Synthesis of benzo[g]isochromenes through Photo-Dehydro-Diels-Alder reaction

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Helvetica Chimica Acta – Vol.89 (2006)

Synthesis of Benzo[g]isochromenes through Photo-Dehydro-Diels–Alder

Reaction

by Pablo Wessig*, Gunnar Müller, Robert Herre, and Andreas Kühn

Institut für Chemie der Humboldt-Universität zu Berlin, Brook-Taylor-Str.2, D-12489 Berlin

(phone: +49-3020937455; fax: +49-3020937450; e-mail: pablo.wessig@chemie.hu-berlin.de)

The Photo-Dehydro-Diels–Alder (PDDA) reaction is shown to be a versatile method for the prep-

aration of highly functionalized naphthalenes.Thus, ketones 1 could be cyclized to the 1H-benzo[g]iso-

chromen-4-(3H)-ones 11 and 12, mostly in good yields.The influence of various substituents on the regio-

selectivity of the reaction was investigated, and the mechanism is discussed based on theoretical calcu-

lations.

1. Introduction. – The Diels–Alder reaction, i.e., the [4+2] cycloaddition of a diene

and an alkene (or alkyne), including hetero-analogues, belongs to the most-versatile

methods for the preparation of carbo- and heterocyclic six-membered rings, and has

been applied in a huge number of natural product syntheses [1].When an enyne or

an arylacetylene A instead of a diene reacts with an alkyne B, cyclic allenes C are

formed, which are unstable in most cases and undergo hydrogen migration to afford

an aromatic ring, i.e., naphthalenes D (Scheme 1).This process is called Dehydro-

Diels–Alder (DDA) reaction, and both thermal [2] and transition-metal-catalyzed

processes [3] are well-known for a long time.

Scheme 1. Dehydro-Diels–Alder Reaction

In contrast to thermally initiated DDA processes, little is known about the photo-

chemical variants of this reaction [4].Very recently, we reported on the first systematic

investigation of the Photo-Dehydro-Diels–Alder (PDDA) reaction and its application

in the synthesis of highly functionalized naphthalenes [5].Herein, we describe the prep-

aration of 1H-benzo[g]isochromen-4-(3H)-ones through intramolecular PDDA reac-

tion of different 4-aryl-1-[(3-arylprop-2-yn)oxy]but-3-yn-2-ones 1 (see Scheme 2

below).

ꢀ 2006 Verlag Helvetica Chimica Acta AG, Zürich

Helvetica Chimica Acta – Vol.89 (2006)

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It should be noted that the 1H-benzo[g]isochromen-4-one¹) scaffold is contained in

some natural products exhibiting very interesting biological activities.The most-

acquainted representative is surely hongconin, a constituent of the plant Eleutherine

americana M^ERR.et H EYNE (Iridaceae), also known as ꢁHong-Congꢂ in Chinese

[6a,b].Hongconin, as well as other constituents with similar structures, have been

shown to exhibit cardioprotective activities, and a series of total syntheses of hongconin

have been reported [6c–h].

2. Results and Discussion. – 2.1. Synthesis of Ketones. To investigate the influence of

structural variations on the photochemical behavior, we prepared a total of 18 com-

pounds (1a–r), either differing in the Ar¹, Ar²substituents (1a–n) or the R substituent

(1o–r), as shown in Schemes 2 and 3 and Table 1.The synthesis of ketones 1a–n com-

menced, in most cases, with ethyl glycolate (2).After alkylation of 2 with propargyl bro-

mide, the resulting ether 3 was subjected to Sonogashira coupling [7] with different aryl

iodides (Ar¹I).The thus obtained compounds 4 were converted [8] into the correspond-

ing Weinreb amides 5 in two steps (with the exception of 5d,f; see below).Treatment of

compounds 5 with different lithium arylacetylenides then afforded the target ketones

1a–n in yields of 44–92% (Table 1).

Table 1. Substituents and Yields of Compounds 1a–n

Entry

Series

Ar¹

Ar²

Yield [%]

1

2

3

4

5

6

7

8

9

10

11

12

13

14

a

b

c

d

e

f

g

h

i

j

k

l

m

n

C

N

C₆

G

79

62

67

64

70

57

66

67

78

61

53

92

37

64

R

N

E

4-Cl-C₆

4-F-C₆H₄

4-Me-C₆H₄

1-Naphthyl

C₆H₅

4-Me-SO₂-C₆

3,5-Me₂-C₆H₃

4-CF₃-C₆H₄

C₆H₅

Mesityl

H₄

C

ACHTREUNG

1-Naphthyl

C

G

ACHTREUNG

Mesityl^a)

C₆H₅

^a) Mesityl=2,4,6-trimethylphenyl.

Notably, the Sonogashira coupling of the 4-fluoro-substituted iodobenzene 6a and

the iodomesitylene 6b with 3 failed.Therefore, compounds 5d and 5f were prepared by

a slightly different route involving the propargyl alcohols 7a and 7b, respectively, as

shown in Scheme 2 and Table 2.

The preparation of the branched ketones 1o–r required a different approach

(Scheme 3).Starting with the aldehydes 8, the propargyl alcohols 9 were prepared by

1

)

Chemical Abstractsꢂ name: 1H-naphtho[2,3-c]pyran-4(3H)-one.

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Scheme 2. Synthesis of the Target Ketones 1a–n

i) [PdCl₂(PPh₃)₂], CuI, (i-Pr)₂

MeOH; 3.MeO(Me)NH·HCl, (i-Pr)

MeO(Me)NH·HCl, (i-Pr)₂NEt, TBTU (=2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium tetra-

ACHTREUNG

AHCTREUNG

fluoroborate).

Table 2. Yields of compounds 4 and 5

Entry

Series

Ar¹

Yield [%]

4

5

1

2

3

4

5

6

a

b

c

d

e

f

Ph

70

68

67

56^a)

46

–

99

87

93

98

25^c)

4-Cl-C₆

4-Me-C

4-F-C₆H₄

1-Naphthyl

Mesityl^b)

G

U

T

^a) From 7a. ^b) Mesityl=2,4,6-trimethylphenyl. ^c) Over two steps from 7b.

treatment with lithium phenylacetylide (LPA).The conversion of 9 into the O-prop-

argyl glycolic acids 10 was performed either by direct alkylation with bromoacetic

acid (1o–q; Method A) or by alkylation with ethyl bromoacetate followed by saponi-

fication (1r; Method B).Finally, the target ketones 1o–r were obtained in two steps

via the corresponding Weinreb amides (WA).

2.2. Photochemical Behavior of the Ketones 1.To find the optimal irradiation con-

ditions, we explored at first the product distribution on irradiation of the parent com-

pound 1a in different solvents.The results are summarized in Table 3.As previously

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Scheme 3. Synthesis of the Target Ketones 1o–r

described [5], we assume that the photochemical ring-closure proceeds via the biradi-

cals BR(1) as intermediates (Scheme 4).At this stage, two regioisomeric 1 H-benzo[g]-

isochromen-4-(3H)-ones, i.e., compounds 11 and 12, may be formed.The highest total

yield (77%) of 11a and 12a was obtained when the reaction was run in t-BuOH as sol-

vent (Table 3, Entry 3).However, the regioselectivity was low ( 11a/12a 1.3 :1) and was

not influenced by the solvent.Interestingly, degassing the solution with N ₂had, at best,

a negative influence on the yields (Entries 1 and 2).

Table 3. Yields and Product Distribution upon Irradiation of 1a.For details, see Exper. Part.

Entry

Solvent

11a+12a [%]

11a/12a

13a [%]

14a+15a [%]

1

2

3

4

MeOH^a)

MeOH^b)

t-BuOH

MeCN

44

41

77

29

1.

1.3:1

3:1

20

18

12

9

0

9

11

^a) Not degassed (aerobic). ^b) Degassed with N₂(anaerobic).

Surprisingly, on irradiation of 1a in MeOH, we obtained the 3-oxabicyclo[4.2.0]oct-

7-en-5-one 13a as a by-product.Presumably, this compound was formed by cyclization

of the biradical BR(1) to the cyclobutadiene CBD(1), competing with the PDDA reac-

tion, and Michael-type addition of the solvent on the isomeric cyclobutadiene CBD(2).

The structure of 13a was unambiguously established by X-ray crystal-structure analysis

(Fig. 1).

It is known that the [2+2] cycloaddition of two acetylene moieties to an anti-aro-

matic cyclobutadiene ring may take place purely thermally from highly strained cyclic

acetylenes [9], or between ethynylsulfones and ynamines [10], or mediated by Co com-

plexes [11].On the other hand, little is known about the photochemical realization of

this reaction.In 1998, Maier and Lautz [12] reported the spectroscopic properties of

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Scheme 4. Photochemical Behavior of 1a–l

cyclobutadiene upon irradiation of the T-shaped acetylene dimer in a Xe matrix at 10

K.

The third kind of by-products, almost always formed in low yields, were the alde-

hydes 14 and the ynones 15 (Scheme 4).They presumably arose from a photochemically

initiated intramolecular hydrogen migration, followed by a Norrish type-II cleavage

[13] of the corresponding 1,4-biradical.At present, we cannot rule out that compounds

14 and 15 are formed by a photochemically initiated one-step retro-ene-like process

[14], rather than in two steps via biradicals.

With the detailed irradiation results of compound 1a at hand, we next investigated

the congeners 1b–n²).In almost all cases, we obtained the corresponding 1 H-benzo-

[g]isochromen-4-(3H)-ones 11 and 12 in moderate-to-good yields, albeit often with

low regioselectivity (Table 4).A considerable preference of 11 over 12 was achieved,

2

)

Even though t-BuOH was well-suited as solvent in the case of 12a, the low solubility of some reac-

tants 1 required the use of MeCN or MeOH.

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Fig.1. X-Ray crystal structures of 13a and 18o.For details, see Table 5.

Table 4. Yields and Product Distribution upon Irradiation of 1b–n in Different Solvents.For details, see

Exper. Part.

Substrate

Solvent

11+12 [%]

11/12

1b

1c

1d

1e

1f

1g

1h

1i

1j

1k

1l

1m^b)

1n^c)

MeOH

MeCN

t-BuOH

MeCN

t-BuOH

MeCN

t-BuOH

MeCN

t-BuOH

52

65

45

42

73

76

0^a)

46

54

34

49

75

1.2 :1

1.6 :1

1.7:1

1.1:1

1.2 :1

–

6.6 :1

1.2 :1

2.4 :1

3.5 :1

1.9 :1

^a)Compounds 14 and 15 were formed exclusively. ^b)The data refer to 16+12m (yield) and 16m/12 (ratio),

c

resp. ) The data refer to 11n+17 (yield) and 11n/17 (ratio), resp.(see Scheme 5).

though, by introduction of a strongly electron-accepting methanesulfonyl (mesyl)

group in 4-position of Ar¹(Table 4; 1j).

Compounds 1m,n, bearing a mesityl group either as Ar¹or as Ar², were investigated

to find out whether Me groups in ortho position are able to suppress the attack of these

positions and, consequently, the formation of the appropriate regioisomers.Although

the naphthalenes 12m (from 1m) and 11n (from 1n) were formed as main products,

we also isolated compounds 16 and 17, originating from an attack of the mesityl

group.In contrast to our previous observation [5], we found that the Me group in

the attacked position does not undergo a 1,2-migration, but is obviously trapped by

the solvent (XH) from cycloallenes CA(1) and CA(3), respectively (Scheme 5).

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Scheme 5. Photochemical Behavior of 1m and 1n

Compounds 1o–1r are branched at the sp³C-atom of the propargyl moiety.Com-

paring the two transition states TS(1) and TS(2) formed from the biradical BR(2), in

the transition state TS(1) a steric hindrance between the upper phenyl group and the

residue R may be expected, in contrast to TS(2) (Scheme 6).Consequently, we

expected that products 19 are preferentially formed, depending on the size of the res-

idue R.In fact, we observed that increasing steric demand of R increases the selectivity

in favor of 19.Whereas a Me group ( 1l) gave rise only to a slight excess of 19, the ratio

18/19 increased to 1:2.3 in the case of an i-Pr group (1p), and the presence of a t-butyl

group (1q) completely suppressed the formation of 18, and only 19 was isolated

(Scheme 6).Remarkably, a Ph group ( 1r) had only a marginal influence, suggesting

Helvetica Chimica Acta – Vol.89 (2006)

Scheme 6. Photochemical Behavior of 1o–r

2701

that p-stacking in 18 partly compensates the steric repulsion.An unambiguous struc-

tural assignment of 18o was possible by X-ray crystal-structure analysis (Fig. 1).

2.3. Mechanism of Photocyclization. The mechanism of the PDDA reaction was

previously discussed in detail [5].Herein, only some special features of the new system

will be elucidated³).For that, we have calculated the geometries and energies of the dif-

ferent species involved in the reaction of the parent compound 1a by means of DFT

methods (B3LYP/6-311++G**//B3LYP/6-31G*), and the results are summarized in

Scheme 7.

After photochemical excitation of the ketones 1, an intersystem crossing (ISC)

takes place, as indicated by the observation that no reaction took place upon addition

of a triplet quencher (isoprene).The efficient ISC can be rationalized by the conversion

3

)

More-detailed supporting information is available on request from the corresponding author (P. W.).

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1

3

of the initially formed (n-p*) state into the (p-p*) state, which favors this process

according to the El-Sayed rules [15].

The first CꢀC-bond formation between two acetylenic C-atoms proceeds via a very

small activation barrier (3.3 kcal/mol), which is considerably smaller than in the previ-

ously investigated system [5].Obviously, the longer chain between the acetylene units

lowers this barrier owing to smaller ring strain in the transition state.The geometry of

this transition state, TS(3), is depicted in Fig. 2.The initial step, which is strongly exo-

thermic (DE=ꢀ34.5 kcal/mol), results in the formation of biradical BR(3) (Scheme 7).

From this key intermediate, three processes may take place: the lower radical center

attacks the upper phenyl ring (A); the upper radical center attacks the lower phenyl

ring (B); or the radical centers recombine (C).Considering the energies of activation

via the corresponding transition states TS(4)–TS(6) at the triplet (T) potential-energy

surface (19.7–21.5 kcal/mol), it is expected that BR(3) is relatively long-lived and

should be trapped by suitable reagents.For this purpose, we irradiated 1a in the pres-

ence of various alkenes, but observed no influence upon the reaction course.Obviously,

at the stage of BR(3) the system turns back to the singlet (S) state, which is very likely

because both the singlet and triplet state of BR(3) are nearly degenerate (DE=0.2

kcal/mol).The singlet energies of activation via TS(4)–TS(6) (see Fig. 2) are much

lower (5.1–8.0 kcal/mol), in accord with the failure of trapping BR(3).The result

that the energy of S-TS(6) is lower than that of S-TS(4) and S-TS(5) (suggesting that

the cyclobutadienes should be the main products, with no PDDA reaction taking

place) should not be overestimated because the calculated energies do not include

the influence of the solvent.

The cycloallenes CA(5) and CA(6), formed via TS(4) and TS(5), are tautomers of

the final PDDA products 11 and 12, which could be formed from the cycloallenes by

step-wise intramolecular hydrogen migration.Admittedly, our calculations indicate

that this process would be characterized by a relatively high activation barrier

(18–19 kcal/mol); therefore, we suppose that hydrogen migration is mediated by the

solvent, as observed previously [5].To corroborate this assumption, we irradiated 1a

in CH₃OD and found, indeed, deuterium incorporation.Finally, regarding the third

G

reaction channel, i.e., the formation of minor amounts of the cleavage products 14

and 15 (see Scheme 4), we could not yet obtain unequivocal information from calcula-

tions.

3. Conclusions. – We reported on the formation of a novel class of highly substituted

arylnaphthalenes of the benzo[g]chromene type by the Photo-Dehydro-Diels–Alder

(PDDA) reaction.We found that the regioselectivity of the final C ꢀC bond-forming

step at the stage of the initially formed biradicals BR can be improved both by strong

electron withdrawing groups (1j) and by bulky substituents (1q) in the linker unit.In

MeOH as solvent, we surprisingly obtained cyclobutenes 13 as by-products.The struc-

ture and energies of some relevant intermediates and transition states were calculated

by means of DFT methods to obtain a detailed insight of the reaction mechanism.

Obviously, the reaction starts from the triplet state giving buta-1,4-diene-1,4-diyl birad-

icals BR(3) (Scheme 7) as key intermediates.At this stage, the system turns back to the

singlet state.Besides the expected PDDA reaction, an alternative reaction channel to

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Scheme 7. Transition States and Calculated Relative Energies of Intermediates

cyclobutadienes exists, which was unknown from previous systems [5].Fortunately, this

process can be suppressed by proper choice of the solvent.

We thank the DFG (We1850/5-1,3; Heisenberg Fellowship to P. W.) for financial support. B. Ziemer is

acknowledged for solving the X-ray structures of 13a and 18o.We also thank the Norddeutscher Verbund

für Hoch- und Hçchstleistungsrechnen (HLRN) for generous allocation of computational capacity.

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Fig.2. Calculated geometries of the transition states TS(3)–TS(6)

Experimental Part

General. The following reagents were prepared according to literature procedures: ethyl (prop-2-yn-

1-yloxy)acetate (3) [16], 1-chloro-4-ethynylbenzene [17], 1-ethynyl-4-methylbenzene [18], 1-ethynyl-4-

fluorobenzene [17], 1-ethynylnaphthalene [19], 1-ethynyl-3,5-dimethylbenzene [20], 2-ethynyl-1,3,5-tri-

methylbenzene [21], 1-ethynyl-4-(trifluoromethyl)benzene [22], 4-phenylbut-3-yn-2-ol (9o) [23], 4-meth-

yl-1-phenylpent-1-yn-3-ol (9p) [24], 4,4-dimethyl-1-phenylpent-1-yn-3-ol (9q) [25], and 1,3-diphenylprop-

2-yn-1-ol (9r) [26].THF was dried over Na metal in the presence of benzophenone as an indicator of dry-

ness, and distilled under N₂atmosphere at atmospheric pressure.CH ₂Cl₂was dried by heating to reflux

over P₄O₁₀, and distilled at atmospheric pressure.All moisture-sensitive reagents were transferred via

syringe under N₂atmosphere.Moisture-sensitive reactions were carried out under N ₂atmosphere.Irra-

diations for photochemical reactions were performed with a 150-W high-pressure Hg-arc lamp (Hanau);

anal.irradiations were performed with a 500-W high pressure Hg-arc lamp ( Osram HBO-500) in a UV

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cuvette (11 cm), using a WG-295 (Schott) filter.Flash column chromatography (FC): silica gel

(230–400 mesh; Fluka).Anal.TLC: silica-gel 60 F₂₅₄plates (Merck), detection under UV light.Mp. :.

Büchi 530; uncorrected.NMR Spectra: Bruker DPX-300 apparatus; in CDCl₃soln.; d in ppm rel.to

residual CHCl₃(¹H: 7.26 ppm, ¹³C: 77.0 ppm), J in Hz.IR: Perkin-Elmer 881; as KBr pastilles or (liquids

and oils) on NaCl crystals as film; in cm^ꢀ1.EI-MS: Hewlett-Packard 5995-A, at 70 eV, 293–593 K; in m/z

(rel.%). HR-EI-MS: MSI Concept-1H.Elemental analyses were carried out by the anal.laboratory of the

institute of chemistry of the Humboldt-University Berlin.

General Procedure (GP A): Sonogashira Coupling of 3 with Iodoarenes to Esters 4.The appropriate

iodoarene (1 equiv.) and [PdCl₂(PPh₃)₂] (5 mol-%) were suspended in anh.THF under N ₂atmosphere,

and stirred for 5 min.CuI (10 mol-%), i-Pr ₂NH (1.2 equiv.), and the appropriate ethyl 2-(prop-2-ynyloxy)-

acetate 3 (1 equiv.) were added, and the course of the reaction was monitored by TLC. After completion

of the reaction, the dark suspension was treated with 20% aq.tartaric acid soln,. the aq.phase was sep-

arated and extracted with t-BuOMe (3).The combined org.layers were washed with 20% aq.tartaric

acid and H₂O, dried (MgSO₄), and concentrated under reduced pressure.Purification by FC (SiO ₂; petro-

leum ether (PE)/AcOEt 100 :4) afforded the corresponding pure products.

Ethyl [(3-Phenylprop-2-yn-1-yl)oxy]acetate (4a). From iodobenzene (2.15 g, 10.55 mmol) according

to GP A in 30 min.Yield: 16. 1 g (70%).Dark-yellow oil.IR (film): 1716, 1489, 1116, 1025, 758, 690. ¹H-

NMR (300 MHz, CDCl₃): 7.50–7.30 (m, 5 H); 4.55 (s, 2 H); 4.26 (s, 2 H); 4.24 (q, J=7.2, 2 H); 1.30 (t,

J=7.2, 3 H). ¹³C-NMR (75.5 MHz, CDCl₃): 169.6 (C_q); 131.4 (CH); 128.0 (CH); 122.0 (C_q); 86.9 (C_q);

83.6 (C_q); 63.9 (CH₂); 60.6 (CH₂); 58.7 (CH₂); 13.8 (Me). EI-MS: 218 (0.5, M⁺), 173 (4), 145 (13), 131

(48), 115 (100), 101 (8).

Ethyl {[3-(4-Chlorophenyl)prop-2-yn-1-yl]oxy}acetate (4b).From 1-chloro-4-iodobenzene (16.8 g,

7.04 mmol) according to GP A in 60 min.Yield: 12. 1 g (68%).Dark-yellow oil.IR (film): 1750, 1488,

1

1205, 1120, 829, 753. H-NMR (300 MHz, CDCl₃): 7.39–7.38 (m, 1 H); 7.37–7.36 (m, 1 H); 7.31–7.30

(m, 1 H); 7.29–7.28 (m, 1 H); 4.53 (s, 2 H); 4.26 (q, J=7.2, 2 H); 4.25 (s, 2 H); 1.30 (t, J=7.2, 3 H).

¹³C-NMR (70 MHz, CDCl₃): 169.9 (C_q); 134.7 (C_q); 133.0 (CH); 128.7 (CH); 120.8 (C_q); 86.1 (C_q);

84.8 (C_q); 66.4 (CH₂); 61.1 (CH₂); 59.0 (CH₂); 14.2 (Me). EI-MS: 252 (0.5, M⁺), 179 (16), 165 (72),

149 (100).

Ethyl {[3-(4-Methylphenyl)prop-2-yn-1-yl]oxy}acetate (4c).From 1-iodo-4-methylbenzene (15.3 g,

7.04 mmol) according to GP A in 60 min.Yield: 11. 0 g (67%).Dark-yellow oil.IR (film): 1749, 1507,

1

1117, 1023, 816. H-NMR (300 MHz, CDCl₃): 7.35–7.32 (m, 2 H); 7.12 (d, J=7.9, 2 H); 4.53 (s, 2 H);

4.25 (s, 2 H); 4.24 (q, J=7.1, 2 H); 2.35 (s, 3 H); 1.30 (t, J=7.1, 3 H). ¹³C-NMR (75.5 MHz, CDCl₃):

170.1 (C_q); 138.8 (C_q); 131.7 (CH); 129.0 (CH); 119.2 (C_q); 87.4 (C_q); 83.0 (C_q); 66.3 (CH₂); 61.0

(CH₂); 59.1 (CH₂); 21.5 (Me); 14.2 (Me).

Ethyl {[3-(4-Fluorophenyl)prop-2-yn-1-yl]oxy}acetate (4d).To a soln.of 1-fluoro-4-iodobenzene ( 6a;

3.00 g, 13.51 mmol) and propargyl alcohol (0.91 g, 16.22 mmol) in Et₃N (40 ml), [PdCl₂(PPh₃)₂] (190 mg, 2

A

mol-%) was added.The mixture was stirred for 10 min, and CuI (26 mg, 1 mol%) was added.The result-

ing mixture was heated under N₂atmosphere at 508.After 3 h, the mixture was allowed to cool to r.t,. and

the ammonium salt was removed by filtration.The solvent was removed under reduced pressure, and the

residue was purified by FC (SiO₂; PE/AcOEt 10 :2) to afford pure 3-(4-fluorophenyl)prop-2-yn-1-ol (7a)

(2.03 g, quant.) as a yellow oil. Part of this material (1.50 g, 9.99 mmol) was dissolved in anh. THF (40 ml)

at ꢀ788. Then, BuLi (6.9 ml, 10.99 mmol; 1.6^Msoln.in hexane) was added, and the mixture was stirred for

45 min. Ethyl 2-bromoacetate (1.67 g, 9.99 mmol) in anh. THF (2 ml) was then added, and the resulting

soln.was allowed to come to rt.,. and stirred for a further 12 h.Quenching with sat.aq.NH

₄Cl soln., aq.

workup, and purification by FC (SiO₂; PE/AcOEt 10 :1) afforded 4d (1.33 g, 56%) as a yellow oil.

Data of 7a. ¹H-NMR (300 MHz, CDCl₃): 7.42–7.39 (s, 2 H); 7.02–6.97 (s, 2 H); 4.48 (s, 2 H); 2.02 (s, 1

1

H). ¹³C-NMR (75.5 MHz, CDCl₃): 162.5 (d, J(F,C)=249.8; C_q); 133.6 (CH); 133.5 (CH); 118.6 (C_q);

115.7 (CH); 115.5 (CH); 86.9 (C_q); 84.6 (C_q); 51.5 (CH₂).

Data of 4d.IR (film): 1749, 1599, 1218, 1120, 837. ¹H-NMR (300 MHz, CDCl₃): 7.44–7.40 (m, 2 H);

7.03–6.87 (m, 2 H); 4.51 (s, 2 H); 4.23 (s, 2 H); 4.23 (q, J=7.2, 2 H); 1.29 (t, J=7.2, 3 H). ¹³C-NMR (70

MHz, CDCl₃): 169.9 (C_q); 162.7 (d, ¹J(F,C)=250, C_q); 133.8 (CH); 133.7 (CH); 118.4 (C_q); 115.8 (CH);

115.7 (CH); 86.2 (C_q); 83.5 (CH); 66.4 (CH₂); 61.0 (CH₂); 59.0 (CH₂); 14.2 (Me). EI-MS: 236 (0.5, M⁺),

163 (5), 133 (100).HR-EI-MS: 2360. 813 ( M⁺, C₁₃

N

2706

Helvetica Chimica Acta – Vol.89 (2006)

Ethyl [(3-Naphthalen-1-ylprop-2-yn-1-yl)oxy]acetate (4e). From 1-iodonaphthalene (0.54 g, 2.11

mmol) according to GP A in 60 min.Yield: 02. 6 g (46%).Dark-yellow oil.IR (film): 1748, 1395, 1019,

932, 800, 773. ¹H-NMR (300 MHz, CDCl₃): 8.30 (d, J=8.18, 1 H); 7.85 (d, J=8.33, 2 H); 7.69 (d,

³J=7.13, 1 H); 7.60–7.50 (m, 2 H); 7.45–7.40 (m, 1 H); 4.71 (s, 2 H); 4.35 (s, 2 H); 4.26 (q, J=7.15, 2

H); 1.30 (t, ³J=7.16, 3 H). ¹³C-NMR (75.5 MHz, CDCl₃): 170.0 (C_q); 133.2 (C_q); 133.1 (C_q); 130.8

(CH); 129.1 (CH); 128.3 (CH); 126.9 (CH); 126.4 (CH); 126.0 (CH); 125.1 (CH); 119.9 (C_q); 88.6

(C_q); 85.4 (C_q); 66.4 (CH₂); 61.0 (CH₂); 59.2 (CH₂); 14.2 (Me). ESI-MS: 291 [M+Na]⁺.HR-ESI-MS:

291.0992 (C

Preparation of 3-(2,4,6-Trimethylphenyl)prop-2-yn-1-ol (7b) by Sonogashira Coupling.Iodomesity-

lene (6b; 2.00 g, 8.13 mmol), [PdCl₂(PPh₃)₂] (0.57 g, 0.81 mmol), and Ph₃P (0.43 g, 1.63 mmol) were dis-

solved in Et₂NH under N₂atmosphere and heated for 30 min at 458. Then, CuI (0.30 g, 1.63 mmol) and

A

O₃

A

AHCTREUNG

popargylic alcohol (0.70 g, 12.19 mmol) were added, and the resulting suspension was stirred at 458.The

course of the reaction was monitored by TLC.After completion of the reaction, the suspension was

diluted with t-BuOMe, washed with H₂O (3) and brine (1).The org.layer was dried (MgSO ₄) and con-

centrated in vacuo.Purification by FC (SiO ₂; PE/AcOEt 10 :1) afforded the title product 7b.Yield: 0.69 g

(49%).Brownish solid.M.p.53 8.IR (KBr): 1475, 1349, 1016, 851, 726, 667. ¹H-NMR (300 MHz, CDCl₃):

6.85 (s, 2 H); 4.57 (s, 2 H); 2.39 (s, 6 H); 2.28 (s, 3 H). ¹³C-NMR (75.5 MHz, CDCl₃): 140.3 (C_q); 137.9

(C_q); 127.6 (arom. CH); 119.2 (C_q); 94.7 (C_q); 83.4 (C_q); 51.9 (CH₂); 21.3 (Me); 21.0 (Me). EI-MS:

174 (97), 159 (100), 141 (32), 128 (41), 115 (38), 105 (11), 91 (21), 77 (16).HR-EI-MS: 1741. 045 ( M⁺,

C₁₂

N

G

tate 4 (1 equiv.) was dissolved in MeOH, and the corresponding portion of 1^NKOH soln.(1 equiv). in

MeOH was added.The resulting soln.was stirred for 12 h, the solvent was removed under reduced pres-

sure, and the residue was poured into a mixture of sat.NaHCO ₃soln.and t-BuOMe.The aq.phase was

acidified with half-conc.HCl to pH 1, and then extracted with t-BuOMe (3).The org.layer was dried

(MgSO₄) and concentrated in vacuo.The resulting residue was dissolved in anh.CH ₂Cl₂under N₂atmos-

phere, and TBTU (=2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate; 1 equiv.)

was added. To this suspension, a soln. of MeO(Me)NH·HCl (1.3 equiv.) and i-Pr

ACHTREUNG

anh.CH ₂Cl₂was added dropwise.The resulting soln.was stirred for a further 12 h.Then

and aq.20% tartaric acid soln.were added, the layers were separated, and the aq.phase was extracted

with t-BuOMe (3).The combined org.layers were washed with sat.NaHCO ₃soln.(1) and H ₂O, dried

(MgSO₄), concentrated in vacuo, and purified by FC (SiO₂; CH₂Cl₂/MeOH 100:1) to afford the corre-

sponding amide 5.

N-Methyl-N-methoxy-2-[(3-phenylprop-2-yn-1-yl)oxy]acetamide (5a).From 4a (1.42 g, 6.51 mmol)

according to GP B.Yield: 15.0 g (99%).Yellow oil.IR (film): 1681, 1488, 1135, 758, 692.

¹H-NMR

(300 MHz, CDCl₃): 7.44–7.41 (m, 2 H); 7.31–7.24 (m, 3 H); 4.57 (s, 2 H); 4.44 (s, 2 H); 3.68 (s, 3 H);

3.18 (s, 3 H). ¹³C-NMR (75.5 MHz, CDCl₃): 131.7 (CH₂); 128.5 (CH₂); 128.3 (CH₂); 122.4 (C_q); 86.9

(C_q); 84.3 (C_q); 66.1 (CH₂); 61.4 (Me); 59.0 (Me). EI-MS: 234 (0.2, [M+H]⁺), 202 (2), 173 (7), 115

(100).HR-EI-MS: 2331. 051 ( M⁺, C₁₇

N

2-{[3-(4-Chlorophenyl)prop-2-yn-1-yl]oxy}-N-methyl-N-methoxyacetamide (5b).From acetate 4b

(1.20 g, 4.75 mmol) according to GP B.Yield: 12.6 g (99%).Yellow oil. ¹H-NMR (300 MHz, CDCl₃):

7.39–7.35 (m, 2 H); 7.31–7.28 (m, 2 H); 4.56 (s, 2 H); 4.44 (s, 2 H); 3.71 (s, 3 H); 3.21 (s, 3 H). ¹³C-

NMR (75.5 MHz, CDCl₃): 134.6 (C_q); 132.9 (CH); 128.6 (CH); 120.9 (C_q); 85.8 (C_q); 85.4 (C_q); 66.3

(CH₂); 66.2 (CH₂); 61.4 (CH₃); 59.0 (Me).

N-Methyl-N-methoxy-2-{[3-(4-methylphenyl)prop-2-yn-1-yl]oxy}acetamide (5c).From acetate 4c

(1.10 g, 4.84 mmol) according to GP B.Yield: 09.6 g (87%).Yellow oil.IR (KBr): 1688, 1509, 1428,

1

1133, 998, 818. H-NMR (300 MHz, CDCl₃): 7.33 (d, J=8.1, 2 H); 7.11 (d, J=7.9, 2 H); 4.56 (s, 2 H);

4.45 (s, 2 H); 3.70 (s, 3 H); 3.20 (s, 3 H); 2.34 (s, 3 H). ¹³C-NMR (75.5 MHz, CDCl₃): 138.7 (C_q); 131.6

(CH); 129.0 (CH); 119.4 (C_q); 87.1 (C_q); 83.6 (C_q); 66.8 (CH₂); 66.1 (CH₂); 61.4 (Me); 59.0 (Me); 38.7

(Me); 21.5 (Me). ESI-MS: 248 ([M+H]⁺).HR-ESI-MS: 2701.100 ([ M+Na]⁺, C₁₄

N

270.1101).

2-{[3-(4-Fluorophenyl)prop-2-yn-1-yl]oxy}-N-methyl-N-methoxyacetamide (5d).From acetate 4d

(1.26 g, 5.33 mmol) according to GP B.Yield: 12.5 g (93%).Yellow oil.IR (film): 1675, 1505, 1219,

Helvetica Chimica Acta – Vol.89 (2006)

2707

838. ¹H-NMR (300 MHz, CDCl₃): 7.44–7.40 (m, 2 H); 7.03–7.00 (m, 2 H); 4.54 (s, 2 H); 4.43 (s, 2 H); 3.70

(s, 3 H); 3.20 (s, 3 H). ¹³C-NMR (75.5 MHz, CDCl₃): 162.7 (d, ¹J(F,C)=249.8, C_q); 133.7 (d, ³J=8.3, CH);

118.6 (C_q); 115.6 (d, ²J=22.8, CH); 115.5 (CH); 85.8 (C_q); 84.1 (C_q); 66.2 (CH₂); 61.4 (Me); 59.0 (CH₂);

38.6 (Me). ESI-MS: 252 ([M+H]⁺).HR-ESI-MS: 2521.031 ([ M+H]⁺, C₁₃

N

N-Methyl-N-methoxy-2-[(3-naphthalen-1-ylprop-2-yn-1-yl)oxy]acetamide (5e).From acetate 4e (243

mg, 0.906 mmol) according to GP B.Yield: 251 mg (98%).Brown oil.IR (film): 1715, 1459, 1199, 990,

801, 774. ¹H-NMR (300 MHz, CDCl₃): 8.34–8.29 (m, 1 H); 7.85–7.81 (m, 2 H); 7.69–7.66 (m, 1 H);

7.58–7.38 (m, 3 H); 4.72 (s, 2 H); 4.54 (s, 2 H); 3.68 (s, 3 H); 3.20 (s, 3 H). ¹³C-NMR (75.5 MHz,

CDCl₃): 133.3 (C_q); 133.0 (C_q); 130.7 (CH); 129.0 (CH); 128.3 (CH); 126.8 (CH); 126.4 (CH); 126.0

(CH); 125.1 (CH); 120.1 (C_q); 89.2 (C_q); 85.1 (C_q); 66.2 (CH₂); 61.4 (Me); 59.2 (CH₂); 38.6 (Me). ESI-

MS: 284 ([M+H]⁺).HR-ESI-MS: 3061. 099 ([ M+Na]⁺, C₁₇

N

N-Methyl-N-methoxy-2-{[3-(2,4,6-trimethylphenyl)prop-2-yn-1-yl]oxy}acetamide (5f).To a soln.of

7b (500 mg, 2.87 mmol) in anh. THF at ꢀ788 under N₂atmosphere, BuLi (2.0 ml, 6.31 mmol; 1.6M

soln.in hexane) was added, and the resulting soln.was stirred for 15 min.Then, the soln.was transferred

via cannula to a soln. of 2-bromoacetic acid (399 mg, 2.87 mmol) and BuLi (2.0 ml, 6.31 mmol) in anh.

THF at ꢀ788 under N₂atmosphere.The mixture was allowed to come to rt.,. and stirred for 24 h.The

reaction was quenched with sat.aq.NaHCO soln., the layers were separated, and the aq. phase was

3

extracted with t-BuOMe (3).Then, the aq.layer was acidified with half-conc.HCl to pH 1, and

extracted with t-BuOMe (3).The combined org.layers were dried (MgSO ₄) and concentrated in

vacuo to afford crude {[3-(2,4,6-trimethylphenyl)prop-2-yn-1-yl]oxy}acetic acid (294 mg, 44%).Part of

this intermediate (274 mg, 1.18 mmol) was dissolved in anh. CH₂Cl₂under N₂atmosphere, and TBTU

(379 mg, 1.18 mmol) was added. To the resulting suspension, a soln. of MeO(Me)NH·HCl (150 mg,

1.53 mmol) and i-Pr₂NEt (350 mg, 2.71 mmol) in anh. CH₂Cl₂was added dropwise.The resulting soln.

U

was then stirred for a further 15 h. t-BuOMe and 20% aq.tartaric acid soln.were added, the layers

were separated, and the aq.phase was extracted with t-BuOMe (3).The combined org.phases were

washed once each with sat.NaHCO ₃soln.and H ₂O, dried (MgSO₄), concentrated under reduced pres-

sure, and purified by FC (SiO₂; CH₂Cl₂/MeOH 100 :1) to afford 5f.Yield: 181 mg (56%).

Data of {[3-(2,4,6-Trimethylphenyl)prop-2-yn-1-yl]oxy}acetic Acid.IR (KBr): 1738, 1200, 1103, 910,

847, 676. ¹H-NMR (300 MHz, CDCl₃): 6.86 (s, 2 H); 4.64 (s, 2 H); 4.35 (s, 2 H); 2.38 (s, 6 H); 2.28 (s, 3 H).

¹³C-NMR (75.5 MHz, CDCl₃): 147.9 (C_q); 140.4 (C_q); 138.2 (C_q); 127.6 (CH); 118.8 (C_q); 90.5 (C_q); 85.6

(C_q); 65.5 (CH₂); 59.4 (CH₂); 21.3 (Me); 20.9 (Me). EI-MS: 232 (49), 173 (62), 157 (100), 145 (31), 128

(43), 115 (46), 105 (12), 91 (12), 77 (15).HR-EI-MS: 2321. 099 ( M⁺, C₁₄

U

N

(CH₂); 21.3 (Me); 21.0 (Me). EI-MS: 275 ([M+H]⁺).HR-ESI-MS: 2761.601 ([ M+H]⁺, C₁₆

N

calc.2761. 600).

General Procedure (GP C) for the Preparation of Acids 10 by Alkylation of Propargyl Alcohols 9. A

solution of the appropriate alcohol 9 (1 equiv.) in anh. THF was dropped slowly under N₂atmosphere to a

suspension of NaH (60% in mineral oil; 2 equiv.) in THF, and the resulting suspension was stirred until

the evolution of H₂ceased.A soln.of 2-bromoacetic acid (1 equiv). in anh.THF was added, and the

resulting suspension was stirred until TLC indicated complete disappearance of the alcohol.Then,

H₂O was added, and the mixture was concentrated under reduced pressure.The residue was taken up

in H₂O and washed with Et₂O (3).The aq.phase was acidified with half-conc.HCl to pH 1, and

A

extracted with AcOEt (3).The combined org.layers were dried (Na ₂SO₄) and concentrated in vacuo.

[(1-Methyl-3-phenylprop-2-yn-1-yl)oxy]acetic Acid (10o).From 9o (2.30 g, 15.73 mmol) according to

GP C.Yield: 25.1 g (78%).Yellow oil.IR (film): 1734, 1728, 1727, 1117, 757.

¹H-NMR (300 MHz,

CDCl₃): 11.20 (s, 1 H); 7.32–7.18 (m, 5 H); 4.50 (q, J=6.4, 1 H); 4.44 (d, J=17, 1 H); 4.26 (d, J=17, 1

H); 1.47 (d, J=6.4, 3 H). ¹³C-NMR (75.5 MHz, CDCl₃): 175.7 (C_q); 131.5 (CH); 128.4 (CH); 128.1

(CH); 121.9 (C_q); 87.1 (C_q); 86.1 (C_q); 66.3 (CH); 64.8 (CH₂); 21.7 (Me). EI-MS: 203 (1.4, M⁺), 162

(11), 145 (42), 128 (100), 77 (29).Anal.calc.for C ₁₂H₁₂O₃: C 70.57, H 5.92; found: C 70.18, H 5.91.

{[1-(1-Methylethyl)-3-phenylprop-2-yn-1-yl]oxy}acetic Acid (10p).From 9p (1.94 g, 11.13 mmol)

according to GP C. Yield: 1.68 g (65%). Colorless solid. M.p. 588.IR (KBr): 1745, 1734, 1727, 1247,

2708

Helvetica Chimica Acta – Vol.89 (2006)

1126, 758. ¹H-NMR (300 MHz, CDCl₃): 10.96 (s, 1 H); 7.34–7.20 (m, 5 H); 4.30 (m, 2 H); 4.20 (d, J=6.0,

1 H); 2.00 (sext., J=6.8, 1 H); 0.99 (m, 6 H). ¹³C-NMR (75.5 MHz, CDCl₃): 175.8 (C_q); 131.6 (CH); 128.4

(CH); 128.2 (CH); 122.3 (C_q); 87.6 (C_q); 85.3 (C_q); 76.1 (CH); 65.1 (CH₂); 33.0 (CH); 18.5 (Me); 17.7

(Me).EI-MS: 231 (17. , M⁺), 189.1 (42), 173 (15), 131 (100), 77 (46). Anal. calc. for C₁₄H₁₆O₃: C 72.39,

H 6.94; found: C 71.98, H 7.04.

{[1-(1,1-Dimethylethyl)-3-phenylprop-2-yn-1-yl]oxy}acetic Acid (10q).From 9q (1,16 g, 6.16 mmol)

according to GP C. Yield: 1.05 g (69%). Colorless solid. M.p. 758.IR (KBr) 1738, 1734, 1122, 760. ¹H-

NMR (300 MHz, CDCl₃): 10.45 (s, 1 H); 7.38–7.17 (m, 5 H); 4.29 (m, 2 H); 4.06 (s, 1 H); 1.02 (s, 9 H).

¹³C-NMR (70 MHz, CDCl₃): 175.9 (C_q); 131.7 (CH); 128.5 (CH); 128.3 (CH); 122.4 (C_q); 87.7 (C_q);

85.5 (C_q); 79.5 (CH); 65.6 (CH₂); 35.8 (C_q); 25.7 (Me). EI-MS: 245 (0.25, M⁺), 189 (59), 131 (100), 77

(26).Anal.calc.for C ₁₅H₁₈O₃: C 73.15, H 7.37; found: C 73.67, H 6.91.

[(1,3-Diphenylprop-2-yn-1-yl)oxy]acetic Acid (10r).To a soln.of 9r (5.00 g, 24.01 mmol) in anh. THF

under N₂atmosphere at ꢀ788 was added dropwise BuLi (16.5 ml, 26.41 mmol; 1.6M soln.in hexane), and

the resulting green soln. was stirred for 10 min. Then, ethyl 2-bromoacetate (4.01 g, 24.01 mmol) was

added, whereupon the color turned to yellow.The soln.was allowed to warm to r.t,. stirred for a further

12 h, quenched with sat.aq.NH ₄Cl soln.n and subjected to regular aq. workup to afford ethyl [(1,3-diphe-

nylprop-2-yn-1-yl)oxy]acetate (4.50 g, 64%) as an orange oil. A portion of the latter (2.00 g, 6.80 mmol) in

MeOH (6.8 ml) was treated dropwise with a 1^MKOH soln.in MeOH.The resulting soln.was stirred for

16 h.The solvent was removed under reduced pressure, and the residue was taken up in sat.aq.NaHCO

3

soln., and extracted with t-BuOMe (2).The aq.phase was acidified with half-conc.HCl to pH 1, and

extracted with t-BuOMe.The combined org.layers were dried (MgSO ₄) and concentrated in vacuo to

afforded 10r as a yellow solid (1.38 g, 77%).

Data of Ethyl [(1,3-diphenylprop-2-yn-1-yl)oxy]acetate.IR (film): 1726, 1287, 1210, 1176, 934, 708.

¹H-NMR (300 MHz, CDCl₃): 7.68–7.65 (m, 2 H); 7.52–7.48 (m, 2 H); 7.44–7.33 (m, 6 H); 5.71 (s, 1

H); 4.42 (d, J=16.4, 1 H); 4.24 (q, J=7.2, 2 H); 4.23 (d, J=16.4, 1 H); 1.30 (t, J=7.2, 3 H). ¹³C-NMR

(75.5 MHz, CDCl₃): 170.2 (C_q); 137.6 (C_q); 131.8 (CH); 128.7 (CH); 128.6 (CH); 128.4 (CH); 128.3

(CH); 128.2 (CH); 127.8 (CH); 122.2 (CH); 88.6 (C_q); 85.5 (C_q); 72.0 (CH); 64.8 (CH₂); 61.0 (CH₂);

14.1 (Me). EI-MS: 294 (0.75, M⁺), 191 (20), 163 (4), 122 (6), 105 (100), 77 (40).HR-EI-MS: 2941. 256

(M⁺, C₁₉

N

Data of 10r.Mp. .32 8.IR (KBr): 1730, 1450, 1244, 1112, 909, 755, 691. ¹H-NMR (300 MHz, CDCl₃):

9.76 (s, 1 H); 7.69–7.65 (m, 1 H); 7.53–7.34 (m, 9 H); 5.72 (s, 1 H); 4.48 (d, J=17.0, 1 H); 4.32 (d, J=17.0,

1 H). ¹³C-NMR (75.5 MHz, CDCl₃): 175.5 (C_q); 137.2 (C_q); 133.8 (CH); 131.8 (CH); 130.1 (CH); 128.9

(CH); 128.8 (CH); 128.6 (CH); 128.5 (CH); 128.4 (CH); 128.3 (CH); 127.8 (CH); 121.9 (C_q); 89.0

(C_q); 85.0 (C_q); 72.2 (CH₂); 64.1 (CH₂).EI-MS: 266 (18. , M⁺), 207 (73), 191 (64), 122 (54), 105 (100),

77 (87).HR-EI-MS: 2660. 941 ( M⁺, C₁₇

N

General Procedure (GP D) for the Preparation of Weinreb Amides (WA) by Conversion of the Acids

10.To a soln.of 10 (1 equiv.) in anh. CH₂Cl₂was added under N₂atmosphere TBTU (1.05 equiv.), and the

resulting suspension was stirred for 30 min.In a separate flask, i-Pr ₂NEt (3.0 equiv.) and MeO-

G

(Me)NH·HCl (1.0 equiv.) were dissolved in anh. CH₂Cl₂, and this soln.was transferred via cannula to

the first flask.The resulting mixture was stirred for 2 h.Then, the mixture was quenched with 20% aq.

tartaric acid soln., the layers were separated, and the aq. phase was extracted with Et

A

bined org.layers were washed once each with H O and sat.NaHCO soln.The org.layer was dried

2

3

(Na₂SO₄) and concentrated under reduced pressure to afford the anal.pure WA compounds.

N-Methyl-N-methoxy-2-[(1-methyl-3-phenylprop-2-yn-1-yl)oxy]acetamide (WAo).From 10o (2.05 g,

10.04 mmol) according to GP D.Yield: 21. 1 g (85%).IR (KBr): 1688, 1684, 1677, 1091, 759. ¹H-NMR

(300 MHz, CDCl₃): 7.36–7.21 (m, 5 H); 4.57 (q, J=6.4, 1 H); 4.41 (s, 2 H); 3.61 (s, 3 H); 3.11 (s, 3 H);

1.52 (d, J=6.4, 3 H). ¹³C-NMR (75.5 MHz, CDCl₃): 131.5 (CH); 128.3 (CH); 128.2 (CH); 122.4 (C_q);

88.2 (C_q); 85.2 (C_q); 65.9 (CH); 65.3 (CH₂); 61.3 (Me); 32.2 (Me); 21.9 (Me). EI-MS: 248 (0.14,

[M+1]⁺), 129 (100), 77 (17).Anal.calc.for C ₁₄H₁₇NO₃: C 68.00, H 6.93, N 5.66; found: C 67.64, H

6.96, N 5.33.

N-Methyl-2-{[1-(1-methylethyl)-3-phenylprop-2-yn-1-yl]oxy}-N-methoxyacetamide (WAp).From

10p (1.50 g, 6.46 mmol) according to GP D.Yield: 14. 3 g (81%).IR (film): 1688, 1489, 1132, 1084. ¹H-

NMR (300 MHz, CDCl₃): 7.47–7.32 (m, 5 H); 4.53 (s, 2 H); 4.39 (d, J=5.7, 1 H); 3.71 (s, 3 H); 3.21 (s,

Helvetica Chimica Acta – Vol.89 (2006)

2709

3 H); 2.16 (sext., J=5.6, 1 H); 1.13 (m, 6 H). ¹³C-NMR (70 MHz, CDCl₃): 165.3 (C_q); 131.3 (CH); 128.0

(CH); 127.9 (CH); 122.3 (C_q); 86.6 (C_q); 86.1 (C_q); 75.2 (CH); 65.1 (CH₂); 61.0 (Me); 38.1 (CH); 32.8

(Me); 18.3 (Me); 17.4 (Me). EI-MS: 215 (14, [MꢀMeOꢀMeN]⁺), 129 (41), 77 (23).Anal.calc.for

C₁₆H₂₁NO₃: C 69.79, H 7.69, N 5.09; found: C 69.23, H 7.17, N 5.33.

2-{[1-(1,1-Dimethylethyl)-3-phenylprop-2-yn-1-yl]oxy}-N-methyl-N-methoxyacetamide

(WAq).

From 10q (0.95 g, 3.86 mmol) according to GP D.Yield: 09.3 g (83%).IR (film): 1688, 1489, 1442,

1

1085, 758. H-NMR (300 MHz, CDCl₃): 7.39–7.19 (m, 5 H); 4.44 (s, 2 H); 4.16 (s, 1 H); 3.62 (s, 3 H);

3.12 (s, 3 H); 1.04 (s, 9 H). ¹³C-NMR (75.5 MHz, CDCl₃): 131.7 (CH); 128.3 (CH); 128.2 (CH); 122.8

(C_q); 86.9 (C_q); 86.7 (C_q); 78.8 (CH); 65.6 (CH₂); 61.4 (Me); 35.8 (C_q); 32.1 (Me); 25.9 (Me). EI-MS:

290 (0.1, [M+1]⁺), 232 (9), 171 (11), 77 (20).Anal.calc.for C ₁₇H₂₃NO₃: C 70.56, H 8.01, N 4.84;

found: C 70.48, H 7.86, N 5.02.

2-[(1,3-Diphenylprop-2-yn-1-yl)oxy]-N-methyl-N-methoxyacetamide (WAr).From 10r (0.47 g, 1.77

mmol) according to GP D.Yield: 04.4 g (80%).IR (film): 1695, 1079, 989, 758, 694.

¹H-NMR (300

MHz, CDCl₃): 7.71–7.65 (m, 2 H); 7.51–7.48 (m, 2 H); 7.43–7.30 (m, 6 H); 5.76 (s, 1 H); 4.62 (d,

J=15.8, 1 H); 4.43 (d, J=15.8, 1 H); 3.66 (s, 3 H); 3.20 (s, 3 H). ¹³C-NMR (75.5 MHz, CDCl₃): 137.9

(C_q); 131.8 (CH); 128.61 (CH); 128.60 (CH); 128.5 (CH); 128.3 (CH); 128.1 (CH); 128.0 (CH); 127.8

(CH); 122.4 (C_q); 88.2 (C_q); 86.1 (C_q); 71.8 (CH); 64.7 (CH₂); 61.4 (Me); 38.6 (Me). EI-MS: 278 (8,

[MꢀMeO]⁺), 249 (28, [MꢀMeOꢀMeN]⁺), 221 (6), 191 (100).ESI-MS: 310 ([ M+H]⁺), 327

([M+NH₄]⁺), 332 ([M+Na]⁺), 641 [2M+Na]⁺).HR-ESI-MS: 3321.268 ([ M+Na]⁺, C₁₉

N

calc.3321. 262).

General Procedure (GP E) for the Preparation of Compounds 1 from the Weinreb Amides 5 and WA,

resp. To a soln. of the appropriate arylacetylene (2.5 equiv.) in anh. THF was added BuLi (2.1 equiv, 1.6^M

soln.in hexane) at ꢀ788 under N₂atmosphere, and the mixture was stirred for 15 min.The resulting soln.

was transferred via cannula to a soln.of the appropriate amide 5 (1 equiv.) in anh. THF under N₂atmos-

phere at ꢀ788, and the resulting soln.was stirred for 1 h at this temp.Then, the mixture was allowed to

come to r.t., and stirred for a further 2 h. The soln. was poured into a vigorously stirred mixture of ice, 1^M

aq.KH PO₄soln., and t-BuOMe.The layers were separated, and the aq.phase was extracted with t-

2

BuOMe (3).The combined org.phases were washed once each with 1 ^Maq.KH PO₄soln.and brine,

2

and dried (MgSO₄).The solvent was removed under reduced pressure to afford crude 1, which was puri-

fied by FC (SiO₂; PE/AcOEt 20 :1).

4-Phenyl-1-[(3-phenylprop-2-yn-1-yl)oxy]but-3-yn-2-one (1a).From 5a (0.50 g, 2.14 mmol), ethynyl-

benzene (0.55 g, 5.36 mmol), and BuLi (4.50 mmol) according to GP E.Yield: 04. 6 g (79%).IR (film):

1

1683, 1488, 1065, 903, 735. H-NMR (300 MHz, CDCl₃): 7.62–7.58 (m, 2 H); 7.50–7.29 (m, 8 H); 4.59

(s, 2 H); 4.50 (s, 2 H). ¹³C-NMR (75.5 MHz, CDCl₃): 184.4 (C_q); 133.2 (CH); 131.8 (CH); 131.1 (CH);

128.7 (CH); 128.3 (CH); 122.2 (C_q); 119.5 (C_q); 93.9 (C_q); 87.5 (C_q); 85.6 (C_q); 83.8 (C_q); 74.9 (CH₂);

59.3 (CH₂).EI-MS: 274 (3, M⁺), 144 (100), 130 (35), 101 (25).HR-EI-MS: 2740. 976 ( M⁺, C₁₉

N

G

calc.2740. 994).

1-{[3-(4-Chlorophenyl)prop-2-yn-1-yl]oxy}-4-phenylbut-3-yn-2-one (1b).From

mmol), ethynylbenzene (0.29 g, 2.80 mmol), and BuLi (2.35 mmol) according to GP E.Yield: 02.1 g

(62%).Mp..66 8.IR (KBr): 1676, 1488, 1069, 820, 755. ¹H-NMR (300 MHz, CDCl₃): 7.54–7.51 (m, 2

H); 7.41–7.39 (m, 1 H); 7.35–7.30 (m, 4 H); 4.51 (s, 2 H); 4.42 (s, 2 H). ¹³C-NMR (75.5 MHz, CDCl₃):

184.3 (C_q); 134.8 (C_q); 133.2 (CH); 133.0 (CH); 131.1 (CH); 128.7 (CH); 120.7 (C_q); 119.4 (C_q); 94.0

(C_q); 68.4 (C_q); 85.6 (C_q); 84.8 (C_q); 75.0 (CH₂); 59.3 (CH₂).EI-MS: 308 (05. , M⁺), 231 (0.3), 215 (14),

165 (0.3), 144 (40), 129 (100). HR-EI-MS: 308.0605 (M⁺, C₁₉

N

C₁₉H₁₃ClO₂: C 73.91, H 4.24, Cl 11.48; found: C 73.73, H 4.23, Cl 11.10.

1-{[3-(4-Methylphenyl)prop-2-yn-1-yl]oxy}-4-phenylbut-3-yn-2-one (1c).From

5c (0.50 g, 2.02

mmol), ethynylbenzene (0.52 g, 5.06 mmol), and BuLi (4.25 mmol) according to GP E.Yield: 03.9 g

(67%). ¹H-NMR (300 MHz, CDCl₃): 7.62–7.58 (m, 2 H); 7.48–7.45 (m, 1 H); 7.41–7.34 (m, 4 H);

7.14–7.11 (m, 2 H); 4.58 (s, 2 H); 4.50 (s, 2 H); 2.35 (s, 3 H). ¹³C-NMR (75.5 MHz, CDCl₃): 184.4 (C_q);

138.8 (C_q); 133.2 (CH); 131.6 (CH); 131.0 (CH); 129.0 (CH); 128.6 (CH); 119.4 (C_q); 119.1 (C_q); 93.9

(C_q); 87.6 (C_q); 85.6 (C_q); 83.0 (C_q); 74.8 (CH₂); 59.3 (CH₂); 21.4 (Me). ESI-MS: 311 ([M+Na]⁺).

HR-ESI-MS: 311.1043 ([M+Na]⁺, C₂₀

N

2710

Helvetica Chimica Acta – Vol.89 (2006)

1-{[3-(4-Fluorophenyl)prop-2-yn-1-yl]oxy}-4-phenylbut-3-yn-2-one (1d).From

5d (0.80 g, 3.18

mmol), ethynylbenzene (0.81 g, 7.96 mmol), and BuLi (6.69 mmol) according to GP E.Yield: 05.9 g

(64%).IR (film): 1684, 1504, 1220, 1064, 836, 758. ¹H-NMR (300 MHz, CDCl₃): 7.61–7.58 (m, 2 H);

7.48–7.36 (m, 5 H); 7.04–6.98 (m, 2 H); 4.57 (s, 2 H); 4.49 (s, 2 H). ¹³C-NMR (75.5 MHz, CDCl₃):

184.3 (C_q); 162.7 (d, ¹J(F,C)=250, C_q); 133.7 (d, J=9, CH); 133.2 (CH); 131.1 (CH); 128.64 (CH);

128.63 (CH); 119.4 (C_q); 118.3 (C_q); 115.7 (d, J=22, CH); 94.0 (C_q); 86.4 (C_q); 85.6 (C_q); 83.5 (C_q);

74.9 (CH₂); 59.2 (CH₂).ESI-MS: 293 ([ M+H]⁺).HR-ESI-MS: 2930.974 ([ M+H]⁺, C₁₉

293.0972).

4-(4-Chlorophenyl)-1-[(3-phenylprop-2-yn-1-yl)oxy]but-3-yn-2-one (1e).From

N

G

mmol), 1-chloro-4-ethynylbenzene (0.73 g, 5.36 mmol), and BuLi (4.50 mmol) according to GP E.

1

Yield: 0.46 g (70%). IR (KBr): 1671, 1488, 1068, 832, 749, 687. H-NMR (300 MHz, CDCl₃): 7.47–7.44

(m, 2 H); 7.39–7.37 (m, 2 H); 7.31–7.24 (m, 5 H); 4.51 (s, 2 H); 4.41 (s, 2 H). ¹³C-NMR (75.5 MHz,

CDCl₃): 184.3 (C_q); 137.5 (C_q); 134.4 (CH); 131.8 (CH); 129.1 (CH); 128.7 (CH); 128.3 (CH); 122.2

(C_q); 117.9 (C_q); 92.5 (C_q); 87.6 (C_q); 86.3 (C_q); 83.7 (C_q); 74.9 (CH₂); 59.3 (CH₂).ESI-MS: 309

([M+H]⁺), 331 ([M+Na]⁺).HR-ESI-MS: 3090. 680 ([ M+H]⁺, C₁₉

A

ACHTREUNG

mmol), 1-ethynyl-4-fluorobenzene (0.64 g, 5.36 mmol), and BuLi (4.50 mmol) according to GP E.

Yield: 0.36 g (57%). Yellow solid. M.p. 548.IR (KBr): 1671, 1503, 1071, 840, 752, 688. ¹H-NMR (300

MHz, CDCl₃): 7.63–7.58 (m, 2 H); 7.47–7.44 (m, 2 H); 7.34–7.31 (m, 3 H); 7.11–7.06 (m, 3 H); 4.59

1

(s, 2 H); 4.48 (s, 2 H). ¹³C-NMR (75.5 MHz, CDCl₃): 184.4 (C_q); 164.2 (d, J(F,C)=254, C_q); 135.6 (d,

J=9, CH); 131.8 (CH); 128.7 (CH); 128.3 (CH); 122.2 (C_q); 116.3 (d, J=22, CH); 101.6 (C_q); 92.9

(C_q); 87.6 (C_q); 83.7 (C_q); 74.9 (CH₂); 59.3 (CH₂).EI-MS: 292 (3, M⁺), 162 (71), 147 (100), 133 (7),

115 (85).HR-EI-MS: 2920. 900 ( M⁺, C₁₉

N

G

5a (0.50 g, 2.14

mmol), 1-ethynyl-4-methylbenzene (0.62 g, 5.36 mmol), and BuLi (4.50 mmol) according to GP E.

1

Yield 0.41 g (66%). Yellow oil. H-NMR (300 MHz, CDCl₃): 7.51–7.44 (m, 4 H); 7.34–7.31 (m, 3 H);

7.21–7.18 (m, 2 H); 4.59 (s, 2 H); 4.49 (s, 2 H); 2.39 (s, 3 H). ¹³C-NMR (75.5 MHz, CDCl₃): 184.4 (C_q);

141.9 (C_q); 133.3 (CH); 131.8 (CH); 129.5 (CH); 128.7 (CH); 128.3 (CH); 122.2 (C_q); 118.3 (C_q); 94.7

(C_q); 87.5 (C_q); 85.5 (C_q); 83.8 (C_q); 74.9 (CH₂); 59.3 (CH₂); 21.8 (Me). ESI-MS: 289 ([M+H]⁺), 306

([M+NH₄]⁺), 311 ([M+Na]⁺), 594 ([2M+NH₄]⁺), 599 ([2M+H]⁺).HR-ESI-MS: 2891. 225 ([ M+H]⁺,

C₂₀

N

G

1-ethynylnaphthalene (0.82 g, 5.36 mmol), and BuLi (4.50 mmol) according to GP E.Yield: 04.6 g

(67%).Yellow oil.IR (film): 1682, 1072, 800, 759. ¹H-NMR (300 MHz, CDCl₃): 8.38 (d, J=8.6, 1 H);

7.98 (d, J=8.3, 1 H); 7.90–7.87 (m, 2 H); 7.66–7.45 (m, 5 H); 7.33–7.31 (m, 3 H); 4.65 (s, 2 H); 4.58

(s, 2 H). ¹³C-NMR (75.5 MHz, CDCl₃): 184.6 (C_q); 133.6 (CH); 132.9 (C_q); 131.9 (CH); 131.8 (CH);

128.7 (CH); 128.5 (CH); 128.3 (CH); 127.8 (CH); 127.0 (CH); 125.7 (CH); 125.1 (CH); 122.2 (C_q);

117.0 (C_q); 92.6 (C_q); 90.4 (C_q); 87.6 (C_q); 83.8 (C_q); 75.0 (CH₂); 59.4 (CH₂).ESI-MS: 342

([M+NH₄]⁺), 347 ([M+Na]⁺), 671 [2M+Na]⁺).HR-ESI-MS: 3471.043 ([ M+Na]⁺, C₂₃

calc.3471. 043).

N

1-[(3-Naphthalen-1-ylprop-2-yn-1-yl)oxy]-4-phenylbut-3-yn-2-one (1i).From 5e (0.23 g, 0.81 mmol),

ethynylbenzene (0.21 g, 2.03 mmol), and BuLi (1.71 mmol) according to GP E.Yield: 02.8 g (78%).

Yellow oil.IR (film): 1682, 1072, 996, 775. ¹H-NMR (300 MHz, CDCl₃): 8.33–8.30 (m, 1 H); 7.87–7.84

(m, 2 H); 7.72–7.69 (m, 1 H); 7.61–7.35 (m, 8 H); 4.76 (s, 2 H); 4.59 (s, 2 H). ¹³C-NMR (75.5 MHz,

CDCl₃): 184.4 (C_q); 133.2 (CH); 133.1 (C_q); 131.1 (CH); 130.9 (CH); 129.2 (CH); 128.7 (CH); 128.3

(CH); 126.9 (CH); 126.5 (CH); 126.0 (CH); 125.1 (CH); 119.8 (C_q); 119.5 (C_q); 94.1 (C_q); 88.6 (C_q);

85.7 (C_q); 85.6 (C_q); 75.0 (CH₂); 59.5 (CH₂).ESI-MS: 342 ([ M+NH₄]⁺), 347 ([M+Na]⁺), 671

([2M+Na]⁺).HR-ESI-MS: 3471. 043 ([ M+Na]⁺, C₂₃

N

4-[4-(Methylsulfonyl)phenyl]-1-[(3-phenylprop-2-yn-1-yl)oxy]but-3-yn-2-one (1j).From 5a (0.30 g,

1.29 mmol), 1-ethynyl-4-(methylsulfonyl)benzene (0.58 g, 3.12 mmol), and BuLi (2.70 mmol) according

to GP E. Yield: 0.27 g (61%). Yellow solid. M.p. 858.IR (KBr): 1684, 1308, 1149, 1055, 758, 654. ¹H-

NMR (300 MHz, CDCl₃): 7.98–7.95 (m, 2 H); 7.78–7.75 (m, 2 H); 7.46–7.43 (m, 2 H); 7.34–7.31 (m,

3 H); 4.59 (s, 2 H); 4.50 (s, 2 H); 3.07 (s, 3 H). ¹³C-NMR (75.5 MHz, CDCl₃): 184.1 (C_q); 142.2 (C_q);

Helvetica Chimica Acta – Vol.89 (2006)

2711

133.9 (CH); 131.7 (CH); 128.8 (CH); 128.3 (CH); 127.6 (CH); 125.2 (C_q); 90.3 (C_q); 87.7 (C_q); 87.6 (C_q);

83.6 (C_q); 74.9 (CH₂); 59.4 (CH₂); 44.3 (Me). ESI-MS: 353 ([M+H]⁺), 375 [M+Na]⁺), 727 [2M+Na]⁺).

HR-ESI-MS: 353.0842 ([M+H]⁺, C₂₀

A

G

N

4-(3,5-Dimethylphenyl)-1-[(3-phenylprop-2-yn-1-yl)oxy]but-3-yn-2-one (1k).From 5a (0.50 g, 2.14

mmol), 1-ethynyl-3,5-dimethylbenzene (0.70 g, 5.36 mmol), and BuLi (4.50 mmol) according to GP E.

Yield: 0.34 g (53%). Yellow oil. IR (film): 1686, 1382, 1032, 853, 756, 689. ¹H-NMR (300 MHz,

CDCl₃): 7.48–7.44 (m, 2 H); 7.35–7.29 (m, 3 H); 7.22 (s, 2 H); 7.10 (s, 1 H); 4.59 (s, 2 H); 4.49 (s, 2

H); 2.30 (s, 6 H). ¹³C-NMR (75.5 MHz, CDCl₃): 184.4 (C_q); 138.4 (C_q); 133.1 (C_q); 131.8 (CH); 130.9

(CH); 128.7 (CH); 128.3 (CH); 122.2 (C_q); 119.0 (C_q); 94.8 (C_q); 87.5 (C_q); 85.2 (C_q); 83.8 (C_q); 74.9

(CH₂); 59.3 (CH₂); 21.0 (Me). EI-MS: 302 (2, M⁺), 287 (3), 272 (18), 157 (100), 131 (38), 115 (70), 77

(76).HR-EI-MS: 3021. 307 ( M⁺, C₂₁

N

1-[(3-Phenylprop-2-yn-1-yl)oxy]-4-[4-(trifluoromethyl)phenyl]but-3-yn-2-one (1l).From 5a (0.39 g,

1.66 mmol), 1-ethynyl-4-(trifluoromethyl)benzene (0.71 g, 4.15 mmol), and BuLi (3.48 mmol) according

to GP E.Yield: 0.52 g (92%).Yellow oil.IR (KBr): 1689, 1321, 1128, 1015, 843, 691. ¹H-NMR (300 MHz,

CDCl₃): 7.72–7.63 (m, 4 H); 7.47–7.43 (m, 2 H); 7.36–7.30 (m, 3 H); 4.59 (s, 2 H); 4.50 (s, 2 H). ¹³C-NMR

(75.5 MHz, CDCl₃): 184.3 (C_q); 133.3 (CH); 131.8 (CH); 128.8 (CH); 125.6 (q, J=4, CH); 125.3 (C_q);

122.1 (C_q); 87.7 (C_q); 86.8 (C_q); 83.8 (C_q); 74.9 (CH₂); 59.4 (CH₂).EI-MS: 342 (5, M⁺), 197 (100), 169

(9), 115 (80).HR-EI-MS: 3420. 868 ( M⁺, C₂₀

A

G

N

4-Phenyl-1-{[3-(2,4,6-trimethylphenyl)prop-2-yn-1-yl]oxy}but-3-yn-2-one (1m).From 5f (0.16 g, 0.59

mmol), ethynylbenzene (0.15 g, 1.48 mmol), and BuLi (1.24 mmol) according to GP E.Yield: 00.7 g

1

(37%). H-NMR (300 MHz, CDCl₃): 7.61–7.57 (m, 2 H); 7.50–7.36 (m, 3 H); 6.86 (s, 2 H); 4.68 (s, 2

H); 4.53 (s, 2 H); 2.39 (s, 6 H); 2.27 (s, 3 H). ¹³C-NMR (75.5 MHz, CDCl₃): 184.5 (C_q); 140.4 (C_q);

138.2 (C_q); 133.2 (CH); 131.1 (CH); 128.7 (CH); 127.6 (CH); 119.5 (C_q); 119.0 (C_q); 93.9 (C_q); 91.0

(C_q); 85.6 (C_q); 85.4 (C_q); 74.6 (CH₂); 59.4 (CH₂); 21.3 (Me); 21.0 (Me). EI-MS: 316 (7, M⁺), 301 (8),

286 (19), 173 (5), 157 (48), 144 (30), 129 (100).HR-EI-MS: 3161. 463 ( M⁺, C₂₂

N

1-[(3-Phenylprop-2-yn-1-yl)oxy]-4-(2,4,6-trimethylphenyl)but-3-yn-2-one (1n).From 5a (0.50 g, 2.14

mmol), 2-ethynyl-1,3,5-trimethylbenzene (0.77 g, 5.36 mmol), and BuLi (4.50 mmol) according to GP E.

Yield: 0.43 g (64%). IR (film): 1677, 1277, 1058, 853, 757. ¹H-NMR (300 MHz, CDCl₃): 7.47–7.43 (m, 2

H); 7.35–7.29 (m, 3 H); 6.90 (s, 2 H); 4.59 (s, 2 H); 4.48 (s, 2 H); 2.46 (s, 6 H); 2.30 (s, 3 H). ¹³C-NMR

(75.5 MHz, CDCl₃): 184.6 (C_q); 142.8 (C_q); 141.3 (C_q); 131.7 (CH); 128.6 (CH); 128.3 (CH); 128.0

(CH); 122.2 (C_q); 116.3 (C_q); 93.5 (C_q); 93.2 (C_q); 87.4 (C_q); 83.8 (C_q); 74.9 (CH₂); 59.3 (CH₂); 21.5

(Me); 20.8 (Me). ESI-MS: 317 ([M+H]⁺), 334 ([M+NH₄]⁺), 339 ([M+Na]⁺), 655 ([2M+Na]⁺).HR-

ESI-MS: 317.1540 ([M+H]⁺, C₂₂

N

1-[(1-Methyl-3-phenylprop-2-yn-1-yl)oxy]-4-phenylbut-3-yn-2-one (1o).From WAo (1.50 g, 6.06

mmol), ethynylbenzene (1.55 g, 15.16 mmol), and BuLi (12.73 mmol) according to GP E.Yield: 12. 6 g

(72%).Yellow oil.IR (film): 1671, 1659, 1061, 757. ¹H-NMR (300 MHz, CDCl₃): 7.36–7.19 (m, 10 H);

4.56 (q, J=6.8, 1 H); 4.43 (m, 2 H); 1.53 (d, J=6.8, 3 H). ¹³C-NMR (75.5 MHz, CDCl₃): 184.9 (C_q);

133.1 (CH); 131.2 (CH); 130.9 (CH); 128.6 (CH); 128.5 (CH); 128.2 (CH); 93.6 (C_q); 87.7 (C_q); 86.1

(C_q); 85.8 (C_q); 74.1 (CH₂); 66.4 (CH); 22.0 (Me). EI-MS: 287 (0.3, M⁺), 273 (0.4), 144 (14), 129

(100), 77 (12).Anal.calc.for C ₂₀H₁₆O₂: C 83.31, H 5.59; found: C 82.91, H 5.71.

1-{[1-(1-Methylethyl)-3-phenylprop-2-yn-1-yl]oxy}-4-phenylbut-3-yn-2-one (1p).From WAp (1.00 g,

3.63 mmol), ethynylbenzene (0.93 g, 9.08 mmol), and BuLi (7.63 mmol) according to GP E.Yield: 0.94 g

(82%).Yellow oil.IR (film): 1685, 1670, 1065, 757. ¹H-NMR (300 MHz, CDCl₃): 7.50–7.21 (m, 10 H);

4.42 (m, 2 H); 4.24 (d, J=5.7, 1 H); 2.08 (sext., J=5.6, 1 H); 1.04 (m, 6 H). ¹³C-NMR (75.5 MHz,

CDCl₃): 185.5 (C_q); 133.1 (CH); 131.7 (CH); 130.9 (CH); 128.6 (CH); 128.4 (CH); 128.2 (CH); 122.4

(C_q); 119.7 (C_q); 93.6 (C_q); 87.6 (C_q); 86.1 (C_q); 85.7 (C_q); 76.3 (CH); 74.4 (CH); 33.3 (CH); 18.6

(Me); 17.8 (Me). EI-MS: 316 (1, M⁺), 215 (18), 129 (100), 77 (36).Anal.calc.for C ₂₂H₂₀O₂: C 83.51,

H 6.37; found C 82.94, H 6.79.

1-{[1-(1,1-Dimethylethyl)-3-phenylprop-2-yn-1-yl]oxy}-4-phenylbut-3-yn-2-one (1q).From

WAq

(0.90 g, 3.11 mmol), ethynylbenzene (0.79 g, 7.78 mmol), and BuLi (6.53 mmol) according to GP E.

1

Yield: 0.84 g (82%). Yellow oil. IR (film): 1688, 1281, 758. H-NMR (300 MHz, CDCl₃): 7.46–7.15 (m,

10 H); 4.34 (m, 2 H); 4.03 (s, 1 H); 1.01 (s, 9 H). ¹³C-NMR (75.5 MHz, CDCl₃): 185.9 (C_q); 133.2

2712

Helvetica Chimica Acta – Vol.89 (2006)

(CH); 132.1 (CH); 131.8 (CH); 128.8 (CH); 126.6 (CH); 128.4 (CH); 122.6 (C_q); 119.8 (C_q); 93.6 (C_q);

87.8 (C_q); 86.5 (C_q); 86.1 (C_q); 79.6 (CH); 74.8 (CH); 36.1 (C_q); 26.0 (Me). EI-MS: 144 (31), 129 (100),

77 (47).Anal.calc.for C ₂₃H₂₂O₂: C 83.60, H 6.71; found: C 83.24, H 6.59.

1-[(1,3-Diphenylprop-2-yn-1-yl)oxy]-4-phenylbut-3-yn-2-one (1r).From WAr (0.44 g, 1.41 mmol),

ethynylbenzene (0.36 g, 3.52 mmol), and BuLi (2.95 mmol) according to GP E.Yield: 0.15 g (30%).Yel-

low oil. ¹H-NMR (300 MHz, CDCl₃): 7.58–7.29 (m, 15 H); 5.73 (s, 1 H); 4.63 (d, J=17.8, 1 H); 4.46 (d,

J=17.8, 1 H). ¹³C-NMR (75.5 MHz, CDCl₃): 184.9 (C_q); 137.6 (C_q); 133.2 (CH); 131.8 (CH); 131.0 (CH);

128.8 (CH); 128.6 (CH); 128.5 (CH); 128.3 (CH); 127.8 (CH); 122.1 (C_q); 119.6 (C_q); 94.0 (C_q); 88.9 (C_q);

86.0 (C_q); 85.6 (C_q); 73.3 (CH₂); 72.3 (CH). EI-MS: 350 (1, M⁺), 207 (19), 129 (100), 77 (65).HR-EI-MS:

350.1307 (M⁺, C₂₅

N

General Procedure (GP F) for the Photolysis of Compounds 1.Irradiation of 1 was performed in

MeOH, t-BuOH, MeCN, or t-BuOMe at concentrations of 10 m^Musing a high-pressure Hg-arc lamp

(150 W).Light of wavelength below 300 nm was absorbed with a Pyrex glass jacket between the lamp

and the reaction vessel.The reaction was monitored by TLC, and the product compositions were deter-

mined when the reactant had completely disappeared (after typically 1–5 h).The soln.was concentrated

under reduced pressure, and purified by FC (SiO₂; PE/AcOEt 20 :1) to afford the pure photoproducts.

For the determination of the ratio of regioisomers, a 0.4 m^Msoln.of 1 in the appropriate solvent was irra-

diated for 1 h.The product mixture was concentrated under reduced pressure, and analyzed by ¹H-NMR

(in CDCl₃).This was done by integration of the methylene signals of the two regioisomers in the crude

reaction mixture.

Product Distribution upon Irradiation of Compounds 1 under Different Reaction Conditions. Irradi-

ation of 1a (see also Table 3). 1) In aerobic MeOH with 250 mg (0.911 mmol) of 1a for 3 h: 12a (48 mg,

19%), 11a (63 mg, 25%), and 13a (56 mg, 20%), and an inseparable 1:1 mixture of 14a/15a (30 mg, 12%).

2) In anaerobic MeOH with 254 mg (0.926 mmol) of 1a for 3 h: 12a (54 mg, 21%), 11a (50 mg, 20%), 13a

(54 mg, 18%), and 14a/15a (24 mg, 9%). 3) In t-BuOH with 456 mg (1.695 mmol) of 1a for 3 h: 12a (175

mg, 38%), 11a (183 mg, 39%), and 14a/15a (44 mg, 9%).The ratio of the PDDA reaction products was

12a/11a 1:1.3. 4) In MeCN with 146 mg (0.532 mmol) of 1a for 3 h: 12a (18 mg, 12%), 11a (25 mg, 17%),

and 14a/15a (16 mg, 11%).

Data of 10-Phenyl-1H-benzo[g]isochromen-4(3H)-one (12a).Mp. .87 8.IR (KBr): 1696, 1295, 1117,

745, 703. ¹H-NMR (300 MHz, CDCl₃): 8.69 (s, 1 H); 8.05–8.01 (m, 1 H); 7.54–7.59 (m, 6 H);

7.29–7.25 (m, 2 H); 4.72 (s, 2 H); 4.43 (s, 2 H). ¹³C-NMR (75.5 MHz, CDCl₃): 194.9 (C_q); 136.7 (C_q);

135.9 (C_q); 135.1 (C_q); 133.7 (C_q); 131.9 (C_q); 130.3 (CH); 129.7 (CH); 129.1 (CH); 128.8 (CH); 128.6

(CH); 128.0 (CH); 127.97 (CH); 127.95 (CH); 127.2 (C_q); 126.4 (CH); 126.2 (CH); 73.7 (CH₂); 67.4

(CH₂).EI-MS: 274 (95, M⁺), 244 (32), 202 (19), 197 (10), 77 (41).HR-EI-MS: 2740. 994 ( M⁺, C₁₉

N

calc.2740. 994).

Data of 5-Phenyl-1H-benzo[g]isochromen-4(3H)-one (11a).Mp. .135 8.IR (KBr): 1698, 1241, 1119,

755, 695. ¹H-NMR (300 MHz, CDCl₃): 7.87 (d, J=7.9, 1 H); 7.73 (s, 1 H); 7.62–7.49 (m, 5 H);

7.44–7.38 (m, 1 H); 7.26–7.23 (m, 2 H); 5.07 (s, 2 H); 4.35 (s, 2 H). ¹³C-NMR (75.5 MHz, CDCl₃):

194.6 (C_q); 143.2 (C_q); 138.9 (C_q); 136.4 (C_q); 135.1 (C_q); 132.1 (C_q); 128.8 (CH); 128.7 (CH); 128.1

(CH); 127.4 (CH); 127.2 (CH); 126.5 (CH); 124.9 (C_q); 123.3 (CH); 74.9 (CH₂); 69.3 (CH₂).EI-MS:

274 (60, M⁺), 244 (100), 202 (12), 77 (34).HR-EI-MS: 2740. 993 ( M⁺, C₁₉

N

Data of 1-Methoxy-7,8-diphenyl-3-oxabicyclo[4.2.0]oct-7-en-5-one (13a).Mp. .93 8.IR (KBr) 1712,

1

1221, 1108, 761, 691. H-NMR (300 MHz, CDCl₃): 7.63–7.60 (m, 4 H); 7.42–7.33 (m, 6 H); 4.38–4.26

(m, 2 H); 4.35 (d, J=12.1, 1 H); 4.30 (d, J=18.8, 1 H); 4.06–3.99 (m, 3 H); 3.72 (d, J=12.1, 1 H); 3.39

(s, 3 H). ¹³C-NMR (75.5 MHz, CDCl₃): 209.7 (C_q); 141.4 (C_q); 138.2 (C_q); 132.7 (C_q); 132.6 (C_q); 129.2

(CH); 128.80 (CH); 128.78 (CH); 128.6 (CH); 127.2 (CH); 126.5 (CH); 80.7 (C_q); 75.9 (CH₂); 69.6

(CH₂); 56.0 (CH); 51.3 (Me). EI-MS: 306 (82, M⁺), 276 (42), 248 (40), 178 (100), 77 (30).HR-EI-MS:

306.1256 (M⁺, C₂₀

N

Irradiation of 1b.In MeOH with 97 mg (0.314 mmol) of 1b for 3 h: 12b (24 mg, 25%) and 11b (26 mg,

27%); ratio 12b/11b 1:1.2.

Data of 10-(4-Chlorophenyl)-1H-benzo[g]isochromen-4(3H)-one (12b). ¹H-NMR (300 MHz,

CDCl₃): 8.74 (s, 1 H); 8.11–8.08 (m, 1 H); 7.62–7.54 (m, 4 H); 7.51–7.35 (m, 2 H); 7.31–7.27 (m, 2

H); 4.76 (s, 2 H); 7.48 (s, 2 H). ¹³C-NMR (75.5 MHz, CDCl₃): 194.7 (C_q); 135.2 (C_q); 135.0 (C_q); 134.5

Helvetica Chimica Acta – Vol.89 (2006)

2713

(C_q); 134.3 (C_q); 133.9 (C_q); 131.9 (C_q); 131.2 (CH); 130.4 (CH); 129.3 (CH); 129.2 (CH); 128.4 (CH);

126.6 (CH); 125.9 (CH); 73.8 (CH₂); 67.3 (CH₂).EI-MS: 308 (69, M⁺), 278 (20), 250 (21), 215 (100),

197 (8).HR-EI-MS: 3080. 604 ( M⁺, C₁₉

A

G

N

Data of 7-Chloro-5-phenyl-1H-benzo[g]isochromen-4(3H)-one (11b). ¹H-NMR (300 MHz, CDCl₃):

7.81 (d, J=8.7, 1 H); 7.71 (s, 1 H); 7.55–7.50 (m, 6 H); 7.22–7.18 (m, 2 H); 5.04 (s, 2 H); 4.32 (s, 2 H). ¹³C-

NMR (75.5 MHz, CDCl₃): 194.4 (C_q); 142.4 (C_q); 138.1 (C_q); 136.8 (C_q); 133.6 (C_q); 133.3 (C_q); 132.7

(C_q); 129.8 (CH); 129.0 (CH); 128.8 (CH); 128.3 (CH); 127.6 (CH); 127.3 (CH); 123.3 (CH); 74.9

(CH₂); 69.2 (CH₂).EI-MS: 308 (70, M⁺), 278 (90), 250 (8), 215 (100), 189 (7), 77 (20).HR-EI-MS:

308.0608 (M⁺, C₁₉

N

Irradiation of 1c.In MeOH with 100 mg (0.347 mmol) of 1c for 3 h: 12c (26 mg, 26%) and 11c (39 mg,

39%); ratio 12c/11c 1:1.6.

Data of 10-(4-Methylphenyl)-1H-benzo[g]isochromen-4(3H)-one (12c).Mp..147 8. ¹H-NMR (300

MHz, CDCl₃): 8.61 (s, 1 H); 7.99–7.91 (m, 1 H); 7.46–7.43 (m, 1 H); 7.28–7.25 (m, 2 H); 7.10–7.07

(m, 2 H); 4.66 (s, 2 H); 4.35 (s, 2 H); 2.41 (s, 3 H). ¹³C-NMR (75.5 MHz, CDCl₃): 195.0 (C_q); 137.8

(C_q); 136.0 (C_q); 135.3 (C_q); 133.9 (C_q); 133.7 (C_q); 133.2 (CH); 131.9 (C_q); 131.7 (CH); 131.1 (C_q);

130.3 (CH); 129.7 (CH); 129.5 (CH); 129.1 (CH); 128.7 (CH); 127.3 (CH); 126.3 (CH); 73.8 (CH₂);

67.5 (CH₂); 21.3 (Me). EI-MS: 288 (40, M⁺), 273 (3), 258 (5), 216 (9), 91 (29).HR-EI-MS: 2881.151

(M⁺, C₂₀

N

G

1

Data of 7-Methyl-5-phenyl-1H-benzo[g]isochromen-4(3H)-one (11c). H-NMR (300 MHz, CDCl₃):

7.65–7.10 (m, 9 H); 4.96 (s, 2 H); 4.24 (s, 2 H); 2.30 (s, 3 H). ¹³C-NMR (75.5 MHz, CDCl₃): 194.7 (C_q);

142.5 (C_q); 139.1 (C_q); 136.4 (C_q); 135.5 (C_q); 133.5 (C_q); 132.9 (C_q); 131.2 (CH); 129.5 (CH); 128.9

(CH); 128.6 (CH); 128.1 (CH); 127.4 (CH); 127.2 (CH); 126.4 (CH); 123.0 (CH); 75.0 (CH₂); 69.4

(CH₂); 21.9 (Me). HR-EI-MS: 288.1151 (M⁺, C₂₀

(100), 216 (20).

G

O^þ₂; calc.2881.150).EI-MS: 288 (90,

M⁺), 258

Irradiation of 1d.In t-BuOH with 356 mg (1.218 mmol) of 1d for 2 h: 12d (51 mg, 14%) and 11d (111

mg, 31%); ratio 12d/11d 1:1.6.

Data of 10-(4-Fluorophenyl)-1H-benzo[g]isochromen-4(3H)-one (12d).Yellow oil.IR (film): 1725,

1

1508, 1242, 1119, 757. H-NMR (300 MHz, CDCl₃): 8.70 (s, 1 H); 8.06–8.03 (m, 1 H); 7.55–7.50 (m, 3

H); 7.37–7.36 (m, 2 H); 7.24–7.23 (m, 2 H); 4.71 (s, 2 H); 4.43 (s, 2 H). ¹³C-NMR (75.5 MHz, CDCl₃):

1

194.8 (C_q); 162.7 (d, J(F,C)=250, C_q); 134.0 (C_q); 131.9 (C_q); 131.5 (d, J=8, CH); 130.4 (CH); 129.3

(CH); 128.3 (CH); 126.6 (CH); 126.0 (CH); 116.1 (CH); 73.7 (CH₂); 67.3 (CH₂).EI-MS: 292 (30,

M⁺), 262 (21), 220 (5), 197 (3).HR-EI-MS: 2920. 901 ( M⁺, C₁₉

N

G

8.IR

(KBr): 1695, 1597, 1195, 1130, 871, 694. ¹H-NMR (300 MHz, CDCl₃): 7.86 (dd, J=9.2, J=5.7, 1 H);

7.73 (s, 1 H); 7.52–7.48 (m, 3 H); 7.42–7.34 (m, 1 H); 7.22–7.12 (m, 3 H); 5.04 (s, 2 H); 4.33 (s, 2 H).

¹³C-NMR (75.5 MHz, CDCl₃): 194.5 (C_q); 160.8 (d, ¹J(F,C)=248, C_q); 138.4 (C_q); 135.8 (C_q); 132.1

(C_q); 129.9 (d, J=9, CH); 128.7 (CH); 128.3 (CH); 127.5 (CH); 125.6 (C_q); 123.7 (CH); 119.4 (d,

J=25, CH); 112.0 (d, J=22, CH); 74.9 (CH₂); 69.2 (CH₂).EI-MS: 292 (68, M⁺), 262 (89), 234 (37).

HR-EI-MS: 292.0899 (M⁺, C₁₉

N

Irradiation of 1e.In MeCN with 100 mg (0.324 mmol) of 1e for 1 h: 12e (15 mg, 15%) and 11e (27 mg,

27%); ratio 12e/11e 1:1.7.

Data of 8-Chloro-10-phenyl-1H-benzo[g]isochromen-4(3H)-one (12e).Yellow oil.Mp..180

8.IR

1

(film): 1695, 1486, 1293, 1118, 964, 707. H-NMR (300 MHz, CDCl₃): 8.58 (s, 1 H); 7.98 (d, J=8.7, 1

H); 7.56–7.46 (m, 5 H); 7.27–7.24 (m, 2 H); 4.70 (s, 2 H); 4.42 (s, 2 H). ¹³C-NMR (75.5 MHz, CDCl₃):

194.5 (C_q); 136.0 (C_q); 135.8 (C_q); 135.5 (C_q); 135.3 (C_q); 135.0 (C_q); 131.8 (CH); 130.2 (C_q); 129.7

(CH); 129.0 (CH); 128.4 (CH); 127.7 (CH); 127.6 (CH); 127.5 (C_q); 125.2 (CH); 73.7 (CH₂); 67.4

(CH₂).ESI-MS: 309 ([ M+H]⁺), 331 ([M+Na]⁺), 639 ([2M+Na]⁺).HR-ESI-MS: 3090. 860 ([ M+H]⁺,

C₁₉

N

Data of 5-(4-Chlorophenyl)-1H-benzo[g]isochromen-4(3H)-one (11e).Yellow solid.M.p.95–99 8.IR

(KBr): 1693, 1384, 1239, 1121, 1088, 860, 759. ¹H-NMR (300 MHz, CDCl₃): 7.57 (d, J=7.9, 1 H); 7.73 (s, 1

H); 7.63–7.58 (m, 1 H); 7.52–7.39 (m, 4 H); 7.18 (m, 2 H). ¹³C-NMR (75.5 MHz, CDCl₃): 194.7 (C_q);

141.8 (C_q); 137.3 (C_q); 136.4 (C_q); 135.2 (C_q); 133.3 (C_q); 132.6 (C_q); 130.3 (CH); 129.0 (CH); 128.43

2714

Helvetica Chimica Acta – Vol.89 (2006)

(CH); 128.36 (CH); 127.6 (CH); 126.7 (CH); 125.0 (C_q); 123.7 (CH); 74.9 (CH₂); 69.3 (CH₂).ESI-MS:

309 ([M+H]⁺), 331 ([M+Na]⁺), 639 ([2M+Na]⁺).HR-ESI-MS: 3090.861 ([ M+H]⁺, C₁₉

N

calc.3090. 682).

Irradiation of 1f.In t-BuOH with 334 mg (1.143 mmol) of 1f for 1.5 h: 12f (116 mg, 35%) and 11f

(126 mg, 38%); ratio 12f/11f 1:1.1.

Data of 8-Fluoro-10-phenyl-1H-benzo[g]isochromen-4(3H)-one (12f).Yellow oil.IR (film): 1692,

1507, 1241, 1119, 961, 758. ¹H-NMR (300 MHz, CDCl₃): 8.68 (s, 1 H); 8.04 (dd, ³J=8.75, ⁴J=5.74, 1

H); 7.58–7.50 (m, 3 H); 7.34–7.24 (m, 3 H); 7.11–7.07 (m, 1 H); 4.71 (s, 2 H); 4.42 (s, 2 H). ¹³C-NMR

(75.5 MHz, CDCl₃): 194.6 (C_q); 136.3 (C_q); 134.8 (C_q); 133.2 (d, ³J=9.3, CH); 129.6 (CH); 129.0

(CH); 128.4 (CH); 127.8 (CH); 126.9 (C_q); 117.2 (d, ²J=25.3, CH); 110.0 (d, ²J=20.3, CH); 73.7

(CH₂); 67.4 (CH₂).EI-MS: 292 (82, M⁺), 262 (9), 234 (100), 215 (7).HR-EI-MS: 2920. 901 ( M⁺, C₁₉

FO^þ₂; calc.2920. 900).

Data of 5-(4-Fluorophenyl)-1H-benzo[g]isochromen-4(3H)-one (11f).Yellow solid.Mp..170

ACHTREUNG

(KBr): 1694, 1507, 1118, 959, 757. ¹H-NMR (300 MHz, CDCl₃): 7.85 (d, J=7.5, 1 H); 7.73 (s, 1 H);

7.63–7.57 (m, 1 H); 7.53–7.50 (m, 1 H); 7.44–7.39 (m, 1 H); 7.20–7.18 (m, 4 H); 5.06 (s, 2 H); 4.33 (s,

2 H). ¹³C-NMR (75.5 MHz, CDCl₃): 194.8 (C_q); 162.2 (d, ¹J(F,C)=246, C_q); 136.4 (C_q); 135.2 (C_q);

134.6 (C_q); 132.9 (C_q); 131.8 (CH); 130.5 (d, J=8, CH); 128.9 (CH); 128.4 (CH); 127.5 (CH); 126.7

(CH); 125.1 (C_q); 123.6 (CH); 75.0 (CH₂); 69.3 (CH₂).EI-MS: 292 (70, M⁺), 262 (100), 234 (32).HR-

EI-MS: 292.0900 (M⁺, C₁₉

N

Irradiation of 1g.In MeCN with 155 mg (05. 38 mmol) of 1g for 1.5 h: 12g (46 mg, 30%) and 11g (72

mg, 46%); ratio 12g/11g 1:1.2.

Data of 8-Methyl-10-phenyl-1H-benzo[g]isochromen-4(3H)-one (12g).IR (film): 1695, 1295, 1118,

798, 700. ¹H-NMR (300 MHz, CDCl₃): 8.64 (s, 1 H); 7.93 (d, J=7.9, 1 H); 7.57–7.44 (m, 3 H);

7.37–7.17 (m, 4 H); 4.68 (s, 2 H); 4.41 (s, 2 H). ¹³C-NMR (75.5 MHz, CDCl₃): 194.9 (C_q); 139.6 (C_q);

136.9 (C_q); 135.3 (C_q); 135.1 (C_q); 133.9 (C_q); 130.2 (C_q); 130.1 (CH); 129.8 (CH); 129.0 (CH); 128.8

(CH); 128.6 (CH); 128.0 (CH); 127.7 (CH); 126.5 (C_q); 125.2 (CH); 116.3 (C_q); 73.7 (CH₂); 67.4

(CH₂); 22.2 (Me). ESI-MS: 289 ([M+H]⁺), 311 ([M+Na]⁺), 599 ([2M+Na]⁺).HR-ESI-MS: 2891. 225

([M+H]⁺, C₂₀

N

Data of 5-(4-Methylphenyl)-1H-benzo[g]isochromen-4(3H)-one (11g).IR (film): 1696, 1211, 1118,

754. ¹H-NMR (300 MHz, CDCl₃): 7.87–7.83 (m, 1 H); 7.70 (s, 1 H); 7.59 (d, J=7.9, 2 H); 7.42–7.31

(m, 3 H); 7.12 (d, J=7.9, 2 H); 5.03 (s, 2 H); 4.31 (s, 2 H); 2.47 (s, 3 H). ¹³C-NMR (75.5 MHz, CDCl₃):

194.7 (C_q); 143.4 (C_q); 136.8 (C_q); 136.4 (C_q); 135.8 (C_q); 135.1 (C_q); 132.9 (C_q); 131.9 (CH); 130.8

(CH); 128.8 (CH); 128.7 (CH); 127.3 (CH); 126.4 (CH); 125.0 (C_q); 123.1 (CH); 74.9 (CH₂); 69.3

(CH₂); 21.4 (Me). ESI-MS: 289 ([M+H]⁺), 311 ([M+Na]⁺), 599 ([2M+Na]⁺).HR-ESI-MS: 2891. 226

([M+H]⁺, C₂₀

N

Irradiation of 1h.In MeCN with 179 mg (05. 52 mmol) of 1h for 2 h: inseparable 1:1 mixture of 15a/

14h (96 mg, 54%). ¹H-NMR (300 MHz, CDCl₃): 9.57 (s, 1 H, 14h); 8.33 (d, ³J=7.91, 1 H, 14h); 8.00 (d,

J=7.3, 1 H, 14h); 7.92–7.88 (m, 2 H, 14h); 7.68–7.35 (m, 8 H, 14h/15a); 2.44 (s, 3 H, 15a). ¹³C-NMR

(75.5 MHz, CDCl₃): 184.6 (C_q, 15a); 176.6 (CHO, 14h); 133.7 (CH, 14h); 133.03 (CH, 14h); 133.00

(CH, 15a); 132.1 (CH, 14h); 130.7 (CH, 15a); 128.6 (CH, 15a); 127.9 (CH, 14h); 127.0 (CH, 14h);

125.6 (CH, 14h); 125.2 (CH, 14h); 119.9 (C_q, 15a); 116.9 (C_q, 14h); 93.4 (C_q, 14h); 93.1 (C_q, 14h); 90.3

(C_q, 15a); 88.2 (C_q, 15a); 32.7 (Me, 15a).

Irradiation of 1i.In MeCN with 228 mg (0.703 mmol) of 1i for 2 h: 15i (67 mg, 49%) and 14a (53 mg,

58%).

1

Data of 3-Phenylprop-2-ynal (14a). H-NMR (300 MHz, CDCl₃) 9.43 (s, 1 H); 7.63–7.59 (m, 2 H);

7.52–7.47 (m, 1 H); 7.43–7.38 (m, 2 H). ¹³C-NMR (75.5 MHz, CDCl₃): 176.8 (CHO); 133.3 (CH);

131.3 (CH); 128.7 (CH); 119.4 (C_q); 95.1 (C_q); 88.4 (C_q).

Data of 4-(Naphthalen-1-yl)but-3-yn-2-one (15i). ¹H-NMR (300 MHz, CDCl₃): 8.31 (d, J=8.3, 1 H);

7.97 (d, J=8.3, 1 H); 7.91–7.83 (m, 2 H); 7.67–7.45 (m, 3 H); 2.57 (s, 3 H). ¹³C-NMR (75.5 MHz, CDCl₃):

184.5 (C_q); 133.2 (CH); 131.5 (CH); 128.5 (CH); 127.7 (CH); 126.9 (CH); 125.7 (CH); 125.2 (CH); 117.4

(C_q); 92.9 (C_q); 88.7 (C_q); 32.9 (CH₃).

Irradiation of 1j.In t-BuOH with 216 mg (0.613 mmol) of 1j in 3 h: inseparable 1:1.8 mixture of 12j/

15j (8 and 15%, resp.) together with 11j (82 mg, 38%); ratio 12j/11j 1:6.6.

Helvetica Chimica Acta – Vol.89 (2006)

2715

Data of 12j/15j. ¹H-NMR (300 MHz, CDCl₃): 8.74 (s, 1 H, 12j); 8.23 (d, J=8.7, 1 H, 12j); 8.18–1.87

(m, 1 H, 12j); 7.99–7.94 (m, 3 H, 15j); 7.77–7.73 (m, 3 H, 12j/15j); 7.57–7.55 (m, 3 H, 12j); 7.28–7.25 (m,

2 H, 12j); 4.74 (s, 2 H, 12j); 4.46 (s, 2 H, 12j); 3.07 (s, 3 H, 15j); 3.04 (s, 3 H, 12j); 2.48 (s, 3 H, 15j). ¹³C-

NMR (75.5 MHz, CDCl₃): 194.3 (C_q, 12j); 184.0 (C_q, 15j); 141.9 (C_q); 140.3 (C_q); 138.0 (C_q); 136.0 (C_q);

135.2 (C_q); 134.0 (C_q); 133.8 (C_q); 133.5 (CH, 15j); 132.1 (CH); 129.6 (CH); 129.3 (CH); 128.9 (CH);

127.6 (CH, 15j); 127.5 (CH); 127.0 (CH); 125.7 (C_q); 122.8 (CH); 90.2 (C_q, 15j); 86.7 (C_q, 15j); 73.7

(CH₂, 12j); 67.3 (CH₂, 12j); 44.3 (Me, 15j); 44.2 (Me, 12j); 32.7 (Me, 15j).

Data of 5-[4-(Methylsulfonyl)phenyl]-1H-benzo[g]isochromen-4(3H)-one (11j).IR (KBr): 1694,

1

3

1298, 1152, 959, 771. H-NMR (300 MHz, CDCl₃): 8.10–8.06 (m, 2 H); 7.89 (d, J=8.12, 1 H); 7.79 (s,

1 H); 7.68–7.58 (m, 1 H); 7.46–7.40 (m, 2 H); 7.35–7.32 (m, 2 H); 5.08 (s, 2 H); 4.34 (s, 2 H); 3.19 (s,

3 H). ¹³C-NMR (75.5 MHz, CDCl₃): 194.7 (C_q); 145.5 (C_q); 140.7 (C_q); 139.3 (C_q); 136.4 (C_q); 135.2

(C_q); 129.9 (CH); 129.2 (CH); 127.9 (CH); 127.7 (CH); 127.2 (CH); 127.1 (CH); 124.7 (C_q); 124.2

(CH); 74.8 (CH₂); 69.2 (CH₂); 44.6 (Me). ESI-MS: 353 ([M+H]⁺), 370 ([M+NH₄]⁺), 375

([M+Na]⁺), 705 ([2M+H]⁺), 722 ([2M+NH₄]⁺), 727 ([2M+Na]⁺).HR-ESI-MS: 3530. 842 ([ M+H]⁺,

C

A

G

N

mg, 27%); ratio 12k/11k 1:1.2.

Data of 7,9-Dimethyl-10-phenyl-1H-benzo[g]isochromen-4(3H)-one (12k).Yellow oil.IR (KBr):

1696, 1443, 1280, 1119, 744, 704. ¹H-NMR (300 MHz, CDCl₃): 8.49 (s, 1 H); 7.59 (s, 1 H); 7.37–7.35

(m, 3 H); 7.18–7.15 (m, 2 H); 7.09 (s, 1 H); 4.46 (s, 2 H); 4.28 (s, 2 H); 2.37 (s, 3 H); 1.81 (s, 3 H). ¹³C-

NMR (75.5 MHz, CDCl₃): 194.9 (C_q); 140.6 (C_q); 135.7 (C_q); 135.6 (CH); 135.4 (C_q); 134.5 (C_q); 133.6

(C_q); 132.0 (CH); 129.7 (CH); 128.6 (CH); 128.5 (CH); 128.3 (CH); 127.8 (CH); 126.5 (C_q); 73.4

(CH₂); 67.6 (CH₂); 24.5 (Me); 21.0 (Me). EI-MS: 302 (50, M⁺), 272 (100), 230 (11), 167 (26).HR-EI-

MS: 302.1307 (M⁺, C₂₁

N

Data of 5-(3,5-Dimethylphenyl)-1H-benzo[g]isochromen-4(3H)-one (11k).Yellow solid.Mp. .163 8.

1

IR (KBr): 1696, 1595, 1238, 1116, 856, 754. H-NMR (300 MHz, CDCl₃): 7.86–7.83 (m, 1 H); 7.69 (s, 1

H); 7.60–7.56 (m, 2 H); 7.42–7.39 (m, 1 H); 7.10 (s, 1 H); 6.84 (s, 2 H); 5.05 (s, 2 H); 4.34 (s, 2 H);

2.39 (s, 6 H). ¹³C-NMR (75.5 MHz, CDCl₃): 194.6 (C_q); 143.7 (C_q); 138.7 (C_q); 137.4 (C_q); 136.3 (C_q);

135.1 (C_q); 132.9 (C_q); 128.9 (CH); 128.7 (CH); 128.4 (CH); 127.3 (CH); 126.6 (CH); 126.3 (CH);

124.8 (C_q); 123.0 (CH); 75.0 (CH₂); 69.4 (CH₂); 21.4 (Me). EI-MS: 302 (100, M⁺), 272 (12), 244 (48),

230 (20), 105 (15).HR-EI-MS: 3021. 307 ( M⁺, C₂₁

N

Irradiation of 1l.In t-BuOH with 151 mg (0.441 mmol) of 1l for 2 h: 12l (10 mg, 7%), 11l (41 mg,

27%), and 15l (15 mg, 16%); ratio 12l/11l 1:2.4.

Data of 10-Phenyl-8-(trifluoromethyl)-1H-benzo[g]isochromen-4(3H)-one (12l).IR (KBr): 1696,

1

1292, 1121, 1068, 797, 674. H-NMR (300 MHz, CDCl₃): 8.73 (s, 1 H); 8.16 (d, J=8.5, 1 H); 7.80 (s, 1

H); 7.71–7.66 (m, 1 H); 7.59–7.53 (m, 3 H); 7.29–7.26 (s, 2 H); 4.73 (s, 2 H); 4.45 (s, 2 H). ¹³C-NMR

(75.5 MHz, CDCl₃): 194.5 (C_q); 137.3 (C_q); 135.6 (C_q); 135.3 (C_q); 134.0 (C_q); 133.0 (C_q); 133.1 (C_q);

131.4 (CH); 129.6 (CH); 129.1 (CH); 128.4 (CH); 127.5 (CH); 123.9 (q, J=4.6, CH); 122.1 (q, J=2.7,

CH); 73.7 (CH₂); 67.3 (CH₂).EI-MS: 342 (69, M⁺), 312 (12), 284 (89), 197 (12).HR-EI-MS: 3420. 868

(M⁺, C₂₀

A

G

N

Data of 5-[4-(Trifluoromethyl)phenyl]-1H-benzo[g]isochromen-4(3H)-one (11l).IR (KBr): 1694,

1324, 1118, 1066, 757. ¹H-NMR (300 MHz, CDCl₃): 7.88 (d, J=8.3, 1 H); 7.78–7.75 (m, 3 H);

7.66–7.33 (m, 5 H); 5.07 (s, 2 H); 4.34 (s, 2 H). ¹³C-NMR (75.5 MHz, CDCl₃): 194.6 (C_q); 136.4 (C_q);

135.2 (C_q); 132.1 (C_q); 132.0 (CH); 131.8 (CH); 129.3 (CH); 129.1 (CH); 128.2 (CH); 127.7 (CH);

126.9 (CH); 125.1 (q, J=3.6, CH); 124.8 (C_q); 74.8 (CH₂); 69.2 (CH₂).EI-MS: 342 (18, M⁺), 312 (22),

284 (5), 197 (15).HR-EI-MS: 3420. 868 ( M⁺, C₂₀

Data of 4-[4-(Trifluoromethyl)phenyl]but-3-yn-2-one (15l). H-NMR (300 MHz, CDCl₃): 7.72–7.65

(m, 4 H); 2.47 (s, 3 H). ¹³C-NMR (75.5 MHz, CDCl₃): 184.2 (C_q); 133.1 (CH); 127.9 (CH); 125.6 (q,

J=4, CH); 125.6 (d, J=37, C_q); 123.7 (C_q); 89.3 (C_q); 87.7 (C_q); 32.7 (Me).

A

G

A

1

Irradiation of 1m.In t-BuOH with 66 mg (0.209 mmol) of 1m for 1.5 h: 12m (25 mg, 38%) and 16 (7

mg, 11%).

Data of 10-(2,4,6-Trimethylphenyl)-1H-benzo[g]isochromen-4(3H)-one (12m). ¹H-NMR (300 MHz,

CDCl₃): 8.69 (s, 1 H); 8.06–8.03 (m, 1 H); 7.73–7.70 (m, 1 H); 7.56–7.45 (m, 2 H); 7.28 (d, J=8.3, 1 H);

2716

Helvetica Chimica Acta – Vol.89 (2006)

4.55 (s, 2 H); 4.43 (s, 2 H); 2.40 (s, 3 H); 1.81 (s, 6 H). ¹³C-NMR (75.5 MHz, CDCl₃): 195.1 (C_q); 137.7

(C_q); 136.3 (C_q); 134.6 (C_q); 134.5 (C_q); 133.7 (C_q); 132.4 (C_q); 132.1 (C_q); 130.6 (CH); 129.4 (CH);

128.7 (CH); 127.7 (CH); 126.6 (CH); 125.2 (CH); 73.8 (CH₂); 67.0 (CH₂); 21.1 (Me); 19.9 (Me). EI-

MS: 316 (35, M⁺), 301 (6), 271 (10), 258 (5).HR-EI-MS: 3161.464 ( M⁺, C₂₂

N

Data of 7,9-Dimethyl-5-phenyl-1H-benzo[g]isochromen-4(3H)-one (16). ¹H-NMR (300 MHz,

CDCl₃): 7.82 (s, 1 H); 7.50–7.47 (m, 2 H); 7.28 (s, 1 H); 7.21–7.18 (m, 2 H); 7.13 (s, 2 H); 5.07 (s, 2

H); 4.31 (s, 2 H); 2.70 (s, 3 H); 2.31 (s, 3 H). ¹³C-NMR (75.5 MHz, CDCl₃): 194.8 (C_q); 139.4 (C_q);

135.9 (C_q); 135.3 (C_q); 133.6 (C_q); 132.8 (CH); 132.0 (CH); 128.9 (CH); 129.8 (C_q); 128.0 (CH); 127.1

(CH); 125.7 (CH); 119.5 (CH); 74.9 (CH₂); 69.7 (CH₂); 23.8 (Me); 20.8 (Me); 17.5 (Me). EI-MS: 302

(29, M⁺), 287 (17), 272 (18), 230 (16), 167 (13), 77 (33).

Irradiation of 1n.In t-BuOH with 122 mg (0.384 mmol) of 1n for 1.5 h: 11n (60 mg, 49%) and 17 (32

mg, 26%).

Data of 5-(2,4,6-Trimethylphenyl)-1H-benzo[g]isochromen-4(3H)-one (11n).Red-yellow solid.IR

(KBr): 1695, 1288, 1118, 715. ¹H-NMR (300 MHz, CDCl₃): 8.77 (s, 1 H); 7.55–7.48 (m, 3 H);

7.27–7.21 (m, 2 H); 7.07 (s, 1 H); 6.86 (s, 1 H); 4.61 (s, 2 H); 4.35 (s, 2 H); 2.71 (s, 3 H); 2.28 (s, 3 H).

¹³C-NMR (75.5 MHz, CDCl₃): 195.1 (C_q); 141.0 (C_q); 139.2 (C_q); 137 (C_q); 136.9 (C_q); 135.9 (C_q);

133.7 (C_q); 129.8 (CH); 129.7 (CH); 128.6 (CH); 127.9 (CH); 127.6 (CH); 126.1 (C_q); 124.1 (CH);

123.5 (CH); 73.7 (CH₂); 67.4 (CH₂); 22.2 (Me); 19.6 (Me). EI-MS: 302 (100, M⁺), 272 (7), 244 (53),

230 (8).HR-EI-MS: 3021. 306 ( M⁺, C₂₁

N

Data of 6,8-Dimethyl-10-phenyl-1H-benzo[g]isochromen-4(3H)-one (17).Yellow oil.IR (KBr):

1687, 1382, 1238, 1118, 855, 751. ¹H-NMR (300 MHz, CDCl₃): 7.87 (d, ³J=8.29, 1 H); 7.71 (s, 1 H);

7.62–7.57 (m, 1 H); 7.43–7.34 (m, 2 H); 7.00 (s, 2 H); 5.07 (s, 2 H); 4.33 (s, 2 H); 2.40 (s, 3 H); 1.72 (s,

6 H). ¹³C-NMR (75.5 MHz, CDCl₃): 194.4 (C_q); 142.6 (C_q); 136.7 (C_q); 136.6 (C_q); 135.5 (C_q); 135.1

(C_q); 131.9 (C_q); 129.0 (CH); 128.1 (CH); 127.7 (CH); 127.5 (CH); 126.8 (CH); 125.0 (C_q); 123.0

(CH); 74.7 (CH₂); 69.5 (CH₂); 21.3 (Me); 20.0 (Me). EI-MS: 316 (82, M⁺), 302 (3), 286 (100), 271

(30), 244 (9).HR-EI-MS: 3161. 464 ( M⁺, C₂₂

N

Irradiation of 1o.In MeOH with 350 mg (12. 14 mmol) of 1o for 2 h: inseparable mixture of 18o/19o

1

(238 mg, 68%) in the ratio 1:1.5. H-NMR (300 MHz, CDCl₃): 8.59 (s, 1 H, 19o); 7.95 (d, J=9.0, 1 H,

18o); 7.94–7.16 (m, 18 H, 18o/19o); 5.10 (q, J=6.4, 1 H, 18o); 5.01 (q, J=6.8, 1 H, 19o); 4.48 (m, 2 H,

19o); 4.45 (m, 2 H, 18o); 1.91 (d, J=6.4, 3 H, 19o); 1.32 (d, J=6.8, 3 H, 18o). ¹³C-NMR (75.5 MHz,

CDCl₃): 195.6 (C_q, 18o); 195.1 (C_q, 19o); 142.8; 140.7; 138.3; 137.0; 135.5; 135.4; 135.1; 132.4 (C_q, 18o/

19o); 131.7; 130.6; 129.5; 129.2; 129.1; 128.5; 128.4; 128.1; 127.9; 127.7; 127.6; 127.0; 126.4; 126.2;

122.8 (CH, 18o/19o); 73.3 (CH₂, 19o); 72.9 (CH, 19o); 69.6 (CH, 18o); 66.7 (CH₂, 18o); 19.8 (Me,

19o); 19.3 (Me, 18o).

Irradiation of 1p.In MeOH with 267 mg (08. 44 mmol) of 1p for 2 h: inseparable mixture of 18p/19p

(166 mg, 62%) in the ratio 1:2.3. ¹H-NMR (300 MHz, CDCl₃): 8.49 (s, 1 H, 18p); 7.88–7.03 (m, 19 H, 18p/

19p); 4.56 (m, 2 H, 19p); 4.51 (m, 1 H, 19p); 4.30 (m, 2 H, 18p); 4.15 (m, 1 H, 18p); 1.86 (m, 1 H, 18p); 1.01

(m, 6 H, 19p); 0.84 (d, J=6.8, 3 H, 18p); 0.45 (d, J=6.8, 3 H, 18p). ¹³C-NMR (75.5 MHz, CDCl₃): 196.6

(C_q, 18p); 195.4 (C_q, 19p); 142.8; 138.9; 137.1; 134.8; 132.4 (C_q, 18p/19p); 131.9; 130.1; 128.9; 128.4; 127.9;

127.6 (CH, 18p/19p); 81.8 (CH, 18p); 77.9 (CH, 19p); 71.5 (CH₂, 18p); 67.6 (CH₂, 19p); 32.3 (CH, 18p);

30.4 (CH, 19p); 19.7 (Me, 18p); 19.2 (Me, 19p); 17.4 (Me, 18p).

Irradiation of 1q.In MeOH with 150 mg (04. 54 mmol) of 1q for 2 h: 19q (62 mg, 41%).

Data of 1-(1,1-Dimethylethyl)-5-phenyl-1H-benzo[g]isochromen-4(3H)-one (19q).IR (film): 1696,

1

1213, 1120, 749, 696. H-NMR (300 MHz, CDCl₃): 7.50–7.00 (m, 10 H); 4.66 (s, 1 H); 4.37 (m, 2 H);

1.03 (s, 9 H). ¹³C-NMR (75.5 MHz, CDCl₃): 195.8 (C_q); 142.0 (C_q); 138.9 (C_q); 136.6 (C_q); 134.6 (C_q);

132.6 (C_q); 130.1 (CH); 128.3 (CH); 127.8 (CH); 127.2 (CH); 126.7 (CH); 125.8 (CH); 83.9 (CH); 71.6

(CH₂); 37.4 (C_q); 27.8 (Me). EI-MS: 330 (4, M⁺), 273 (86), 202 (100), 77 (42).Anal.calc.for

C₂₃H₂₂O₂: C 83.60, H 6.71; found: C 82.98, H 6.61.

Irradiation of 1r.In t-BuOH with 120 mg (0.342 mmol) of 1r for 2 h: 18r (25 mg, 21%) and 19r (41

mg, 34%); ratio 18r/19r 1:1.6.

Data of 1,10-Diphenyl-1H-benzo[g]isochromen-4(3H)-one (18r).Mp..182 8.IR (film): 1691, 1586,

1293, 1101, 960, 754, 700. ¹H-NMR (300 MHz, CDCl₃): 8.77 (s, 1 H); 8.12–8.07 (m, 1 H); 7.74–7.41

(m, 1 H); 7.60–7.47 (m, 4 H); 7.42–7.33 (m, 2 H); 7.28–7.20 (m, 2 H); 7.15–10 (m, 1 H); 7.01–6.98

Helvetica Chimica Acta – Vol.89 (2006)

2717

(m, 2 H); 6.69 (d, J=7.5, 1 H); 5.93 (s, 1 H); 4.26 (d, J=18.1, 1 H); 4.15 (d, J=18.1, 1 H). ¹³C-NMR (75.5

MHz, CDCl₃): 195.7 (C_q); 137.8 (C_q); 137.0 (C_q); 136.5 (C_q); 135.5 (C_q); 134.4 (C_q); 132.2 (C_q); 130.3

(CH); 130.2 (CH); 129.9 (C_q); 129.5 (CH); 129.3 (CH); 129.2 (CH); 128.5 (CH); 128.4 (CH); 128.3

(CH); 128.09 (CH); 128.07 (CH); 127.8 (CH); 127.6 (C_q); 126.72 (CH); 126.65 (CH); 75.6 (CH); 67.3

(CH₂).EI-MS: 350 (3, M⁺), 320 (7), 202 (18), 149 (100), 77 (49).HR-EI-MS: 3501. 304 ( M⁺, C₂₅

N

calc.3501. 307).

Data of 1,5-Diphenyl-1H-benzo[g]isochromen-4(3H)-one (19r).IR (film): 1728, 1377, 1119, 844, 699.

¹H-NMR (300 MHz, CDCl₃): 7.75–7.71 (m, 2 H); 7.57–7.36 (m, 11 H); 7.29–7.26 (m, 2 H); 6.03 (s, 1 H);

4.38 (s, 1 H); 4.37 (s, 1 H). ¹³C-NMR (75.5 MHz, CDCl₃): 194.9 (C_q); 143.1 (C_q); 139.03 (C_q); 139.00 (C_q);

138.90 (C_q); 134.9 (C_q); 132.7 (C_q); 130.9 (CH); 129.0 (CH); 128.8 (CH); 128.7 (CH); 128.63 (CH); 128.57

(CH); 128.2 (CH); 128.0 (CH); 127.8 (CH); 127.2 (CH); 126.7 (CH); 125.6 (CH); 125.3 (C_q); 80.9 (CH);

72.5 (CH₂).EI-MS: 350 (28, M⁺), 320 (79), 202 (3), 149 (100), 77 (10).HR-EI-MS: 350.1307 ( M⁺, C₂₅

O^þ₂; calc.3501. 307).

X-Ray Crystallography.The crystallographic data of 1-methoxy-7,8-diphenyl-3-oxabicyclo[4.2.0]oct-

A

ACHTREUNG

7-en-5-one (13a) and of 1-methyl-10-phenyl-1H-benzo[g]isochromen-4(3H)-one (18o) are collected in

Table 5.Details of the structure investigations are available on request from the Cambridge Crystallo-

graphic Data Centre, on quoting the depository numbers CCDC-299200 (13a) and CCDC-299199

(18o).The data of an analog of 13a bearing a 4-chlorphenyl group instead of a phenyl group in 8-position

have also been deposited (CCDC-299201).

Table 5. Crystallographic Data of 13a and 18o

13a

C₂₀H₁₈

306.34

180(2)

18o

C₂₀H₁₆

288.33

180(2)

Empirical formula

Formula weight

Temperature [K]

Wavelength []

G

U

O₂

0.71073

Crystal system, space group Monoclinic, C 2/c

Unit cell dimensions: a [] 20.800(6)

b [] 6.8731(14)

Triclinic, P -1

6.203(2)

10.741(4)

11.452(4)

83.23(4)

77.90(4)

80.48(4)

733.0(5)

2, 1.306

c [] 23.935(7)

a [8]

b [8]

g [8]

90

111.88(3)

90

3175.1(14)

8, 1.282

0.085

Volume [³]

Z, calc.density [Mg/m ³]

Absorption coefficient

[mm^–1]

0.083

F(000)

1296

304

Crystal size [mm]

q-Range for data collection 2.22 to 25.258

0.760.760.40

0.580.500.36

2.54 to 25.258

Limiting indices

ꢀ24ꢁhꢁ24; –8 ꢁ k ꢁ 8; –28 ꢁ l ꢁ 28 ꢀ7ꢁhꢁ7; ꢀ12ꢁkꢁ12;

ꢀ13ꢁlꢁ13

Refl.collected/unique

Completeness to q (=25.258) 99.7%

10237/2872 ( R(int)=0.1098)

4932/2481 (R(int)=0.0498)

93.4%

Max. and min. transmission 0.9667 and 0.9380

Refinement

Data; restraints; parameters 2872; 0; 281

0.9707 and 0.9533

Full-matrix least-squares on F²

2481; 0; 222

Full-matrix least-squares on F²

Goodness-of-fit on F²

Final R indices (I > 2s(I))

R Indices (all data)

1.058

0.949

R1=0.0523, wR2=0.1275

R1=0.0610, wR2=0.1326

0.0061(13)

R1=0.0612, wR2=0.1478

R1=0.1007, wR2=0.1696

0.084(17)

Extinction coefficient

Largest diff.peak and hole 03. 98 and ꢀ0.335 e A^ꢀ3

0.203 and ꢀ0.209 e A^ꢀ3

2718

Helvetica Chimica Acta – Vol.89 (2006)

Quantum-Chemical Calculations. Geometry optimizations were performed with the Gaussian-03

program package [27] using the B3LYP hybrid functional [28] and the 6-31G* basis set.At the same

level of theory, frequency calculations were carried out to characterize each structure as minimum

(triplet-1a, BR(3), CA(5), CA(6)) or transition state (TS(3)–TS(6)), resp., and to obtain the zero-

point vibrational energies.Afterwards, single-point calculations were performed with the same DFT

functional using the extended basis set 6-311++G** to obtain improved energies.The energies of all cal-

culated species are summarized in Table 6.

Table 6. Results of Quantum-Chemical Calculations.ꢁSꢂ and ꢁTꢂrefer to singlet and triplet states, resp., and

ꢁAꢂ and ꢁBꢂ denote different conformers.

b

c

e

f

g

Compound

S/I^a)

E₁)

E₂)

ZPE^d)

E₃)

E_rel

)

E_a)

1a

TS(3)

T-BR(3)

S-BR(3)

T-TS(4)-A

T-TS(4)-B

S-TS(4)-A

S-TS(4)-B

T-TS(5)-A

T-TS(5)-B

S-TS(5)-A

S-TS(5)-B

T-TS(6)

3/0

3/1

3/0

1/0

3/1

1/1

3/1

1/1

3/1

1/1

3/0

1/0

3/0

1/0

ꢀ882.6588433

ꢀ882.6514335

ꢀ882.7193023

ꢀ882.7196085

ꢀ882.6886345

ꢀ882.6887996

ꢀ882.7089089

ꢀ882.7084357

ꢀ882.6919149

ꢀ882.6910808

ꢀ882.7099952

ꢀ882.709098

ꢀ882.6869116

ꢀ882.7168799

ꢀ882.7265088

ꢀ882.7267044

ꢀ882.7388198

ꢀ882.7369100

ꢀ882.7360407

ꢀ882.7349839

ꢀ882.740898

ꢀ882.7401708

ꢀ882.7756857

ꢀ882.8940822

ꢀ882.8877381

ꢀ882.9506586

ꢀ882.9507643

ꢀ882.9171218

ꢀ882.9171075

ꢀ882.9396493

ꢀ882.9387624

ꢀ882.9204862

ꢀ882.9196566

ꢀ882.9402898

ꢀ882.9394051

ꢀ882.9157172

ꢀ882.9453217

ꢀ882.9542775

ꢀ882.9545939

ꢀ882.968590

ꢀ882.9668307

ꢀ882.9637126

ꢀ882.9629742

ꢀ882.9695724

ꢀ882.9688943

ꢀ883.0005656

169.43389

168.71386

170.42390

170.30794

170.89353

170.95596

170.97892

171.12683

171.14256

170.98826

171.25701

171.10479

169.67684

171.00078

171.65612

171.65519

172.91494

171.66791

172.28960

172.09589

172.54964

172.36466

171.87959

ꢀ553855.4

ꢀ553852.2

ꢀ553889.9

ꢀ553890.1

ꢀ553868.4

ꢀ553882.5

ꢀ553881.8

ꢀ553870.3

ꢀ553869.9

ꢀ553882.6

ꢀ553882.2

ꢀ553868.8

ꢀ553886.0

ꢀ553891.0

ꢀ553891.2

ꢀ553898.7

ꢀ553898.8

ꢀ553896.3

ꢀ553896.0

ꢀ553899.7

ꢀ553899.4

ꢀ553919.8

ꢂ0

+3.3

3.3

ꢀ34.5

ꢀ34.7

ꢀ13.0

ꢀ27.1

ꢀ26.4

ꢀ14.9

ꢀ14.5

ꢀ27.2

ꢀ26.8

ꢀ13.3

ꢀ30.6

ꢀ35.6

ꢀ35.8

ꢀ43.3

ꢀ43.4

ꢀ40.9

ꢀ40.6

ꢀ44.3

ꢀ44.0

ꢀ64.4

21.5

7.6

8.3

19.6

20.0

7.5

7.9

21.2

4.1

S-TS(6)

T-CA(5)-A

T-CA(5)-B

S-CA(5)-A

S-CA(5)-B

T-CA(6)-A

T-CA(6)-B

S-CA(6)-A

S-CA(6)-B

CB(3)

^a) Ratio of spin multiplicity (S) to number of imaginary frequencies (I). ^b) Energy at the B3LYP/6-31G*

level (in a.u.). ^c) Energy at the B3LYP/6-311++G** energy level (in a.u.). ^d) Zero-point energy (in kcal/

f

g

mol). ^e) E₃=E₂+ZPE (in kcal/mol). ) Relative energy compared to 1a. ) Activation energy.

REFERENCES

[1] K.C.Nicolaou, S.A.Snyder, T.Montagnon, G.Vassilikogiannakis,

Angew. Chem., Int. Ed. 2002, 41,

1668.

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Received June 22, 2006

Article Doi

Synthesis of benzo[g]isochromenes through Photo-Dehydro-Diels-Alder reaction

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