.71 (s, 3H, OCH₃), 2.88 {sept, 1H, CH(CH₃)₂}, 2.12 (br s, 1H,

CHOH), 1.47 (s, 6H, 2-CH₃), 1.23 {d, 6H, J¼6.9 Hz, CH(CH₃)₂}. ¹³C

CHOH), 1.42 (s, 6H, 2-CH₃). ¹³C NMR (50 MHz, CDCl₃):

d 161.0, 155.0,

136.9,133.5,132.1,130.4,128.9,128.2,127.0,125.2,125.1,113.9,107.0,

102.8, 76.6, 71.8, 55.6, 28.1. MS (FAB): m/z (%): 322 (30, [M^þ]), 307

(100, [M^þꢀCH₃]), 305 (95, [M^þꢀOH]). Anal. Calcd for C₂₁H₂₂O₃: C,

78.23; H, 6.88. Found: C, 78.34; H, 6.81.

NMR (50 MHz, CDCl₃): d 160.8, 154.9, 149.1, 139.4, 133.5, 127.4, 127.1,

125.3, 113.9, 106.8, 102.6, 73.1, 55.5, 34.2, 28.3, 24.3. MS (FAB): m/z

(%): 338 (20, [M^þ]), 323 (100, [M^þꢀCH₃]), 321 (30, [M^þꢀOH]). Anal.

Calcd for C₂₂H₂₆O₃: C, 78.07; H, 7.74. Found: C, 78.12; H, 7.71.

3.2.12. (4-Dimethylamino-phenyl)-(7-methoxy-2,2-dimethyl-

2H-chromen-4-yl)-methanol 1l

Yield¼59% as yellow solid; mp 90 ^ꢁC (dichloromethane); R_f¼0.4

3.2.17. (7-Methoxy-2,2-dimethyl-2H-chromen-4-yl)-naphthalen-

1-yl-methanol 1q

(15% ethyl acetate in hexane). IR (KBr): 2429, 2972, 1613, 1521, 1146,

757 cm^ꢀ1. ¹H NMR (200 MHz, CDCl₃):

d

7.20 (d, 2H, J¼8.8 Hz, ArH),

Yield¼54% as a yellow oil; R_f¼0.6 (15% ethyl acetate in hexane).

6.80 (d, 1H, J¼8.5 Hz, ArH), 6.61 (d, 2H, J¼8.8 Hz, ArH), 6.30 (d, 1H,

J¼2.5 Hz, ArH), 6.20 (dd, 1H, J₁¼8.5 Hz, J₂¼2.5 Hz, ArH), 5.69 (s, 1H,

3-H), 5.47 (s, 1H, CHOH), 3.63 (s, 3H, OCH₃), 2.86 {s, 6H, N(CH₃)₂},

1.38 (s, 3H, 2-CH₃), 1.18 (s, 3H, 2-CH₃). ¹³C NMR (50 MHz, CDCl₃):

IR (Neat): 3434, 2958, 1614, 1277, 1210, 1145, 1068, 759 cm^ꢀ^{1 1}H

.

NMR (200 MHz, CDCl₃):

d 8.45–8.36 (m, 1H, ArH), 8.04 (d, 1H,

J¼8.2 Hz, ArH), 7.91–7.81 (m, 2H, ArH), 7.58–7.45 (m, 3H, ArH), 6.96

(d, 1H, J¼8.2 Hz, ArH), 6.45–6.40 (m, 2H, ArH), 5.64 (s, 1H, 3-H), 5.59

(s, 1H, CHOH), 3.76 (s, 3H, OCH₃), 2.15 (br s, 1H, CHOH), 1.35 (s, 6H,

2-CH₃). MS (FAB): m/z (%): 346 (30, [M^þ]), 331 (100, [M^þꢀCH₃]),

329 (40, [M^þꢀOH]). Anal. Calcd for C₂₃H₂₂O₃: C, 79.74; H, 6.40.

Found: C, 79.65; H, 6.43.

d

160.8, 154.9, 144.6, 134.7, 129.9, 128.6, 125.2, 124.6, 113.0, 106.8,

102.5, 72.8, 55.5, 40.9, 30.1, 28.3. MS (FAB): m/z (%): 339 (40, [M^þ]),

322 (100, [M^þꢀOH]). Anal. Calcd for C₂₁H₂₅NO₃: C, 74.31; H, 7.42; N,

4.13. Found: C, 74.20; H, 7.45; N, 4.19.

3.2.13. (2-Chloro-phenyl)-(7-methoxy-2,2-dimethyl-2H-chromen-

4-yl)-methanol 1m

3.2.18. 1-(7-Methoxy-2,2-dimethyl-2H-chromen-4-yl)-

propan-1-ol 1r

Yield¼60% as a yellow oil; R_f¼0.4 (15% ethyl acetate in hexane).

Yield¼66% as a yellow oil; R_f¼0.5 (10% ethyl acetate in hexane).

IR (Neat): 3434, 2969, 1614, 1503, 1276, 1199, 1146, 759 cm^ꢀ1

.

¹H

IR (Neat): 3467, 2968, 1613, 1503, 1276, 1146, 758 cm^ꢀ^{1 1}H NMR

.

NMR (200 MHz, CDCl₃):

d

7.39–7.29 (m, 2H, ArH), 7.17–7.12 (m, 2H,

(200 MHz, CDCl₃):

d

7.05 (d, 1H, J¼8.7 Hz, ArH), 6.34–6.26 (m, 2H,

ArH), 6.83 (d, 1H, J¼8.5 Hz, ArH), 6.33–6.23 (m, 2H, ArH), 5.99 (s, 1H,

ArH), 5.61 (s, 1H, 3-H), 4.86 (s, 1H, CHOH), 3.67 (s, 3H, OCH₃), 2.02–

1.95 (m, 2H, CH₂CH₃), 1.69 (br s, 1H, CHOH), 1.36 (s, 6H, 2-CH₃), 0.89

3-H), 5.46 (s, 1H, CHOH), 3.64 (s, 3H, OCH₃), 2.36 (br s, 1H, CHOH),

1.34 (s, 6H, 2-CH₃). ¹³C NMR (50 MHz, CDCl₃):

d

160.9, 154.9, 139.3,

(t, 3H, J¼7.5 Hz, CH₂CH₃). ¹³C NMR (50 MHz, CDCl₃):

d 160.7, 154.8,

133.9, 132.5, 130.0, 129.7, 128.8, 127.6, 125.8, 124.6, 113.9, 107.0,

102.8, 76.9, 68.9, 55.6, 28.1. MS (FAB): m/z (%): 330 (20, [M^þ]), 315

(100, [M^þꢀCH₃]), 313 (15, [M^þꢀOH]). Anal. Calcd for C₁₉H₁₉ClO₃: C,

68.98; H, 5.79. Found: C, 69.11; H, 5.76.

135.0, 132.1, 131.3, 124.9, 114.2, 106.7, 102.5, 76.0, 55.6, 28.2, 21.5,

12.4. MS (FAB): m/z (%): 248 (50, [M^þ]), 233 (100, [M^þꢀCH₃]), 231

(25, [M^þꢀOH]). Anal. Calcd for C₁₅H₂₀O₃: C, 72.55; H, 8.12. Found: C,

72.62; H, 8.19.

3.2.14. (7-Methoxy-2,2-dimethyl-2H-chromen-4-yl)-

(3-nitro-phenyl)-methanol 1n

3.2.19. 1-(7-Methoxy-2,2-dimethyl-2H-chromen-4-yl)-

butan-1-ol 1s

Yield¼53% as a dark yellow oil; R_f¼0.5 (25% ethyl acetate in

Yield¼64% as a yellow oil; R_f¼0.5 (10% ethyl acetate in hexane).

hexane). IR (Neat): 3453, 1613, 1530, 1351, 1146, 759 cm^ꢀ1. ¹H NMR

IR (Neat): 3487, 2965, 1613, 1503, 1272, 1199, 1159, 1127, 758 cm^ꢀ1

.

M.K. Parai et al. / Tetrahedron 64 (2008) 9962–9976

9969

¹H NMR (200 MHz, CDCl₃):

d

7.17 (d, 1H, J¼9.2 Hz, ArH), 6.45–6.40

(200 MHz, CDCl₃):

d

7.64 (d, 1H, J¼8.2 Hz, ArH), 6.45–6.39 (m, 2H,

(m, 2H, ArH), 5.54 (s, 1H, 3-H), 4.61–4.55 (m, 1H, CHOH), 3.75 (s, 3H,

OCH₃), 1.96 (br s, 1H, CHOH), 1.71–1.63 (m, 2H, CH₂CH₂CH₃), 1.53–

1.44 (m, 2H, CH₂CH₂CH₃), 1.39 (d, 6H, J¼4.8 Hz, 2-CH₃), 0.93 (t, 3H,

ArH), 4.93 (t, 1H, J¼7.3 Hz, CHOH), 3.75 (s, 3H, OCH₃), 2.01 (br s, 1H,

CHOH), 1.88–1.84 (m, 2H, CHCH₂CH₂CH₃), 1.81 (s, 3H, ]CCH₃), 1.51–

1.67 (m, 2H, CHCH₂CH₂CH₃), 1.41 {s, 3H, C(CH₃)₂}, 1.27 {s, 3H,

C(CH₃)₂}, 0.90 (t, 3H, J¼7.2 Hz, CHCH₂CH₂CH₃). ¹³C NMR (50 MHz,

J¼7.2 Hz, CH₂CH₂CH₃). ¹³C NMR (50 MHz, CDCl₃):

d 160.8, 155.0,

134.9, 124.4, 123.7, 114.1, 106.9, 102.8, 76.4, 71.0, 55.5, 38.8, 28.2,

28.0, 19.4, 14.0. MS (FAB): m/z (%): 262 (60, [M^þ]), 247 (100,

[M^þꢀCH₃]), 245 (30, [M^þꢀOH]). Anal. Calcd for C₁₆H₂₂O₃: C, 73.25;

H, 8.45. Found: C, 73.13; H, 8.41.

CDCl₃): d 159.8, 154.3, 132.6, 128.6, 126.3, 115.4, 106.7, 102.7, 78.7,

55.5, 28.2, 26.0, 25.0, 19.9, 14.4. MS (FAB): m/z (%): 276 (80, [M^þ]),

261 (100, [M^þꢀCH₃]), 259 (20, [M^þꢀOH]). Anal. Calcd for

C₂₀H₂₁FO₃: C, 73.15; H, 6.45. Found: C, 73.12; H, 6.48.

3.2.20. 1-(7-Methoxy-2,2-dimethyl-2H-chromen-4-yl)-

but-2-en-1-ol 1t

3.2.25. (4-Chloro-phenyl)-(7-methoxy-2,2,3-trimethyl-2H-

chromen-4-yl)-methanol 14e

Yield¼65% as a yellow oil; R_f¼0.6 (15% ethyl acetate in hexane).

Yield¼66% as a white solid; mp 130 ^ꢁC (dichloromethane);

R_f¼0.4 (10% ethyl acetate in hexane). IR (Neat): 3465, 2978, 1611,

IR (Neat): 3455, 2974, 1613, 1503, 1276, 1199, 1147, 758 cm^ꢀ^{1 1}H

.

NMR (200 MHz, CDCl₃):

d

7.19 (d, 2H, J¼9.2 Hz, ArH), 6.44–6.39 (m,

1576, 1501, 1157, 1085, 811 cm^ꢀ1. ¹H NMR (200 MHz, CDCl₃):

d 7.37–

2H, ArH), 5.80–5.60 (m, 2H, CH]CHCH₃), 5.59 (s, 1H, 3-H), 5.01 (d,

1H, J¼6.0 Hz, CHOH), 3.76 (s, 3H, OCH₃), 1.71 (d, 3H, J¼6.0 Hz,

7.25 (m, 4H, ArH), 6.94 (d, 1H, J¼8.6 Hz, ArH), 6.39 (d, 1H, J¼2.5 Hz,

ArH), 6.25 (dd, 1H, J₁¼8.6 Hz, J₂¼2.5 Hz, ArH), 6.00 (s, 1H, CHOH),

3.73 (s, 3H, OCH₃), 2.37 (br s,1H, CHOH),1.85 (s, 3H, ]CCH₃),1.46 {s,

3H, C(CH₃)₂}, 1.41 {s, 3H, C(CH₃)₂}. ¹³C NMR (50 MHz, CDCl₃):

CH]CHCH₃), 1.41 (s, 6H, 2-CH₃). ¹³C NMR (50 MHz, CDCl₃):

d 160.9,

155.0, 133.6, 132.2, 129.1, 125.0, 124.4, 114.0, 106.9, 102.7, 76.5, 71.7,

55.6, 28.2, 18.1. MS (FAB): m/z (%): 260 (30, [M^þ]), 245 (100,

[M^þꢀCH₃]), 243 (30, [M^þꢀOH]). Anal. Calcd for C₁₆H₂₀O₃: C, 73.82;

H, 7.74. Found: C, 73.78; H, 7.67.

d

160.1, 154.5, 141.2, 134.7, 133.1, 128.9, 127.8, 127.2, 126.3, 114.4,

106.9, 102.9, 79.0, 69.9, 55.6, 25.7, 25.2, 14.6. MS (FAB): m/z (%): 344

(90, [M^þ]), 331 (60, [M^þꢀCH₃]), 329 (100, [M^þꢀOH]). Anal. Calcd

for C₂₀H₂₁ClO₃: C, 69.66; H, 6.14. Found: C, 69.57; H, 6.05.

3.2.21. (4-Chloro-phenyl)-(7-methoxy-2,2-dimethyl-2H-

chromen-4-yl)methanol 1u

3.2.26. (4-Methoxy-phenyl)-(7-methoxy-2,2,3-trimethyl-2H-

chromen-4-yl)-methanol 14f

Yield¼60% as yellow oil; R_f¼0.5 (15% ethyl acetate in hexane). IR

(Neat): 3406, 2924, 1593, 1216, 759 cm^ꢀ1

.

¹H NMR (300 MHz,

Yield¼62% as a pale yellow viscous oil; R_f¼0.4 (10% ethyl acetate

CDCl₃):

d

7.37–7.28 (m, 4H, ArH), 6.89 (d, 1H, J¼8.6 Hz, ArH), 6.38 (s,

in hexane). IR (Neat): 3474, 2931, 1599, 1507, 1166, 1020, 831 cm^ꢀ1

.

1H, ArH), 6.31–6.27 (m, 1H, ArH), 5.62 (s, 1H, ArH), 5.58 (s, 1H), 3.71

¹H NMR (200 MHz, CDCl₃):

d

7.33 (d, 2H, J¼8.8 Hz, ArH), 6.98 (d, 1H,

(s, 3H, OCH₃), 2.21 (br s, 1H, OH), 1.45 {s, 6H, (CH₃)₂}. ¹³C NMR

J¼8.6 Hz, ArH), 6.87 (d, 2H, J¼8.8 Hz, ArH), 6.40 (d, 1H, J¼2.5 Hz,

ArH), 6.26 (dd, 1H, J₁¼8.6 Hz, J₂¼2.5 Hz, ArH), 6.01 (s, 1H, CHOH),

3.79 (s, 3H, OCH₃), 2.24 (br s,1H, CHOH),1.86 (s, 3H, ]CCH₃),1.48 {s,

3H, C(CH₃)₂}, 1.42 {s, 3H, C(CH₃)₂}. ¹³C NMR (50 MHz, CDCl₃):

(75 MHz, CDCl₃):

d 160.9, 155.0, 140.5, 134.1, 133.4, 129.2, 128.8,

126.1, 125.2, 113.5, 106.9, 102.8, 76.7, 72.9, 55.6, 28.2, 28.1. MS (FAB):

m/z (%): 331 (30, [M^þþH]). Anal. Calcd for C₁₉H₁₉ClO₃: C, 68.98; H,

5.79. Found: C, 68.91; H, 5.85.

d

160.0, 159.0, 154.5, 134.7, 134.2, 128.0, 127.1, 126.5, 114.7, 114.2,

106.8, 102.8, 79.1, 70.2, 55.6, 25.8, 25.21,14.6. MS (FAB): m/z (%): 340

(50, [M^þ]), 323 (100, [M^þꢀOH]). Anal. Calcd for C₂₁H₂₄O₄: C, 74.09;

H, 7.11. Found: C, 74.22; H, 7.09.

3.2.22. (7-Methoxy-2,2,3-trimethyl-2H-chromen-4-yl)-

phenyl-methanol 14a

Yield¼67% as a white solid; mp 135 ^ꢁC (dichloromethane);

R_f¼0.4 (10% ethyl acetate in hexane). IR (Neat): 3471, 2985, 2362,

1606, 1503, 1361, 1198, 1029, 704 cm^ꢀ1. ¹H NMR (200 MHz, CDCl₃):

3.2.27. (4-Dimethylamino-phenyl)-(7-methoxy-2,2,3-trimethyl-

2H-chromen-4-yl)-methanol 14g

d

7.45–7.25 (m, 5H, ArH), 6.97 (d, 1H, J¼8.6 Hz, ArH), 6.40 (d, 1H,

Yield¼59% as a white solid; mp 142 ^ꢁC (dichloromethane);

R_f¼0.5 (15% ethyl acetate in hexane). IR (KBr): 3444, 2926, 1594,

J¼2.6 Hz, ArH), 6.24 (dd, 1H, J₁¼8.6 Hz, J₂¼2.6 Hz, ArH), 6.06 (s, 1H,

CHOH), 3.69 (s, 3H, OCH₃), 2.27 (br s, 1H, CHOH), 1.87 (s, 3H,

]CCH₃), 1.42 {s, 3H, C(CH₃)₂}, 1.40 {s, 3H, C(CH₃)₂}. ¹³C NMR

1351, 1160, 765 cm^ꢀ^{1 1}H NMR (200 MHz, CDCl₃):

. d 7.27 (d, 1H,

J¼8.4 Hz, ArH), 7.03 (d, 1H, J¼8.6 Hz, ArH), 6.71 (d, 1H, J¼8.8 Hz,

ArH), 6.40 (d, 1H, J¼2.5 Hz, ArH), 6.27 (dd, 1H, J₁¼8.6 Hz, J₂¼2.5 Hz,

ArH), 5.98 (s, 1H, CHOH), 3.70 (s, 3H, OCH₃), 2.92 (s, 6H, N–(CH₃)₂),

(50 MHz, CDCl₃):

d 160.0, 154.5, 142.7, 134.4, 128.8, 128.1, 127.3,

126.4, 125.7, 114.7, 106.8, 102.8, 79.1, 70.4, 55.5, 25.8, 25.2, 14.6. MS

(FAB): m/z (%): 310 (70, [M^þ]), 295 (100, [M^þꢀCH₃]), 293 (50,

[M^þꢀOH]). Anal. Calcd for C₂₀H₂₂O₃: C, 77.39; H, 7.14. Found: C,

77.47; H, 7.17.

1.84 (s, 3H, ]CCH₃), 1.48 {s, 3H, C(CH₃)₂}, 1.40 {s, 3H, C(CH₃)₂}. ¹³

C

NMR (50 MHz, CDCl₃): d 159.9,154.4,150.1,133.9,130.4,128.1,126.9,

126.6, 115.1, 113.0, 106.8, 102.8, 79.1, 70.5, 55.6, 41.0, 30.1, 25.9, 25.1,

14.6. MS (FAB): m/z (%): 354 (100, [M^þ]). Anal. Calcd for C₂₂H₂₇NO₃:

C, 74.76; H, 7.70; N, 3.96. Found: C, 74.70; H, 7.68; N, 4.02.

3.2.23. (3-Methoxy-phenyl)-(7-methoxy-2,2,3-trimethyl-2H-

chromen-4-yl)-methanol 14b

Yield¼60% as a light yellow liquid; R_f¼0.5 (10% ethyl acetate in

3.2.28. (2H-Chromen-4-yl)-(3-methoxy-phenyl)-methanol 18

Yield¼48% as yellow oil; R_f¼0.5 (15% ethyl acetate in hexane).

The compound was not stable and used as such for the next step.

hexane). IR (Neat): 3465, 3013, 1610, 1503, 1263, 1217, 1159,

767 cm^ꢀ^{1 1}H NMR (200 MHz, CDCl₃):

. d 7.25–7.19 (m, 1H, ArH),

7.03–6.90 (m, 3H, ArH), 6.80–6.79 (m, 1H, ArH), 6.39 (d, 1H,

J¼2.5 Hz, ArH), 6.25 (dd, 1H, J₁¼8.6 Hz, J₂¼2.6 Hz, ArH), 6.01 (s, 1H,

CHOH), 3.77 (s, 3H, OCH₃), 3.67 (s, 3H, OCH₃), 1.86 (s, 3H, ]CCH₃),

1.48 {s, 3H, C(CH₃)₂}, 1.41 {s, 3H, C(CH₃)₂}. MS (FAB): m/z (%): 340

(90, [M^þ]), 325 (100, [M^þꢀCH₃]), 323 (60, [M^þꢀOH]). Anal. Calcd

for C₂₁H₂₄O₄: C, 74.09; H, 7.11. Found: C, 74.03; H, 7.07.

3.2.29. (2-Isopropyl-2H-chromen-4-yl)-phenyl-methanol 20a

Yield¼(58%) as a dark yellow viscous oil; R_f¼0.5 (10% ethyl

acetate in hexane). The compound was not stable and used as such

for the next step.

3.2.30. (2-Isopropyl-2H-chromen-4-yl)-(3-methoxy-phenyl)-

methanol 20b

3.2.24. (4-Fluoro-phenyl)-(7-methoxy-2,2,3-trimethyl-2H-

chromen-4-yl)-methanol 14c

Yield¼55% as a dark yellow oil; R_f¼0.6 (15% ethyl acetate in

Yield¼52% as pale yellow oil; R_f¼0.4 (10% ethyl acetate in

hexane). IR (neat): 3438, 1604, 1488, 1217, 766 cm^ꢀ^{1 1}H NMR

.

hexane). IR (Neat): 3453, 2961, 1613, 1503, 1160, 758 cm^ꢀ1. ¹H NMR

(200 MHz, CDCl₃): d 7.30–7.23 (m, 1H, ArH), 7.09–7.01 (m, 4H, ArH),

9970

M.K. Parai et al. / Tetrahedron 64 (2008) 9962–9976

6.85–6.72 (m, 3H, ArH), 5.91 (d, 1H, J¼3.4 Hz, ]CH), 5.66 (s, 1H,

CHOH), 4.67–4.62 {m, 1H, CHCH(CH₃)₂}, 3.78 (s, 3H, OCH₃), 2.15 (br

s, 1H, CHOH), 2.12–2.00 {m, 1H, CH(CH₃)₂}, 1.03 {d, 6H, CH(CH₃)₂}.

MS (FAB): m/z (%): 309 (80, [M^þ]), 293 (100, [M^þꢀOH]), 267 (100,

[M^þꢀCH(CH₃)₂]). Anal. Calcd for C₂₀H₂₂O₃: C, 77.39; H, 7.14. Found:

C, 77.45; H, 7.11.

7.04–6.89 (m, 1H, ArH), 5.94 (s, 1H, ]CH), 5.69 (s, 1H, CHOH), 2.35

(br s, 1H, CHOH), 1.39 {s, 6H, C(CH₃)₂}. ¹³C NMR (50 MHz, CDCl₃):

d

149.2, 145.7, 137.2, 135.6, 134.7, 133.2, 131.1, 131.0, 129.2, 129.3,

126.3, 126.1, 123.8, 123.3, 96.5, 73.0, 40.5, 28.7. MS (FAB): m/z (%):

327 (40, [M^þ]), 312 (100, [M^þꢀCH₃]), 310 (80, [M^þꢀOH]). Anal.

Calcd for C₁₈H₁₇NO₃S: C, 66.03; H, 5.23; N, 4.28. Found: C, 65.91; H,

5.29; N, 4.34.

3.2.31. (4-Chloro-phenyl)-(2,2-dimethylchroman-4-yl)-

methanol 22

3.2.36. (2,2-Dimethyl-2H-thiochromen-4-yl)-(4-methoxy-phenyl)-

methanol 28b

Yield¼67% as yellow oil; R_f¼0.5 (15% ethyl acetate in hexane). IR

(Neat): 3406, 2924, 1593, 1216, 759 cm^ꢀ1

.

¹H NMR (300 MHz,

Yield¼49% as brown viscous oil; R_f¼0.5 (15% ethyl acetate in

CDCl₃):

(m, 1H, ArH), 6.73–6.64 (m, 2H, ArH), 5.67 (s, 1H), 5.54 (s, 1H), 1.37

{s, 6H, (CH₃)₂}. ¹³C NMR (75 MHz, CDCl₃):

151.9, 138.7, 132.5, 131.8,

d 7.29–7.20 (m, 4H, ArH), 6.99–6.93 (m, 1H, ArH), 6.92–6.89

hexane). IR (Neat): 3379, 2923, 2361, 1612, 1352, 770 cm^ꢀ1. ¹H NMR

(200 MHz, CDCl₃):

d

7.24 (d, 2H, J¼8.5 Hz, ArH), 7.16–7.12 (m, 1H,

d

ArH), 7.02–6.90 (m, 3H, ArH), 6.79 (d, 2H, J¼8.6 Hz, ArH), 6.06 (s, 1H,

127.9, 125.6, 127.2, 122.6, 119.3, 118.6, 115.6, 98.7, 74.5, 71.0, 26.5,

26.4. MS (ESI): m/z (%): 325 (100, [M^þþNa]), 285 (30, [M^þꢀOH]).

Anal. Calcd for C₁₈H₁₉ClO₂: C, 71.40; H, 6.32. Found: C, 71.33; H,

6.23.

]CH), 5.60 (s, 1H, CHOH), 3.74 (s, 3H, OCH₃), 1.45, 1.43 {s, 6H,

(CH₃)₂}. ¹³C NMR (50 MHz, CDCl₃):

d 159.4, 137.5, 134.8, 133.5, 133.1,

131.2, 129.4, 128.8, 128.3, 127.7, 125.8, 125.4, 114.8, 114.4, 74.2, 55.6,

40.7, 30.1. MS (FAB): m/z (%): 312 (40, [M^þ]), 306 (100, [M^þꢀCH₃]),

304 (20, [M^þꢀOH]). Anal. Calcd for C₁₉H₂₀O₂S: C, 73.04; H, 6.45.

Found: C, 73.14; H, 6.51.

3.2.32. (4-Chloro-phenyl)-(7-methoxy-2,2-dimethyl-2H-

thiochromen-4-yl)-methanol 26a

Yield¼53% as brown viscous yellow oil; R_f¼0.6 (15% ethyl ace-

3.2.37. (4-Dimethylamino-phenyl)-(2,2-dimethyl-2H-thiochromen-

4-yl)-methanol 28c

tate in hexane). IR (Neat): 3417, 2364, 1596, 1277, 1224, 1051,

770 cm^ꢀ1. ¹H NMR (200 MHz, CDCl₃):

d

7.28–7.18 (m, 5H, ArH), 7.06

Yield¼51% as a dark brown oil; R_f¼0.5 (15% ethyl acetate in

(d, 1H, J¼8.7 Hz, ArH), 6.75 (d, 1H, J¼2.4 Hz, ArH), 6.44 (dd, 1H,

hexane). IR (Neat): 3405, 2922, 1611, 1520, 1354, 761 cm^ꢀ1. ¹H NMR

J₁¼8.7 Hz, J₂¼2.4 Hz, ArH), 5.83 (s, 1H, ]CH), 5.58 (s, 1H, CHOH),

(200 MHz, CDCl₃): d 7.18–7.04 (m, 4H, ArH), 6.90–6.83 (m, 2H, ArH),

3.67 (s, 3H, OCH₃), 2.20 (br s, 1H, CHOH), 1.37 {s, 6H, C(CH₃)₂}. ¹³

C

6.54 (d, 2H, J¼8.6 Hz, ArH), 6.04 (s, 1H, ]CH), 5.48 (s, 1H, CHOH),

NMR (50 MHz, CDCl₃): 157.5, 139.6, 135.3, 133.8, 132.4, 130.3, 127.6,

127.2, 125.6, 122.4, 111.77, 110.2, 73.2, 54.2, 39.6, 27.9. MS (FAB): m/z

(%): 346 (40, [M^þ]), 329 (100, [M^þꢀOH]). Anal. Calcd for

2.82 {s, 6H, –N(CH₃)₂}, 2.02 (br s, 1H, CHOH), 1.38 {d, 6H, J¼4.6 Hz,

C(CH₃)₂}. ¹³C NMR (50 MHz, CDCl₃):

d 159.3, 137.5, 134.8, 133.6,

129.4, 128.8, 128.3, 127.9, 127.7, 126.5, 125.8, 125.4, 114.3, 113.1, 74.2,

40.7, 38.2, 30.1. MS (FAB): m/z (%): 325 (50, [M^þ]), 308 (100,

[M^þꢀOH]). Anal. Calcd for C₂₀H₂₃NOS: C, 73.81; H, 7.12; N, 4.30.

Found: C, 73.97; H, 7.17; N, 4.23.

C

₁₉H₁₉ClO₂S: C, 65.79; H, 5.52. Found: C, 65.66; H, 5.61.

3.2.33. (7-Methoxy-2,2-dimethyl-2H-thiochromen-4-yl)-

phenyl-methanol 26b

Yield¼48% as a yellow viscous yellow oil; R_f¼0.5 (15% ethyl ac-

3.2.38. (2,2-Dimethyl-2H-thiochromen-4-yl)-phenyl-methanol 28d

Yield¼56% as a yellow oil; R_f¼0.5 (15% ethyl acetate in hexane).

etate in hexane). IR (Neat): 3441, 2366, 1500, 1351, 670 cm^ꢀ^{1 1}H

.

NMR (200 MHz, CDCl₃):

d

7.34–7.17 (m, 5H, ArH), 7.08 (d, 1H,

IR (Neat): 3530, 2958, 1502, 1359, 1005, 688 cm^ꢀ^{1 1}H NMR

.

J¼8.7 Hz, ArH), 6.75 (d, 1H, J¼2.4 Hz, ArH), 6.44 (dd, 1H, J₁¼8.7 Hz,

J₂¼2.4 Hz, ArH), 5.87 (s, 1H, ]CH), 5.61 (s, 1H, CHOH), 3.65 (s, 3H,

OCH₃), 2.09 (br s, 1H, CHOH), 1.37 {s, 6H, C(CH₃)₂}. ¹³C NMR

(200 MHz, CDCl₃): d 7.42–7.24 (m, 7H, ArH), 7.19–6.91 (m, 2H, ArH),

6.09 (s, 1H, ]CH), 5.82 (s, 1H, CHOH), 2.15 (br s, 1H, CHOH), 1.46

{d, 6H, J¼8.6 Hz, C(CH₃)₂}. ¹³C NMR (75 MHz, CDCl₃):

d 142.2, 136.9,

(50 MHz, CDCl₃):

d

158.9, 142.5, 136.9, 135.1, 131.3, 129.0, 128.2,

133.2, 133.1, 130.7, 128.5, 127.9, 127.7, 127.3, 126.9, 125.4, 125.0, 74.4,

40.2, 29.0, 28.9. MS (FAB): m/z (%): 282 (50, [M^þ]), 265 (100,

[M^þꢀOH]). Anal. Calcd for C₁₈H₁₈OS: C, 76.56; H, 6.42. Found: C,

76.41; H, 6.49.

127.3, 127.0, 124.2, 113.1, 111.6, 75.1, 55.6, 41.0, 29.5. MS (FAB): m/z

(%): 312 (50, [M^þ]), 295 (100, [M^þꢀOH]). Anal. Calcd for C₁₉H₂₀O₂S:

C, 73.04; H, 6.45. Found: C, 73.09; H, 6.39.

3.2.34. (7-Methoxy-2,2-dimethyl-2H-thiochromen-4-yl)-

(3-nitro-phenyl)-methanol 26c

3.2.39. (4-Chloro-phenyl)-(2,2-dimethyl-2H-thiochromen-4-yl)-

methanol 28e

Yield¼53% as a brown oil; R_f¼0.5 (25% ethyl acetate in hexane).

Yield¼68% as a colourless viscous oil; R_f¼0.5 (15% ethyl acetate

IR (Neat): 3434, 2970, 1718, 1610, 1270, 1148, 1051, 771 cm^ꢀ1

.

¹H

in hexane). IR (Neat): 3430, 1601, 1463, 1436, 1257, 1218, 758 cm^ꢀ1

.

NMR (200 MHz, CDCl₃):

d

8.22 (s, 1H, ArH), 8.02 (d, 1H, J¼2.5 Hz,

¹H NMR (200 MHz, CDCl₃):

d 7.31–7.17 (m, 6H, ArH), 7.07–6.96 (m,

ArH), 7.58 (d, 1H, J¼7.7 Hz, ArH), 7.38 (t, 1H, J¼7.9 Hz, ArH), 7.07 (d,

1H, J¼8.7 Hz, ArH), 6.70 (d, 1H, J¼2.5 Hz, ArH), 6.40 (dd, 1H,

J₁¼8.7 Hz, J₂¼2.5 Hz, ArH), 5.78 (s, 1H, ]CH), 5.62 (s, 1H, CHOH),

2H, ArH), 6.03 (s, 1H, ]CH), 5.68 (d, 1H, J¼2.8 Hz, CHOH), 2.27 (d,

1H, J¼2.8 Hz, CHOH), 1.45 {s, 3H, C(CH₃)₂}, 1.43 {s, 3H, C(CH₃)₂}. ¹³

C

NMR (50 MHz, CDCl₃): d 140.9, 137.1, 134.1, 133.9, 133.6, 130.8, 129.1,

3.66 (s, 3H, OCH₃), 2.52 (br s, 1H, CHOH), 1.38 {s, 6H, C(CH₃)₂}. ¹³

C

128.7, 128.4, 128.0, 125.7, 125.5, 40.6, 29.3. MS (FAB): m/z (%): 316

(100, [M^þ]). Anal. Calcd for C₁₈H₁₇ClOS: C, 68.23; H, 5.41. Found: C,

68.31; H, 5.46.

NMR (50 MHz, CDCl₃): d 159.1, 148.8, 144.7, 136.5, 135.5,133.1, 132.9,

129.8, 127.1, 123.3, 123.0, 122.1, 113.3, 111.8, 74.9, 55.6, 41.0, 29.3. MS

(FAB): m/z (%): 357 (60, [M^þ]), 342 (100, [M^þꢀCH₃]), 340 (50,

[M^þꢀOH]). Anal. Calcd for C₁₉H₁₉NO₄S: C, 63.85; H, 5.36; N, 3.92.

Found: C, 63.91; H, 5.43; N, 3.78.

3.2.40. 4-[(2,2-Dimethyl-2H-thiochromen-4-yl)-hydroxy-methyl]-

benzonitrile 28f

Yield¼64% as a pale yellow semi-solid; R_f¼0.5 (20% ethyl acetate

3.2.35. (2,2-Dimethyl-2H-thiochromen-4-yl)-(3-nitro-phenyl)-

methanol 28a

in hexane). IR (Neat): 3433, 2231, 1606, 1217, 758 cm^ꢀ^{1 1}H NMR

.

(200 MHz, CDCl₃): d 7.61–7.48 (m, 4H, ArH), 7.30–7.21 (m, 2H, ArH),

Yield¼52% as brown oil; R_f0.5 (20% ethyl acetate in hexane). IR

7.11–6.96 (m, 2H, ArH), 5.98 (s, 1H, ]CH), 5.73 (d, 1H, J¼2.4 Hz,

(Neat): 3431, 2925, 2362, 1529, 1349, 768 cm^ꢀ1. ¹H NMR (200 MHz,

CHOH), 2.59 (br s, 1H, CHOH), 1.44 {s, 3H, C(CH₃)₂}, 1.43 {s, 3H,

CDCl₃):

d

8.25 (s, 1H, ArH), 8.05 (d, 1H, J¼8.1 Hz, ArH), 7.59 (d, 1H,

C(CH₃)₂}. ¹³C NMR (50 MHz, CDCl₃):

d

147.8, 136.8, 135.3, 133.8,

J¼7.6 Hz, ArH), 7.44–7.36 (m, 1H, ArH), 7.18 (t, 2H, J¼9.2 Hz, ArH),

132.7, 130.4, 128.5, 128.2, 127.7, 125.8, 125.5, 119.1, 111.7, 75.0, 40.6,

M.K. Parai et al. / Tetrahedron 64 (2008) 9962–9976

9971

29.2. MS (FAB): m/z (%): 307 (100, [M^þ]). Anal. Calcd for C₁₉H₁₇NOS:

C, 74.23; H, 5.57; N, 4.56. Found: C, 74.31; H, 5.53; N, 4.61.

the reaction was monitored by TLC. After consumption of the

starting material the reaction mixture was poured into ice-water

and extracted with ethyl acetate. The organic layer was dried on

Na₂SO₄and concentrated. The crude was chromatographed

through silica gel column to furnish the product. In case of

substrates containing basic nitrogen the reaction mixture was

neutralized by using NaHCO₃after pouring it to ice.

3.2.41. (2,4-Dichloro-phenyl)-(2,2-dimethyl-2H-thiochromen-

4-yl)-methanol 28g

Yield¼63% as a pale yellow semi-solid; R_f¼0.5 (20% ethyl acetate

in hexane). IR (Neat): 3404, 1587, 1466, 1217, 759 cm^ꢀ^{1 1}H NMR

.

(200 MHz, CDCl₃):

(s, 1H, CHOH), 2.24 (br s, 1H, CHOH), 1.36 {s, 3H, C(CH₃)₂}, 1.31

{s, 3H, C(CH₃)₂}. ¹³C NMR (50 MHz, CDCl₃):

138.4, 136.1, 134.7,

d 7.32–6.96 (m, 7H, ArH), 6.07 (s, 1H, ]CH), 5.84

3.3.1. (7-Methoxy-2,2-dimethyl-chroman-4-yl)-phenyl-

methanone 2d

d

134.6, 133.6, 131.0, 129.8, 128.5, 128.0, 127.9, 125.8, 124.8, 69.8, 40.1,

Yield¼73% as light yellow viscous oil; R_f¼0.6 (15% ethyl acetate

29.2. MS (FAB): m/z (%): 350 (100, [M^þ]). Anal. Calcd for

in hexane). IR (Neat): 1683, 1618, 1504, 1208, 1127, 758 cm^ꢀ^{1 1}H

.

C

₁₈H₁₆Cl₂OS: C, 61.54; H, 4.59. Found: C, 61.48; H, 4.55.

NMR (200 MHz, CDCl₃): d 7.96–7.91 (m, 2H, ArH), 7.57–7.42 (m, 3H,

ArH), 6.79 (dd, 1H, J₁¼8.5 Hz, J₂¼2.5 Hz, ArH), 6.43–6.37 (m, 2H,

ArH), 4.75–4.66 (m, 1H, 4-H), 3.75 (s, 3H, OCH₃), 2.16–2.10 (m, 2H,

3-H), 1.43 (s, 3H, 2-CH₃), 1.35 (s, 3H, 2-CH₃). ¹³C NMR (50 MHz,

3.2.42. (2,2-Dimethyl-2H-thiochromen-4-yl)-p-tolyl-methanol 28h

Yield¼61% as a pale yellow viscous oil; R_f¼0.6 (15% ethyl acetate

in hexane). IR (Neat): 3399, 1594, 1437, 760 cm^ꢀ1

.

¹H NMR

CDCl₃): d 201.9, 160.3, 155.0, 137.0, 133.5, 129.9, 129.2, 129.1, 112.1,

(200 MHz, CDCl₃):

d

7.30–6.95 (m, 8H, ArH), 6.11 (s, 1H, ]CH), 5.69

108.0, 102.7, 74.5, 55.6, 42.4, 37.9, 29.8, 24.9. MS (FAB): m/z (%): 297

(15, [M^þþH]), 191 (100, [M^þꢀCOC₆H₅]). Anal. Calcd for C₁₉H₂₀O₃: C,

77.00; H, 6.80. Found: C, 76.86; H, 6.81.

(d, 1H, J¼3.4 Hz, CHOH), 2.31 (s, 3H, CH₃), 2.07 (d, 1H, J¼3.4 Hz,

CHOH), 1.47 {s, 3H, C(CH₃)₂}, 1.45 {s, 3H, C(CH₃)₂}. ¹³C NMR

(75 MHz, CDCl₃):

d 139.6, 138.0, 137.2, 133.5, 133.3, 131.2, 130.2,

129.7,129.3,128.3,127.7,127.4,125.7, 125.4, 74.6, 40.6, 29.4, 21.5. MS

(FAB): m/z (%): 295 (100, [M^þꢀH]). Anal. Calcd for C₁₉H₂₀OS: C,

76.98; H, 6.80. Found: C, 76.91; H, 6.75.

3.3.2. (7-Methoxy-2,2-dimethyl-chroman-4-yl)-(2-methoxy-

phenyl)-methanone 2e

Yield¼65% as light yellow semi solid; R_f¼0.6 (15% ethyl acetate

in hexane). IR (Neat): 2974, 1679, 1616, 1163, 1128, 758 cm^ꢀ^{1 1}H

.

3.2.43. (2,3-Dihydro-benzo[b]thiepin-5-yl)-(4-ﬂuoro-phenyl)-

methanol 45

NMR (200 MHz, CDCl₃): d 7.61–7.47 (m, 2H, ArH), 7.06–6.89 (m, 3H,

ArH), 6.46–6.37 (m, 2H, ArH), 4.77 (m, 1H, 4-H), 3.87 (s, 3H, OCH₃),

3.74 (s, 3H, OCH₃), 2.08–1.99 (m, 2H, 3-H),1.37 (s, 3H, 2-CH₃),1.29 (s,

Yield¼59% as light yellow viscous oil; R_f¼0.5 (15% ethyl acetate

in hexane). IR (neat): 3399, 2926, 2362, 1604, 1508, 1222, 765 cm^ꢀ1

.

3H, 2-CH₃). ¹³C NMR (50 MHz, CDCl₃):

d 205.5, 159.9, 158.3, 155.1,

¹H NMR (200 MHz, CDCl₃):

d

7.48–7.44 (m, 1H, ArH), 7.36–7.28 (m,

133.7, 130.8, 130.4, 129.6, 121.4, 112.7, 112.0, 107.6, 102.4, 74.6, 55.9,

55.6, 45.6, 37.3, 29.3, 25.4. MS (FAB): m/z (%): 327 (40, [M^þþH]), 191

(100, [M^þꢀCOC₆H₄OCH₃]), 135 (30, [M^þꢀC₁₂H₁₅O₂]). Anal. Calcd for

2H, ArH), 7.16–7.14 (m, 2H, ArH), 7.08–7.04 (m, 1H, ArH), 6.91–6.82

(m, 2H, ArH), 6.35 (t, 1H, J¼7.8 Hz, ]CH), 5.52 (s, 1H, CHOH), 3.37–

3.26 (m, 2H, SCH₂CH₂), 2.48 (br s, 1H, CHOH), 2.21–1.98 (m, 2H,

C₂₀H₂₂O₄: C, 73.60; H, 6.79. Found: C, 73.56; H, 6.80.

SCH₂CH₂). ¹³C NMR (50 MHz, CDCl₃):

d 165.0, 160.1, 144.3, 143.6,

138.1, 135.6, 134.4, 129.6, 129.3, 129.1, 128.6, 128.2, 128.0, 115.6,

115.2, 76.6, 43.6, 26.2. MS (FAB): m/z (%): 286 (100, [M^þ]). Anal.

Calcd for C₁₇H₁₅FOS: C, 71.30; H, 5.28. Found: C, 71.38; H, 5.23.

3.3.3. (7-Methoxy-2,2-dimethyl-chroman-4-yl)-(3-methoxy-

phenyl)-methanone 2f

Yield¼78% as yellow viscous oil; R_f¼0.4 (10% ethyl acetate in

hexane). IR (Neat): 2974, 1683, 1616, 1584, 1504, 1262, 1164,

3.2.44. (E)-(8-Methoxy-2,3-dihydrobenzo[b]thiepin-5-yl)-

757 cm^ꢀ1. ¹H NMR (200 MHz, CDCl₃):

d 7.44–7.39 (m, 2H, ArH), 7.27

(3-methoxyphenyl)methanol 46

(t, 1H, J¼7.6 Hz, ArH), 7.02 (dd, 1H, J₁¼8.3 Hz, J₂¼2.5 Hz, ArH), 6.70

(d, 1H, J¼8.9 Hz, ArH), 6.33–6.28 (m, 2H, ArH), 4.64–4.55 (m, 1H,

4-H), 3.72 (s, 3H, OCH₃), 3.64 (s, 3H, OCH₃), 2.06–1.95 (m, 2H, 3-H),

1.33 (s, 3H, 2-CH₃), 1.25 (s, 3H, 2-CH₃). ¹³C NMR (50 MHz, CDCl₃):

Yield¼64% as light yellow viscous oil; R_f¼0.4 (15% ethyl acetate in

hexane). IR (Neat): 3429, 2931, 2839, 1595, 1485, 1283, 1045,

758 cm^ꢀ1. ¹H NMR (200 MHz, CDCl₃): 7.19–7.11 (m, 2H, ArH), 7.03–

6.99 (m, 2H, ArH), 6.80–6.73 (m, 2H, ArH), 6.40 (t,1H, J¼8.7 Hz, ArH),

5.58 (s,1H), 3.76 (s, 3H, OCH₃), 3.75 (s, 3H, OCH₃), 3.45–3.35 (m, 2H),

2.25–2.15 (m, 2H). ¹³C NMR (50 MHz, CDCl₃): 160.0, 158.6, 144.2,

143.9,135.7,129.6,129.2,129.0,128.7,120.2,119.9,114.7,113.9,112.5,

55.7, 43.5, 26.4. MS (FAB): m/z (%): 329 (90, Mþ1), 311 (45, Mꢀ17).

Anal. Calcd for C₁₉H₂₀O₃S: C, 69.48; H, 6.14. Found: C, 69.57; H, 6.17.

d

201.6, 160.3, 155.0, 138.4, 130.1, 129.9, 121.7, 120.0, 113.6, 112.2,

108.0,102.7, 74.5, 55.8, 55.6, 42.4, 37.9, 29.9, 24.9. MS (FAB): m/z (%):

327 (50, [M^þþH]), 191 (100, [M^þꢀCOC₆H₄OCH₃]), 135 (30,

[M^þꢀC₁₂H₁₅O₂]). Anal. Calcd for C₂₀H₂₂O₄: C, 73.60; H, 6.79. Found:

C, 73.53; H, 6.75.

3.3.4. (2,4-Dimethoxy-phenyl)-(7-methoxy-2,2-dimethyl-

chroman-4-yl)-methanone 2g

3.2.45. (E)-(8-Methoxy-2,3-dihydrobenzo[b]thiepin-5-yl)-

(phenyl)methanol 47

Yield¼20% as yellow viscous oil; R_f¼0.4 (10% ethyl acetate in

Yield¼62% as light yellow viscous oil; R_f¼0.5 (15% ethyl acetate in

hexane). IR (Neat): 2927, 1659, 1610, 1445, 1265, 1160, 780 cm^ꢀ1. ¹H

hexane). IR (Neat): 3423, 2928, 2368, 1594, 1487, 1286, 1228, 1046,

NMR (200 MHz, CDCl₃):

d

7.76 (d, 1H, J¼8.6 Hz, ArH), 6.87 (d, 1H,

758 cm^ꢀ1.¹H NMR (200 MHz, CDCl₃):

d

7.38–7.34 (m, 2H, ArH), 7.25–

J¼8.3 Hz, ArH), 6.59–6.37 (m, 4H, ArH), 4.74–4.94 (m, 1H, 4-H), 3.87

(s, 3H, OCH₃), 3.86 (s, 3H, OCH₃), 3.69 (s, 3H, OCH₃), 2.07–1.99 (m,

2H, 3-H), 1.25 (s, 6H, 2-CH₃). MS (FAB): m/z (%): 357 (50, [M^þþH]),

191 (50, [M^þꢀCOC₆H₃(OCH₃)₂]), 165 (100, [M^þꢀC₁₂H₁₅O₂]). Anal.

Calcd for C₂₁H₂₄O₅: C, 70.77; H, 6.79. Found: C, 70.88; H, 6.73.

7.03 (m, 5H, ArH), 6.69 (dd, 1H, J₁¼2.64 Hz, J₂¼8.5 Hz, ArH), 6.29 (t,

1H, J¼7.7 Hz, ArH), 5.51 (s,1H), 3.66 (s, 3H, OCH₃), 3.35–3.26 (m, 2H),

2.18–1.95 (m, 2H). ¹³C NMR (50 MHz, CDCl₃):

d 159.6, 144.2, 143.9,

135.7, 129.6, 129.5, 128.8, 128.2, 127.7, 114.7, 113.9, 112.5, 75.7, 55.7,

43.5, 26.4. MS (FAB): m/z (%): 281 (100, Mꢀ17). Anal. Calcd for

C

₁₈H₁₈O₂S: C, 72.45; H, 6.08. Found: C, 72.57; H, 6.01.

3.3.5. (7-Methoxy-2,2-dimethyl-chroman-4-yl)-thiophene-2-yl-

methanone 2i

3.3. General procedure of the PBr₃reaction on allylic alcohols

Yield¼58% as yellow oil; R_f¼0.6 (15% ethyl acetate in hexane). IR

(Neat): 2977, 1658, 1506, 1204, 1165, 1127, 752 cm^ꢀ^{1 1}H NMR

.

Compound (0.1 mmol) was taken in dry benzene (2 ml) and

cooled at 0 ^ꢁC. PBr₃(1 equiv) was added to this stirred solution and

(200 MHz, CDCl₃):

J¼4.2 Hz, ArH), 6.84 (d, 1H, J¼9.2 Hz, ArH), 6.42–6.39 (m, 2H, ArH),

d 7.65–7.57 (m, 2H, ArH), 7.12–7.07 (t, 1H,

9972

M.K. Parai et al. / Tetrahedron 64 (2008) 9962–9976

4.53–4.44 (m, 1H, 4-H), 3.75 (s, 3H, OCH₃), 2.22–2.06 (m, 2H, 3-H),

1.46 (s, 3H, 2-CH₃), 1.33 (s, 3H, 2-CH₃). ¹³C NMR (50 MHz, CDCl₃):

CH(CH₃)₂), 2.16–1.97 (m, 2H, 3-H), 1.43 (s, 3H, 2-CH₃), 1.34 (s, 3H,

2-CH₃), 1.27 {d, 6H, J¼6.9 Hz, CH(CH₃)₂}. MS (FAB): m/z (%): 339 (50,

[M^þþH]), 191 (100, [M^þꢀCOꢀC₆H₄–CH–(CH₃)₂]). Anal. Calcd for

d

194.8, 160.5, 155.0, 143.7, 134.5, 133.2, 130.1, 128.6, 111.8, 108.1,

102.7, 74.5, 55.6, 44.4, 38.3, 29.9, 24.5. MS (FAB): m/z (%): 303 (60,

[M^þþH]), 191 (100, [M^þꢀCO–C₄H₃S]). Anal. Calcd for C₁₇H₁₈O₃S: C,

67.52; H, 6.00. Found: C, 66.48; H, 5.97.

C₂₂H₂₆O₃: C, 78.07; H, 7.74. Found: C, 77.83; H, 7.73.

3.3.11. (7-Methoxy-2,2-dimethyl-chroman-4-yl)-naphthalen-2-yl-

methanone 2q

3.3.6. Furan-2-yl-(7-methoxy-2,2-dimethyl-chroman-4-yl)-

methanone 2j

Yield¼75% as white crystalline solid; mp 142 ^ꢁC (dichloro-

methane); R_f¼0.5 (10% ethyl acetate in hexane). IR (KBr): 2968,

Yield¼67% as yellow viscous oil; R_f¼0.6 (15% ethyl acetate in

1674, 1593, 1351, 1159, 776 cm^ꢀ1. ¹H NMR (200 MHz, CDCl₃):

d 8.42–

hexane). IR (Neat): 1672, 1619, 1505, 1464, 1163, 1128, 769 cm^ꢀ1. ¹H

8.37 (m, 1H, ArH), 8.00 (d, 1H, J¼8 Hz, ArH), 7.92–7.80 (m, 2H, ArH),

7.59–7.46 (m, 3H, ArH), 6.98 (d, 1H, J¼8.2 Hz, ArH), 6.49–6.43 (m,

2H, ArH), 4.78–4.69 (m, 1H, 4-H), 3.76 (s, 3H, OCH₃), 2.13–2.03 (m,

2H, 3-H), 1.39 (s, 3H, 2-CH₃), 1.30 (s, 3H, 2-CH₃). ¹³C NMR (50 MHz,

NMR (200 MHz, CDCl₃):

d

7.60 (d, 1H, J¼1.6 Hz, ArH), 7.11 (d, 1H,

J¼4.1 Hz, ArH), 6.78 (d, 1H, J¼9.1 Hz, ArH), 6.54–6.51 (m, 1H, ArH),

6.43–6.38 (m, 2H, ArH), 4.55–4.46 (m, 1H, 4-H), 3.74 (s, 3H, OCH₃),

2.22–2.00 (m, 2H, 3-H), 1.44 (s, 3H, 2-CH₃), 1.32 (s, 3H, 2-CH₃). ¹³

C

CDCl₃): d 205.4, 160.3, 155.2, 136.9, 134.4, 132.9, 130.9, 130.3, 128.8,

NMR (50 MHz, CDCl₃):

d

190.7, 160.3, 155.1, 152.6, 147.0, 129.9, 118.9,

128.4, 127.2, 127.0, 126.0, 124.8, 111.7, 108.0, 102.7, 74.5, 55.6, 45.3,

37.6, 29.6, 25.1. MS (FAB): m/z (%): 347 (90, [M^þþH]), 191 (100,

[M^þꢀCOC₁₀H₇]). Anal. Calcd for C₂₃H₂₂O₃: C, 79.74; H, 6.40. Found:

C, 79.81; H, 6.42.

112.8, 111.6, 108.0, 102.6, 74.5, 55.6, 42.8, 37.5, 29.8, 24.5. MS (FAB):

m/z (%): 287 (20, [M^þþH]), 191 (100, [M^þꢀCOꢀC₄H₃O]). Anal. Calcd

for C₁₇H₁₈O₄: C, 71.31; H, 6.34. Found: C, 71.38; H, 6.33.

3.3.7. (2-Chloro-phenyl)-(7-methoxy-2,2-dimethyl-chroman-4-yl)-

methanone 2m

3.3.12. 1-(7-Methoxy-2,2-dimethyl-chroman-4-yl)-

propan-1-one 2r

Yield¼60% as light yellow semi solid; R_f¼0.5 (12% ethyl acetate

Yield¼61% as yellow viscous oil; R_f¼0.4 (10% ethyl acetate in

in hexane). IR (Neat): 2976, 1678, 1609, 1440, 1268, 1159, 759 cm^ꢀ1

.

hexane). IR (Neat): 2975, 1678, 1611, 1442, 1268, 1167, 1128,

¹H NMR (200 MHz, CDCl₃):

d

7.41–7.19 (m, 4H, ArH), 6.95 (d, 1H,

761 cm^ꢀ^{1 1}H NMR (200 MHz, CDCl₃):

. d 6.81–6.75 (m, 1H, ArH),

J¼8.5 Hz, ArH), 6.44–6.31 (m, 2H, ArH), 4.55–4.50 (m, 1H, 4-H), 3.69

(s, 3H, OCH₃), 1.98–1.84 (m, 2H, 3-H), 1.32 (s, 3H, 2-CH₃), 1.20 (s, 3H,

2-CH₃). MS (FAB): m/z (%): 332 (40, [M^þþH]), 281 (100, [M^þꢀCH₃,

ꢀCl]). Anal. Calcd for C₁₉H₁₉ClO₃: C, 68.98; H, 5.79. Found: C, 68.89;

H, 5.88.

6.48–6.36 (m, 2H, ArH), 3.79–3.75 (m, 1H, 4-H), 3.74 (s, 3H, OCH₃),

2.41–2.33 (m, 2H, COCH₂CH₃), 1.97–1.85 (m, 2H, 3-H), 1.42 (s, 3H,

2-CH₃), 1.27 (s, 3H, 2-CH₃), 0.87 (t, 3H, J¼7.3 Hz, COCH₂CH₃). MS

(FAB): m/z (%): 249 (50, [M^þþH]), 191 (100, [M^þꢀCOCH₂CH₃]). Anal.

Calcd for C₁₅H₂₀O₃: C, 72.55; H, 8.12. Found: C, 72.58; H, 8.04.

3.3.8. (7-Methoxy-2,2-dimethyl-chroman-4-yl)-(3-nitro-phenyl)-

methanone 2n

3.3.13. 1-(7-Methoxy-2,2-dimethyl-chroman-4-yl)-butan-1-one 2s

Yield¼63% as yellow viscous oil; R_f¼0.5 (12% ethyl acetate in

hexane). IR (Neat): 2971, 1705, 1618, 1504, 1163, 1128, 758 cm^ꢀ1. ¹H

Yield¼82% as light yellow solid; mp 70 ^ꢁC (dichloromethane);

R_f¼0.5 (20% ethyl acetate in hexane). IR (KBr): 1689, 1615, 1532,

NMR (200 MHz, CDCl₃):

d

6.79 (d, 1H, J¼8.5 Hz, ArH), 6.48–6.38 (m,

1350,1210,1129, 770 cm^ꢀ1. ¹H NMR (200 MHz, CDCl₃):

d

8.66 (d,1H,

2H, ArH), 3.83–3.87 (m, 1H, 4-H), 3.75 (s, 3H, OCH₃), 2.37 (t, 2H,

J¼7.1 Hz, COCH₂CH₂CH₃), 1.95 (d, 2H, J¼8.9 Hz, 3-H), 1.65–1.54 (m,

2H, COCH₂CH₂CH₃), 1.42 (s, 3H, 2-CH₃), 1.24 (s, 3H, 2-CH₃), 0.87 (t,

J¼7.8 Hz, ArH), 8.32 (dd, 1H, J₁¼8.2 Hz, J₂¼2.2 Hz, ArH), 8.08 (d, 1H,

J¼7.8 Hz, ArH), 7.56 (t, 1H, J¼7.9 Hz, ArH), 6.67 (d, 1H, J¼8.3 Hz,

ArH), 6.37–6.29 (m, 2H, ArH), 4.64–4.55 (m, 1H, 4-H), 3.67 (s, 3H,

OCH₃), 2.06–2.00 (m, 2H, 3-H), 1.36 (s, 3H, 2-CH₃), 1.28 (s, 3H,

3H, J¼7.3 Hz, COCH₂CH₂CH₃). ¹³C NMR (50 MHz, CDCl₃):

d 212.2,

160.4, 155.0, 129.7, 110.8, 108.0, 102.7, 74.3, 55.5, 47.8, 41.5, 36.6,

29.8, 24.5, 17.7, 14.1. MS (FAB): m/z (%): 263 (40, [M^þþH]), 191 (100,

[M^þꢀCOCH₂CH₂CH₃]). Anal. Calcd for C₁₆H₂₂O₃: C, 73.25; H, 8.45.

Found: C, 73.37; H, 8.53.

2-CH₃). ¹³C NMR (50 MHz, CDCl₃):

d 199.7, 160.6, 154.9, 148.9, 137.9,

134.8, 130.4, 129.8, 127.7, 124.1, 111.0, 108.3, 102.9, 74.5, 55.6, 43.3,

37.6, 29.7, 24.8. MS (FAB): m/z (%): 342 (50, [M^þþH]), 191 (100,

[M^þꢀCOC₆H₄NO₂]). Anal. Calcd for C₁₉H₁₉NO₅: C, 66.85; H, 5.61; N,

4.10. Found: C, 66.91; H, 5.52; N, 4.17.

3.3.14. 1-(7-Methoxy-2,2-dimethyl-chroman-4-yl)-

but-2-en-1-one 2t

3.3.9. 4-(7-Methoxy-2,2-dimethyl-chroman-4-carbonyl)-

benzonitrile 2o

Yield¼69% as yellow viscous oil; R_f¼0.6 (15% ethyl acetate in

hexane). IR (Neat): 2978, 1686, 1618, 1505, 1200, 1163, 765 cm^ꢀ1. ¹H

Yield¼74% as light brown semi solid; R_f¼0.6 (20% ethyl acetate

NMR (200 MHz, CDCl₃): d 6.97–6.86 (m, 1H, CH]CHCH₃), 6.72 (d,

in hexane). IR (Neat): 2973, 1680, 1612, 1507, 1200, 1117, 980 cm^ꢀ1

.

2H, J¼8.3 Hz, CH]CHCH₃), 6.39–6.31 (m, 2H, ArH), 6.09–6.00 (m,

1H, ArH), 3.82–3.76 (m, 1H, 4-H), 3.69 (s, 3H, OCH₃), 1.90–1.74 (m,

5H, 3-H, CH]CHCH₃), 1.39 (s, 3H, 2-CH₃), 1.18 (s, 3H, 2-CH₃). ¹³C

¹H NMR (200 MHz, CDCl₃):

J¼8.5 Hz, ArH), 6.75 (d, 1H, J¼8.1 Hz, ArH), 6.45–6.38 (m, 2H, ArH),

4.60–4.59 (m, 1H, 4-H), 3.76 (s, 3H, OCH₃), 2.12–2.05 (m, 2H, 3-H),

1.44 (s, 3H, 2-CH₃), 1.34 (s, 3H, 2-CH₃). ¹³C NMR (50 MHz, CDCl₃):

d

7.95 (d, 2H, J¼8.5 Hz, ArH), 7.74 (d, 2H,

NMR (50 MHz, CDCl₃):

d 200.6, 160.4, 155.0, 144.2, 130.1, 128.7,

110.9, 108.0, 102.7, 74.4, 55.5, 46.0, 36.8, 29.8, 24.5, 18.6. MS (FAB):

m/z (%): 261 (40, [M^þþH]), 191 (100, [M^þꢀCOCH]CHCH₃]). Anal.

Calcd for C₁₆H₂₀O₃: C, 73.82; H, 7.74. Found: C, 73.77; H, 7.73.

d

200.5, 160.6, 154.8, 139.6, 132.9, 129.7, 118.2, 116.7, 111.0, 108.3,

103.0, 74.5, 55.6, 43.7, 37.6, 29.7, 24.7. MS (FAB): m/z (%): 322 (20,

[M^þþH]), 191 (100, [M^þꢀCOꢀC₆H₄CN]). Anal. Calcd for C₂₀H₁₉NO₃:

C, 74.75; H, 5.96; N, 4.36. Found: C, 74.82; H, 6.04; N, 4.39.

3.3.15. (4-Chloro-phenyl)-(7-methoxy-2,2-dimethylchroman-4-

yl)methanone 2u

3.3.10. (4-Isopropyl-phenyl)-(7-methoxy-2,2-dimethyl-chroman-4-

yl)-methanone 2p

Yield¼60% as colourless oil; R_f¼0.6 (15% ethyl acetate in hexane).

IR (Neat): 3406, 2924, 1593, 1216, 759 cm^ꢀ^{1 1}H NMR (300 MHz,

.

Yield¼69% as yellow viscous oil; R_f¼0.5 (10% ethyl acetate in

CDCl₃):

d

7.85 (d, 2H, J¼8.5 Hz, ArH), 7.41 (d, 2H, J¼8.5 Hz, ArH),

hexane). IR (Neat): 2966, 1679, 1618, 1504, 1163, 1128, 769 cm^ꢀ1. ¹H

6.77–6.74 (m, 1H, ArH), 6.43–6.38 (m, 2H, ArH), 4.64–4.58 (m, 1H),

3.78 (s, 3H, OCH₃), 2.19–1.99 (m, 2H), 1.49 (s, 3H, CH₃), 1.39 (s, 3H,

NMR (200 MHz, CDCl₃):

d

7.89 (d, 2H, J¼8.3 Hz, ArH), 7.31 (d, 2H,

J¼8.3 Hz, ArH), 6.79 (d, 1H, J¼7.9 Hz, ArH), 6.42–6.37 (m, 2H, ArH),

4.70–4.64 (m, 1H, 4-H), 3.74 (s, 3H, OCH₃), 3.00–2.93 (m, 1H,

CH₃). ¹³C NMR (75 MHz, CDCl₃):

d

199.0, 158.7, 153.2, 138.4, 133.4,

129.1, 128.1, 127.8, 110.1, 106.5, 101.2, 98.7, 72.9, 53.9, 41.3, 36.1, 28.4,

M.K. Parai et al. / Tetrahedron 64 (2008) 9962–9976

9973

28.1, 23.1. MS (ESI): m/z (%): 332 (98, [M^þþ2]), 331 (98, [M^þþ1]).

3.3.21. 4-(2,4-Dimethoxy-benzylidine)-7-methoxy-2,2-dimethyl-

Anal. Calcd for C₁₉H₁₉ClO₃: C, 68.98; H, 5.79. Found: C, 69.12; H,

5.76.

chroman 8

Yield¼56% as white solid; mp 150 ^ꢁC (dichloromethane); R_f¼0.4

(15% ethyl acetate in hexane). IR (KBr): 2928,1612,1505,1462,1288,

3.3.16. (4-Fluoro-phenyl)-(7-methoxy-2,2-dimethyl-chroman-4-

yl)-methanone 3

1209, 1159, 1041, 760 cm^ꢀ1. ¹H NMR (200 MHz, CDCl₃):

d 7.49 (d, 1H,

J¼8.7 Hz, ArH), 7.04–6.99 (m, 2H, ArH), 6.94 (s, 1H, ]CH–Ar), 6.41

Yield¼77% white crystalline solid; mp 81 ^ꢁC (dichloromethane);

R_f¼0.5 (12% ethyl acetate in hexane). IR (KBr): 2975, 1683, 1617,

(m, 3H, ArH), 6.30 (m, 1H, ArH), 3.75 (s, 3H, OCH₃), 3.74 (s, 3H,

OCH₃), 3.70 (s, 3H, OCH₃), 2.56 (s, 2H, 3-H), 1.20 (s, 6H, 2-CH₃). ¹³

C

1596, 1504, 1161, 845 cm^ꢀ1. ¹H NMR (200 MHz, CDCl₃):

d

7.90–7.83

NMR (50 MHz, CDCl₃): d 160.8,160.2,159.2,154.6,131.2,128.9 125.6,

(m, 2H, ArH), 7.06–6.99 (m, 2H, ArH), 6.68 (d, 1H, J¼8.7 Hz, ArH),

119.8, 116.9, 108.3, 104.2, 101.8, 98.9, 75.7, 55.9, 55.7, 38.0, 28.5, 27.1.

MS (FAB): m/z (%): 340 (100, [M^þ]), 325 (60, [M^þꢀCH₃]). Anal. Calcd

for C₂₁H₂₄O₄: C, 74.09; H, 7.11. Found: C, 74.00; H, 7.12.

6.34–6.29 (m, 2H, ArH), 4.56–4.51 (m, 1H, 4-H), 3.66 (s, 3H, OCH₃),

2.06–1.96 (m, 2H, 3-H), 1.35 (s, 3H, 2-CH₃), 1.26 (s, 3H, 2-CH₃). ¹³

C

NMR (50 MHz, CDCl₃): d 200.1, 160.2, 155.1, 133.1, 132.1, 129.8, 116.4,

116.0, 111.7, 108.1, 102.8, 74.8, 55.6, 42.7, 37.9, 29.8, 24.8. MS (FAB):

3.3.22. 7-Methoxy-2,2-dimethyl-4-(2,4,6-trimethoxy-benzylidene)-

chroman 9

m/z (%): 315 (70, [M^þþH]), 191 (100, [M^þꢀOC₇H₄F). Anal. Calcd for

C

₁₉H₁₉FO₃: C, 72.60; H, 6.09. Found: C, 72.67; H, 6.07.

Yield¼65% as white solid; mp 150 ^ꢁC (dichloromethane); R_f¼0.6

(20% ethyl acetate in hexane). IR (KBr): 2930, 1608, 1206, 1127,

3.3.17. (7-Methoxy-2,2-dimethyl-chroman-4-yl)-(4-methoxy-

phenyl)-methanone 4

761 cm^ꢀ1.¹HNMR(200 MHz, CDCl₃):

d

7.59(d,1H, J¼8.7 Hz,ArH), 6.65

(s, 1H, ]CH), 6.56 (dd, 1H, J₁¼8.5 Hz, J₂¼2.6 Hz, ArH), 6.36 (d, 1H,

J¼2.6 Hz, ArH), 6.17 (s, 2H, ArH), 3.84 (s, 3H, OCH₃), 3.77 (s, 9H, OCH₃),

Yield¼67% as white solid; mp 105 ^ꢁC (dichloromethane); R_f¼0.6

(15% ethyl acetate in hexane). IR (KBr): 2774, 1674, 1600, 1506, 1261,

2.29 (s, 2H, 3-H),1.29 (s, 6H, 2-CH₃).¹³C NMR (50 MHz, CDCl₃):

d 160.8,

1168, 1127 cm^ꢀ1. ¹H NMR (200 MHz, CDCl₃):

d

7.86 (d, 2H, J¼8.8 Hz,

159.2,154.5,131.2,125.8,115.9,112.8,108.6,108.0,101.8, 91.1, 76.0, 56.1,

55.7,39.0,27.1.MS(FAB):m/z(%):370(80, [M^þ]), 355(100,[M^þꢀCH₃]).

Anal. Calcd for C₂₂H₂₆O₅: C, 71.33; H, 7.07. Found: C, 71.47; H, 6.99.

ArH), 6.85 (d, 2H, J¼8.8 Hz, ArH), 6.70 (d, 1H, J¼8.0 Hz, ArH), 6.33–

6.28 (m, 2H, ArH), 4.62–4.52 (m, 1H, 4-H), 3.78 (s, 3H, OCH₃), 3.66

(s, 3H, OCH₃), 2.09–1.91 (m, 2H, 3-H), 1.35 (s, 3H, 2-CH₃), 1.26 (s,

3H, 2-CH₃). ¹³C NMR (50 MHz, CDCl₃):

d

200.2, 163.9, 160.2, 155.0,

3.3.23. 7-Methoxy-2,2-dimethyl-4-thiophen-2-yl-methylene-

chroman 10

131.6, 130.0, 114.3, 112.6, 107.9, 102.7, 74.6, 55.8, 55.6, 42.1, 38.0,

29.9, 24.9. MS (FAB): m/z (%): 327 (90, [M^þþH]), 191 (100,

[M^þꢀCOC₆H₄OCH₃]), 135 (100, [M^þꢀC₁₂H₁₅O₂]). Anal. Calcd for

Yield¼18% as a white solid; mp 105 ^ꢁC (dichloromethane);

R_f¼0.5 (10% ethyl acetate in hexane). IR (KBr): 2962, 1598, 1381,

C

₂₀H₂₂O₄: C, 73.60; H, 6.79. Found: C, 73.53; H, 6.77.

1162, 1351, 1162, 707 cm^ꢀ1. ¹H NMR (200 MHz, CDCl₃):

d 7.53 (d, 1H,

J¼8.8 Hz, ArH), 7.28–7.24 (m, 1H, ArH), 7.12 (s, 1H, ]CH–), 7.07–7.03

(m, 2H, ArH), 6.52 (dd, 1H, J₁¼8.8 Hz, J₂¼2.6 Hz, ArH), 6.39 (d, 1H,

J¼2.5 Hz, ArH), 3.79 (s, 3H, OCH₃), 2.86 (s, 2H, 3-H), 1.35 (s, 6H,

3.3.18. 7-Methoxy-4-(4-methoxy-benzylidine)-2,2-dimethyl-

chroman 5

Yield¼15% as white crystalline solid; mp 97 ^ꢁC (dichloro-

methane); R_f¼0.4 (10% ethyl acetate in hexane). IR (KBr): 2972,

2-CH₃). ¹³C NMR (50 MHz, CDCl₃):

d 161.3, 155.0, 141.2, 129.4, 127.7,

127.5, 125.1, 125.0, 114.1, 108.6, 102.2, 71.2, 55.7, 38.2, 27.2. MS (FAB):

m/z (%): 286 (100, [M^þ]). Anal. Calcd for C₁₇H₁₈O₂S: C, 71.30; H, 6.34.

Found: C, 71.41; H, 6.32.

1612,1509,1248, 759 cm^ꢀ1. ¹H NMR (200 MHz, CDCl₃):

d 7.52 (d,1H,

J¼8.7 Hz, ArH), 7.22 (d, 2H, J¼8.4 Hz, ArH), 6.97 (s, 1H, ]CH–Ar),

6.89 (d, 2H, J¼8.4 Hz, ArH), 6.51 (d, 1H, J¼8.7 Hz, ArH), 6.37 (s, 1H,

ArH), 3.82 (s, 3H, OCH₃), 3.77 (s, 3H, OCH₃), 2.69 (s, 2H, 3-H), 1.27 (s,

3.3.24. 7-Methoxy-2,2-dimethyl-4-(3-phenyl-allylidene)-

chroman 11

6H, 2-CH₃). ¹³C NMR (50 MHz, CDCl₃):

d 161.0, 158.5, 154.7, 130.9,

129.2,125.3,120.9,115.4,114.0,108.4,101.9, 75.5, 55.6, 37.6, 27.0. MS

Yield¼25% as yellow viscous oil; R_f¼0.6 (10% ethyl acetate in

(FAB): m/z (%): 310 (100, [M^þ]), 295 (80, [M^þꢀCH₃]). Anal. Calcd for

hexane). IR (Neat): 2928, 1610, 1498, 1270, 1161, 757 cm^ꢀ1. ¹H NMR

C

₂₀H₂₂O₃: C, 77.39; H, 7.14. Found: C, 77.46; H, 7.18.

(200 MHz, CDCl₃): d 7.46–7.13 (m, 7H, ArH, AlkeneH), 6.72–6.59 (m,

2H, ArH, AlkeneH), 6.24 (dd, 1H, J₁¼8.6 Hz, J₂¼2.5 Hz, ArH), 6.29 (d,

1H, J¼2.5 Hz, ArH), 3.71 (s, 3H, OCH₃), 2.61 (s, 2H, 3-H), 1.28 (s, 6H,

2-CH₃). MS (FAB): m/z (%): 306 (90, [M^þ]), 291 (20, [M^þꢀCH₃]).

Anal. Calcd for C₂₁H₂₂O₂: C, 82.32; H, 7.24. Found: C, 82.44; H, 7.18.

3.3.19. 1-Benzyl-3-(7-methoxy-2,2-dimethyl-chroman-4-

ylidenemethyl)-1H-Indole 6

Yield¼32% as light yellow viscous oil; R_f¼0.5 (10% ethyl acetate

in hexane). IR (Neat): 2971, 2929, 1611, 1164, 754 cm^ꢀ^{1 1}H NMR

.

(200 MHz, CDCl₃):

d

7.68 (d,1H, J¼7.9 Hz, ArH), 7.57 (d,1H, J¼8.8 Hz,

3.3.25. [4-(7-Methoxy-2,2-dimethyl-chroman-4-ylidenemethyl)-

phenyl]-dimethyl-amine 12

ArH), 7.23–7.03 (m, 10H, ArH, ]CH), 6.47 (dd, 1H, J₁¼8.6 Hz,

J₂¼2.5 Hz, ArH), 6.32 (d, 1H, J¼2.5 Hz, ArH), 5.28 (s, 2H, CH₂C₆H₅),

3.71 (s, 3H, OCH₃), 2.67 (s, 2H, 3-H), 1.22 (s, 6H, 2-CH₃). MS (FAB):

m/z (%): 410 (100, [M^þþH]), 409 (70, [M^þ]), 394 (40, [M^þꢀCH₃]).

Anal. Calcd for C₂₈H₂₇NO₂: C, 82.12; H, 6.65; N, 3.42. Found: C,

82.23; H, 6.58; N, 3.48.

Yield¼67% as light yellow solid; mp 120 ^ꢁC (dichloromethane);

R_f¼0.5 (10% ethyl acetate in hexane). IR (KBr): 2971, 2926, 1610,

1520, 1351, 816 cm^ꢀ^{1 1}H NMR (200 MHz, CDCl₃):

. d 7.52 (d, 1H,

J¼8.8 Hz, ArH), 7.20 (d, 2H, J¼8.5 Hz, ArH), 6.96 (s, 1H, ]CH–Ar),

6.72 (d, 2H, J¼8.5 Hz, ArH), 6.50 (dd, 1H, J₁¼8.1 Hz, J₂¼2.6 Hz, ArH),

6.37 (d, 1H, J¼2.6 Hz, ArH), 3.77 (s, 3H, OCH₃), 2.97 {s, 6H, N(CH₃)₂},

2.73 (s, 2H, 3-H), 1.27 (s, 6H, 2-CH₃). ¹³C NMR (50 MHz, CDCl₃):

3.3.20. 7-Methoxy-4-(2-methoxy-benzylidine)-2,2-dimethyl-

chroman 7

d

160.8, 154.6, 149.0, 130.8, 127.9, 125.2, 121.4, 115.8, 112.9, 108.3,

Yield¼19% as yellow viscous oil; R_f¼0.6 (15% ethyl acetate in

102.0, 75.6, 55.6, 41.1, 37.7, 27.1. MS (FAB): m/z (%): 323 (100, [M^þ]),

308 (30, [M^þꢀCH₃]). Anal. Calcd for C₂₁H₂₅NO₂: C, 77.98; H, 7.79; N,

4.33. Found: C, 77.90; H, 7.77; N, 4.27.

hexane). IR (Neat): 2974, 1616, 1507, 1246, 758 cm^ꢀ^{1 1}H NMR

.

(300 MHz, CDCl₃):

d

7.57 (d, 1H, J¼8.7 Hz, ArH), 7.26–7.17 (m, 2H,

ArH), 7.11 (s, 1H, ]CH–Ar), 7.02–7.63 (m, 2H, ArH), 6.52 (dd, 1H,

J₁¼8.7 Hz, J₂¼2.5 Hz, ArH), 6.38 (d, 1H, J¼2.5 Hz, ArH), 3.82 (s, 3H,

OCH₃), 3.77 (s, 3H, OCH₃), 2.65 (s, 2H, 3-H), 1.28 (s, 6H, 2-CH₃). MS

(FAB): m/z (%): 310 (100, [M^þ]), 295 (60, [M^þꢀCH₃]). Anal. Calcd for

3.3.26. (7-Methoxy-2,2,3-trimethyl-chroman-4-yl)-phenyl-

methanone 15a

Yield¼84% as white solid; mp 105 ^ꢁC (dichloromethane); R_f¼0.6

(10% ethyl acetate in hexane). IR (Neat): 2957, 1673, 1617, 1160, 1125,

C

₂₀H₂₂O₃: C, 77.39; H, 7.14. Found: C, 77.27; H, 7.19.

9974

M.K. Parai et al. / Tetrahedron 64 (2008) 9962–9976

702 cm^ꢀ1. ¹H NMR (200 MHz, CDCl₃):

d

7.81 (d, 2H, J¼7.4 Hz, ArH),

55.6, 51.5, 40.2, 28.1, 19.1, 15.5. MS (FAB): m/z (%): 345 (90, [M^þþH]),

205 (100, [M^þꢀCOC₆H₄Cl]). Anal. Calcd for C₂₀H₂₁ClO₃: C, 69.66; H,

6.14. Found: C, 69.77; H, 6.13.

7.54–7.38 (m, 3H, ArH), 6.72 (d, 1H, J¼8.4 Hz, ArH), 6.44 (d, 1H,

J¼1.9 Hz, ArH), 6.36 (d, 1H, J¼8.4 Hz, ArH), 4.19 (d, 1H, J¼11.3 Hz,

ArCH), 3.74 (s, 3H, OCH₃), 2.51–2.42 (m, 1H, CHCH₃), 1.45 {s, 3H,

C(CH₃)₂},1.21 {s, 3H, C(CH₃)₂}, 0.92(d, 3H, J¼6.7 Hz, CHCH₃).¹³C NMR

3.3.31. 7-Methoxy-4-(4-methoxy-benzylidene)-2,2,3-trimethyl-

chroman 16

(50 MHz, CDCl₃):

d 202.67, 160.3, 154.3, 137.6, 133.4, 129.5, 129.1,

113.6,108.0,102.7, 78.3, 55.6, 50.9, 40.2, 28.1,19.6,15.7. MS (FAB): m/z

(%):311 (70, [M^þþH]), 310 (40, [M^þ]), 205 (100, [M^þꢀCOC₆H₅]). Anal.

Calcd for C₂₀H₂₂O₃: C, 77.39; H, 7.14. Found: C, 77.47; H, 7.10.

Yield¼71% as colourless liquid; R_f¼0.6 (8% ethyl acetate in

hexane). IR (Neat): 2928, 1609, 1509, 1457, 1248, 1157, 1036,

830 cm^ꢀ1. ¹H NMR (200 MHz, CDCl₃):

d

7.41 (d, 1H, J¼8.7 Hz, ArH),

7.17 (d, 2H, J¼7.4 Hz, ArH), 6.87–6.75 (m, 3H, ArH, ]CH–Ar), 6.45

(dd, 1H, J₁¼8.7 Hz, J₂¼2.5 Hz, ArH), 6.31 (d, 1H, J¼2.5 Hz, ArH), 3.76

(s, 3H, OCH₃), 3.72 (s, 3H, OCH₃), 2.76–2.70 (m, 1H, CHCH₃), 1.44 {s,

3H, C(CH₃)₂}, 1.30 {s, 3H, C(CH₃)₂}, 1.03 (d, 3H, J¼6.8 Hz, CHCH₃). MS

(FAB): m/z (%): 329 (50, [M^þþH]), 205 (100, [M^þꢀCOC₆H₄F]). Anal.

Calcd for C₂₁H₂₄O₃: C, 77.75; H, 7.46. Found: C, 77.82; H, 7.56.

3.3.27. (3-Methoxy-phenyl)-(7-methoxy-2,2,3-trimethyl-chroman-

4-yl)-methanone 15b

Yield¼79% as colourless oil; R_f¼0.5 (10% ethyl acetate in hex-

ane). IR (Neat): 2973, 2935, 1677, 1615, 1548, 1261, 1165, 1037,

761 cm^ꢀ1. ¹H NMR (200 MHz, CDCl₃):

d 7.45–7.33 (m, 3H, ArH), 7.12

(d, 1H, J¼2.5 Hz, ArH), 6.35 (d, 1H, J¼8.7 Hz, ArH), 6.43 (d, 1H,

J¼2.5 Hz, ArH), 6.35 (dd, 1H, J₁¼8.4 Hz, J₂¼2.5 Hz, ArH), 4.18 (d, 1H,

J¼11.3 Hz, ArCH), 3.81 (s, 3H, OCH₃), 3.74 (s, 3H, OCH₃), 2.32–2.61

(m, 1H, CHCH₃), 1.45 {s, 3H, C(CH₃)₂}, 1.25 {s, 3H, C(CH₃)₂}, 0.93 (d,

3.3.32. [4-(7-Methoxy-2,2,3-trimethyl-chroman-4-ylidenemethyl)-

phenyl]-dimethyl-amine 17

Yield¼73% as pale yellow viscous oil; R_f¼0.7 (10% ethyl acetate

3H, J¼6.8 Hz, CHCH₃). ¹³C NMR (50 MHz, CDCl₃):

d 202.5, 160.3,

in hexane). IR (Neat): 2920, 1595, 1433, 1348, 1158, 1115, 1056,

160.2, 154.4, 139.0, 130.0, 129.1, 122.2, 120.1, 113.6, 108.0, 102.7, 78.4,

55.7, 55.6, 50.8, 40.2, 28.1, 19.6, 15.7. MS (FAB): m/z (%): 341 (50,

[M^þþH]), 205 (100, [M^þꢀCOC₆H₄OCH₃]). Anal. Calcd for C₂₁H₂₄O₄:

C, 74.09; H, 7.11. Found: C, 74.00; H, 7.09.

613 cm^ꢀ1. ¹H NMR (200 MHz, CDCl₃):

d

7.41 (d, 1H, J¼8.7 Hz, ArH),

7.17 (d, 1H, J¼8.8 Hz, ArH), 6.73–6.67 (m, 3H, ArH, ]CH–Ar), 6.44

(dd, 1H, J₁¼8.7 Hz, J₂¼2.5 Hz, ArH), 6.30 (d, 1H, J¼2.5 Hz, ArH), 3.71

(s, 3H, OCH₃), 2.92 {s, 6H, N(CH₃)₂}, 2.82–2.78 (m, 1H, CHCH₃), 1.30

{s, 3H, C(CH₃)₂}, 1.18 {s, 3H, C(CH₃)₂}, 1.12 (d, 3H, J¼6.8 Hz, CHCH₃).

MS (FAB): m/z (%): 338 (100, [M^þþH]). Anal. Calcd for C₂₂H₂₇NO₂: C,

78.30; H, 8.06; N, 4.15. Found: C, 78.22; H, 8.09; N, 4.20.

3.3.28. (4-Fluoro-phenyl)-(7-methoxy-2,2,3-trimethyl-chroman-

4-yl)-methanone 15c

Yield¼83% as light yellow solid; mp 120 ^ꢁC (dichloromethane);

R_f¼0.6 (10% ethyl acetate in hexane). IR (Neat): 2960, 1674, 1618,

3.3.33. Chroman-4-yl-(3-methoxy-phenyl)-methanone 19

1594, 1507, 1161, 1126, 779 cm^ꢀ1. ¹H NMR (200 MHz, CDCl₃):

d

7.91–

Yield¼55% as yellow oil; R_f¼0.6 (10% ethyl acetate in hexane). IR

7.84 (m, 2H, ArH), 7.12–7.03 (t, 2H, ArH), 6.69 (d, 1H, J¼8.7 Hz, ArH),

6.43 (d, 1H, J¼2.5 Hz, ArH), 6.35 (dd, 1H, J₁¼8.4 Hz, J₂¼2.5 Hz, ArH),

4.12 (d, 1H, J¼11.2 Hz, ArCH), 3.74 (s, 3H, OCH₃), 2.48–2.39 (m, 1H,

CHCH₃), 1.45 {s, 3H, C(CH₃)₂}, 1.20 {s, 3H, C(CH₃)₂}, 0.92 (d, 3H,

(Neat): 2932, 1682, 1587, 1488, 1455, 1260, 1227, 1010 cm^ꢀ1. ¹H NMR

(200 MHz, CDCl₃): d 7.62–7.38 (m, 3H, ArH), 7.18–7.12 (m, 2H, ArH),

6.91–6.82 (m, 3H, ArH), 4.81 (t, 1H, J¼5.9 Hz, ArCH), 4.31–4.21 {m,

2H, OCH₂}, 3.85 (s, 3H, OCH₃), 2.30–2.27 (m, 2H, ArCHCH₂). ¹³C NMR

J¼6.8 Hz, CHCH₃). ¹³C NMR (50 MHz, CDCl₃):

d

200.9, 168.5, 163.4,

(50 MHz, CDCl₃): d 201.1, 160.2, 155.3, 145.6, 137.8, 130.0, 128.7,

160.4, 154.2, 133.6, 132.4, 132.2, 128.9, 116.3, 115.9, 113.3, 108.1,

102.8, 78.4, 55.6, 51.3, 40.2, 28.1, 19.5, 15.6. MS (FAB): m/z (%): 329

(50, [M^þþH]), 205 (100, [M^þꢀCOC₆H₄F]). Anal. Calcd for C₂₀H₂₁FO₃:

C, 73.15; H, 6.45. Found: C, 73.08; H, 6.42.

121.5, 120.7, 120.1, 117.5, 113.3, 63.6, 55.7, 42.6, 26.3. MS (FAB): m/z

(%): 269 (100, [M^þþH]), 135 (95, ꢀCOC₆H₄OCH₃). Anal. Calcd for

C

₁₇H₁₆O₃: C, 76.10; H, 6.01. Found: M^þC, 75.93; H, 6.03.

3.3.34. (2-Isopropyl-chroman-4-yl)-phenyl-methanone 21a

Yield¼15% as yellow oil and mixture of diastereomers; R_f¼0.5

(10% ethyl acetate in hexane). IR (Neat): 2964, 1667, 1630, 1589,

3.3.29. 1-(7-Methoxy-2,2,3-trimethyl-chroman-4-yl)-propan-

1-one 15d

Yield¼75% as light yellow viscous oil; R_f¼0.5 (7% ethyl acetate in

1363, 1220, 754 cm^ꢀ^{1 1}H NMR (400 MHz, CDCl₃):

. d 7.93–7.89 (m,

hexane). IR (Neat): 2970, 1703, 1618, 1504, 1267, 1162, 1128,

2H, ArH), 7.55–7.39 (m, 3H, ArH), 7.08–7.06 (m, 1H, ArH), 6.85–6.70

(m, 3H, ArH), 4.78–4.76 (m, 1H, ArCH), 3.86–3.79 {m, 1H, CHCH

(CH₃)₂}, 2.11–2.00 (m, 2H, ArCHCH₂), 1.81–1.79 {m, 1H, CH(CH₃)₂},

1.05–0.79 {m, 6H, CH(CH₃)₂}. MS (FAB): m/z (%): 280 (50, [M^þþH]),

175 (60, M^þꢀCOC₆H₄). Anal. Calcd for C₁₉H₂₀O₂: C, 81.40; H, 7.19.

Found: C, 81.26; H, 7.27.

759 cm^ꢀ1. ¹H NMR (200 MHz, CDCl₃):

d

6.63 (d, 1H, J¼7.9 Hz, ArH),

6.38–6.32 (m, 2H, ArH), 3.67 (s, 3H, OCH₃), 3.26 (d, 1H, J¼11.2 Hz,

ArCH), 2.18 (t, 2H, J¼7.27 Hz, COCH₂CH₂CH₃), 2.09–2.05 (m, 1H,

CHCH₃), 1.55–1.43 (m, 2H, COCH₂CH₂CH₃), 1.36 {s, 3H, C(CH₃)₂}, 1.01

{s, 3H, C(CH₃)₂}, 0.92 (d, 3H, J¼6.8 Hz, CHCH₃), 0.76 (t, 3H, J¼7.3 Hz,

COCH₂CH₂CH₃). ¹³C NMR (50 MHz, CDCl₃):

d 212.3, 160.4, 154.6,

128.9, 111.8, 108.0, 102.7, 78.1, 56.0, 55.5, 40.6, 39.0, 28.2, 19.1, 17.7,

15.4, 14.1. MS (FAB): m/z (%): 277 (20, [M^þþH]), 205 (100,

[M^þꢀCOCH₂CH₂CH₃]). Anal. Calcd for C₁₆H₂₂O₃: C, 73.25; H, 8.45.

Found: C, 73.12; H, 8.38.

3.3.35. (2-Isopropyl-chroman-4-yl)-(3-methoxy-phenyl)-

methanone 21b

Yield¼26% as yellow oil and mixture of diastereomers; R_f¼0.5

(5% ethyl acetate in hexane). IR (Neat): 2963,1683,1586,1486,1458,

1430, 1259, 1143, 756 cm^ꢀ1. ¹H NMR (200 MHz, CDCl₃):

d 7.59–7.36

3.3.30. (4-Chloro-phenyl)-(7-methoxy-2,2,3-trimethyl-chroman-4-

yl)-methanone 15e

(m, 3H, ArH), 7.16–7.10 (m, 2H, ArH), 6.91–6.75 (m, 3H, ArH), 4.80–

4.76 (m, 1H, ArCH), 3.96–3.89 {m, 1H, CHCH(CH₃)₂}, 3.84 (s, 3H,

OCH₃), 2.16–2.03 (m, 2H, ArCHCH₂), 1.90–1.84 {m, 1H, CH(CH₃)₂},

1.05–0.93 {m, 6H, CH(CH₃)₂}. MS (FAB): m/z (%): 311 (90, [M^þþ1]),

135 (50, M^þꢀC₉H₉O). Anal. Calcd for C₂₀H₂₂O₃: C, 77.39; H, 7.14.

Found: C, 77.32; H, 7.21.

Yield¼87% as light yellow solid; mp 107 ^ꢁC (dichloromethane);

R_f¼0.5 (8% ethyl acetate in hexane). IR (Neat): 2977, 2934, 1677,

1616, 1503, 1201, 1162, 1096, 763 cm^ꢀ1. ¹H NMR (200 MHz, CDCl₃):

d

7.77 (d, 2H, J¼8.5 Hz, ArH), 7.37 (d, 2H, J¼8.5 Hz, ArH), 6.68 (d, 1H,

J¼8.5 Hz, ArH), 6.45 (d, 1H, J¼2.4 Hz, ArH), 6.35 (dd, 1H, J₁¼8.5 Hz,

J₂¼2.5 Hz, ArH), 4.09 (d, 1H, J¼11.2 Hz, ArCH), 3.74 (s, 3H, OCH₃),

2.46–2.37 (m, 1H, CHCH₃), 1.44 {s, 3H, C(CH₃)₂},1.19 {s, 3H, C(CH₃)₂},

3.3.36. (4-Chloro-phenyl)-(2,2-dimethylchroman-4-yl)-

methanone 23

0.92 (d, 3H, J¼6.7 Hz, CHCH₃). ¹³C NMR (50 MHz, CDCl₃):

d

201.2,

Yield¼30% as colourless oil; R_f¼0.6 (10% ethyl acetate in hex-

160.4, 154.2, 139.8, 135.5, 131.0, 129.3, 128.9, 113.2, 108.1, 102.9, 78.4,

ane). IR (Neat): 3406, 2924, 1593, 1216, 759 cm^ꢀ^{1 1}H NMR

.

M.K. Parai et al. / Tetrahedron 64 (2008) 9962–9976

9975

(300 MHz, CDCl₃):

d

7.86 (d, 2H, J¼8.5 Hz, ArH), 7.44 (d, 2H,

ArH), 5.19 (s, 1H, ]CH₂), 5.10 (s, 1H, ]CH₂), 4.17 (s, 2H, CH₂Ar), 3.67

(s, 3H, OCH₃), 2.10 (s, 3H, CH₃). ¹³C NMR (50 MHz, CDCl₃): 158.2,

140.9, 138.8, 138.4, 132.5, 129.9, 129.3, 124.6, 124.5, 123.0, 122.5,

117.7, 114.3, 55.6, 32.4, 25.4. MS (FAB): m/z (%): 294 (30, [M^þ]), 279

(100, [M^þꢀCH₃]). Anal. Calcd for C₁₉H₁₈OS: C, 77.51; H, 6.16. Found:

C, 77.55; H, 6.11.

J¼8.5 Hz, ArH), 7.19–7.13 (m, 1H, ArH), 6.88 (m, 3H, ArH), 4.72–4.66

(m, 1H), 2.19–2.02 (m, 2H), 1.45 (s, 3H, CH₃), 1.35 (s, 3H, CH₃). MS

(ESI): m/z (%): 300 (30, Mþ1), 283 (100, [M^þꢀOH]). Anal. Calcd for

C

₁₈H₁₇ClO₂: C, 71.88; H, 5.70. Found: C, 71.95; H, 5.78.

3.3.37. (4-Chloro-phenyl)-(7-methoxy-2,2-dimethyl-thiochroman-

4-yl)-methanone 27a

3.3.42. Dimethyl-[4-(3-methyl-2-methylene-2H-thiochromen-4-yl-

methyl)-phenyl]-amine 29c

Yield¼50% as light yellow oil; R_f¼0.6 (15% ethyl acetate in

hexane). IR (Neat): 2926, 2373, 1650, 1479, 1224, 769 cm^ꢀ1. ¹H NMR

Yield¼59% as light orange viscous oil; R_f¼0.6 (15% ethyl acetate

(200 MHz, CDCl₃):

d

7.81 (d, 2H, J¼8.3 Hz, ArH), 7.37 (d, 2H,

in hexane). IR (Neat): 3406, 2928, 2367, 1519, 1218, 769 cm^ꢀ^{1 1}H

.

J¼8.3 Hz, ArH), 7.25 (d, 1H, J¼8.5 Hz, ArH), 6.71 (d, 1H, J¼2.4 Hz,

ArH), 6.53 (dd, 1H, J₁¼8.5 Hz, J₂¼2.4 Hz, ArH), 4.61–4.52 (m, 1H,

ArCH), 3.79 (s, 3H, OCH₃), 2.29–2.07 (m, 2H, ArCHCH₂), 1.51 {s, 3H,

NMR (200 MHz, CDCl₃): d 7.72–7.61 (m, 1H, ArH), 7.45–7.32 (m, 1H,

ArH), 7.16–7.12 (m, 2H, ArH), 6.86 (d, 2H, J¼8.6 Hz, ArH), 6.52 (d, 2H,

J¼8.6 Hz, ArH), 5.20–5.12 (m, 2H, ]CH₂), 4.12 (s, 2H, CH₂Ar), 2.80

C(CH₃)₂}, 1.42 {s, 3H, C(CH₃)₂}. ¹³C NMR (75 MHz, CDCl₃):

d

199.3,

{s, 6H, N(CH₃)₂}, 2.11 (s, 3H, CH₃). ¹³C NMR (50 MHz, CDCl₃):

d 148.2,

159.2, 138.9, 134.1, 134.0, 130.4, 130.2, 129.9, 127.5, 127.1, 126.7,

120.8, 114.4, 55.2, 49.0, 42.1, 31.0, 30.2, 28.1. MS (FAB): m/z (%): 347

(100, [M^þþH]). Anal. Calcd for C₁₉H₁₉ClO₂S: C, 65.79; H, 5.52.

Found: C, 65.73; H, 5.49.

138.8, 138.3, 130.1, 128.9, 124.4, 123.2, 122.3, 117.6, 113.8, 41.8, 32.3,

25.4. MS (FAB): m/z (%): 307 (100, [M^þ]), 292 (60, [M^þꢀCH₃]). Anal.

Calcd for C₂₀H₂₁NS: C, 78.13; H, 6.88; N, 4.56. Found: C, 78.20; H,

6.94; N, 4.55.

3.3.38. (7-Methoxy-2,2-dimethyl-thiochroman-4-yl)-phenyl-

methanone 27b

3.3.43. 4-Benzyl-3-methyl-2-methylene-2H-thiochromene 29d

Yield¼52% as colourless oil; R_f¼0.6 (10% ethyl acetate in

Yield¼51% as pale yellow semi solid; R_f¼0.5 (10% ethyl acetate in

hexane). IR (Neat): 3462, 2927, 1596, 1434, 730 cm^ꢀ^{1 1}H NMR

.

hexane). IR (Neat): 2931, 2363, 1678, 1596, 1223, 1045, 771 cm^ꢀ1. ¹H

(200 MHz, CDCl₃):

7.28–7.09 (m, 7H, ArH), 5.27 (s, 1H, ]CH₂), 5.17 (s, 1H, ]CH₂), 4.31

(s, 2H, CH₂Ar), 2.17 (s, 3H, CH₃). ¹³C NMR (50 MHz, CDCl₃):

142.7,

d 7.81–7.77 (m, 1H, ArH), 7.50–7.45 (m, 1H, ArH),

NMR (200 MHz, CDCl₃):

d

7.83 (d, 2H, J¼8.5 Hz, ArH), 7.47–7.32 (m,

3H, ArH), 6.78 (d, 1H, J¼8.5 Hz, ArH), 6.64 (d, 1H, J¼2.6 Hz, ArH),

6.46 (dd, 1H, J₁¼8.5 Hz, J₂¼2.6 Hz, ArH), 4.61–4.55 (m, 1H, ArCH),

3.68 (s, 3H, OCH₃), 2.23–2.04 (m, 2H, ArCHCH₂), 1.41 {s, 3H,

d

140.9, 140.5, 138.8, 138.4, 129.5, 128.8, 128.4, 126.3, 124.6, 124.5,

123.0, 122.5, 117.7, 33.3, 30.1, 25.4. MS (FAB): m/z (%): 264 (100,

[M^þ]). Anal. Calcd for C₁₈H₁₆S: C, 81.77; H, 6.10. Found: C, 81.74; H,

6.19.

C(CH₃)₂}, 1.33 {s, 3H, C(CH₃)₂}. ¹³C NMR (75 MHz, CDCl₃):

d 198.3,

159.2, 136.1, 134.5, 133.4, 131.2, 128.9, 127.5, 127.1, 121.8, 114.4, 55.6,

48.7, 42.0, 31.4, 30.2, 28.6. MS (FAB): m/z (%): 312 (100, [M^þ]). Anal.

Calcd for C₁₉H₂₀O₂S: C, 73.04; H, 6.45. Found: C, 72.91; H, 6.44.

3.3.44. 4-(4-Chloro-benzyl)-3-methyl-2-methylene-2H-

thiochromene 29e

3.3.39. (7-Methoxy-2,2-dimethyl-thiochroman-4-yl)-(3-nitro-

phenyl)-methanone 27c

Yield¼62% as colourless viscous oil. IR (Neat): 3406, 2924, 1593,

1216, 759 cm^ꢀ1

.

¹H NMR (200 MHz, CDCl₃):

d

7.83 (d, 1H, J¼8 Hz,

Yield¼60% as brown viscous oil; R_f¼0.5 (15% ethyl acetate in

ArH), 7.50 (d, 1H, J¼8 Hz, ArH), 7.40–7.20 (m, 2H, ArH), 7.19 (d, 2H,

J¼8 Hz, ArH), 7.10 (d, 2H, J¼8 Hz, ArH), 5.30 (s, 1H, ]CH₂), 5.17 (s,

1H, ]CH₂), 4.29 (s, 2H, CH₂Ar), 2.17 (s, 3H, CH₃). ¹³C NMR (50 MHz,

hexane). IR (KBr): 2925, 1670, 1600, 1348, 1238, 1033, 711 cm^ꢀ1. ¹H

NMR (200 MHz, CDCl₃):

d

8.65 (s, 1H, ArH), 8.27 (d, 1H, J¼8.1 Hz,

ArH), 8.01 (d, 1H, J¼7.7 Hz, ArH), 7.51 (t, 1H, J¼7.9 Hz, ArH), 6.74 (d,

1H, J¼8.5 Hz, ArH), 6.66 (d, 1H, J¼2.6 Hz, ArH), 6.45 (dd, 1H,

J₁¼8.5 Hz, J₂¼2.6 Hz, ArH), 4.59–4.50 (m, 1H, ArCH), 3.67 (s, 3H,

OCH₃), 2.23–1.96 (m, 2H, ArCHCH₂), 1.40 {d, 6H, J¼7.3 Hz, C(CH₃)₂}.

CDCl₃): d 142.6, 140.2, 138.5, 138.4, 137.8, 131.7, 129.3, 128.5, 124.3,

124.2, 122.4, 122.1, 117.4, 32.2, 25.0. MS (FAB): m/z (%): 297 (30,

[M^þꢀH]). Anal. Calcd for C₁₈H₁₅ClS: C, 72.35; H, 5.06. Found: C,

72.22; H, 4.88.

¹³C NMR (50 MHz, CDCl₃):

d 199.8, 159.0, 148.9, 137.1, 135.2, 130.4,

130.2, 127.5, 124.6, 122.7, 112.8, 112.4, 55.6, 49.0, 42.7, 31.0, 30.0,

3.3.45. 4-(3-Methyl-2-methylene-2H-thiochromen-4-yl-methyl)-

benzonitrile 29f

28.8. MS (FAB): m/z (%): 358 (100, [M^þ]). Anal. Calcd for

C

3.90.

₁₉H₁₉NO₄S: C, 63.85; H, 5.36; N, 3.92. Found: C, 63.97; H, 5.36; N,

Yield¼65% as pale yellow viscous oil. R_f¼0.6 (10% ethyl acetate in

hexane). IR (Neat): 3405, 1728, 1608, 1216, 759 cm^ꢀ^{1 1}H NMR

.

(200 MHz, CDCl₃):

d

7.85 (d, 1H, J¼8 Hz, ArH), 7.54 (d, 2H, J¼8 Hz,

3.3.40. 3-Methyl-2-methylene-4-(3-nitro-benzyl)-2H-

thiochromene 29a

ArH), 7.42–7.20 (m, 5H, ArH), 5.29 (s, 1H, ]CH₂), 5.09 (s, 1H, ]CH₂),

4.35 (s, 2H, CH₂Ar), 2.16 (s, 3H, CH₃). ¹³C NMR (50 MHz, CDCl₃):

Yield¼63% as pale yellow oil; R_f¼0.5 (15% ethyl acetate in hex-

d 145.8, 139.9, 138.5, 137.8, 132.3, 128.7, 127.3, 124.5, 124.3, 122.3,

ane). IR (Neat): 3451, 2924, 2368, 1529, 1349, 1218, 768 cm^ꢀ1

.

¹H

122.1, 117.5, 110.0, 32.9, 29.6, 25.0. MS (FAB): m/z (%): 288 (40,

[M^þꢀH]). Anal. Calcd for C₁₉H₁₅NS: C, 78.86; H, 5.22; N, 4.84.

Found: C, 78.71; H, 5.28; N, 4.83.

NMR (200 MHz, CDCl₃): d 7.97–7.93 (m, 2H, ArH), 7.76–7.71 (m, 1H,

ArH), 7.36–7.17 (m, 2H, ArH), 5.23 (s, 1H, ]CH₂), 5.06 (s, 1H, ]CH₂),

4.32 (s, 2H, CH₂Ar), 2.10 (s, 3H, CH₃). ¹³C NMR (50 MHz, CDCl₃):

d

148.9, 143.7, 142.7, 140.2, 139.0, 138.3, 134.4, 129.8, 127.7, 124.9,

3.3.46. 4-(2,4-Dichloro-benzyl)-3-methyl-2-methylene-2H-

thiochromene 29g

124.8, 123.4, 122.8, 122.5, 121.7, 118.1, 32.9, 25.4. MS (FAB): m/z (%):

309 (60, [M^þ]). Anal. Calcd for C₁₈H₁₅NO₂S: C, 69.88; H, 4.89; N,

4.53. Found: C, 69.97; H, 4.88; N, 4.47.

Yield¼61% as colourless viscous oil; R_f¼0.5 (10% ethyl acetate in

hexane). IR (Neat): 3422, 1649, 1517, 1216, 761 cm^ꢀ^{1 1}H NMR

.

(200 MHz, CDCl₃):

d

7.82 (d, 1H, J¼7.8 Hz, ArH), 7.60 (d, 2H, J¼8 Hz,

3.3.41. 4-(4-Methoxy-benzyl)-3-methyl-2-methylene-2H-

thiochromene 29b

ArH), 7.48–7.26 (m, 5H, ArH), 5.26 (s, 1H, ]CH₂), 5.06 (s, 1H, ]CH₂),

4.30 (s, 2H, CH₂Ar), 2.16 (s, 3H, CH₃). ¹³C NMR (50 MHz, CDCl₃):

Yield¼53% as white solid; R_f¼0.5 (10% ethyl acetate in hexane).

d 143.2, 140.0, 138.4, 138.3, 137.6, 132.5, 129.8, 129.0, 127.1, 124.5,

IR (KBr): 3415, 2929, 2362,1611, 1510,1247, 1035, 743 cm^ꢀ1. ¹H NMR

124.4, 122.3, 122.2, 117.4, 30.2, 24.9. MS (FAB): m/z (%): 333 (100,

[M^þꢀH]). Anal. Calcd for C₁₈H₁₄Cl₂S: C, 64.87; H, 4.23. Found: C,

64.93; H, 4.24.

(200 MHz, CDCl₃):

d 7.72–7.69 (m, 1H, ArH), 7.40–7.39 (m, 1H, ArH),

7.21–7.16 (m, 2H, ArH), 6.97–6.92 (m, 2H, ArH), 6.72–6.66 (m, 2H,

9976

M.K. Parai et al. / Tetrahedron 64 (2008) 9962–9976

3.3.47. 3-Methyl-4-(4-methyl-benzyl)-2-methylene-2H-

thiochromene 29h

Maloy, Shagufta and Ajay thank CSIR for providing fellowships. We

thank SAIF, CDRI, Lucknow for providing spectral data and referee

for the constructive criticism.

Yield¼57% as brown oil; R_f¼0.7 (8% ethyl acetate in hexane). IR

(Neat): 3432, 1216, 760 cm^ꢀ1. ¹H NMR (200 MHz, CDCl₃):

d 7.80 (d,

1H, J¼7.8 Hz, ArH), 7.51 (d, 1H, J¼8 Hz, ArH), 7.38–7.26 (m, 2H, ArH),

7.15–6.90 (m, 4H, ArH), 5.26 (s, 1H, ]CH₂), 5.18 (s, 1H, ]CH₂), 4.27

(s, 2H, CH₂Ar), 2.28 (s, 3H, CH₃), 2.17 (s, 3H, CH₃). ¹³C NMR (75 MHz,

Supplementary data

Supplementary data associated with this article can be found in

the online version, at doi:10.1016/j.tet.2008.07.106.

CDCl₃):

d 143.0, 141.1, 140.8, 139.2, 138.8, 129.1, 128.7, 128.3, 126.6,

124.5, 124.3, 123.4, 122.9, 117.6, 33.5, 31.2, 23.1. MS (FAB): m/z (%):

277 (90, [M^þꢀH]). Anal. Calcd for C₁₉H₁₈S: C, 81.97; H, 6.52. Found:

C, 81.94; H, 6.45.

References and notes

3.3.48. 4-Bromo-5-(4-ﬂuoro-benzylidene)-2,3,4,5-tetrahydro-

benzo[b]thiepine 48

1. (a) Miyaura, N.; Ishikawa, M.; Suzuki, A. Tetrahedron Lett. 1992, 33, 2571–2574;

(b) Effenberger, F.; Kesmarszky, T. Chem. Ber. 1992, 125, 2103 and references

therein.

2. Corey, E. J.; Kirst, H. A.; Katzenellenbogen, J. A. J. Am. Chem. Soc. 1970, 92,

6314–6320.

3. (a) Shi, Y.-L.; Shi, M. Org. Lett. 2005, 7, 3057–3060 and references cited therein;

(b) Jang, K. H.; Lee, B. H.; Choi, B. W.; Lee, H.-S.; Shin, J. J. Nat. Prod. 2005, 68,

716–723.

Yield¼51% as brown viscous oil; R_f¼0.7 (10% ethyl acetate in

hexane). IR (Neat): 3442, 2360, 1651, 1525, 1217, 1022, 771 cm^ꢀ1. ¹H

NMR (200 MHz, CDCl₃): d 7.47–7.38 (m, 3H, ArH), 7.18–6.97 (m, 5H,

ArH), 6.86 (s, 1H, ]CHAr), 4.99–4.94 (m, 1H, CHBr), 3.58–3.48 (m,

2H, SCH₂), 2.29–2.21 (m, 1H, SCH₂CH₂), 2.06–1.98 (m, 1H, SCH₂CH₂).

4. (a) Van der Drift, R. C.; Bouwman, E.; Drent, E. J. Organomet. Chem. 2002, 650,

¹³C NMR (50 MHz, CDCl₃):

d 161.3, 140.3, 138.5, 134.4, 134.1, 130.3,

´

1–27; (b) Uma, R.; Crevisy, C.; Gree, R. Chem. Rev. 2003, 103, 27 and references

therein; (c) Trost, B. M. Angew. Chem., Int. Ed. Engl. 1995, 34, 259.

5. (a) Andrist, A. H.; Slivon, L. E.; Graas, J. E. J. Org. Chem. 1978, 43, 634–637; (b)

Otsuka, S.; Tani, K. Synthesis 1991, 665; (c) Tanaka, K.; Fu, G. C. J. Org. Chem.

2001, 66, 8177–8186 and references therein; (d) Kitamura, M.; Manabe, K.;

Noyori, R.; Takaya, H. Tetrahedron Lett. 1987, 28, 4719–4720; (e) Larson, G. L.;

Prieto, J. A.; Hernandez, A. Tetrahedron Lett. 1981, 22, 1575–1578; (g) Bankston,

D.; Fang, F.; Huie, E.; Xie, S. J. Org. Chem. 1999, 64, 3461–3466; (h) Negishi, E.;

Zhang, Y.; Bagheri, V. Tetrahedron Lett. 1987, 28, 5793–5796; (i) Denmark, S. E.;

Rivera, I. J. Org. Chem. 1994, 59, 6887–6889; (j) Hanessian, S.; Delorme, D.;

Beaudoin, S.; Leblanc, Y. J. Am. Chem. Soc. 1984, 106, 5754–5756; (k) Denmark,

S. E.; Amburgey, J. J. Am. Chem. Soc. 1993, 115, 10386–10387; (l) Corey, E. J.;

Seibel, W. L. Tetrahedron Lett. 1986, 27, 905–908; (m) Liebeskind, L. S.; Mitchell,

D.; Foster, B. S. J. Am. Chem. Soc. 1987, 109, 7908–7910; (n) Hutchinson, D. K.;

Fuchs, P. L. J. Am. Chem. Soc. 1987, 109, 4755–4756; (o) Shibasaki, M.; Sodeoka,

M.; Ogawa, Y. J. Org. Chem. 1984, 49, 4096–4098; (p) Negishi, E.; Zhang, Y.;

Cederbaum, F. E.; Webb, M. B. J. Org. Chem. 1986, 51, 4080–4082; (q) Cho, S. H.;

Liebeskind, L. S. J. Org. Chem. 1987, 52, 2631–2634.

129.8, 128.8, 126.4, 126.1, 125.7, 123.4, 114.3, 113.0, 39.3, 32.4, 31.3.

MS (FAB): m/z (%): 349 (100, [M^þ]). Anal. Calcd for C₁₇H₁₄BrFS: C,

58.46; H, 4.04. Found: C, 58.60; H, 4.11.

3.3.49. (E)-4-Bromo-8-methoxy-5-(3-methoxybenzyl)-2,3-

dihydrobenzo[b]thiepine 49

Yield¼53% as brown viscous oil; R_f¼0.7 (10% ethyl acetate in

hexane). IR (Neat): 3012, 2937, 2369, 1600, 1477, 1219, 1042,

768 cm^ꢀ1. ¹H NMR (300 MHz, CDCl₃):

d

7.44 (d, 1H, J¼8.7 Hz, ArH),

7.29 (s, 1H, ArH), 7.18 (t, 1H, J¼7.8 Hz, ArH), 6.92 (dd, 1H, J₁¼2.1 Hz,

J₂¼9.0 Hz, ArH), 6.72 (t, 3H, J¼7.8 Hz, ArH), 4.15 (s, 2H, Ar–CH₂), 3.86

(s, 3H, OCH₃), 3.75 (s, 3H, OCH₃), 3.58–3.51 (m, 2H, SCH₂), 3.44–3.36

(m, 2H). ¹³C NMR (75 MHz, CDCl₃):

d 159.8, 157.4, 141.0, 139.8, 134.4,

6. (a) Shagufta; Parai, M. K.; Panda, G. Tetrahedron Lett. 2005, 46, 8849–8852; (b)

Shagufta; Srivastava, A. K.; Panda, G. Tetrahedron Lett. 2006, 47, 1065–1070.

7. (a) Tani, K.; Yamagata, T.; Akutagawa, S.; Kumobayashi, H.; Taketomi, T.; Takaya,

H.; Miyashita, A.; Noyori, R.; Otsuka, S. J. Am. Chem. Soc. 1984, 106, 5208–5217;

(b) See Ref. 5b; (c) Chapuis, C.; Barthe, M.; de Saint Laumer, J.-Y. Helv. Chim. Acta

2001, 84, 230.

134.0, 130.5, 129.5, 122.8, 120.4, 114.1, 114.0, 111.3, 105.0, 55.5, 55.0,

32.3, 32.1, 31.3. MS (FAB): m/z (%): 390 (97, M^þ), 391 (78, Mþ1), 392

(100, Mþ2), 393 (22, Mþ3). Anal. Calcd for C₁₉H₁₉BrO₂S: C, 58.32;

H, 4.89. Found: C, 58.37; H, 4.86.

8. Akuamoah, R. K.; Brown, P. E.; Marcus, W. Y.; Steele, J. E. J. Chem. Soc., Perkin

Trans. 1 1995, 197.

3.3.50. (E)-5-Benzyl-4-bromo-8-methoxy-2,3-

dihydrobenzo[b]thiepine 50

9. (a) Gabbutt, C. D.; Hartley, D. J.; Hepworth, J. D.; Heron, B. M.; Kanjia, M.;

Rahman, M. M. Tetrahedron 1994, 50, 2507–2522; (b) Gabbutt, C. D.; Hepworth,

J. D.; Heron, B. M. J. Chem. Soc., Perkin Trans. 1 1994, 653.

10. The Conformational Analysis of Cyclohexenes, Cyclohexadienes and Related

Hydroaromatic Compounds, Methods in Stereochemical Analysis; Rabideau, P. W.,

Ed.; Wiley-VCH: Germany, 1989; p 1.

11. (a) Johnson, F. Chem. Rev. 1968, 68, 375; (b) Hoffman, R. W. Chem. Rev. 1989, 89,

1841–1860; (c) The Conformational Analysis of 1,4-Cyclohexadienes and

Related Hydroaromatics. In The Conformational Analysis of Cyclohexenes, Cyclo-

hexadienes and Related Hydroaromatic Compounds; Rabideau, P. W., Ed.; Wiley-

VCH: Germany, 1989a; pp 47–63; (d) Gundermann, K. D. Angew. Chem., Int. Ed.

Engl. 1963, 2, 674–683; (e) Smith, D. G. J. Chem. Soc., Perkin Trans. 1 1990,

3187–3191; (f) Mackenzie, N. E.; Thomson, R. H. J. Chem. Soc., Perkin Trans. 1

1982, 395–402.

Yield¼57% as pale yellow oil; R_f¼0.7 (10% ethyl acetate in

hexane). IR (Neat): 3062, 2995, 2835, 2366, 1602, 1478, 1268, 1233,

1059, 760 cm^ꢀ1. ¹H NMR (300 MHz, CDCl₃):

d

7.39 (d, 1H, J¼8.7 Hz,

ArH), 7.24 (t, 3H, J¼9.6 Hz, ArH), 7.17 (d, 1H, J¼6.9 Hz, ArH), 7.11 (d,

2H, J¼7.5 Hz, ArH), 6.89 (dd, 1H, J₁¼2.1 Hz, J₂¼9.0 Hz, ArH), 4.15

(s, 2H, ArCH₂), 3.83 (s, 3H, OCH₃), 3.49 (t, 2H, J¼6.2 Hz, SCH₂), 3.38

(d, 2H, J¼6.3 Hz). ¹³C NMR (50 MHz, CDCl₃):

d 158.6, 141.8, 138.4,

134.4, 134.1, 132.5, 128.5, 127.2, 124.8, 114.0, 111.3, 108.0, 55.5, 33.3,

32.6, 31.0. MS (FAB): m/z (%): 360 (98, M^þ), 361 (42, Mþ1), 362 (100,

Mþ2), 363 (32, Mþ3). Anal. Calcd for C₁₈H₁₇BrOS: C, 59.84; H, 4.74.

Found: C, 59.88; H, 4.75.

12. Tondon, V. K.; Khanna, J. M.; Anand, N.; Srimal, R. C.; Prasad, C. R.; Kar, K. Indian

J. Chem. 1975, 13, 1–8.

13. (a) De´silets, S.; St-Jacques, M. J. Am. Chem. Soc. 1987, 109, 1641–1648; (b)

´

Desilets, S.; St-Jacques, M. Tetrahedron 1988, 44, 7027–7036; (c) Menard, D.;

St-Jacques, M. Tetrahedron 1983, 39, 1041–1060; (d) Lachapelle, A.; St-Jacques,

M. Can. J. Chem. 1987, 65, 2575.

Acknowledgements

This research project was partly supported by Department of

Science and Technology (SR/S1/OC-23/2005), New Delhi, India.

14. Shagufta; Raghunandan, R.; Maulik, P. R.; Panda, G. Tetrahedron Lett. 2005, 46,

5337–5341.

Article Doi

An unexpected reaction of phosphorous tribromide on chromanone, thiochromanone, 3,4-dihydro-2H-benzo[b]thiepin-5-one, 3,4-dihydro-2H-benzo[b]oxepin-5-one and tetralone derived allylic alcohols: a case study

DOI: 10.1016/j.tet.2008.07.106

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