Photochemical synthesis of highly functionalized cyclopropyl ketones

Helvetica Chimica Acta Vol. 86 (2003)

865

Photochemical Synthesis of Highly Functionalized Cyclopropyl Ketones

by Pablo Wessig* and Olaf M¸hling

Institut f¸r Chemie der Humboldt-Universit‰t zu Berlin, Brook-Taylor-Strasse 2, D-12489 Berlin

(phone: 49-30-20937455; fax: 49-30-20936940; e-mail: pablo.wessig@chemie.hu-berlin.de)

A series of di- and trisubstituted cyclopropyl ketones 11 were prepared by irradiation of ketones 3 and 5,

which bear a leaving group adjacent to the carbonyl C-atom. The required ketones 3 could be easily synthesized

either by functionalization of ketones 1 with a hypervalent iodine reagent, 2, or by O-sulfonylation of a-hydroxy

ketones 7. The nitrates 5 were obtained by treatment of the corresponding a-bromo ketones with AgNO₃. The

irradiation of 3 and 5 must be performed in the presence of an acid scavenger (1-methyl-1H-imidazole) to

obtain the cyclopropanes 11 in good yields. The synthetic efficiency of the method was, among other things,

demonstrated by the preparation of a highly strained bicyclo[2.1.0]pentane 11i in good yield. The mechanism of

the photochemical cyclization was investigated by means of photokinetic measurements, as well as by quantum-

chemical calculations. It was shown that the presence of the leaving group substantially influences all steps of the

photochemical reaction cascade. The X-ray crystal structures of 11j and exo-11k were also determined.

1. Introduction. Cyclopropanes represent a unique class of cyclic compounds due

to both the enormous synthetic potential and the broad occurrence as a structure

element of natural products. Though cyclopropanes may be considered formally as the

smallest cycloalkanes, the electronic properties of this small ring differ substantially

from those of larger homologues. The high reactivity of cyclopropanes and the distinct

tendency for ring opening can be explained by the considerable ring strain (27 kcal/

mol).

Currently, organic chemists have a variety of methods for the preparation of

cyclopropanes [1]. Most convenient methods are cycloaddition reactions of a carbene

or a carbenoid with an alkene. This applies to such popular reactions as the Simmons-

Smith reaction [2] and the reaction of diazoalkanes with alkenes in the presence of

transition-metal catalysts¹). On the other hand, only few efficient cyclization methods

are known [4].

Photochemical methods, which often fit the latter concept, are attractive

alternatives to the thermal reactions. From thermodynamic point of view, the ring

closure is facilitated because the excitation energy of the photochemical process may

compensate the energy needed for the construction of the ring strain. One photo-

chemical reaction that has proven to be particularly useful for the synthesis of carbo-

and heterocyclic compounds, is the Norrish Yang reaction [5]. In the most popular

type of this reaction, a photochemically excited CO group abstracts a H-atom from

the g-position to give the 1,4-biradical, which can subsequently cyclize to the

cyclobutane. This special type of the Norrish Yang reaction is also called Yang

cyclization (cf. Scheme 1,a).

1

)

For Cu, see [3a]; for Rh, see [3b]; for Pd, see [3c]; for Mo, see [3d].

866

Helvetica Chimica Acta Vol. 86 (2003)

Scheme 1. Yang Cyclization (a), Acid Elimination in OH-Substituted Radicals (b), and Spin-Center Shift in

Biradicals (c)

While many applications of the Norrish Yang reaction on the synthesis of four-,

five-, and six-membered rings are known, it was utilized for a very limited number of

cyclopropane syntheses [6]. In most of these cases, it was either proven or it is very

likely that the initial step is a photoelectron transfer (PET) and, consequently, the

method is limited to reactants bearing functional groups with a low oxidation potential

in a particular position. Unfortunately, the preparative value is restricted because

electron-rich cyclopropanes undergo oxidative ring opening easily.

In this paper, we report a novel photochemical method for the preparation of

benzoylcyclopropanes (for a preliminary communication, see [7]). The basic idea of

our approach is to make use of a well-known behavior of radicals, namely the tendency

of OH-substituted radicals bearing a leaving group at the adjacent atom, to undergo

rapid elimination of an acid. During this process, the location of the highest spin density

is shifted to the neighboring atom, as shown in Scheme 1,b.

If the concept of acid elimination in OH-substituted radicals is applied to biradicals

formed in the Norrish Yang reaction, the number of atoms between the radical centers

could be altered, which consequently influences the size of ring formed in the reaction.

Thus, if 1,4-biradicals formed by g-H abstraction are subjected to acid elimination, 1,3-

biradicals are produced, and, therefore, cyclopropanes could be prepared (Scheme 1,c).

We propose to call this approach −spin-center shift in biradicals×.

Naturally, only few reactions of monoradicals can be applied to biradicals due to

their very short lifetimes [8]. On the other hand, based on the well-known velocities of

acid elimination in OH-substituted radicals, this process should be fast enough to

proceed within the lifetime of a triplet biradical, whereas singlet biradicals will

presumably be too short-lived. As discussed below in detail, we found that only

biradicals derived from esters of very strong acids undergo the spin-center shift.

Especially, sulfonates and nitrates have proved to be reliable.

In this work, the preparation of such sulfonates and nitrates as well as their

photochemical transformation to cyclopropyl ketones will be discussed. Furthermore,

Helvetica Chimica Acta Vol. 86 (2003)

867

mechanistic details of the reaction will be clarified by means of density-functional

theory calculations.

2. Results and Discussion. 2.1. Preparation of 2-Oxoalkyl Sulfonates and Nitrates.

To investigate the photochemical cyclization of reactants bearing a broad variety of

different substituents, we needed some flexible methods for the introduction of the

leaving group. In this work, we used three different synthetic routes.

The simplest and most-convenient method for preparation of 2-oxoalkyl sulfonates

is the treatment of ketones with hypervalent iodine reagents (Method A, Scheme 2).

Thus, ketones 1 react with 1-hydroxy-1-phenyl-l³-iodanyl methanesulfonate (2) to the

corresponding 2-oxoalkyl methanesulfonates 3 [9]. Unfortunately, this method works

well only when the side chain R is not branched. Ketones with branched residues R

afforded the desired products at best in low yields. In these cases, we switched from

sulfonate to nitrate as the leaving group. 2-Oxoalkyl nitrates 5 can be prepared easily by

bromination of ketones to a-bromo ketones 4 and subsequent exchange of bromide for

nitrate with AgNO₃(Method B) [10]. It should be noted that 2-oxoalkyl nitrates are

highly sensitive even against weak bases and easily undergo a disproportionation to 1,2-

diketones [11].

The second way to 2-oxoalkyl sulfonates starts with primary alcohols 6, which were

first oxidized to the corresponding aldehydes by means of pyridinium chlorochromate

(PCC). Afterwards, the aldehydes were treated with lithiated 2-phenyl-2-(trimethylsi-

lyloxy)acetonitrile, which may be considered a benzoyl anion equivalent. This

−Umpolung× approach was originally developed by H¸nig and Marschner [12]²). The

obtained a-silyloxy ketones were desilylated to give a-hydroxy ketones 7 in good yields

(Table 1).

The next step, the sulfonylation of the OH group, turned out to be somewhat

difficult. Treating of a-hydroxy ketones 7 with MsCl or TsCl led in some cases to

products that were contaminated with the corresponding a-chloro ketones, probably

formed by a S_n2 displacement of sulfonate by chloride. This drawback may be

circumvented by utilization of sulfonyl anhydrides instead of chlorides. Nevertheless,

another side reaction takes place when mesyl anhydride is used. Especially when the

reactant is sterically hindered, and, therefore, an excess of the reagents is required, an

intramolecular aldol reaction between the Me group of methanesulfonate and the

CO group is observed, as already described [14]. Therefore, tosyl anhydride is the

reagent of choice (Method C). The three methods for the preparation of 2-oxoalkyl

sulfonates and 2-oxoalkyl nitrates are summarized in Scheme 2 (cf. Tables 1 and 2).

The required ketones 1 and alcohols 6 are either commercially available or were

prepared according to literature procedures. In some cases, new syntheses were

developed, which are summarized in Scheme 3 and will be briefly outlined.

The Michael addition of ethyl cyanoacetate 9 to phenyl vinyl ketone 8 afforded the

a-cyano d-oxo ester 10, which was converted to the d-oxo nitrile 1e according to the

2

)

We also considered to prepare the ketones 8 by CoreyÀSeebach reaction [13], but orienting investigation

revealed that the cleavage of 1,3-dithiane ring of the primary product from the reaction between the

lithiated 2-phenyl-1,3-dithiane and an aldehyde is often accompanied by an oxidation of the OH group to

give 1,2-diketones.

868

Helvetica Chimica Acta Vol. 86 (2003)

Scheme 2. Preparation of 2-Oxoalkyl Sulfonates 3 and 2-Oxoalkyl Nitrates 5

Table 1. Synthesis of 2-Hydroxy Ketones 7^a)

Reactant

R

Product

Yield [%]^b)

6a^c)

6b^c)

6c^c)

6d

BnO(CH₂)₂

PhCH(Me)

CH₂CH(CH₂)₂

PhCꢀC(CH₂)₂

Cyclopropyl-(CH₂)₂

Cyclobutyl

Cyclopentyl

Indan-2-yl

Cyclohexyl

4-(t-Bu)-cyclohexyl

Tetrahydropyran-4-yl

N-Tosylpiperidin-4-yl

N-Boc-piperidin-4-yl

7a

7b

7c

7d

7e

7f

7g

7h

7i

63

73

43

45

38

73

75

68

71

57

63

56

67

6e

6f^c)

6g^c)

6h

6i^c)

6j

7j

7k

7l

6k

6l

6m^c)

7m

^a) See Scheme 3. ^b) Three steps (1. PCC, 2. PhC(OTMS)(CN)Li, 3. HF/MeCN). ^c) Commercially available.

procedure described by Krapcho [15]. The commercially available pentenol 6c was

used as a reactant for the preparation of 3-cyclopropylpropan-1-ol (6e) by the

Simmons Smith cyclopropanation [2]. The straightforward ring opening of oxetane by

lithium acetylides catalyzed by BF₃¥ Et₂O [16] was utilized for the preparation of

pentynol 6d. The HOCH₂-substituted carbo- and heterocyclic compounds 6f 6m are

either commercially available (6f,g,i,m) or could be easily synthesized by BH₃¥ Me₂S

reduction of the corresponding carboxylic acids (for details, see Exper. Part).

2.2. Photochemical Cyclization to Cyclopropyl Ketones 11. As mentioned above, in

the course of the Norrish Yang reaction, the O-atom of an excited CO group

Helvetica Chimica Acta Vol. 86 (2003)

869

Table 2. Syntheses of 2-Oxoalkyl Sulfonates 3 and 2-Oxoalkyl Nitrates 5.

Reactant

Method

Product

R

X

Yield [%]

1a^a)

1b^a)

1c^a)

1d^a)

1e

7a

7b

7c

7d

7e

7f

7g

7h

7i

7j

7k

7l

A

C

B

3a

3b

3c

3d

3e

3f

3g

3h

3i

3j

3k

3l

3m

3n

3o

3p

3q

3r

Et

Pr

i-Pr

Ph(CH₂)₂

NC(CH₂)₂

BnO(CH₂)₂

PhCH(Me)

CH₂CH(CH₂)₂

PhCꢀ(CH₂)₂

Cyclopropyl-(CH₂)₂

Cyclobutyl

Cyclopentyl

Indan-2-yl

MsO

TsO

NO₃

85

80

33

48

70

75

79

82

77

91

74

91

82

88

87

84

81

87

67^c)

33^c)

Cyclohexyl

4-(t-Bu)-cyclohexyl

Tetrahydropyran-4-yl

N-Tosylpiperidin-4-yl

N-Boc-piperidin-4-yl

MeOCOCH(Me)

MeOCOCH(Bn)

7m

1f^b)

1g^b)

5a

5b

^a) Commercially available. ^b) See [17]. ^c) Two steps.

Scheme 3. Synthesis of Some Ketones 1 and Alcohols 6 Used as Reactants

preferably attacks a CÀH bond at the g-position. Resulting from the H-migration, a

1,4-biradical is formed (cf. Scheme 1). Referring to the lifetimes of those biradicals, one

must first distinguish between singlet and triplet biradicals. The former are very short-

lived [18], and it is, therefore, unlikely that any chemical reaction could take place

other than those affording closed-shell products (cleavage and cyclization). This

870

Helvetica Chimica Acta Vol. 86 (2003)

situation is completely different in the case of triplet biradicals. Their lifetimes range

from 10 ns to 1 ms. Lifetimes of ca. 100 ns are most commonly observed [19]. Though

these values do not seem to be large from the practical chemist×s point of view, they are

large enough for several chemical processes to occur while triplet biradicals persist. The

elimination of an acid from an OH-substituted radical bearing a leaving group at the

adjacent atom is one such fast reaction [20]. To ensure that only triplet biradicals are

formed, we always used the benzoyl chromophore because it is well-known that, upon

irradiation, benzoyl ketones are transferred solely to the n-p*-excited triplet state [5].

Reaction conditions for the cyclopropane synthesis were optimized by chosing the

simplest reactant, 1-benzoylpropyl methanesulfonate (3a), for systematic photochem-

ical investigations. The results are depicted in Scheme 4. Upon irradiation (l_irr.

ꢁ

300 nm), 3a readily provides the desired cyclopropyl phenyl ketone (11a; Path A),

but the yields depend considerably on the solvent used. Whereas CH₂Cl₂furnished

satisfactory results, in Et₂O we observed the products of a Norrish-Type-II cleavage

from the primarily formed biradical BR-1 (Path B). Obviously, the acid elimination

step is not much faster than the conventional deactivation processes of 1,4-biradicals.

On the other hand, the irradiation in CH₂Cl₂revealed another serious problem. In the

course of the photolysis, a very strong acid is formed (MsOH), and, whereas

cyclopropyl phenyl ketone 11a itself is stable under the irradiation conditions, it readily

undergoes ring opening to the unsaturated ketone 13 when acid is present (Path C).

Therefore, the addition of an acid scavenger is necessary. The scavenger must fulfill two

Scheme 4. Photochemical Behavior of 1-Benzoylpropyl Methanesulfonate (3a)

Helvetica Chimica Acta Vol. 86 (2003)

871

preconditions, namely, its basicity and nucleophilicity must not be sufficient to attack

the sensitive sulfonate moiety, and its oxidation potential must be high enough to avoid

quenching of the excited CO group by charge transfer [21]. After testing various

compounds, we found that 1-methyl-1H-imidazole is most suitable. Applying the

optimized conditions (CH₂Cl₂, 2 equiv. 1-methyl-1H-imidazole, irradiation wavelength

> 300 nm), we obtained the cyclopropyl ketone 11a in 87% yield (Table 3).

Table 3. Synthesis of Cyclopropyl Phenyl Ketones 11.

Reactant

R¹

R²

X

Product

Yield [%]

Remarks^a)

3a

3b

3c

3d

3e

3f

3g

3h

3i

3j

3k

3l

3m

3n

3o

3p

3q

3r

H

Me

H

Ph

CN

BnO

H

Me

H

Ph

H

MsO

TsO

NO₃

11a

11b

11c

11d

11e

11c

11f

11g

11h

11i

11j

11k

11l

11m

11n

11o

11p

11q

11r

87

63

90

78

65

46

44

80

34

68

61

80

78

86

79

74

78

69

59

37

trans 16% 15

trans

cis/trans 63 : 37

trans

cis/trans 63 : 37

CH₂CH

PhCꢀC

Cyclopropyl

À(CH₂)₂À

À(CH₂)₃À

cis/trans 50 : 50

cis/trans 60 : 40 42% 3i

cis/trans 30 : 70

exo 7% 16

exo

b

ÀC₆H₄(CH₂)À )

À(CH₂)₄À

exo/endo 80 : 20

exo

À(CH)₂CH(t-Bu)CH₂À

À(CH)₂OCH₂À

À(CH)₂N(Ts)CH₂À

À(CH)₂N(BOC)CH₂À

5a

5b

H

Ph

MeOCO

trans

1,2-trans-2,3-cis

^a) The indicated ratios represent the photostationary equilibrium. ^b) 3m 2-[a-(Tosyloxy)phenacyl]indan.

Another interesting phenomenon must be mentioned here. The biradicals BR-2

may be considered to exist as two mesomeric species BR-2a and BR-2b that differ in

the position of the spin center in the enolate radical moiety. Whereas BR-2b gives the

desired cyclopropane 11a, the products of BR-2a would be the dihydrofuran 14. We

recently reported the photochemical synthesis of 1,3-oxazin-4-ones; in this case, the

enolate radical moiety reacted solely as an O-centered radical [22]. In the case of

biradicals BR-2, we isolated exclusively the cyclopropyl ketone 11a, and no indication

for the formation of 14 was found. Obviously, the regioselectivity of the ring closure of

biradicals formed in the course of a spin-center shift sensitively depends on the

functional groups present between the two radical centers (Scheme 4).

872

Helvetica Chimica Acta Vol. 86 (2003)

To verify that the new method represents a general route to highly functionalized

cyclopropyl ketones, we investigated the photochemical behavior of differently

substituted ketones 3 and 5. It must be noted that products 11 of the photochemical

ring closure still contain the same chromophore as the reactants 3 and 5, and, therefore,

one must take into account both internal light filtering and photochemical reactions of

the products. Whereas the former is obviously not a problem, as shown by the high

product yield of 11a, the photochemical reactivity of cyclopropanes 11 deserves special

attention.

The introduction of alkyl groups into the resulting cyclopropanes raises an

interesting question. It is well-known that cyclopropyl phenyl ketones bearing a cis-

oriented alkyl group at the cyclopropane ring undergo efficient ring opening by

intramolecular H-transfer, followed by a Norrish-Type-II cleavage of the biradical [23].

Therefore, when ring closure of Me-substituted ketones 3b and 3c does not proceed

stereoselectively, a mixture of the trans-substituted cyclopropane 11b and the

unsaturated ketone 15 is expected. We found that the stereoselectivity of the ring

closure and, consequently, the extent to which 15 is formed, remarkably depends on

the position of the Me group. 1-Benzoylbutyl methanesulfonate (3b) furnishes 63%

of trans-2-methylcyclopropyl phenyl ketone (11b) together with 16% of the un-

saturated ketone 15, whereas 11b is the only product of the irradiation of 1-benzoyl-

2-methylpropyl methanesulfonate (3c). This result can be explained easily by

consideration of the appropriate 1,3-biradicals. In BR-3, a 1,3-interaction between

benzoyl (Bz) and Me group causes an only moderate diastereoselectivity, while,

in BR-4, a much stronger 1,2-interaction is responsible for the high selectivity

(Scheme 5).

The stereochemical course of the cyclization of g- and b-Ph substituted phenyl

propyl ketones 3d and 3g was surprising at first. No matter at which position the Ph

Scheme 5. Photochemical Behavior of Ketones 3b and 3c

Helvetica Chimica Acta Vol. 86 (2003)

873

group was placed, we always obtained a 63 :37 mixture of diastereoisomers of phenyl 2-

phenylcyclopropyl ketone (11c), although the yields differed significantly. The same

ratio of diastereoisomers was obtained by irradiation of each of the pure isomers cis-11c

and trans-11c. Obviously, aryl-substituted cyclopropyl phenyl ketones undergo photo-

chemical cis/trans isomerization (Scheme 6) [24]. The slightly preferred formation of

the cis-isomer may be explained by a weak p-p interaction between the Bz group and

the Ph group.

Scheme 6. Photochemical Behavior of Ketones 3d and 3g

The particular importance of dipole dipole interactions with respect to the

diastereoselectivity of the ring closure is revealed by the photochemical behavior of

esters 5a and 5b, the nitrile 3e, and the ether 3f. In all of these cases, only the trans-

configured products were obtained. The only moderate yields upon irradiation of

nitrates 5a and 5b arise not so much from photochemical but from purely thermal side

reactions. They are highly sensitive to the presence of base, even the very weak base 1-

methyl-1H-imidazole. The photochemical behavior of 5b is remarkable, because the

product 11r also contains a Ph group, and one would expect, referring to the

isomerization of 11c, that a mixture of diastereoisomers would be formed. But, in spite

of low yields due to thermal decomposition, we isolated only the product with 1,2-trans-

2,3-cis-configuration. Obviously, the ring closure is dominated by dipole dipole

interactions between the two CO-bearing residues.

Compounds 3h and 3i, bearing vinyl and phenylethynyl groups at the terminal C-

atom, respectively, generate triplet biradicals BR-5 and BR-6. In BR-5, the remote

radical center is part of an allyl moiety, whereas BR-6 contains a propargyl moiety at

the same position (Scheme 7). From thermodynamic point of view, one would expect

that the cyclization of BR-5 occurs in a 1,5-fashion to give a cyclopentene as product.

On the other hand, BR-6 could undergo ring closure to a cyclobutenylcarbene without

a change in spin state³). An analogous cyclization of 1-alkynyl-1,5-biradicals was

described recently [25]. However, in both cases the cyclopropyl ketones 11f and 11g

3

)

DFT Calculations (B3PW91/6-31G*) revealed that the cyclization of the triplet pent-1-yne-3,5-diyl

biradical to triplet (cyclobut-1-enyl)carbene is exothermic (ca. 8 kcal/mol).

874

Helvetica Chimica Acta Vol. 86 (2003)

Scheme 7. Formation of Biradicals BR-5 BR-7 from 4-Vinyl- (3h), 4-(Phenylethinyl)- (3i), and 4-(Cyclo-

propyl)- (3j) 2-(tosyloxy)butyrophenones

were obtained as diastereoisomeric mixture. Apparently, the ring closure proceeds very

fast, and, therefore, there is no time for the conformational changes necessary for the

alternative 1,5- and 1,4-cyclization. To substantiate this hypothesis, we prepared the 4-

cyclopropyl-2-(tosyloxy)-1-phenylbutan-1-one (3j). It is well-known that cyclopropyl-

carbinyl radicals undergo a very fast ring opening (k 4.0 ¥ 10⁷s^À1), and this reaction

was often utilized for the determination of radical lifetimes [26]. Consequently, the

formation of dicyclopropyl ketone 11h in 68% yield and without any indication of an

opening of the terminal cyclopropyl ring proves that the sum of the lifetimes of the

primarily formed 1,4-biradical and biradical BR-7 is considerably smaller than 25 ns.

This value is in good agreement with the data previously described by Caldwell et al. for

diarylcyclopropanes [27] (Scheme 7).

Bicyclic compounds bearing a cyclopropane moiety are wide-spread in natural

products, and, therefore, we decided to apply our method to the synthesis of these

interesting molecules. Irradiation of readily accessible ketones 3k 3r furnished the

desired bicyclic ketones 11i 11p in good-to-excellent yields. It is noteworthy that, in all

cases with exception of 3m, only the exo-diastereoisomer could be isolated. The

synthesis of bicyclo[2.1.0]pent-5-yl phenyl ketone (−benzoyl housane×) 11i is partic-

ularly interesting by virtue of the considerable ring strain of this compound. In addition

to 11i, we isolated the unsaturated ketone 16 in 7% yield. To clarify whether 16 is an

alternative product of biradical BR-8 or is formed by a subsequent photochemical

reaction of housane 11i, we irradiated 11i separately and found that no formation of 16

occurs (Scheme 8).

Helvetica Chimica Acta Vol. 86 (2003)

875

Scheme 8. Preparation of Bicyclic Ketones 11i and 11p.

The configuration of the bicyclic compounds 11i 11p was unambiguously

established by X-ray analyses of 11j and exo-11k (Fig. 1 and Table 4)⁴).

2.3. Photokinetic Investigations and Quantum-Chemical Calculations. The efficient

cyclization of ketones 3 and 5 to cyclopropyl ketones 11 brings up some questions.

Though we did not determine the exact quantum yields of this reaction, the very rapid

decomposition of the reactants upon irradiation clearly indicates that this process must

be considerably more efficient than the −classical× Norrish Yang reaction. To

investigate the reasons for this efficiency, we determined the rate constant of the

initial intramolecular H-transfer for both 2-[(methylsulfonyl)oxy]-1-phenylbutan-1-

one (3a) and 1-phenylbutan-1-one (1a). Thus, the rates of photochemical decom-

position of 1a and 3a in the presence of different amounts of the triplet quencher 2,5-

4

)

Crystallographic data (excluding structure factors) for 11j and exo-11k have been deposited with the

Cambridge Crystallographic Data Centre (CCDC) as supplementary publication No. CCDC-192089 (11j)

and CCDC-193677 (exo-11k). Copies of the data can be obtained, free of charge, on application to the

CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (fax: 44 (1223) 336033; e-mail: deposit@ccdc.ca-

m.ac.uk).

876

Helvetica Chimica Acta Vol. 86 (2003)

Table 4. Crystallographic Data of 11j and exo-11k

11j

exo-11k

Empirical formula

Formula weight

Temp.

C₁₃H₁₄O

186.24

180(2) K

C₁₇H₁₄O

234.28

180(2) K

Wavelength

0.71073 ä

Crystal system

Space group

Monoclinic

P 21/n

Orthorhombic

P 21 21 21

Unit-cell dimensions

a 6.290(3) ä, a 908

b 8.815(5) ä, b 99.98(5)8

c 18.103(8) ä, g 908

988.5(9) ä³

a 5.6170(6) ä, a 908

b 7.9674(9) ä, b 908

c 26.487(4) ä, g 908

1185.4(3) ä³

4, 1.313 Mg/m³

0.080 mm^À1

V

Z, D_calc.

Absorption coefficient

F(000)

4, 1.251 Mg/m³

0.077 mm^À1

400

496

Crystal size

q Range

0.88 Â 0.80 Â 0.56 mm

0.60 Â 0.40 Â 0.12 mm

2.28 27.488

2.98 25.238

Limiting indices

À 8 ꢂ h ꢂ 8, À11 ꢂ k ꢂ 11, À23 ꢂ l ꢂ 4 À 6 ꢂ h ꢂ 6, À9 ꢂ k ꢂ 9, À31 ꢂ l ꢂ 31

Reflections collected / unique 4499 / 2217 (R(int) 0.0233)

6933/1292 (R(int) 0.0466)

99.8%

Completeness to q 27.48

Max./min. transmission

Refinement method

97.8%

0.9581 and 0.9352

Full-matrix least-squares on F²

2217 / 0 / 184

0.9905 and 0.9536

Full-matrix least-squares on F²

1292 / 0 / 220

Data/restraints/parameters

Goodness-of-fit on F²

Final R indices (I > 2s(I)

R Indices (all data)

Extinction coefficient

D1 (max; min)

1.066

0.881

R1 0.0398, wR2 0.1081

R1 0.0421, wR2 0.1108

0.068(7)

0.332 and À0.164 e.A^À3

R1 0.0264, wR2 0.0488

R1 0.0424, wR2 0.0510

0.0103(15)

0.119 and À0.131 e.A^À3

Fig. 1. X-Ray structure of 11j and exo-11k

dimethylhexadiene were measured, and the lifetimes of triplet excited ketones were

determined by Stern Volmer plots. We found lifetimes of 115 ns for 1a (which is in

good agreement with the values published in [28]), and, surprisingly, only 3.4 ns for 3a.

Obviously, the leaving groups influence the reaction course not even at the stage of the

Helvetica Chimica Acta Vol. 86 (2003)

877

first biradical (BR-1; Scheme 4), but already in the initial stage of intramolecular H-

transfer.

To discover an explanation for these findings, we performed DFT calculations on

two simple model systems, 2-(mesyloxy)butanal (I) and butanal (VI) (B3PW91/

6-311 G**//B3PW91/6-31G*; for details, see Exper. Part; the structures are

collected in Fig. 2, the energies are summarized in Table 5). The first remarkable

Table 5. Calculated Energies of Species I VIII

c

Entry

E^a)

[a.u.]

ZPE^b)

[kcal/mol]

E ZPE

E_REL

)

[kcal/mol]

Ia

Ib

À 895.3836451

À 895.3802291

À 895.3715884

À 895.3664576

À 895.3857923

À 895.3827549

À 895.3798296

À 895.4018012

À 232.3230499

À 232.3081846

À 232.3234866

96.81

96.69

93.71

93.72

96.15

95.98

95.35

93.94

69.63

66.70

69.02

À 561765.38

À 561763.35

À 561760.91

À 561757.69

À 561767.39

À 561765.66

À 561764.44

À 561779.64

À 145715.40

À 145709.01

À 145716.29

Æ 0.0

2.0

4.5

7.7

À 2.0

À 0.3

0.9

À 14.3

Æ 0.0

6.4

À 0.9

IIa

IIb

IIIa

IIIb

IV

V

VI

VII

VIII

^a) Electronic energy (B3PW91/6-311 G**). ^b) Zero-point vibrational energy (B3PW91/6-31G*). ^c) Energy

differences referring to Ia and VI, respectively.

result concerns the preferred conformation of the triplet state of I. In the gauche

conformer with the lowest energy Ia, the CÀO(Ms) bond is nearly eclipsed to the p_z

orbital of the C-atom of the CO group (dihedral angle OÀCÀCÀO À69.028, the

CO C-atom is considerably pyramidalized). The other conformer Ib, the

OÀCÀCÀO dihedral angle of which amounts to À178.428, is by 2 kcal/mol less

favorable. Furthermore, the CÀO(Ms) bond of Ia is significantly stretched compared

with Ib, whereas the (carbonyl)CÀ(a)C bond of Ia is remarkably shorter than the

corresponding bond of Ib. This phenomenon becomes understandable with the

qualitative MO scheme depicted in Scheme 9. By combination of three orbitals of the

CO group (p, n, p*) and two orbitals of the CÀO(Ms) bond (s,s*) five localized MOs

are obtained. In the ground state, the n orbital of the CO group represents the

HOMO and the combination (p* s*) the LUMO. The latter MO is characterized by a

s* antibonding contribution of the CÀO(Ms) bond and a p-bonding contribution of

the (carbonyl)CÀ(a)C bond. Upon photochemical n-p* excitation, this orbital is singly

occupied, explaining the above-mentioned changes in bond length.

The structural and energetic differences between Ia and Ib, caused by the above

discussed hyperconjugation between CÀO(Ms) bond and the excited CO group,

increase by turning to the transition states IIa and IIb of the intramolecular H-transfer.

The energy of IIb, which corresponds to Ib, is by 3.2 kcal/mol higher than the energy of

IIa. Furthermore, the presence of the leaving group in I lowers the activation barrier of

the H-transfer by ca. 2 kcal/mol, compared with the unsubstituted 1-phenylbutan-1-one

(VI) and the corresponding transition state VII. The initially formed biradical

878

Helvetica Chimica Acta Vol. 86 (2003)

Fig. 2. Calculated structures I VIII. *) The structures were mirrored for better clearness.

880

Helvetica Chimica Acta Vol. 86 (2003)

Scheme 9

conformer IIIa may be converted to another conformer IIIb by rotation around the

CÀO(Ms) bond. Conformer IIIb, which is slightly less favorable from an energetic

point of view, is characterized by an intramolecular H-bond between the OH group and

an O-atom of the Ms group. The structure of this conformer already indicates the

subsequent elimination of MsOH via the transition state IV. Thus, the CÀO(Ms) bond

in IIIb is remarkably stretched, compared with IIIa (1.508 vs. 1.542 ä). The acid

elimination giving the H-bonded complex V between the 1-oxobutane-2,4-diyl

biradical and MsOH occurs via a very low activation barrier of 1.2 kcal/mol. Bearing

in mind that this step is certainly irreversible, one now has found the key for

understanding the high efficiency of the reaction. It is well-known that the main reason

for the low quantum yields of the triplet Norrish Yang reaction is the H back-transfer,

which proceeds with a simultaneous intersystem crossing to the singlet state [5e]. When

a leaving group is present, as in the model system I or in compounds 3 and 5, the H

back-transfer competes with the very fast and, above all, irreversible acid elimination.

Consequently, the high efficiency of the cyclopropyl ketone formation is now clearly

understandable.

Helvetica Chimica Acta Vol. 86 (2003)

881

3. Conclusions. In the present study, we describe a novel and straightforward

method for the preparation of highly functionalized cyclopropyl ketones 11. The

method is based on the Norrish Yang reaction of ketones, which bear a leaving group

adjacent to the CO C-atom. In such cases, the primarily formed biradicals are subject

to rapid and efficient acid elimination. The main feature of this process is the shift of

spin density from the former CO C-atom to the C-atom that bears the leaving group.

Therefore, we call this overall process spin-center shift.

Our method is not only suitable for preparation of monocyclic cyclopropanes (i.e.,

11a 11h, 11q, and 11r) but also permits the synthesis of bicyclic compounds (i.e., 11i

11p). The formation of highly strained −housane× 11i in good yield is particularly

remarkable because it impressively demonstrates the preparative potential of the

method.

Though the mechanism of our photochemical cyclopropane synthesis and the

−classical× Norrish Yang reaction agree in some points, there are also appreciable

differences. We found by triplet-quenching experiments that the rate of the initial H-

abstraction by the excited CO group becomes larger by approximately two orders of

magnitude as a result of introduction of the leaving group. Furthermore, we observed a

high efficiency of product formation, even though the formed cyclopropyl ketones 11

bear the same chromophoric group as the reactants 3 and 5. These experimental

findings could be easily explained by the results of density-functional calculations on

model systems I VIII bearing a CHO group instead of the Bz group in 3 and 5. At

present, further applications of the method to more-complicated molecules are under

investigation.

This work was supported by the Deutsche Forschungsgemeinschaft (DFG, We 1830-3/1-2). We also thank B.

Ziemer for the X-ray-analysis of 11j and exo-11k

Experimental Part

General. The following reagents were commercially available: 1-phenylbutan-1-one (1a), 1-phenylpentan-1-

one (1b), 3-methyl-1-phenylbutan-1-one (1c), 1,4-diphenylbutan-1-one 1d, 3-benzyloxypropan-1-ol (6a), 2-

phenylpropan-1-ol (6b), pent-4-en-1-ol (6c), cyclobutylmethanol (6f), cyclopentylmethanol (6g), cyclohexylme-

thanol (6i), 1-[(tert-butoxy)carbonyl]piperidine-4-methanol (6m), ethyl 2-cyanoacetate (9), trans-4-(tert-butyl)-

cyclohexanecarboxylic acid (17), piperidine-4-carboxylic acid (18). The following reagents were prepared

according to literature procedures: methyl 2-methyl-4-oxo-4-phenylbutanoate (1f) [17], methyl 2-benzyl-4-oxo-

4-phenylbutanoate (1g) [17], 1-hydroxy-1-phenyl-l³-iodanyl methanesulfonate (HMIB; 2) [28], 2-phenyl-2-

(trimethylsilyloxy)acetonitrile [29], p-toluenesulfonic anhydride [30], 5-Phenylpent-4-yn-1ol (6d) [16], phenyl

vinyl ketone 8 [31], indan-2-carboxylic acid (19) [32], 3,4,5,6-tetrahydro-2H-pyran-4-carboxylic acid (20) [33].

THF and Et₂O were dried over Na metal in the presence of benzophenone as an indicator of dryness and

distilled at atmospheric pressure. CH₂Cl₂and 1,2-dichloroethane were dried by heating under reflux over P₂O₅

and distilled at atmospheric pressure. All moisture-sensitive reagents were transferred via syringe under N₂or

Ar; moisture-sensitive reactions were carried out under N₂or Ar. Flash column chromatography (FCC): silica

gel, 230 400 mesh (Fluka). Anal. TLC: precoated Merck silica gel 60 F₂₅₄plates; detection by UV light. M.p.:

B¸chi 530, uncorrected. IR: Perkin-Elmer-881, solids as KBr pastes, liquids and oils on NaCl crystals as film, in

cm^À1. NMR: CDCl₃, CD₂Cl₂, and (D₆)DMSO solns.; Bruker DPX-300 equipment; chemical shifts d in ppm;

calibration: CDCl₃(¹H: 0.00 ppm Me₄Si; ¹³C: 77.0 ppm), (D₆)DMSO (¹H: 2.49 ppm; ¹³C: 39.5 ppm), CD₂Cl₂

(¹H: 5.32 ppm; ¹³C: 53.8 ppm); Some compounds were obtained as mixture of two diastereoisomers. In these

cases, the data of the minor product are given in square brackets; the relative configuration of the products were

1

determined by NOE, NOESY, H,¹H-COSY and H,¹³C-COSY experiments. EI-MS: Hewlett-Packard 5995 A,

70 eV at 293 593 K, m/z (%). HR-EI-MS: MSI Concept 1 H. Elemental Analysis were carried out by the

analytical laboratory of the Institute of Chemistry of the Humboldt-University Berlin. Photochemistry: prep.

882

Helvetica Chimica Acta Vol. 86 (2003)

irradiations with a 150-W high pressure Hg-arc lamp (Hanau); anal. irradiations with a 500-W high pressure

Hg-arc lamp (OSRAM HBO-500), UV cuvette 1 Â 1 cm, filter WG 295 (Schott).

Quantum-Chemical Calculations. The geometry optimization of molecules I VIII were performed with the

program package Gaussian 98 [34], the B3PW91 hybrid functional⁵), and the 6-31G* basis set. At the same level

of theory, frequency calculations were carried out to characterize each structure as minimum (Ia,b, IIIa,b, V, VI,

and VIII) or transition state (IIa,b, IV, and VII) and to obtain the zero-point vibrational energies. Afterwards,

single-point calculations were performed with the same DFT functional and the extended basis set 6-311

G** basis set in order to obtain improved energies.

General Procedure A (GP A) for the 2-Mesyloxylation of Ketones 1a 1e. To a stirred mixture of the

appropriate ketone 1a 1e (10.0 mmol) in MeCN or CH₂Cl₂(25 ml) was added HMIB (2; 3.16 g, 10.0 mmol).

The mixture was stirred at r.t. or heated under reflux until TLC indicated disappearance of the ketone 1. The

mixture was concentrated to an oil (when MeCN was used as solvent), diluted with CH₂Cl₂(25 ml), washed with

brine (25 ml) and H₂O (25 ml), dried (MgSO₄), and concentrated under reduced pressure. Purification of the

residue by FCC (petroleum ether/AcOEt 10 :1 10 :3) gave the 2-mesyloxy ketones 3a 3e.

General Procedure B (GP B) for the Synthesis of 2-Hydroxy Ketones 7a 7m. The appropriate alcohol 6a

6m (20.0 mmol) in CH₂Cl₂(10 ml) was added in one portion to a magnetically stirred suspension of PCC (6.47 g,

30.0 mmol) in anh. CH₂Cl₂(50 ml). After TLC indicated disappearance of the alcohol (1.5 4 h), the

supernatant liquid was decanted from the black gum and filtered through a short column of Florisil, Celite, and

silica gel. The insoluble residue was washed five times with 25-ml portions of Et₂O. The combined org. layers

were passed through the same short column, and the solvent was removed under reduced pressure. The

aldehyde was used immediately for the next reaction without further purification. In a dry 250-ml two-necked

round-bottomed flask fitted with a N₂bubbler, a rubber septum, and a magnetic stir bar was placed dry Et₂O

(50 ml) and (i-Pr)₂NH (2.23 g, 22.0 mmol). The soln. was cooled to À788 (dry ice/acetone), and 22.0 mmol of a

1.6m solution of BuLi in hexane was added dropwise. After 0.5 h, a soln. of 20.0 mmol of freshly distilled 2-

phenyl-2-(trimethylsilyloxy)acetonitrile and dry Et₂O (5 ml) was added dropwise, and the resultant mixture was

stirred for 0.75 h, followed by a dropwise addition of the aldehyde in 5 ml dry Et₂O. The mixture was kept at

À708 for an additional 2 3 h and quenched by addition of sat. aq. NH₄Cl soln. (30 ml). After warming to r.t.,

the aq. layer was extracted with Et₂O (2 Â 20 ml), and the combined org. extracts were washed with sat. aq.

NH₄Cl soln. (2 Â 30 ml) and dried (MgSO₄). Concentration in vacuo gave a yellow-brown oil that was dissolved

in 30 ml of MeCN. The magnetically stirred soln. was cooled to 08, and HF (40%, aq.) was added dropwise until

TLC indicated completion of the desilylation. After addition of solid NaHCO₃, the mixture was stirred for an

additional 0.5 h, diluted with Et₂O (30 ml), filtered, dried (MgSO₄), and the solvent was removed under

reduced pressure. Purification of the residue by FCC (petroleum ether/AcOEt 100 :5 10 :3) gave the 2-

hydroxy ketones 7a 7m.

General Procedure C (GP C) for the Mesylation of 2-Hydroxy Ketones 7a and 7b. To a magnetically stirred

soln. of the appropriate 2-hydroxy ketone 7a or 7b (15.0 mmol) and dry CH₂Cl₂(30 ml) were added at 08 Et₃N

(1.52 g, 15.0 mmol) and MsCl (1.72 g, 15.0 mmol). After TLC indicated completion of the reaction (0.5 3 h),

the mixture was diluted with CH₂Cl₂(20 ml), washed with 2m HCl (20 ml), and sat. aq. NaHCO₃soln. (3 Â

20 ml), dried (MgSO₄), and the solvent was removed under reduced pressure. Purification of the residue by

FCC (petroleum ether/AcOEt 10 :1 10 :3) gave the 2-mesyloxy ketones 3f and 3g.

General Procedure D (GP D) for the Tosylation of 2-Hydroxy Ketones 7c 7m. To a magnetically stirred

soln. of the appropriate 2-hydroxy ketone 7c 7m (15.0 mmol) and dry CH₂Cl₂(30 ml) were added at 08

pyridine (1.19 g, 15.0 mmol) and Ts₂O (4.90 g, 15.0 mmol). After TLC indicated completion of the reaction

(0.5 6 h), the mixture was diluted with CH₂Cl₂(20 ml), washed with 2m HCl (20 ml) and sat. aq. NaHCO₃soln.

(3 Â 20 ml), dried (MgSO₄), and the solvent was removed under reduced pressure. Purification of the residue by

FCC (petroleum ether/AcEtO 10 :1 10 :3) gave the 2-tosyloxy ketones 3h 3r.

General Procedure E (GP E) for the 2-Bromination of Ketones 1f and 1g. To a magnetically stirred soln. of

the appropriate ketone 1f or 1g (30.0 mmol) and CH₂Cl₂(50 ml) was added dropwise Br₂(4.79 g, 30.0 mmol) in

30 ml of CH₂Cl₂until no discoloration of the mixture was observed. Complete conversion was detected by TLC.

Evaporation in vacuo gave the 2-bromo ketones 4a and 4b.

General Procedure F (GP F) for the 2-Nitrooxylation of 2-Bromo Ketones 4a and 4b. To a soln. of the

appropriate 2-bromo ketone 4a or 4b (10.0 mmol) and dry MeCN (100 ml) was added AgNO₃(80.0 mmol), and

5

)

B3PW91 is Becke×s 3-parameter functional [35a] with the nonlocal correlation provided by the Perdew 91

expression [35b].

Helvetica Chimica Acta Vol. 86 (2003)

883

the mixture was stirred at r.t. until TLC indicated complete conversion (2 10 d). The mixture was filtered to

remove AgBr partially. Remaining AgBr could be removed after concentration in vacuo, addition of Et₂O

(20 ml), and filtration. Evaporation under reduced pressure and purification of the residue by FCC (petroleum

ether/AcOEt 10 :1 10 :3) gave the 2-nitrooxy ketones 5a and 5b.

General Procedure G (GP G) for the Synthesis of Alcohols 6h, 6j, 6k, and 6l. To a magnetically stirred soln.

of BH₃¥ Me₂S (3.65 g, 48.0 mmol) and dry THF (100 ml) was added the appropriate carboxylic acid 17, 19, 20,

and 21 (40.0 mmol) in dry THF (20 ml). The mixture was refluxed until TLC indicated complete conversion of

the carboxylic acid (1 3 h). After removing the solvent under reduced pressure, the residue was hydrolyzed by

addition of H₂O at 08. The aq. layer was extracted with CH₂Cl₂(3 Â 50 ml), and the combined org. extracts were

washed with sat. aq. NaHCO₃soln. (2 Â 50 ml) and dried (MgSO₄). Concentration in vacuo gave the alcohols

6h, 6j, 6k, and 6l.

General Procedure H (GP H) for the Photochemical Synthesis of Cyclopropyl Phenyl Ketones 11a 11d and

11f 11r. Irradiations of ketones 3a 3e, 3g 3r, 5a, and 5b were performed in CH₂Cl₂(200 or 400 ml) at

concentrations of 0.01 mmol/ml in the presence of 1-methyl-1H-imidazole (2 equiv.), with a high-pressure Hg-

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

lamp and the reaction vessel. The reaction was monitored by TLC and aborted when the reactant had

completely disappeared (30 60 min). The soln. was washed with H₂O (2 Â 100 ml), dried (MgSO₄), and

concentrated in vacuo to 10% of the original volume. To the soln. was added silica gel (5 g), and the remaining

solvent was removed under reduced pressure. The residue was purified immediately by FCC (petroleum ether/

AcOEt 100 :3 100 :15) to give the 11a 11d and 11f 11r.

Ethyl 2-Cyano-5-oxo-5-phenylpentanoate (10). To a magnetically stirred soln. of 8 (1.32 g, 10.0 mmol), 9

(1.13 g, 10.0 mmol) in dry THF (40 ml) were added K₂CO₃(0.14 g, 1.01 mmol) and 18-crown-6 (0.27 g,

1.02 mmol). After 45 min, TLC indicated complete conversion of the reactants. The mixture was hydrolyzed

with H₂O (10 ml), diluted with Et₂O (100 ml), washed with H₂O (2 Â 100 ml), dried (MgSO₄), and the solvent

was removed under reduced pressure. Purification of the residue by FCC (petroleum ether/AcOEt 100 :15)

gave 10 (1.45 g, 59%). Colorless solid. M.p. 89 918. IR (KBr): 1744, 1731, 1686, 1597, 1580, 1449, 1365, 1208.

¹H-NMR (300 MHz, CDCl₃): 8.00 7.92 (m, 2 H); 7.62 7.55 (m, 1 H); 7.52 7.42 (m, 2 H); 4.28 (q, J 7.2, 2 H);

3.82 (dd, J 6.0, 8.3, 1 H); 3.25 (t, J 7.2, 2 H); 2.55 2.25 (m, 2 H); 1.32 (t, J 7.2, 3 H). ¹³C-NMR (75 MHz,

CDCl₃): 197.6, 165.7 (CO); 136.1 (arom. C_q); 133.5, 128.6, 127.8 (arom. CH); 116.3 (C_q); 62.9 (CH₂); 36.4

(CH); 34.6 (CH₂); 23.9 (CH₂); 13.9 (Me). EI-MS: 245 (16, M ), 133 (16), 105 (100, PhCO ), 77 (48, Ph ), 51

(8). Anal. calc. for C₁₄H₁₅NO₃(245.27): C 68.56, H 6.16, N 5.71; found: C 68.67, H 6.36, N 5.33.

5-Oxo-5-phenylpentanenitrile (1e). The ester 10 (1.23 g, 5.01 mmol), NaCl (0.30 g, 5.13 mmol) and H₂O

(2 ml) in DMSO (18 ml) were refluxed until TLC indicated complete conversion of 10 (20 h). The mixture was

diluted with H₂O (60 ml) and extracted with Et₂O (6 Â 50 ml). The combined org. extracts were washed with

H₂O (2 Â 100 ml), dried (MgSO₄), and the solvent was removed under reduced pressure. Purification of the

residue by FCC (petroleum ether/AcOEt 10 :2) gave 1e (0.41 g, 48%). Colorless oil. IR (film): 1684, 1597, 1448,

1234, 691. ¹H-NMR (300 MHz, CDCl₃): 8.00 7.92 (m, 2 H); 7.62-7.53 (m, 1 H); 7.52 7.42 (m, 2 H); 3.17 (t, J

7.2, 2 H); 2.52 (t, J 7.2, 2 H); 2.11 (quint., J 7.2, 2 H). ¹³C-NMR (75 MHz, CDCl₃): 198.0 (CO); 136.3

(arom. C_q); 133.3, 128.6, 127.8 (arom. CH); 119.3 (C_q); 36.2 (CH₂); 19.6 (CH₂); 16.5 (CH₂). EI-MS: 173 (8, M ),

105 (100, PhCO ), 77 (41, Ph ), 51 (15). Anal. calc. for C₁₁H₁₁NO (173.21): C 76.28, H 6.40, N 8.09; found:

C 75.92, H 6.28, N 8.17.

1-Benzoylpropyl Methanesulfonate (3a). GP A (CH₂Cl₂, 24 h reflux) starting from 1a afforded 3a in 85%

yield. Colorless solid. M.p. 59 608. ¹H-NMR (300 MHz, CDCl₃): 7.96 7.92 (m, 2 H); 7.67 7.62 (m, 1 H); 7.55

7.50 (m, 2 H); 5.92 5.87 (m, 1 H); 3.15 (s, 3 H); 2.19 1.90 (m, 2 H); 1.08 (t, J 7.2, 3 H). ¹³C-NMR (75 MHz,

CDCl₃): 195.2 (CO); 134.1 (arom. C_q); 134.1, 129.0, 128.5 (arom. CH); 82.2 (CH); 39.3 (Me); 26.0 (CH₂); 9.5

(Me). IR (KBr): 1689, 1356, 1175, 959, 910, 864, 698. EI-MS: 146 (5, [M À MsOH] ), 105 (100, PhCO ), 77 (35,

Ph ), 51 (13). Anal. calc. for C₁₁H₁₄O₄S (242.29): C 54.53, H 5.82, S 13.23; found: C 54.53, H 5.92, S 13.43.

1-Benzoylbutyl Methanesulfonate (3b). GP A (CH₂Cl₂, 24 h reflux) starting from 1b afforded 3b in 80%

yield. Colorless solid. M.p. 59 618. IR (KBr): 1690, 1354, 1210, 1171, 977, 933, 701. ¹H-NMR (300 MHz, CDCl₃):

7.96 7.92 (m, 2 H); 7.68 7.61 (m, 1 H); 7.54 7.48 (m, 2 H); 5.96 5.91 (m, 1 H); 3.13 (s, 3 H); 1.97 1.84 (m,

2 H); 1.62 1.50 (m, 2 H); 0.94 (t, J 7.2, 3 H). ¹³C-NMR (75.5 MHz, CDCl₃): 195.3 (CO); 134.1 (arom. C_q);

134.1, 129.0, 128.5 (arom. CH); 80.1 (CH); 39.3 (Me); 34.4 (CH₂); 18.4 (CH₂); 13.4 (CH₃). EI-MS: 160 (5, [M À

MsOH] ), 105 (100, PhCO ), 77 (28, Ph ), 55 (7), 51 (8). Anal. calc. for C₁₂H₁₆O₄S (256.32): C 56.23, H 6.29,

S 12.51; found: C 55.63, H 6.21, S 12.66.

1-Benzoyl-2-methylpropyl Methanesulfonate (3c). GP A (CH₂Cl₂, 24 h r.t.) starting from 1c afforded 3c in

1

33% yield. Colorless solid. M.p. 69 718. IR (KBr): 1696, 1363, 1178, 974, 941, 874, 694. H-NMR (300 MHz,

884

Helvetica Chimica Acta Vol. 86 (2003)

CDCl₃): 7.93 7.89 (m, 2 H); 7.66 7.59 (m, 1 H); 7.54 7.48 (m, 2 H); 5.78 5.76 (d, J 4.2, 1 H); 3.12 (s, 3 H);

2.41 2.30 (m, 1 H); 1.12 (t, J 6.8, 3 H); 0.92 (t, J 7.1, 3 H ) . ¹³C-NMR (75.5 MHz, CDCl₃): 195.3 (CO);

134.7 (arom. C_q), 134.0, 128.9, 128.4 (arom. CH); 85.4 (CH); 39.1 (Me); 31.1 (CH); 19.2 (Me); 16.2 (Me). EI-

MS: 160 (4, [M À MsOH] ), 105 (100, PhCO ), 77 (28, Ph ), 55 (10), 51 (9). Anal. calc. for C₁₂H₁₆O₄S (256.32):

C 56.23, H 6.29, S 12.51; found: C 55.82, H 6.15, S 12.73.

1-Benzoyl-3-phenylpropyl Methanesulfonate (3d). GP A (MeCN, 24 h reflux) starting from 1d afforded 3d

in 48% yield. Colorless solid. M.p. 52 578. IR (KBr): 1692, 1361, 1354, 1174, 934, 700. ¹H-NMR (300 MHz,

CDCl₃): 7.73 7.69 (m, 2 H); 7.62 7.55 (m, 1 H); 7.45 7.39 (m, 2 H); 7.37 7.19 (m, 5 H); 5.91 5.86 (m, 1 H);

3.15 (s, 3 H); 2.98 2.77 (m, 2 H); 2.28 2.16 (m, 2 H). ¹³C-NMR (75 MHz, CDCl₃): 195.0 (CO); 139.5, 133.7

(arom. C_q); 134.1, 128.9, 128.7, 128.4, 126.5 (arom. CH); 80.0 (CH); 39.4 (Me); 34.0 (CH₂); 31.1 (CH₂). EI-MS:

222 (3, [M À MsOH] ), 214 (17, PhCOCH₂OMs ), 135 (40), 105 (100, PhCO ), 91 (26, PhCH₂), 77 (39, Ph ),

51 (11). Anal. calc. for C₁₇H₁₈O₄S (318.39): C 64.13, H 5.70, S 10.07; found: C 63.83, H 5.83, S 9.89.

1-Benzoyl-3-cyanopropyl Methanesulfonate (3e). GPA (MeCN, 24 h reflux) starting from 1e afforded 3e in

70% yield. Colorless solid. M.p. 60 628. IR (KBr): 1727, 1698, 1364, 1289, 1278, 1173, 943. ¹H-NMR (300 MHz,

CDCl₃): 7.97 7.93 (m, 2 H); 7.71 7.65 (m, 1 H); 7.58 7.52 (m, 2 H); 6.05 (dd, J 3.8, 8.7, 1 H); 3.18 (s, 3 H);

2.73 2.51 (m, 2 H); 2.45 2.33 (m, 1 H); 2.29 2.16 (m, 1 H). ¹³C-NMR (75 MHz, CDCl₃): 193.5 (CO); 133.3

(arom. C_q); 134.8, 129.3, 128.5 (arom. CH); 125.9 (C_q); 77.9 (CH); 39.4 (Me); 28.2 (CH₂); 13.4 (CH₂). EI-MS:

105 (100, PhCO ), 77 (33, Ph ), 51 (10). Anal. calc. for C₁₂H₁₃NO₄S (267.30): C 53.92, H 4.90, N 5.24, S 12.00;

found: C 53.68, H 4.78, N 5.41, S 12.32.

4-Benzyloxy-2-hydroxy-1-phenylbutan-1-one (7a). GP B starting from 6a afforded 7a in 63% yield.

Colorless oil. ¹H-NMR (300 MHz, CDCl₃): 7.95 7.89 (m, 2 H); 7.63 7.25 (m, 8 H); 5.32 5.28 (m, 1 H); 4.48 (s,

2 H); 3.70 3.60 (m, 2 H); 2.27 2.16 (m, 1 H); 1.86 1.75 (m, 1 H). ¹³C-NMR (75 MHz, CDCl₃): 201.8 (CO);

138.2, 129.6 (arom. C_q); 133.7, 128.9, 128.5, 128.0, 127.9, 127.6 (arom. CH); 73.1 (CH₂); 70.6 (CH); 66.1 (CH₂);

36.1 (CH₂).

(2SR,3RS)-2-Hydroxy-1,3-diphenylbutan-1-one (7b). GP B starting from 6b afforded 7b in 63% yield.

1

Colorless oil. H-NMR (300 MHz, CDCl₃): 7.96 7.89 (m, 2 H); 7.60 7.10 (m, 8 H); 5.27 5.23 (m, 1 H); 3.23

(dq, J 7.2, 1 H); 1.08 (d, J 7.2, 3 H). ¹³C-NMR (75 MHz, CDCl₃): 201.4 (CO), 143.8, 133.9 (arom. C_q);

134.0, 128.9, 128.6, 128.5, 127.7, 126.8 (arom. CH); 77.0 (CH); 43.3 (CH); 13.3 (Me). NMR Data: identical to

those reported in [12].

2-Hydroxy-1-phenyl-hex-5-en-1-one (7c). GP B starting from 6c afforded 7c in 43% yield. Colorless oil. IR

(film): 3472, 2926, 1681, 1597, 1449, 1271, 1076, 980, 915, 699. ¹H-NMR (300 MHz, CDCl₃): 7.95 7.86 (m, 2 H);

7.67 7.58 (m, 1 H); 7.57 7.47 (m, 2 H); 5.87 5.73 (m, 1 H); 5.13 5.97 (m, 3 H); 3.75 (d, J 6.4, OH); 2.39

2.16 (m, 2 H); 2.01 1.89 (m, 1 H); 1.68 1.57 (m, 1 H). ¹³C-NMR (75 MHz, CDCl₃): 201.9 (CO); 137.3 (olef.

CH); 133.5 (arom. C_q); 133.9, 128.9, 128.5 (arom. CH); 115.7 (olef. CH₂); 72.3 (CH); 35.0 (CH₂); 29.1 (CH₂).

EI-MS: 190 (4, M ), 136 (20), 105 (100, PhCO ), 77 (42, Ph ), 51 (17). Anal. calc. for C₁₂H₁₄O₂(190.24):

C 75.76, H 7.42; found: C 75.63, H 7.27.

1,6-Diphenyl-2-hydroxy-hex-5-yn-1-one (7d). GP B starting from 6d afforded 7d in 45% yield. Colorless oil.

IR (film): 1688, 1598, 1490, 1450, 1272, 757, 693. ¹H-NMR (300 MHz, CDCl₃): 7.84 7.78 (m, 2 H); 7.46 7.39 (m,

1 H); 7.33 7.19 (m, 4 H); 7.14 7.08 (m, 3 H); 5.18 5.09 (m, 1 H); 3.62 (d, J 6.0, OH); 2.65 2.51 (m, 1 H);

2.49 2.35 (m, 1 H); 2.09 1.95 (m, 1 H); 1.66 1.52 (m, 1 H). ¹³C-NMR (75 MHz, CDCl₃): 201.4 (CO); 133.2,

123.5 (arom. C_q); 134.0, 131.5, 128.8, 128.6, 128.2, 127.7 (arom. CH); 88.8, 81.7 (C_q); 71.8 (CH); 35.1 (CH₂); 15.8

(CH₂). EI-MS: 264 (14, M ), 158 (18), 136 (100), 105 (80, PhCO ), 91 (15, PhCH₂), 77 (84, Ph ), 51 (16). Anal.

calc. for C₁₈H₁₆O₂(264.32): C 81.79, H 6.10; found: C 81.53, H 5.97.

4-Cyclopropyl-2-hydroxy-1-phenylbutan-1-one (7e). GP B starting from 6e afforded 7e in 38% yield.

Colorless oil. IR (film): 3474, 3076, 3000, 2930, 2855, 1682, 1597, 1449, 1273, 1085, 1016, 984, 698. ¹H-NMR

(300 MHz, CDCl₃): 7.88 7.81 (m, 2 H); 7.59 7.51 (m, 1 H); 7.49 7.38 (m, 2 H); 5.05 (dd, J 3.4, 8.3, 1 H);

1.99 1.85 (m, 1 H); 1.64 1.48 (m, 1 H); 1.45 1.33 (m, 1 H); 1.29 1.13 (m, 1 H); 0.67 0.51 (m, 1 H); 0.44

0.25 (m, 2 H); 0.04 (À0.08) (m, 2 H). ¹³C-NMR (75 MHz, CDCl₃): 192.4 (CO); 134.4 (arom. C_q); 133.9,

128.8, 128.5 (arom. CH); 72.8 (CH); 35.9 (CH₂); 29.9 (CH₂); 10.4 (CH); 4.7 (CH₂); 4.1 (CH₂). EI-MS: 204 (3,

M ), 136 (17), 120 (18), 105 (100, PhCO ), 77 (49, Ph ), 51 (13). Anal. calc. for C₁₃H₁₆O₂(204.26): C 76.44,

H 7.90; found: C 76.12, H 7.72.

2-Cyclobutyl-2-hydroxy-1-phenylethan-1-one (7f). GP B starting from 6f afforded 7f in 73% yield.

Colorless solid. M.p. 38 408. ¹H-NMR (300 MHz, CDCl₃): 7.93 7.85 (m, 2 H); 7.60 7.51 (m, 1 H); 7.50 7.40

(m, 2 H); 5.02 (d, J 3.8, 1 H); 3.97 (s, OH), 2.81 2.67 (m, 1 H); 2.36 2.20 (m, 1 H); 2.02 1.68 (m, 4 H);

1.60 1.45 (m, 1 H). ¹³C-NMR (75 MHz, CDCl₃): 200.7 (CO); 133.8 (arom. C_q); 133.3, 128.3, 128.0 (arom.

CH); 73.9 (CH); 39.1 (CH); 23.7 (CH₂); 20.4 (CH₂); 17.6 (CH₂). IR (KBr): 3440, 2936, 2853, 1676, 1597, 1579,

Helvetica Chimica Acta Vol. 86 (2003)

885

1407, 1277, 1216, 1144. EI-MS: 190 (11, M ), 105 (100), 85 (65), 77 (94, Ph ), 67 (82), 51 (79), 41 (65), 39 (46).

Anal. calc. for C₁₂H₁₄O₂(190.24): C 75.76, H 7.42; found: C 75.83, H 7.84.

2-Cyclopentyl-2-hydroxy-1-phenylethan-1-one (7g). GP B starting from 6g afforded 7g in 75% yield.

Colorless solid. M.p. 52 548. IR (KBr): 3444, 2960, 2868, 1676, 1597, 1579, 1448, 1278, 1104. ¹H-NMR

(300 MHz, CDCl₃): 7.88 7.82 (m, 2 H); 7.59 7.50 (m, 1 H); 7.48 7.39 (m, 2 H); 5.08 (dd, J 5.7, 3.0, 1 H); 3.59

(d, J 6.4, OH); 2.27 2.11 (m, 1 H); 1.79 1.05 (m, 8 H). ¹³C-NMR (75 MHz, CDCl₃): 202.1 (CO); 134.2

(arom. C_q); 133.8, 128.8, 128.4 (arom. CH); 74.4 (CH); 43.8 (CH); 29.5 (CH₂); 25.8 (CH₂); 25.7 (CH₂); 24.3

(CH₂). EI-MS: 204 (3, M ), 136 (66), 105 (81), 81 (100), 77 (93, Ph ), 51 (77), 41 (82), 39 (61). Anal. calc. for

C₁₃H₁₆O₂(204.26): C 76.44, H 7.90; found: C 76.18, H 7.67.

2-Hydroxy-2-(indan-2-yl)-1-phenylethan-1-one (7h). GP B starting from 6h afforded 7h in 68% yield.

Colorless crystals. M.p. 124 1258. IR (KBr): 3438, 2942, 2922, 1677, 1599, 1580, 1449, 1272, 1230, 1114. ¹H-NMR

(300 MHz, CDCl₃): 7.90 7.85 (m, 2 H); 7.59 7.52 (m, 1 H); 7.48 7.40 (m, 2 H); 7.12 6.97 (m, 4 H); 5.22 (d,

J 2.6, 1 H); 3.70 (br., s, OH); 3.24 3.13 (m, 1 H); 3.03 2.67 (m, 3 H); 2.42 2.32 (m, 1 H). ¹³C-NMR

(75 MHz, CDCl₃): 201.8 (CO); 142.5, 142.2, 134.0 (arom. C_q); 134.1, 128.9, 128.5, 126.3, 124.3, 124.2 (arom.

CH); 73.8 (CH); 44.3 (CH); 35.7 (CH₂); 31.4 (CH₂). EI-MS: 252 (2, M ), 224 (5), 146 (33), 105 (100, PhCO ),

91 (44, PhCH₂), 77 (28, Ph ), 51 (6). HR-EI-MS: 252.11497 (C₁₇H₁₆O₂; calc. 252.11503). Anal. calc. for

C₁₇H₁₆O₂(252.31): C 80.93, H 6.93; found: C 80.57, H 6.53.

2-Cyclohexyl-2-hydroxy-1-phenylethan-1-one (7i). GP B starting from 6i afforded 7i in 71% yield. Colorless

1

solid. M.p. 83 858. IR (KBr): 3440, 2933, 2853, 1679, 1597, 1578, 1448, 1275, 1216, 1108. H-NMR (300 MHz,

CDCl₃): 7.94 7.88 (m, 2 H); 7.66 7.59 (m, 1 H); 7.55 7.47 (m, 2 H); 4.94 (dd, J 6.4, 2.3, 1 H); 3.60 (d, J 6.8,

OH); 1.85 1.48 (m, 6 H); 1.31 0.93 (m, 5 H). ¹³C-NMR (75 MHz, CDCl₃): 202.2 (CO); 134.2 (arom. C_q);

133.8, 128.8, 128.5 (arom. CH); 77.3 (CH); 42.6 (CH); 30.2 (CH₂); 26.5 (CH₂); 25.8 (2 CH₂); 24.8 (CH₂). EI-MS:

218 (7, M ), 136 (67), 107 (53), 95 (100), 77 (91, Ph ), 67 (33), 55 (58), 51 (47), 41 (65), 39 (28). Anal. calc. for

C₁₄H₁₈O₂(218.29): C 77.03, H 8.31; found: C 76.55, H 8.23.

trans-2-[4-(tert-Butyl)cyclohexyl]-2-hydroxy-1-phenylethan-1-one (7j). GP B starting from 6j afforded 7j

in 57% yield. Colorless solid. M.p. 81 828. IR (KBr): 3504, 2937, 2862, 1672, 1598, 1579, 1449, 1263, 1216, 1127,

984. ¹H-NMR (300 MHz, CDCl₃): 7.86 7.81 (m, 2 H); 7.59 7.52 (m, 1 H); 7.47 7.40 (m, 2 H); 4.89 (d, J 2.6,

1 H); 3.27 (br., s, OH); 1.85 1.72 (m, 2 H); 1.68 1.57 (m, 2 H); 1.56 1.44 (m, 1 H); 1.16 1.09 (m, 2 H); 0.95

0.63 (m, 3 H); 0.71 (s, 9 H). ¹³C-NMR (75.5 MHz, CDCl₃): 202.2 (CO); 134.2 (arom. C_q); 133.8, 128.8, 128.4

(arom. CH); 76.8 (CH); 47.3 (CH); 42.5 (CH); 32.3 (C_q); 30.4 (CH₂); 27.4 (3 Me); 27.2 (CH₂); 26.5 (CH₂); 24.9

(CH₂). EI-MS: 274 (3, M ), 151 (33), 136 (58), 105 (63, PhCO ), 95 (60), 81 (41), 77 (33, Ph ), 57 (100), 41

(28). Anal. calc. for C₁₈H₂₆O₂(274.40): C 78.79, H 9.55; found: C 78.28, H 9.64.

2-Hydroxy-1-phenyl-2-(3,4,5,6-tetrahydro-2H-pyran-3-yl)ethan-1-one (7k). GP B starting from 6k afforded

7k in 63% yield. Colorless solid. M.p. 113 1158. ¹H-NMR (300 MHz, CDCl₃): 7.87 7.81 (m, 2 H); 7.62 7.54 (m,

1 H); 7.50 7.42 (m, 2 H); 4.92 (d, J 2.3, 1 H); 3.97 3.88 (m, 1 H); 3.86 3.77 (m, 1 H); 3.34 3.21 (m, 1 H);

3.17 3.04 (m, 1 H); 2.15 1.75 (m, 3 H); 1.60 1.51 (m, 1 H); 0.99 0.89 (m, 1 H). ¹³C-NMR (75.5 MHz,

CDCl₃): 201.5 (CO); 133.9 (arom. C_q); 134.1, 128.9, 128.4 (arom. CH); 76.0 (CH); 67.7 (CH₂); 67.3 (CH₂); 39.8

(CH); 25.2 (CH₂); 25.0 (CH₂). EI-MS: 220 (1, M ), 105 (100, PhCO ), 77 (53, Ph ), 51 (18). Anal. calc. for

C₁₈H₁₆O₃(220.26): C 70.89, H 7.32; found: C 70.48, H 7.19.

2-Hydroxy-2-{1-[(4-methylphenyl)sulfonyl]piperidin-4-yl}-1-phenylethan-1-one (7l). GP B starting from 6l

afforded 7l in 56% yield. Colorless solid. M.p. 102 1058. IR (KBr): 3481, 2924, 2849, 1677, 1596, 1448, 1366,

1268, 1161, 1093, 934. ¹H-NMR (300 MHz, CDCl₃): 7.79 7.73 (m, 2 H); 7.58 7.47 (m, 3 H); 7.44 7.36 (m, 2 H);

7.23 7.17 (m, 2 H); 4.92 4.86 (m, 1 H); 3.83 3.73 (m, 1 H); 3.70 3.60 (m, 1 H); 2.32 (s, 3 H); 2.15 2.05 (m,

1 H); 1.97 1.38 (m, 5 H); 1.13 1.03 (m, 1 H). ¹³C-NMR (75.5 MHz, CDCl₃): 201.2 (CO); 143.4, 133.7, 132.9

(arom. C_q); 134.2, 129.5, 129.0, 128.3, 127.6 (arom. CH); 75.4 (CH); 46.2 (CH₂); 45.7 (CH₂); 39.9 (CH); 28.3

(CH₂); 23.7 (CH₂); 21.4 (Me). EI-MS: 373 (1, M ), 355 (4), 268 (14), 238 (14), 200 (44), 155 (48, Ts ), 112 (24),

105 (76, PhCO ), 91 (100, PhCH₂), 82 (58), 77 (42, Ph ), 42 (30). Anal. calc. for C₂₀H₂₃NO₄S (373.47): C 64.32,

H 6.21, N 3.75, S 8.59; found: C 63.93, H 6.11, N 3.99, S 8.46.

2-{1-[(tert-Butoxy)carbonyl]piperidin-4-yl}-2-hydroxy-1-phenylethan-1-one (7m). GP B starting from 6m

afforded 7m in 67% yield. Colorless solid. M.p. 99 1018. IR (KBr): 3407, 2939, 2852, 1676, 1429, 1366, 1234,

1169, 1137. ¹H-NMR (300 MHz, CDCl₃): 7.87 7.81 (m, 2 H); 7.62 7.54 (m, 1 H); 7.50 7.41 (m, 2 H); 4.93 (d,

J 3.0, 2 H); 4.15 4.06 (m, 1 H); 4.04 3.93 (m, 1 H); 2.62 2.50 (m, 1 H); 2.44 2.31 (m, 1 H); 1.90 1.71 (m,

1 H); 1.71 1.59 (m, 2 H); 1.36 (s, 9 H); 1.33 1.23 (m, 1 H); 1.06 0.97 (m, 1 H). ¹³C-NMR (75.5 MHz, CDCl₃):

201.5, 154.6 (CO); 133.9 (arom. C_q); 134.2, 129.0, 128.5 (arom. CH); 79.5 (C_q), 76.0 (CH); 43.8 (br., CH₂); 43.2

(br., CH₂); 40.9 (CH); 29.0 (CH₂); 28.4 (3 Me); 24.2 (CH₂). EI-MS: 245 (5), 202 (4), 140 (9), 105 (34, PhCO ),

886

Helvetica Chimica Acta Vol. 86 (2003)

82 (43), 77 (29, Ph ), 57 (100), 41 (37). Anal. calc. for C₁₈H₂₅NO₄(319.40): C 67.69, H 7.89, N 4.39; found:

C 67.35, H 7.57, N 4.60.

1-Benzoyl-3-(benzyloxy)propyl Methanesulfonate (3f). GP C starting from 7a afforded 3f in 75% yield.

Colorless solid. M.p. 62 648. IR (KBr): 1695, 1366, 1169, 1068, 971, 936, 737, 696. ¹H-NMR (300 MHz, CDCl₃):

7.95 7.92 (m, 2 H); 7.61 7.55 (m, 1 H); 7.49 7.41 (m, 2 H); 7.39 7.26 (m, 5 H); 6.23 6.18 (m, 1 H); 4.50 (s,

2 H); 3.67 3.58 (m, 2 H); 3.07 (s, 3 H); 2.35 2.23 (m, 1 H); 2.12 2.00 (m, 1 H). ¹³C-NMR (75.5 MHz, CDCl₃):

194.9 (CO); 137.8, 133.7 (arom. C_q); 133.9, 128.8, 128.5, 128.3, 127.6 (arom. CH); 78.2 (CH); 73.1 (CH₂); 64.8

(CH₂); 38.9 (Me); 32.9 (CH₂). EI-MS: 146 (19), 105 (100, PhCO ), 91 (57, PhCH₂), 77 (51, Ph ), 65 (12), 51

(17). Anal. calc. for C₁₈H₂₀O₅S (348.41): C 62.05, H 5.79, S 9.20; found: C 61.77, H 5.70, S 9.28.

(1SR,2RS)-1-Benzoyl-2-phenylpropyl Methanesulfonate (3g). GP C starting from 7b afforded 3g in 79%

yield. Colorless solid. M.p. 95 1018. IR (KBr): 1683, 1354, 1175, 1006, 957, 914, 866, 761, 697. ¹H-NMR

(300 MHz, CDCl₃): 7.86 7.82 (m, 2 H); 7.59 7.52 (m, 1 H); 7.47 7.40 (m, 2 H); 7.29 7.13 (m, 5 H); 5.93 (d, J

4.9, 1 H); 3.51 3.35 (m, 1 H); 2.88 (s, 3 H); 1.37 (d, J 7.2, 3 H). ¹³C-NMR (75 MHz, CDCl₃): 195.0 (CO);

140.3, 134.7 (arom. C_q); 133.8, 128.8, 128.6, 128.3, 127.8, 127.5 (arom. CH); 84.5 (CH); 41.9 (CH); 38.7 (Me); 14.8

(Me). EI-MS: 222 (11, [M À MsOH] ), 105 (100, PhCO ), 77 (28, Ph ), 51 (8). Anal. calc. for C₁₇H₁₈O₄S

(318.39): C 64.13, H 5.70, S 10.07; found: C 63.84, H 5.78, S 10.16.

1-Benzoylpent-4-enyl 4-Methylbenzene-1-sulfonate (3h). GP D starting from 7c afforded 3h in 82% yield.

Yellowish oil. IR (film): 3068, 2925, 1704, 1597, 1448, 1364, 1190, 1175, 1096. ¹H-NMR (300 MHz, CDCl₃): 7.80

7.74 (m, 2 H); 7.70 7.64 (m, 2 H); 7.54 7.47 (m, 1 H); 7.41 7.33 (m, 2 H); 7.20 7.14 (m, 2 H); 5.73 5.55 (m,

2 H); 4.97 4.86 (m, 2 H); 2.32 (s, 3 H); 2.21 1.79 (m, 4 H). ¹³C-NMR (75.5 MHz, CDCl₃): 194.8 (CO); 145.0,

133.9, 133.1 (arom. C_q); 135.9 (olef. CH); 133.8, 129.7, 128.7, 128.6, 128.0 (arom. CH); 116.7 (olef. CH₂); 80.2

(CH); 31.8 (CH₂); 28.9 (CH₂); 21.6 (Me). EI-MS: 155 (15, Ts ), 105 (100, PhCO ), 91 (30, PhCH₂), 77 (39,

Ph ), 65 (14), 51 (12), 39 (11). Anal. calc. for C₁₉H₂₀O₄S (344.43): C 66.26, H 5.85, S 9.31; found: C 65.94,

H 5.48, S 9.69.

1-Benzoyl-5-phenylpent-4-ynyl 4-Methylbenzene-1-sulfonate (3i). GP D starting from 7d afforded 3i in

77% yield. Colorless solid. M.p. 99 1018. IR (KBr): 1702, 1596, 1363, 1189, 1176, 969, 886, 782. ¹H-NMR

(300 MHz, CDCl₃): 7.87 7.78 (m, 2 H); 7.70 7.63 (m, 2 H); 7.48 7.40 (m, 1 H); 7.30 (d, J 7.9, 2 H); 7.28 7.13

(m, 5 H); 7.07 (d, J 7.9, 2 H); 5.84 (dd, J 4.5, 7.9, 1 H); 2.39 (t, J 7.2, 2 H); 2.17 (s, 3 H); 2.08 1.94 (m, 2 H).

¹³C-NMR (75.5 MHz, CDCl₃): 193.9 (CO); 144.9, 133.6, 132.7, 123.0 (arom. C_q); 133.8, 131.3, 129.6, 128.6,

128.4, 128.1, 127.8, 127.7 (arom. CH); 87.0, 82.3 (C_q); 79.1 (CH); 31.4 (CH₂); 21.3 (Me); 15.5 (CH₂). EI-MS: 290

(15), 246 (10, [M À TsOH] ), 155 (9, Ts ), 135 (75), 115 (20), 105 (100, PhCO ), 91 (35, PhCH₂), 77 (48, Ph ),

65 (14), 51 (10). Anal. calc. for C₂₅H₂₁O₄S (418.51): C 71.75, H 5.30, S 7.66; found: C 71.24, H 5.19, S 7.82.

1-Benzoyl-3-cyclopropylpropyl 4-Methylbenzene-1-sulfonate (3j). GP D starting from 7e afforded 3j in

1

91% yield. Colorless oil. H-NMR (300 MHz, CDCl₃): 7.83 7.75 (m, 2 H); 7.69 7.63 (m, 2 H); 7.55 7.48 (m,

1 H); 7.42 7.34 (m, 2 H); 7.20 7.13 (m, 2 H); 5.62 (t, J 6.8, 1 H); 2.32 (s, 3 H); 1.98 1.87 (m, 2 H); 1.32 1.17

(m, 2 H); 0.62 0.48 (m, 1 H); 0.42 0.28 (m, 2 H); 0.04 (À0.17) (m, 2 H). ¹³C-NMR (75.5 MHz, CDCl₃): 194.9

(CO); 144.9, 134.0, 133.2 (arom. C_q); 133.7, 129.6, 128.7, 128.6, 128.0 (arom. CH); 81.0 (CH); 32.8 (CH₂); 29.9

(CH₂); 21.6 (Me); 10.0 (CH); 4.7 (CH₂); 4.1 (CH₂). Anal. calc. for C₂₀H₂₂O₄S (358.45): C 67.01, H 6.19, S 8.95;

found: C 66.85, H 6.29, S 9.09.

1-Cyclobutyl-2-oxo-2-phenylethyl 4-Methylbenzene-1-sulfonate (3k). GP D starting from 7f afforded 3k in

1

74% yield. Colorless oil. IR (KBr): 1687, 1595, 1448, 1359, 1172, 969, 947. H-NMR (300 MHz, CDCl₃): 7.93

7.88 (m, 2 H); 7.68 7.60 (m, 3 H); 7.55 7.50 (m, 2 H); 7.18 7.12 (m, 2 H); 5.85 (d, J 7.2, 1 H); 2.96 2.79 (m,

1 H); 2.32 (s, 3 H); 2.18 1.78 (m, 6 H). ¹³C-NMR (75.5 MHz, CDCl₃): 194.7 (CO); 144.8, 134.7, 133.1 (arom.

C_q); 134.0, 129.6, 128.9, 128.5, 128.0 (arom. CH); 83.0 (CH); 36.8 (CH); 23.3 (2 CH₂); 21.6 (Me); 17.9 (CH₂). EI-

MS: 172 (3, [M À TsOH] ), 155 (16, Ts ), 105 (100, PhCO ), 91 (38, PhCH₂), 77 (34, Ph ), 65 (23), 51 (7).

Anal. calc. for C₁₉H₂₀O₄S (344.43): C 66.26, H 5.85, S 9.31; found: C 66.15, H 5.69, S 9.48.

1-Cyclopentyl-2-oxo-2-phenylethyl 4-Methylbenzene-1-sulfonate (3l). GP D starting from 7g afforded 3l in

91% yield. Colorless solid. M.p. 68 708. IR (KBr): 2952, 2870, 1699, 1596, 1448, 1370, 1176, 941. ¹H-NMR

(300 MHz, CDCl₃): 7.82 7.75 (m, 2 H); 7.67 7.60 (m, 2 H); 7.53 7.45 (m, 1 H); 7.40 7.31 (m, 2 H); 7.16 7.10

(m, 2 H); 5.35 (d, J 7.2, 1 H); 2.42 2.27 (m, 1 H); 2.30 (s, 3 H); 1.73 1.16 (m, 8 H). ¹³C-NMR (75.5 MHz,

CDCl₃): 195.0 (CO); 144.9, 134.5, 133.0 (arom. C_q); 133.6, 129.6, 128.7, 128.6, 128.0 (arom. CH); 84.2 (CH);

42.1 (CH); 28.4 (CH₂); 28.3 (CH₂); 25.2 (CH₂); 24.8 (CH₂); 21.5 (Me). EI-MS: 186 (5, [M À TsOH] ), 155 (25,

Ts ), 105 (100, PhCO ), 91 (44, PhCH₂), 81 (39), 77 (39, Ph ), 65 (14), 51 (8). Anal. calc. for C₂₀H₂₂O₄S

(358.45): C 67.01, H 6.19, S 8.95; found: C 67.22, H 6.18, S 8.58.

1-(2,3-Dihydro-1H-inden-2-yl)-2-oxo-2-phenylethyl 4-Methylbenzene-1-sulfonate (3m). GP D starting

from 7h afforded 3m in 82% yield. Colorless solid. M.p. 120 1228. IR (KBr): 1694, 1595, 1449, 1370, 1189,

Helvetica Chimica Acta Vol. 86 (2003)

887

1171, 933. ¹H-NMR (300 Hz, CDCl₃): 7.84 7.76 (m, 2 H); 7.65 7.60 (m, 2 H); 7.54 7.47 (m, 1 H); 7.40 7.32 (m,

2 H); 7.17 7.10 (m, 2 H); 7.04 6.97 (m, 4 H); 5.55 (d, J 7.2, 1 H); 3.05 2.91 (m, 1 H); 2.90 2.80 (m, 2 H);

2.79 2.71 (m, 2 H); 2.35 (s, 3 H). ¹³C-NMR (75.5 MHz, CDCl₃): 194.7 (CO); 145.0, 141.3, 141.2, 134.5, 132.8

(arom. C_q); 133.8, 129.6, 128.7, 128.6, 128.0, 126.6, 126.5, 124.4, 124.3 (arom. CH); 82.8 (CH); 42.0 (CH); 34.9

(CH₂); 34.7 (CH₂); 21.6 (Me). EI-MS: 290 (19), 234 (3, [M À TsOH] ), 155 (17, Ts ), 135 (100), 115 (14), 105

(62, PhCO ), 91 (37, PhCH₂), 77 (42, Ph ), 65 (12), 51 (9). Anal. calc. for C₂₄H₂₂O₄S (406.50): C 70.91, H 5.46,

S 7.89; found: C 70.49, H 5.65, S 7.74.

1-Cyclohexyl-2-oxo-2-phenylethyl 4-Methylbenzene-1-sulfonate (3n). GP D starting from 7i afforded 3n in

88% yield. Colorless solid. M.p. 64 678. IR (KBr): 2932, 2853, 1689, 1597, 1449, 1366, 1172, 939. ¹H-NMR

(300 MHz, CDCl₃): 7.81 7.73 (m, 2 H); 7.66 7.59 (m, 2 H); 7.54 7.46 (m, 1 H); 7.41 7.32 (m, 2 H); 7.17 7.10

(m, 2 H); 5.28 (d, J 5.9, 1 H); 2.30 (s, 3 H); 1.96 1.80 (m, 1 H); 1.78 1.35 (m, 5 H); 1.20 0.93 (m, 5 H).

¹³C-NMR (75.5 MHz, CDCl₃): 195.1 (CO); 144.8, 134.8, 133.0 (arom. C_q); 133.6, 129.6, 128.6, 128.0 (arom.

CH); 85.1 (CH); 40.5 (CH); 28.9 (CH₂); 27.8 (CH₂); 25.7 (2 CH₂); 25.5 (CH₂); 21.6 (Me). EI-MS: 200 (5, [M À

TsOH] ), 155 (22, Ts ), 105 (100, PhCO ), 95 (53), 91 (41, PhCH₂), 77 (38, Ph ), 65 (12), 51 (7). Anal. calc.

for C₂₁H₂₄O₄S (372.48): C 67.72, H 6.49, S 8.61; found: C 67.40, H 6.22, S 8.43.

trans-1-[4-(tert-Butyl)cyclohexyl]-2-oxo-2-phenylethyl 4-Methylbenzene-1-sulfonate (3o). GP D starting

from 7j afforded 3o in 87% yield. Colorless solid. M.p. 97 998. IR (KBr): 2935, 2857, 1678, 1597, 1449, 1367,

1172, 941. ¹H-NMR (300 MHz, CDCl₃): 7.83 7.75 (m, 2 H); 7.67 7.60 (m, 2 H); 7.56 7.47 (m, 1 H); 7.40 7.31

(m, 2 H); 7.18 7.10 (m, 2 H); 5.68 (d, J 6.2, 1 H); 2.31 (s, 3 H); 2.00 1.86 (m, 1 H); 1.82 1.66 (m, 3 H); 1.63

1.52 (m, 1 H); 1.35 1.08 (m, 2 H); 1.02 0.80 (m, 3 H); 0.70 (s, 9 H). ¹³C-NMR (75.5 MHz, CDCl₃): 196.2

(CO); 144.8, 134.5, 132.4 (arom. C_q); 133.6, 129.6, 128.5, 128.3, 128.0 (arom. CH); 85.1 (CH); 47.4 (CH); 40.6

(CH); 32.4 (C_q); 29.3 (CH₂); 27.4 (3 Me); 26.6 (CH₂); 26.5 (CH₂); 21.6 (CH₂); 21.6 (Me). Anal. calc. for

C₂₅H₃₂O₄S (428.59): C 70.06, H 7.53, S 7.48; found: C 69.91, H 7.49, S 7.58.

2-Oxo-2-phenyl-1-(3,4,5,6-tetrahydro-2H-pyran-4-yl)ethyl 4-Methylbenzene-1-sulfonate (3p). GP D start-

ing from 7k afforded 3p in 84% yield. Colorless solid. M.p. 139 1418. IR (KBr): 2954, 2857, 1697, 1596, 1449,

1369, 1237, 1210, 1181, 1090, 1071, 1009, 949, 934, 918, 876, 851, 718. ¹H-NMR (300 MHz, CDCl₃): 7.82 7.77 (m,

2 H); 7.66 7.60 (m, 2 H); 7.57 7.49 (m, 1 H); 7.44 7.35 (m, 2 H); 7.18 7.12 (m, 2 H); 5.29 (d, J 6.8, 2 H);

3.92 3.79 (m, 2 H); 3.26 3.15 (m, 2 H); 2.32 (s, 3 H); 2.20 2.08 (m, 1 H); 1.63 1.21 (m, 4 H). ¹³C-NMR

(75.5 MHz, CDCl₃): 194.6 (CO); 145.1, 134.7, 132.8 (arom. C_q); 133.9, 129.7, 128.7, 128.5, 128.1 (arom. CH);

83.8 (CH); 67.3 (CH₂); 67.0 (CH₂); 38.0 (CH); 28.6 (CH₂); 28.0 (CH₂); 21.6 (Me). EI-MS: 374 (1, M ), 269 (18),

202 (10, [M À TsOH] ), 155 (60, Ts ), 105 (100, PhCO ), 91 (44, PhCH₂), 77 (34, Ph ). Anal. calc. for

C₂₀H₂₂O₅S (374.45): C 64.15, H 5.92, S 8.56; found: C 63.94, H 5.98, S 8.72.

1-{1-[(4-Methylphenyl)sulfonyl]piperidin-4-yl}-2-oxo-2-phenylethyl 4-Methylbenzene-1-sulfonate (3q). GP

D starting from 7l afforded 3q in 81% yield. Colorless solid. M.p. 97 998. IR (KBr): 1691, 1597, 1448, 1357, 1338,

1163, 933. ¹H-NMR (300 MHz, CDCl₃): 7.76 7.69 (m, 2 H); 7.65 7.58 (m, 2 H); 7.54 7.45 (m, 2 H); 7.40 7.31

(m, 1 H); 7.24 7.12 (m, 2 H); 5.25 (d, J 6.4, 1 H); 3.75 3.60 (m, 2 H); 2.33 (s, 3 H); 2.32 (s, 3 H); 2.11 1.96

(m, 2 H); 1.85 1.62 (m, 2 H); 1.53 1.28 (m, 3 H). ¹³C-NMR (75.5 MHz, CDCl₃): 194.3 (CO); 145.3, 143.6,

134.5, 132.8, 132.6 (arom. C_q); 134.0, 129.8, 129.6, 128.8, 128.6, 128.0, 127.6 (arom. CH); 83.0 (CH); 45.7 (CH₂);

45.6 (CH₂); 38.1 (CH); 27.4 (CH₂); 26.6 (CH₂); 21.6 (CH₃); 21.5 (Me). EI-MS: 355 (7, [M À TsOH] ), 200 (60),

155 (26, Ts ), 105 (100, PhCO ), 91 (81, PhCH₂), 82 (37), 77 (30, Ph ), 65 (19), 42 (10). Anal. calc. for

C₂₇H₂₉NO₆S₂(527.65): C 61.46, H 5.54, N 2.65, S 12.15; found: C 61.34, H 5.55, N 2.87, S 12.25.

1-{1-[(tert-Butoxy)carbonyl]piperidin-4-yl}-2-oxo-2-phenylethyl 4-Methylbenzene-1-sulfonate (3r). GP D

starting from 7m afforded 3r in 87% yield. Colorless solid. M.p. 123 1248. IR (KBr): 1688, 1594, 1401, 1362,

1171, 925. ¹H-NMR (300 MHz, CDCl₃): 7.81 7.75 (m, 2 H); 7.65 7.59 (m, 2 H); 7.56 7.49 (m, 1 H); 7.43 7.34

(m, 2 H); 7.18 7.11 (m, 2 H); 5.30 (d, J 6.4, 1 H); 4.11 3.90 (m, 2 H); 2.59 2.43 (m, 2 H); 2.31 (s, 3 H);

2.10 1.96 (m, 1 H); 1.72 1.61 (m, 1 H); 1.35 (s, 9 H); 1.40 1.14 (m, 3 H). ¹³C-NMR (75.5 MHz, CDCl₃): 194.6,

154.4 (CO); 145.1, 134.6, 132.7 (arom. C_q); 133.9, 129.7, 128.7, 128.6, 128.0 (arom. CH); 83.6 (C_q); 43.6 (br.,

CH₂); 43.1(br., CH₂); 39.0 (CH); 28.3 (3 Me); 27.9 (CH₂); 27.1 (CH₂); 21.6 (Me). EI-MS: 301 (2, [M À

TsOH] ), 245 (16), 201 (15), 160 (16), 140 (13), 105 (100, PhCO ), 96 (25), 91 (36, PhCH₂), 82 (76), 77 (49,

Ph ), 57 (93), 41 (65). Anal. calc. for C₂₅H₃₁NO₆S (473.58): C 63.40, H 6.60, N 2.96, S 6.77; found: C 63.64,

H 6.62, N 3.17, S 6.37.

Methyl 3-Bromo-2-methyl-4-oxo-4-phenylbutanoate (4a). GP E starting from 1f afforded 4a in 100% yield

(mixture of diastereoisomers, ds 55 :45; the data of the minor product are given in square brackets). Yellow-

brown oil. IR (film): 1742, 1699, 1646, 1285, 1261, 858. ¹H-NMR (300 MHz, CDCl₃): 8.06 8.00 (m, 2 H); 7.65

7.56 (m, 1 H); 7.54 7.45 (m, 2 H); 5.32 [5.34] (d, J 9.8 [10.2], 1 H); 3.65 [3.78] (s, 3 H); 3.43 3.32 [3.54 3.45]

(m, 1 H); 1.53 [1.26] (d, J 7.2 [6.8], 3 H). ¹³C-NMR (75.5 MHz, CDCl₃): 193.1 [191.6], 174.1 [173.9] (CO);

888

Helvetica Chimica Acta Vol. 86 (2003)

134.1 [134.3] (arom. C_q); 133.7 [134.0], 128.8 [128.7] (arom. CH); 52.2 (Me); 48.3 [45.8] (CH); 42.4 [43.7] (CH);

16.2 (Me). EI-MS: 105 (100, PhCO ), 77 (35, Ph ), 51 (13). Anal. calc. for C₁₂H₁₃BrO₃(285.13): C 50.55,

H 4.60, Br 28.02; found: C 50.68, H 4.61, Br 27.89.

Methyl 2-Benzyl-3-bromo-4-oxo-4-phenylbutanoate (4b). GP E starting from 1g afforded 4b in 100% yield

(mixture of diastereoisomers, ds 60 :40; the data of the minor product are given in square brackets). Yellow-

brown oil. ¹H-NMR (300 MHz, CDCl₃): 7.88 7.83 [7.94 7.90] (m, 2 H); 7.58 7.34 (m, 3 H); 7.28 7.03 (m, 5 H);

5.15 [5.28] (d, J 10.6 [10.2], 1 H); 3.69 3.10 (m, 2 H); 3.45 [3.53] (s, 3 H); 2.89 2.70 (m, 1 H). ¹³C-NMR

(75.5 MHz, CDCl₃): 192.9 [191.5], 172.5 [172.7] (CO); 136.8 [137.1], 134.2 (arom. C_q); 133.7 [134.1], 129.1,

128.9, 128.8, 128.7, 128.6, 128.5, 127.1 [127.0] (arom. CH); 51.9 [51.3] (Me); 49.2 (CH); 45.9 [45.3] (CH); 35.8

[37.1] (CH₂).

Methyl 2-Methyl-3-(nitrooxy)-4-oxo-4-phenylbutanoate (5a). GP F starting from 4a afforded 5a in 67%

yield (mixture of diastereoisomers, ds 75 :25; the data of the minor product are given in square brackets).

Colorless oil. IR (film): 1742, 1699, 1646, 1285, 1261, 1226, 858, 695. ¹H-NMR (300 MHz, CDCl₃): 8.02 7.96 (m,

2 H); 7.69 7.63 (m, 1 H); 7.57 7.49 (m, 2 H); 6.60 [6.29] (d, J 4.2 [7.5], 1 H); 3.74 [3.64] (s, 3 H); 3.26 3.10

(m, 1 H); 1.20 [1.48] (d, J 7.2 [ 7.5 ] , 3 H ) . ¹³C-NMR (75.5 MHz, CDCl₃): 192.4 [193.5], 171.4 [171.7] (CO);

133.5 [131.9] (arom. C_q); 134.4 [134.5], 129.1 [130.3], 128.3 [128.7] (arom. CH); 81.5 [82.1] (CH); 52.7 [52.4]

(Me); 39.7 [40.2] (CH); 10.2 [11.3] (CH). EI-MS: 105 (100, PhCO ), 77 (53, Ph ), 51 (14), 15 (10). Anal. calc.

for C₁₂H₁₃NO₆(267.23): C 53.93, H 4.90, N 5.24; found: C 54.43, H 4.89, N 5.66

Methyl 2-Benzyl-3-(nitrooxy)-4-oxo-4-phenylbutanoate (5b). GP F starting from 4b afforded 5b in 33%

yield (mixture of diastereoisomers, ds 60 :40; the data of the minor product are given in square brackets).

Colorless oil. ¹H-NMR (300 MHz, CDCl₃): 7.94 7.00 (m, 10 H); 6.05 [6.43] (d, J 5.3, 1 H); 3.59 [3.56] (s, 3 H);

3.46 3.38 (m, 1 H); 3.19 3.09 (m, 1 H); 2.98 2.86 (m, 1 H). ¹³C-NMR (75.5 MHz, CDCl₃): 193.0 [192.6], 170.0

[170.7] (CO); 134.6 [134.0] (arom. C_q); 134.3, 134.1, 130.4, 129.0, 128.9, 128.7, 128.5, 128.4, 128.2, 127.3, 126.8

(arom. CH); 80.6 [81.3] (CH); 52.3 [52.5] (Me); 48.0 [47.7] (CH); 34.0 [32.3] (CH₂).

3-(Cyclopropyl)propan-1-ol (6e). In a dry 250-ml two-necked round-bottomed flask fitted with a N₂

bubbler, a rubber septum and a magnetic stirrer bar were placed at 08 dry 1,2-dichloroethane (50 ml), Et₂Zn

(44.4 ml, 0.9m in hexane, 40.0 mmol), and chloroiodomethane (14.2 g, 80.5 mmol). After stirring at r.t. for

45 min, 6c (1.73 g, 20.1 mmol) in 5 ml of dry 1,2-dichloroethane was added dropwise to the mixture. After 16 h,

the mixture was quenched with sat. aq. NH₄Cl soln. (50 ml), and, after phase separation, the aq. layer was

extracted with CH₂Cl₂(3 Â 30 ml). The combined org. extracts were washed with brine (30 ml), dried (MgSO₄),

and concentrated under reduced pressure. Colorless liquid (1.79 g, 89%). ¹H-NMR (300 MHz, CDCl₃): 3.61 (t,

J 6.8, 2 H); 1.65 1.50 (m, 2 H); 1.25 1.16 (m, 2 H); 0.66 0.53 (m, 1 H); 0.37 0.31 (m, 2 H); À0.02

(À0.09) (m, 2 H). ¹³C-NMR (75.5 MHz, CDCl₃): 62.8 (CH₂); 32.7 (CH₂); 30.9 (CH₂); 10.6 (CH); 4.4 (CH₂).

(2,3-Dihydro-1H-inden-2-yl)methanol (6h). GP G starting from 19 afforded 6h in 89% yield. Colorless oil.

IR (film): 3600 3100, 2933, 2846, 1482, 1034, 741. ¹H-NMR (300 MHz, CDCl₃): 7.20 7.05 (m, 4 H); 3.61 (d, J

6.4, 2 H); 3.10 2.91 (m, 2 H); 2.76 2.60 (m, 3 H). ¹³C-NMR (75.5 MHz, CDCl₃): 142.6 (arom. C_q); 126.2, 124.6

(arom. CH); 66.5 (CH₂); 41.4 (CH); 35.7 (2 CH₂). EI-MS: 148 (52, M ), 131 (95), 115 (100), 91 (21, PhCH₂).

Anal. calc. for C₁₀H₁₂O (148.20): C 81.04, H 8.16; found: C 81.03, H 7.91.

trans-[4-(tert-Butyl)cyclohexyl]methanol (6j). GP G starting from 17 afforded 6j in 91% yield. Colorless

oil. IR (film): 3600 3100, 2941, 2865, 1596, 1364, 1034. ¹H-NMR (300 MHz, CDCl₃): 3.42 (d, J 6.0, 2 H);

1.83 1.77 (m, 4 H, OH); 1.47 1.31 (m, 2 H); 0.82 (s, t-Bu); 1.04 0.80 (m, 4 H). ¹³C-NMR (75.5 MHz, CDCl₃):

68.8 (CH₂); 48.2 (CH); 40.6 (CH); 29.9 (2 CH₂); 27.6 (Me₃C); 26.7 (2 CH₂). EI-MS: 170 (1, M ), 137 (7), 113

(52), 95 (88), 81 (36), 67 (11), 57 (100), 41 (46). Anal. calc. for C₁₁H₂₂O (170.29): C 77.58, H 13.02; found:

C 77.59, H 13.10.

3,4,5,6-Tetrahydro-4(hydroxymethyl)-2H-pyran (6k). GP G starting from 20 afforded 6k in 99% yield.

1

Colorless oil. H-NMR (300 MHz, DMSO): 4.49 (t, J 5.3, OH); 3.81 (dd, J 10.9, 3.8, 2 H); 3.30 3.18 (m,

4 H); 1.59 1.50 (m, 3 H); 1.20 1.08 (m, 2 H). ¹³C-NMR (75.5 MHz, DMSO): 66.9 (2 CH₂); 66.2 (CH₂); 37.6

(CH); 29.6 (2 CH₂). Anal. calc. for C₆H₁₂O₂(116.16): C 62.04, H 10.41; found: C 61.87, H 10.52.

{1-[(4-Methylphenyl)sulfonyl]piperidin-4-yl}methanol (6l). GP G starting from 21 afforded 6l in 93% yield.

Colorless solid. M.p. 110 1128. IR (KBr): 3556, 2943, 2917, 2858, 1596, 1331, 1158, 1094, 1028, 929, 908, 819, 728.

¹H-NMR (300 MHz, CDCl₃): 7.55 (d, J 8.3, 2 H); 7.24 (d, J 8.3, 2 H); 3.71 (d, J 11.7, 2 H); 3.37 (d, J 6.0,

2 H); 2.35 (s, 3 H); 2.22 2.10 (m, 2 H); 1.70 (d, J 11.7, 2 H); 1.42 1.16 (m, 3 H). ¹³C-NMR (75.5 MHz,

CDCl₃): 143.4, 133.1 (arom. C_q); 129.6, 127.6 (arom. CH); 67.0 (CH₂); 46.0 (2 CH₂); 37.8 (CH); 28.0 (2 CH₂); 21.5

(Me). EI-MS: 155 (11, Ts ), 114 (100), 96 (22), 91 (53, PhCH₂), 65 (27), 55 (20), 42 (40), 31 (44). Anal. calc. for

C₁₃H₁₉NO₃S (269.36): C 57.97, H 7.11, N 5.20, S 11.90; found: C 58.04, H 7.06, N 5.09, S 11.91.

Helvetica Chimica Acta Vol. 86 (2003)

889

(Cyclopropyl)(phenyl)methanone (11a). GP H starting from 3a afforded 11a in 87% yield. Colorless oil.

¹H-NMR (300 MHz, CDCl₃): 8.04 8.00 (m, 2 H); 7.56 7.44 (m, 3 H); 2.67 (m, 1 H); 1.28 1.20 (m, 2 H); 1.10

1.00 (m, 2 H). ¹³C-NMR (75.5 MHz, CDCl₃): 200.6 (CO); 137.9 (arom. C_q); 132.6, 128.4, 127.9 (arom. CH);

17.1 (CH); 11.6 (2 CH₂). IR (film): 1667, 1148, 1385, 1225, 992, 706. EI-MS: 146 (17, M ), 105 (100, PhCO ), 77

(67, Ph ), 51 (37), 41 (16), 39 (25). Anal. calc. for C₁₀H₁₀O (164.19): C 82.16, H 6.89; found: C 81.96, H 6.93.

trans-(2-Methylcyclopropyl)(phenyl)methanone (11b). GP H starting from 3b afforded 11b in 63% yield

and 15 in 16% yield (separated by FCC); starting from 3c afforded 11b in 90% yield.

Data of 11b: Colorless oil. IR (film): 1665, 1448, 1402, 1222, 699. ¹H-NMR (300 MHz, CDCl₃): 8.03 7.99

(m, 2 H); 7.57 7.45 (m, 3 H); 2.45 2.38 (m, 1 H); 1.67 1.56 (m, 1 H); 1.54 1.47 (m, 1 H); 1.23 (d, J 5.9,

3 H); 0.94 0.87 (m, 1 H). ¹³C-NMR (75.5 MHz, CDCl₃): 200.0 (CO); 138.0 (arom. C_q); 132.5, 128.4, 127.9

(arom. CH); 26.3 (CH); 21.2 (CH); 20.0 (CH₂); 18.2 (Me). EI-MS: 160 (15, M ), 105 (100, PhCO ), 77 (49,

Ph ), 57 (19), 55 (19), 51 (19), 43 (21). Anal. calc. for C₁₁H₁₂O (160.21): C 82.46, H 7.55; found: C 81.78, H 7.54.

1

1-Phenylpent-4-en-1-one (15). Colorless oil. H-NMR (300 MHz, CDCl₃): 8.00 7.96 (m, 2 H); 7.57 7.42

(m, 3 H); 5.98 5.83 (m, 1 H); 5.13 4.98 (m, 2 H); 3.10 3.04 (m, 2 H); 2.54 2.45 (m, 2 H). ¹³C-NMR

(75.5 MHz, CDCl₃): 199.4 (CO), 137.2 (CH), 136.9 (arom. C_q), 132.9, 128.5, 128.0 (arom. CH); 115.2 (CH₂);

37.7 (CH₂); 28.1 (CH₂).

(2-Methylcylopropyl)(phenyl)methanone (11c). GP H starting from 3d afforded cis-11c in 49% yield and

trans-11c in 29% yield; starting from 3g, cis-11c in 28% yield and trans-11c in 16 % yield were obtained.

Separation by FCC.

Data of cis-11c: Colorless solid. M.p. 67 698. IR (KBr): 1661, 1448, 1390, 1217, 1004, 710. ¹H-NMR

(300 MHz, CDCl₃): 7.93 7.88 (m, 2 H); 7.54 7.47 (m, 1 H); 7.44 7.37 (m, 2 H); 7.22 7.08 (m, 5 H); 3.14 3.06

(m, 1 H); 2.94 2.84 (m, 1 H); 2.17 2.08 (m, 1 H); 1.50 1.42 (m, 1 H). ¹³C-NMR (75.5 MHz, CDCl₃): 196.1

(CO); 138.6, 135.9 (arom. C_q); 132.5, 129.0, 128.4, 128.0, 127.9, 126.6 (arom. CH); 29.5 (CH); 27.0 (CH); 11.6

(CH₂). EI-MS: 222 (7, M ), 115 (34), 105 (100, PhCO ), 77 (86, Ph ), 51 (38). Anal. calc. for C₁₆H₁₄O (222.28):

C 86.45, H 6.35; found: C 85.97, H 6.52.

Data of trans-11c: Colorless solid. M.p. 45 478. IR (film): 1666, 1448, 1397, 1223, 1024, 697. ¹H-NMR

(300 MHz, CDCl₃): 8.01 7.97 (m, 2 H); 7.59 7.52 (m, 1 H); 7.49 7.41 (m, 2 H); 7.35 7.16 (m, 5 H); 2.94 2.87

(m, 1 H); 2.74 2.67 (m, 1 H); 1.96 1.89 (m, 1 H); 1.59 1.52 (m, 1 H). ¹³C-NMR (75.5 MHz, CDCl₃): 198.5

(CO); 140.5, 137.7 (arom. C_q); 132.9, 128.6, 128.1, 126.6, 126.2 (arom. CH); 30.0 (CH); 29.3 (CH); 19.2 (CH₂).

EI-MS: 222 (6, M ), 115 (31), 105 (100, PhCO ), 77 (94, Ph ), 51 (45). Anal. calc. for C₁₆H₁₄O (222.28):

C 86.45, H 6.35; found: C 85.72, H 6.36.

trans-2-Benzoylcyclopropanecarbonitrile (11d). GP H starting from 3e afforded 11d in 65% yield. Colorless

1

oil. H-NMR (300 MHz, CDCl₃): 8.05 8.00 (m, 2 H); 7.69 7.62 (m, 1 H); 7.57 7.50 (m, 2 H); 3.31 3.24 (m,

1 H); 2.20 2.13 (m, 1 H); 1.72 1.60 (m, 2 H). ¹³C-NMR (75.5 MHz, CDCl₃): 195.0 (CO); 136.2 (arom. C_q);

134.0, 128.9, 128.3 (arom. CH); 119.8 (C_q); 24.0 (CH); 16.8 (CH₂); 7.3 (CH). EI-MS: 171 (16, M ), 105 (100,

PhCO ), 77 (46, Ph ), 51 (20). HR-EI-MS: 171.19528 (C₁₁H₉NO; calc. 171.19530).

(2-Benzyloxycylopropyl)(phenyl)methanone (11e). GP H starting from 3f failed, because FCC (silica gel)

caused decomposition of the product. Therefore, 3f (13.9 mg, 0.04 mmol) and 1-methyl-1H-imidazole (9.85 mg,

0.12 mmol) were irradiated in CD₂Cl₂(0.7 ml) in a NMR tube (conditions: 500-W high-pressure Hg-arc lamp

(OSRAM HBO-500), filter WG 295 (Schott)). The yield was determined via ¹H-NMR by adding benzoine

(0.04 mmol) after irradiation. Yield: 46%. ¹H-NMR (300 MHz, CD₂Cl₂): 7.99 7.15 (m, 10 H), 4.61 (d, J 7.2,

2 H); 3.77 3.71 (m, 1 H); 2.89 2.83 (m, 1 H); 1.63 1.57 (m, 1 H); 1.52 1.45 (m, 1 H). ¹³C-NMR (75.5 MHz,

CD₂Cl₂): 195.2 (CO); 137.5, 133.2 (arom. C_q); 134.0, 128.7, 128.5, 128.2, 127.7 (arom. CH); 73.2 (CH₂); 64.5

(CH); 26.3 (CH); 18.1 (CH₂).

(2-Ethenylcyclopropyl)(phenyl)methanone (11f). GP H starting from 3h afforded 11f as an inseparable cis/

trans mixture (50 :50) in 80% yield. Colorless oil. IR (film): 1665, 1448, 1383, 1223, 1018, 701. ¹H-NMR

(300 MHz, CDCl₃): 8.02 7.95 (m, 4 H); 7.60 7.42 (m, 6 H); 5.73 5.47 (m, 2 H); 5.26 5.23 (m, 1 H); 5.20 5.17

(m, 1 H); 5.05 (dd, J 10.2, 1.5, 1 H (trans)); 4.98 (dd, J 10.0, 1.9, 1 H (cis)); 3.00 2.91 (m, 1 H (cis)); 2.73-

2.66 (m, 1 H (trans)); 2.31 2.14 (m, 2 H); 1.74 1.65 (m, 2 H); 1.36 1.28 (m, 1 H (cis)); 1.24 1.15 (m, 1 H

(trans)). ¹³C-NMR (75.5 MHz, CDCl₃): 198.6, 197.5 (CO); 138.4 (olef. CH (cis)); 137.8 (arom. C_q); 134.9 (olef.

CH (trans)); 132.8, 132.6, 128.5, 128.4, 128.0 (arom. CH); 116.1 (olef. CH₂(cis)); 115.0 (olef. CH₂(trans)); 29.4

(CH (trans)); 28.5 (CH (cis)); 26.6 (CH (trans)); 25.8 (CH (cis)); 18.1 (CH₂(trans)); 14.2 (CH₂(cis)). EI-MS:

171 (2, [M À 1] ); 105 (100, PhCO ), 77 (43, Ph ), 51 (17). Anal. calc. for C₁₂H₁₂O (172.22): C 83.69, H 7.02;

found: C 83.32, H 6.96.

(Phenyl)[2-(phenylethenyl)cyclopropyl]methanone (11g). GP H starting from 3i afforded cis-11g in 20%

yield, trans-11g in 14% yield and 3i in 42% yield (separated by FCC).

890

Helvetica Chimica Acta Vol. 86 (2003)

Data of cis-11g: Colorless oil. ¹H-NMR (300 MHz, CDCl₃): 8.01 7.96 (m, 2 H); 7.54 7.47 (m, 1 H); 7.45

7.38 (m, 2 H); 7.23 7.17 (m, 2 H); 7.16 7.10 (m, 3 H); 3.00 2.91 (m, 1 H); 2.24 2.15 (m, 1 H); 1.85 1.78 (m,

1 H); 1.37 1.29 (m, 1 H). ¹³C-NMR (75.5 MHz, CDCl₃): 195.0 (CO); 138.1, 123.2 (arom. C_q); 132.8, 131.8,

128.5, 128.2, 128.0, 127.7 (arom. CH); 87.0, 80.0 (C_q); 25.5 (CH); 14.7 (CH₂); 12.7 (CH). EI-MS: 246 (26, M ),

230 (10), 165 (4), 128 (15), 105 (100, PhCO ), 91 (20, PhCH₂), 77 (48, Ph ), 51 (16). HR-EI-MS: 246.10446

(C₁₄H₁₈O; calc. 246.10447).

Data of trans-11g: Colorless oil. ¹H-NMR (300 MHz, CDCl₃): 8.02 7.96 (m, 2 H); 7.57 7.50 (m, 1 H),

7.48 7.40 (m, 2 H); 7.37 7.31 (m, 2 H); 7.25 7.20 (m, 3 H); 3.04 2.96 (m, 1 H); 2.22 2.14 (m, 1 H); 1.73 1.65

(m, 1 H); 1.45 1.38 (m, 1 H). ¹³C-NMR (75.5 MHz, CDCl₃): 197.6 (CO); 139.9, 123.1 (arom. C_q); 133.2, 131.7,

128.6, 128.3, 128.2, 128.0 (arom. CH); 90.1, 78.0 (C_q); 27.2 (CH); 19.8 (CH₂); 14.1 (CH). EI-MS: 246 (9, M ),

230 (5), 165 (23), 147 (52), 128 (19), 105 (100, PhCO ), 91 (34, PhCH₂), 77 (38, Ph ), 51 (16). HR-EI-MS:

246.10442 (C₁₄H₁₈O; calc. 246.10447).

(2-Cyclopropylcyclopropyl)(phenyl)methanone (11h). GP H starting from 3j afforded 11h as an

inseparable cis/trans-mixture (15 :85) in 68% yield. Colorless oil.

Data of trans-11h: ¹H-NMR (300 MHz, CDCl₃): 7.97 7.91 (m, 2 H); 7.53 7.45 (m, 1 H); 7.44 7.36 (m,

2 H); 2.47 2.40 (m, 1 H); 1.60 1.50 (m, 1 H); 1.39 1.32 (m, 1 H); 0.90 0.79 (m, 2 H); 0.46 0.36 (m, 2 H);

0.17 0.11 (m, 2 H). ¹³C-NMR (75.5 MHz, CDCl₃): 199.8 (CO); 139.0 (arom. C_q); 132.6, 128.5, 128.0 (arom.

CH); 29.3 (CH); 24.5 (CH); 16.5 (CH₂); 12.2 (CH); 4.1 (CH₂); 2.8 (CH₂). EI-MS: 186 (9, M ), 157 (13), 105

(100, PhCO ), 77 (50, Ph ), 51 (14). HR-EI-MS: 186.10443 (C₁₃H₁₄O; calc. 186.10447).

Data of cis-11h: ¹H-NMR (300 MHz, CDCl₃): 7.97 7.91 (m, 2 H); 7.53 7.45 (m, 1 H); 7.44 7.36 (m, 2 H);

2.69 2.60 (m, 1 H); 1.53 1.44 (m, 1 H); 1.10 1.00 (m, 2 H); 0.75 0.59 (m, 1 H); 0.49 0.39 (m, 2 H); 0.25

0.20 (m, 1 H); 0.06 (À0.02) (m, 1 H). ¹³C-NMR (75.5 MHz, CDCl₃): 198.9 (CO); 138.0 (arom. C_q); 132.4,

128.4, 128.0 (arom. CH); 29.8 (CH); 24.3 (CH); 13.3 (CH₂); 8.4 (CH); 4.9 (CH₂); 4.5 (CH₂). EI-MS: 186 (10,

M ), 157 (15), 105 (100, PhCO ), 77 (50, Ph ), 51 (14). HR-EI-MS: 186.10439 (C₁₃H₁₄O; calc. 186.10447).

exo-(Bicyclo[2.1.0]pent-5-yl)(phenyl)methanone (11i). GP H starting from 3k afforded 11i in 61% yield

and 16 in 9% yield (separated by FCC).

Data of 11i: Colorless oil. IR (film): 1664, 1448, 1399, 1372, 1224, 699. ¹H-NMR (300 MHz, CDCl₃): 8.07

8.03 (m, 2 H); 7.63 7.50 (m, 3 H); 2.89 (s, 1 H); 2.40 2.34 (m, 2 H); 2.27 (s, 2 H); 1.72 (d, J 7.9, 2 H).

¹³C-NMR (75.5 MHz, CDCl₃): 199.2 (CO); 138.1 (arom. C_q); 132.5, 128.3, 127.9 (arom. CH); 35.9 (CH); 30.2

(2 CH); 24.3 (2 CH₂). EI-MS: 172 (5, M ), 144 (10), 105 (100, PhCO ), 67 (13), 51 (18), 39 (14). HR-EI-MS:

172.08852 (C₁₂H₁₂O; calc. 172.08881). Anal. calc. for C₁₂H₁₂O (172.22): C 83.69, H 7.02; found: C 83.10, H 7.20.

3-Cyclopropyl-1-phenylprop-2-enone (16). Colorless oil. IR (film): 1664, 1609, 1447, 1379, 1271, 938, 698.

¹H-NMR (300 MHz, CDCl₃): 7.97 7.91 (m, 2 H); 7.57 7.42 (m, 3 H); 7.25 (d, J 15.1, 1 H); 6.55 (dd, J 10.2,

1 H); 1.79 1.64 (m, 1 H); 1.08 1.00 (m, 2 H); 0.78 0.70 (m, 2 H). ¹³C-NMR (75.5 MHz, CDCl₃): 189.9

(CO); 155.3 (CH); 138.1 (arom. C_q); 132.4, 128.4, 128.3 (arom. CH); 122.8 (CH); 15.4 (CH); 9.2 (2 CH₂). EI-

MS: 172 (23, M ), 105 (100, PhCO ), 77 (86, Ph ), 51 (41), 39 (33). HR-EI-MS: 172.08849 (C₁₂H₁₂O; calc.

172.08881). Anal. calc. for C₁₂H₁₂O (172.22): C 83.69, H 7.02; found: C 82.96, H 7.13.

exo-(Bicyclo[3.1.0]hex-6-yl)(phenyl)methanone (11j). GP H starting from 3l afforded 11j in 80% yield.

Colorless crystals. M.p. 59 618. IR (KBr): 1656, 1450, 1405, 1389, 1234, 687. ¹H-NMR (300 MHz, CDCl₃): 7.99

7.91 (m, 2 H); 7.57 7.41 (m, 3 H); 2.47 (t, J 3.0, 1 H); 2.17 2.10 (m, 2 H); 2.00 1.66 (m, 5 H); 1.36 1.19 (m,

1 H). ¹³C-NMR (75.5 MHz, CDCl₃): 199.8 (CO); 138.2 (arom. C_q); 132.4, 128.3, 127.9 (arom. CH); 32.8 (2

CH); 27.5 (2 CH₂); 26.6 (CH); 20.6 (CH₂). EI-MS: 186 (100, M ), 158 (72), 77 (79, Ph ), 51 (89), 39 (75). HR-

EI-MS: 186.10451 (C₁₃H₁₄O; calc. 186.10447). Anal. calc. for C₁₃H₁₄O (186.25): C 83.83, H 7.58; found: C 83.45,

H 7.34.

(Phenyl)[(1SR,1aRS,6aSR)-1,1a,6,6a-Tetrahydrocyclopropa[a]indene-1-yl]methanone (11k). GP H start-

ing from 3m afforded exo-11k in 62% yield and endo-11k in 16% yield (separated by FCC).

Data of exo-11k: Colorless crystals. M.p. 148 1498. IR (KBr): 1647, 1384, 1375, 1229, 1021, 757, 694.

¹H-NMR (300 MHz, CDCl₃): 7.88 7.83 (m, 2 H); 7.49 7.42 (m, 1 H); 7.38 7.25 (m, 3 H); 7.18 7.06 (m, 3 H);

3.33 3.23 (m, 1 H); 3.13 3.02 (m, 2 H); 2.67 2.59 (m, 1 H); 2.19 2.16 (m, 1 H). ¹³C-NMR (75.5 MHz,

CDCl₃): 198.2 (CO); 144.2, 142.2, 137.6 (arom. C_q); 132.8, 128.5, 128.0, 126.4, 125.3, 123.9 (arom. CH); 38.3

(CH); 35.9 (CH); 35.8 (CH₂); 30.0 (CH). EI-MS: 234 (33, M ), 129 (43), 105 (100, PhCO ), 77 (41, Ph ), 51

(10). Anal. calc. for C₁₇H₁₄O (234.29): C 87.15, H 6.02; found: C 87.38, H 5.99.

Data of endo-11k: Colorless crystals. M.p. 70 728. IR (KBr): 1666, 1448, 1399, 1231, 1220, 990, 760, 723,

1

712, 687. H-NMR (300 MHz, CDCl₃): 7.83 7.78 (m, 2 H); 7.43 7.36 (m, 1 H); 7.33 7.25 (m, 2 H); 7.09 7.03

(m, 2 H); 7.01 6.94 (m, 1 H); 6.92 6.84 (m, 1 H); 3.55 3.46 (m, 1 H); 3.19 3.08 (m, 2 H); 2.61 (t, J 8.3,

1 H); 2.42 2.34 (m, 1 H). ¹³C-NMR (75.5 MHz, CDCl₃): 196.7 (CO); 144.0, 139.7, 138.1 (arom. C_q); 132.5,

Helvetica Chimica Acta Vol. 86 (2003)

891

128.2, 127.9, 126.4, 125.9, 124.6, 124.2 (arom. CH); 33.7 (CH); 32.4 (CH₂); 28.4 (CH); 24.4 (CH). EI-MS: 234

(30, M ), 129 (51), 105 (100, PhCO ), 77 (39, Ph ), 51 (12). Anal. calc. for C₁₇H₁₄O (234.29): C 87.15, H 6.02;

found: C 87.26, H 6.17.

exo-(Bicyclo[4.1.0]hept-7-yl)(phenyl)methanone (11l). GP H starting from 3n afforded 11l in 86% yield.

Colorless oil. IR (film): 1662, 1447, 1414, 1220, 693. ¹H-NMR (300 MHz, CDCl₃): 7.99 7.91 (m, 2 H); 7.52 7.39

(m, 3 H); 2.45 (t, J 4.0, 1 H); 2.05 1.86 (m, 4 H); 1.82 1.66 (m, 2 H); 1.42 1.21 (m, 4 H). ¹³C-NMR

(75.5 MHz, CDCl₃): 199.7 (CO); 138.0 (arom. C_q); 132.1, 128.1, 127.5 (arom. CH); 31.1 (CH); 26.3 (2 CH);

22.9 (2 CH₂); 20.8 (2 CH₂). EI-MS: 200 (78, M ), 105 (100, PhCO ), 77 (77, Ph ), 51 (25). HR-EI-MS:

200.12008 (C₁₄H₁₆O; calc. 200.12012). Anal. calc. for C₁₄H₁₆O (200.28): C 83.96, H 8.05; found: C 83.64, H 8.18.

(1SR,3SR,6RS,7RS)-[3-(tert-Butyl)bicyclo[4.1.0.]hept-7-yl](phenyl)methanone (11m). GP H starting

from 3o afforded 11m in 79% yield. Colorless oil. ¹H-NMR (300 MHz, CDCl₃): 7.93 7.87 (m, 2 H); 7.52

7.45 (m, 1 H); 7.44 7.37 (m, 2 H); 2.34 (t, J 4.1, 1 H); 2.27 2.17 (m, 1 H); 2.04 1.90 (m, 2 H); 1.88 1.80 (m,

1 H); 1.55 1.42 (m, 3 H); 0.88 0.79 (m, 2 H); 0.78 (s, 9 H). ¹³C-NMR (75.5 MHz, CDCl₃): 196.0 (CO); 138.2

(arom. C_q); 132.4, 128.4, 127.9 (arom. CH); 42.2 (CH); 32.3 (C_q); 32.1 (CH); 29.4 (CH); 27.3 (3 Me); 26.5 (CH);

25.2 (CH₂); 24.4 (CH₂); 24.3 (CH₂). EI-MS: 256 (23, M ), 199 (23), 157 (33), 136 (38), 121 (34), 105 (100,

PhCO ), 77 (49, Ph ), 57 (37). HR-EI-MS: 256.18267 (C₁₈H₂₄O; calc. 256.18272).

(Phenyl)(exo-1a,2,4,5-tetrahydro-1H,5aH-cyclopropa[c]pyran-1-yl)methanone (11n). GP H starting from

3p afforded 11n in 74% yield. Colorless needles. M.p. 31 338. ¹H-NMR (300 MHz, CDCl₃): 7.98 7.91 (m, 2 H);

7.53 7.46 (m, 1 H); 7.45 7.37 (m, 2 H); 3.98 (d, J 11.7, 1 H); 3.81 (dd, J 11.9, 3.2, 1 H); 3.73 3.61 (m, 1 H);

3.30 3.16 (m, 1 H); 2.70 (t, J 4.1, 1 H); 2.05 1.86 (m, 3 H); 1.85 1.75 (m, 1 H). ¹³C-NMR (75.5 MHz,

CDCl₃): 199.5 (CO); 137.8 (arom. C_q); 132.7, 128.5, 128.0 (arom. CH); 65.0 (CH₂); 64.3 (CH₂); 30.4 (CH); 25.2

(CH); 22.9 (CH₂); 22.7 (CH). EI-MS: 202 (16, M ), 157 (63), 144 (27), 105 (100, PhCO ), 77 (64, Ph ), 51 (22).

HR-EI-MS: 202.09938 (C₁₃H₁₄O₂; calc. 202.09938).

(Phenyl){exo-1a,2,4,5-tetrahydro-3-[(4-methylphenyl)sulfonyl]-1H,5H-cyclopropa[c]pyridin-1-yl}methane

(11o). GP H starting from 3q afforded 11o in 78% yield. Colorless oil. ¹H-NMR (300 MHz, CDCl₃): 7.94 7.88

(m, 2 H); 7.61 7.48 (m, 3 H); 7.45 7.38 (m, 2 H); 7.30 7.24 (m, 2 H); 3.79 (d, J 11.6, 1 H); 3.50 3.40 (m,

1 H); 2.82 (dd, J 11.9, 3.6, 1 H); 2.71 (t, J 4.3, 1 H); 2.37 (s, 3 H); 2.27 (dt, J 11.5, 5.3, 1 H); 2.12 1.80 (m,

4 H). ¹³C-NMR (75.5 MHz, CDCl₃): 199.1 (CO); 143.7, 137.4, 133.3 (arom. C_q); 133.0, 129.8, 128.6, 128.3, 127.6

(arom. CH); 44.2 (CH₂); 43.1 (CH₂); 29.5 (CH); 25.0 (CH); 23.2 (CH₂); 22.2 (CH); 21.5 (Me). EI-MS: 355 (1,

M ), 200 (100), 171 (14), 155 (18, Ts ), 105 (94, PhCO ), 91 (47, PhCH₂), 77 (33, Ph ), 51 (7). HR-EI-MS:

355.12414 (C₂₀H₂₁NO₃S; calc. 355.12421).

{exo-3-[(tert-Butoxy)carbonyl]-1a,2,4,5-tetrahydro-1H,5aH-cyclopropa[c]pyridin-1-yl}(phenyl)metha-

none (11p). GP H starting from 3r afforded 11p in 69% yield. Colorless oil. ¹H-NMR (300 MHz, CDCl₃): 7.88

7.82 (m, 2 H); 7.64 7.55 (m, 1 H); 7.51 7.42 (m, 2 H); 3.83 (d, J 11.2, 1 H); 3.50 3.40 (m, 1 H); 2.93 2.81 (m,

1 H); 2.67 (t, J 4.8, 1 H); 2.32 2.23 (m, 1 H); 2.15 1.82 (m, 4 H); 1.35 (s, 9 H). ¹³C-NMR (75.5 MHz, CDCl₃):

201.5, 154.6 (CO); 133.8 (arom. C_q); 134.2, 129.1, 128.7 (arom. CH); 80.1 (C_q); 42.8 (br., CH₂); 41.7 (br., CH₂);

32.5 (CH); 28.6 (CH₂); 28.4 (3 Me); 27.5 (CH); 23.2 (CH). EI-MS: 301 (1, M ), 245 (16), 200 (15), 159 (16), 125

(20), 105 (57, PhCO ), 77 (40, Ph ), 57 (100), 51 (13). HR-EI-MS: 301.16783 (C₁₈H₂₃NO₃; calc. 301.16779).

trans-Methyl 2-Benzoylcyclopropane-1-carboxylate (11q). GP H starting from 5a afforded 11q in 59%

1

yield. Colorless oil. IR (film): 1732, 1673, 1445, 1337, 1209, 1173, 711. H-NMR (300 MHz, CDCl₃): 8.04 8.00

(m, 2 H); 7.63 7.57 (m, 1 H); 7.52 7.46 (m, 2 H); 3.74 (s, 3 H); 3.24 3.17 (m, 1 H); 2.43 2.36 (m, 1 H); 1.68

1.57 (m, 2 H). ¹³C-NMR (75.5 MHz, CDCl₃): 197.0, 172.8 (CO); 137.0 (arom. C_q); 133.4, 128.7, 128.3 (arom.

CH); 52.2 (Me); 26.0 (CH); 24.4 (CH); 17.9 (CH₂). EI-MS: 204 (4, M ), 149 (37), 105 (100, PhCO ), 77 (59,

Ph ), 71 (24), 57 (32), 55 (23), 43 (28), 41 (26). Anal. calc. for C₁₂H₁₂O₃(204.22): C 70.57, H 5.92; found:

C 69.92, H 5.94.

Methyl (1SR,2SR,3RS)-2-Benzoyl-3-phenylcyclopropane-1-carboxylate (11r). GP H starting from 5b

afforded 11r in 37% yield. Colorless solid. M.p. 64 668. ¹H-NMR (300 MHz, CDCl₃): 7.96 7.92 (m, 2 H); 7.58

7.13 (m, 8 H); 3.79 (s, 3 H); 3.61 3.55 (m, 1 H); 3.39 3.32 (m, 1 H); 3.27 3.22 (m, 1 H). ¹³C-NMR (75.5 MHz,

CDCl₃): 193.2, 172.7 (CO); 137.5, 133.6 (arom. C_q); 133.2, 128.9, 128.8, 128.6, 128.2, 128.1, 127.3 (arom. CH);

52.4 (Me); 35.9 (CH); 35.0 (CH); 25.7 (CH). NMR Data: identical to those reported in [36].

1-[(4-Methylphenyl)sulfonyl]piperidine-4-carboxylic Acid (21). To a stirred soln. of 18 (10.0 g, 77.4 mmol)

and 25 ml of 2n NaOH was added TsCl (16.2 g, 85.2 mmol). After 24 h, the mixture was washed with Et₂O (3 Â

15 ml), acidified to pH 1, and extracted with CH₂Cl₂(4 Â 20 ml). The combined org. extracts were dried

(MgSO₄) and concentrated under reduced pressure. Colorless solid (11.4 g, 52%). ¹H-NMR (300 MHz, CDCl₃):

7.66 7.61 (m, 2 H); 7.35 7.30 (m, 2 H); 3.68 3.62 (m, 2 H); 2.44 (s, 3 H); 2.50 2.40 (m, 2 H); 2.33 2.24 (m,

892

Helvetica Chimica Acta Vol. 86 (2003)

1 H); 2.03 1.96 (m, 2 H); 1.89 1.79 (m, 2 H). ¹³C-NMR (75.5 MHz, CDCl₃): 179.6 (CO); 143.7, 132.9 (arom.

C_q); 129.7, 127.7 (arom. CH); 45.3 (2 CH₂); 39.7 (CH); 27.2 (2 CH₂); 21.5 (Me).

REFERENCES

[1] a) Methoden Org. Chem. (Houben-Weyl),Vol. IV/4, Eds. S. Beckmann, H. Geiger, 1971, p. 445, b) Methods

Org. Chem. (Houben-Weyl), Vol. E17, Eds. A. De Meijere, E. Schaumann, Thieme, Stuttgart, 1997.

[2] a) H. E. Simmons, R. D. Smith, J. Am. Chem. Soc. 1958, 80, 5323; b) H. E. Simmons, R. D. Smith, J. Am.

Chem. Soc. 1959, 81, 4256; H. E. Simmons, T. L. Cairns, S. A. Vladuchick, C. M. Hoiness, Org. React. 1973,

20, 1; c) J. Furukawa, N. Kawabata, J. Nishimura, Tetrahedron Lett. 1966, 7, 3353.

[3] a) W. E. v. Doering, W. R. Roth, Tetrahedron 1963, 19, 715; b) S. Bien, Y. Segal, J. Org. Chem. 1977, 42,

1685; c) R. Paulissen, A. J. Hubert, P. Teyssie, Tetrahedron Lett. 1972, 1465, d) M. P. Doyle, J. G. Davidson,

J. Org. Chem. 1980, 45, 1538.

[4] H. Shapiro, J. H. Duncan, J. C. Clopton, J. Am. Chem. Soc. 1967, 89, 1442; Z. Majerski, Z. Hamersak, R.

Sarac-Arneri, J. Org. Chem. 1988, 53, 5053; J. P. Freeman, J. Org. Chem. 1963, 28, 2385; C. G. Overberger,

N. R. Byrd, R. B. Mesrobian, J. Am. Chem. Soc. 1956, 78, 1961.

[5] a) P. J. Wagner, Acc. Chem. Res. 1971, 4, 168; b) P. J. Wagner, Top. Curr. Chem. 1976, 66, 1; c) P. J. Wagner,

Acc. Chem. Res. 1989, 22, 83; d) P. J. Wagner, B.-S. Park, in −Organic Photochemistry×, Ed. A. Padwa,

Marcel Dekker Inc., New York-Basel, 1991, 227; e) P. J. Wagner, in −CRC Handbook of Organic

Photochemistry and Photobiology×, Eds. W. M. Horspool and P. S. Song, CRC Press, Boca Raton, New

York, London, Tokyo, 1995, 449.

[6] a) H. J. Roth, M. H. ElRaie, T. Schrauth, Arch. Pharm. 1974, 307, 584; b) A. Abdul-Baki, F. Rotter, T.

Schrauth, H. J. Roth, Arch. Pharm. 1978, 311, 341; c) H. J. Roth, H. George, Arch. Pharm. 1970, 303, 725;

d) W. Weigel, S. Schiller, H.-G. Henning, Tetrahedron 1997, 53, 7855; e) H. Zimmerman, J. Nuss, A.

Tantillo, J. Org. Chem. 1988, 53, 3792. f) M. Yoshioka, S. Miyazoe, T. Hasegawa, J. Chem. Soc., Perkin

Trans. 1 1993, 2781.

[7] P. Wessig, O. M¸hling, Angew. Chem., Int. Ed. 2001, 40, 1064.

[8] P. J. Wagner, K. Liu, Y. Noguchi, J. Am. Chem. Soc. 1981, 103, 3837.

[9] a) G. F. Koser, A. G. Relenyi, A. N. Kalos, L. Rebrovic, R. H. Wettach, J. Org. Chem. 1982, 47, 2487, and

refs. cit. therein; b) J. S. Lodaya, G. F. Koser, J. Org. Chem. 1988, 53, 210.

[10] a) A. F. Ferris, K. W. McLean, I. G. Marks, W. D. Emmons, J. Am. Chem. Soc. 1953, 75, 4078; b) D. N.

Kevill, N. H. Cromwell, J. Org. Chem. 1964, 29, 499.

[11] W. D. Emmons, J. P. Freeman, J. Am. Chem. Soc. 1955, 77, 4415.

[12] a) S. H¸nig, C. Marschner, Chem. Ber. 1989, 122, 1329; b) S. H¸nig, C. Marschner, Chem.Ber. 1990, 123, 107.

[13] a) D. Seebach, E. J. Corey, J. Org. Chem. 1975, 40, 231; b) B.-T. Grˆbel, D. Seebach, Synthesis 1977, 357.

[14] X. Creary, J. Org. Chem. 1980, 45, 2419.

[15] A. P. Krapcho, Synthesis 1982, 10, 805.

[16] a) M. Yamaguchi, Y. Nobayashi, I. Hirao, Tetrahedron Lett. 1983, 24, 5121; b) M. Yamaguchi, Y.

Nobayashi, I. Hirao, Tetrahedron 1984, 40, 4261.

[17] U. Lindemann, D. Wulff-Molder, P. Wessig, J. Photochem. Photobiol. A: Chemistry 1998, 119, 73.

[18] S. Feyter, E. Diau, A. Zewail, Angew. Chem. 2000, 112, 266.

[19] L. J. Johnston, J. C. Scaiano, Chem. Rev. 1989, 89, 521.

[20] a) G. Koltzenburg, G. Behrens, D. Schulte-Frohlinde, J. Am. Chem. Soc. 1982, 104, 7311; b) G. Koltzenburg,

D. Schulte-Frohlinde, Z. Naturforsch., C 1982, 37, 1205.

[21] S. G. Cohen, H. M. J. Chao, J. Am. Chem. Soc. 1968, 90, 165.

[22] P. Wessig, J. Schwarz, U. Lindemann, M. C. Holthausen, Synthesis 2001, 1258.

[23] a) L. J. Johnston, J. C. Scaiano, J. W. Sheppard, J. P. Bays, Chem. Phys. Lett. 1986, 124, 193; b) R. A.

Caldwell, S. C. Gupta, J. Am. Chem. Soc. 1989, 111, 740.

[24] a) G. W. Griffin, J. Covell, R. C. Petterson, R. M. Dodson, G. Klose, J. Am. Chem. Soc. 1965, 87, 1410;

b) H. E. Zimmerman, S. S. Hixson, E. F. McBridge, J. Am. Chem. Soc. 1970, 92, 2000; c) H. E. Zimmerman,

C. M. Moore, J. Am. Chem. Soc. 1970, 92, 2023; d) G. W. Griffin, E. J. O×Connell, H. A. Hammond, J. Am.

Chem. Soc. 1963, 85, 1001.

[25] J. I. Kravitz, P. Margaretha, W. C. Agosta, Tetrahedron Lett. 1991, 32, 31.

[26] M. Newcomb, S. Y. Choi, J. H. Horner, J. Org. Chem. 1999, 64, 1225.

[27] R. A. Caldwell, K. Mizuno, N. Ichinose, Y. Otsuji, J. Am. Chem. Soc. 1985, 107, 5797.

Helvetica Chimica Acta Vol. 86 (2003)

893

[28] P. J. Stang, B. W. Surber, Z.-C. Chen, K. A. Roberts, A. G. Anderson, J. Am. Chem. Soc. 1987, 109, 228.

[29] R. Somanathan, I. A. Rivero, A. Gama, A. Ochoa, G. Aguirre, Synth. Commun. 1998, 28, 2043.

[30] P. Peterli-Roth, M. P. Maguire, E. Leon, H. Rapoport, J. Org. Chem. 1994, 59, 4186.

[31] C. Mannich, G. Heilner, Chem. Ber. 1922, 55B, 365.

[32] T. Tomiyama, S. Wakabayashi, M. Yokota, J. Med. Chem. 1989, 32, 1988.

[33] C. Straessler, A. Linden, H. Heimgartner, Helv. Chim. Acta 1997, 80, 1528.

[34] Gaussian 98, Revision A.9, M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R.

Cheeseman, V. G. Zakrzewski, J. A. Montgomery Jr., R. E. Stratmann, J. C. Burant, S. Dapprich, J. M.

Millam, A. D. Daniels, K. N. Kudin, M. C. Strain, O. Farkas, J. Tomasi, V. Barone, M. Cossi, R. Cammi, B.

Mennucci, C. Pomelli, C. Adamo, S. Clifford, J. Ochterski, G. A. Petersson, P. Y. Ayala, Q. Cui, K.

Morokuma, D. K. Malick, A. D. Rabuck, K. Raghavachari, J. B. Foresman, J. Cioslowski, J. V. Ortiz, A. G.

Baboul, B. B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R. Gomperts, R. L. Martin, D. J.

Fox, T. Keith, M. A. Al-Laham, C. Y. Peng, A. Nanayakkara, M. Challacombe, P. M. W. Gill, B. Johnson,

W. Chen, M. W. Wong, J. L. Andres, C. Gonzalez, M. Head-Gordon, E. S. Replogle, and J. A. Pople,

Gaussian, Inc., Pittsburgh PA, 1998.

[35] a) A. D. Becke, J. Chem. Phys. 1993, 98, 5648; b) J. P. Perdew, J. A. Chevary, S. H. Vosko, K. A. Jackson,

M. R. Pederson, D. J. Singh, C. Fiolhais, Phys. Rev. 1992, B 46.

[36] B. Alcaide, L. Casarrubios, G. Dominguez, A. Retamosa, M. A. Sierra, Tetrahedron 1996, 52, 13215.

Received October 31, 2002

Article Doi

Photochemical synthesis of highly functionalized cyclopropyl ketones

DOI: 10.1002/hlca.200390086

Source and publish data:

Authors:

Article abstract of DOI:10.1002/hlca.200390086

Full text of DOI:10.1002/hlca.200390086

Products guided by the article

R&D Labs maybe for 582299-08-9

Relevant to this article

Hot Product