Scholarly article on 2-(diphenyl-phosphinoyl)-1-phenyl-prop-2-en-1-ol 862012-89-3 from Synthesis p. 1405

PAPER

1405

Titanocene-Mediated Intramolecular Radical Vinylations

R

adical Intramole

c

o

ular

V

inylat

m

ions inique Leca, Kai Song, Matthias Albert, Monica Grangeio Gonçalves, Louis Fensterbank,* Emmanuel Lacôte,*

Max Malacria*

Laboratoire de chimie organique (UMR CNRS 7611), Université Pierre et Marie Curie, 4 Place Jussieu, B. 229, 75005 Paris, France

Fax +33(1)44277360; E-mail: louis.fensterbank@upmc.fr; E-mail: lacote@ccr.jussieu.fr; E-mail: max.malacria@upmc.fr

Received 28 February 2005

Dedicated to Prof. Bernd Giese for his outstanding achievements

Different approaches have been introduced to address

these conditions. Intermolecular vinylations have been pi-

oneered by Utimoto and Russell.³They used both hetero-

atom-centered (S, I) and metal-centered (Hg, Sn) leaving

Abstract: A new titanium-mediated domino intramolecular radical

vinylation is described. It relies on the radical b-elimination of sulf-

oximyl and phosphinoyl radicals, and leads efficiently to exo-alky-

lidene pyrrolidines with one stereogenic center b to the nitrogen.

The reaction of phosphine oxides has been shown to effectively fol- radicals. These seminal reports have been greatly expand-

ed: Zard⁴and Fuchs⁵optimized the use of vinyl sulfones

low a radical pathway.

while Clark introduced sulfimides.⁶Chlorine, bromine⁷

Key words: radical reactions, titanium, cyclizations, phosphorus,

and nitrosyl⁸radicals are also good candidates. Oshima

epoxides

replaced tin and mercury with less toxic indium.⁹Yet, in

all these cases, control of the regioselectivity in the addi-

tion step remains a problem. Specially introduced orient-

ing groups (such as phenyl rings) are used to favor the

Introduction

desired addition. Moreover, the reactions often require too

During the last decade, radical reactions have gained wide

harsh conditions to be used in asymmetric processes. A

acceptance as efficient ways to build complex frame-

logical solution for regiocontrol has been to switch to in-

works under mild conditions.¹This is due in large part to

tramolecular systems.

the broad array of transformations they can accommodate.

The stereoelectronic requirements of cyclizations are gen-

erally strong enough to allow highly regioselective pro-

cesses, and thus provide optimal efficiency for the

vinylations. The leaving group can be placed either on the

tether or on the double bond. Examples of the former in-

volve sulfides¹⁰and sulfonamides.¹¹In the course of pre-

vious work, we serendipitously observed that silicon

groups could be radical leaving groups under special cir-

cumstances.¹²This led us to think about the potentialities

offered by the radical b-elimination tool, which we felt

could open the way to enantioselective vinylations (Cad-

dick had showed that a similar strategy using racemic

sulfoxides could lead to the formation of polycyclic

heterocycles¹³). This turned out to be the case when enan-

tiopure sulfoxides were used.¹⁴Yet, our system relied on

the use of a chiral auxiliary with an equivalent of toxic

tributyltin hydride (TBTH). We wanted to increase the ap-

peal of our reaction by (i) reducing the amount of radical

mediator used, and (ii) if possible, by using only catalytic

amounts of chiral sources. It rapidly appeared to us that

the strongest potential was offered by titanocene deriva-

tives as single electron-transfer agents.¹⁵In 1988, Nugent

and RajanBabu reported that Cp₂TiCl was able to transfer

one electron to oxiranes, leading to the formation of b-ti-

tanoxy radicals, which could be used further in synthetic

processes.¹⁶This seminal work was made even more use-

ful when Gansäuer rendered this reaction catalytic,¹⁷and

soon thereafter asymmetric.¹⁸

One can generate radicals not only on carbon atoms, but

also on hetero atoms. Such reactive species can be used to

create C–C bonds. Eventually, it has been shown that rad-

ical reactions could exhibit high diastereo- and enantiose-

lectivities.²Yet, in spite of all these achievements, some

simple transformations remain elusive. Enantioselective

vinylation is one of those processes, for which there are no

general methods available (Scheme 1).

R

+

LG

R

LG

Scheme 1 General mechanism for radical vinylation

Addition of a radical in the a position of a leaving group

leads to a new radical that can undergo elimination to

yield the desired olefin and a new radical. Whenever the

leaving group is chiral, asymmetric induction can take

place, and enantioselective vinylation can be envisaged.

Several problems need to be solved in order to get a clean

reaction: (i) addition of the incoming radical needs to be

totally regioselective; (ii) elimination of the outgoing rad-

ical should be faster than elimination of the incoming one;

(iii) the outgoing radical should not add onto the newly

formed olefin; and (iv) in the case of chain processes, con-

ditions have to be devised to regenerate the initial radical

from its precursor.

Unfortunately, we observed that sulfoxides were not com-

patible with the titanium-based system. They were pre-

sumably reduced rapidly to the corresponding sulfides,

SYNTHESIS 2005, No. 9, pp 1405–1420

Advanced online publication: 02.05.2005

DOI: 10.1055/s-2005-865357; Art ID: C01105SS

x

.

x

.2

0

5

1406

D. Leca et al.

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with simultaneous loss of the chirality on sulfur. We thus To prepare pecursors 8a–c and 9a–c, we coupled allyl

looked for radical leaving groups that would tolerate the bromides 1a–c (racemic) and 2a–c (enantiopure), with to-

reducing conditions imposed by titanium and its accom- sylamine 3 in the presence of potassium carbonate in

panying reducing metals (manganese or zinc). We select- DMF. The bromides were easily prepared according to

ed sulfoximines, anticipating that they should be less Maignan’s procedure.²⁵When the starting olefin was tet-

prone to reduction than sulfoxides. Because we had rasubstituted, oxiranes 4a–c and 5a–c were obtained to-

shown in 1999 that b-phosphinoyl radicals could undergo gether with varying amounts of dienes 6a–c and 7a–c,

elimination,¹⁹we also decided to fully examine their use- arising from vinylogous E₂¢-elimination of a bromide ion.

fulness in radical vinylations. We report herein the results Formation of the dienes was observed, regardless of the

we have gathered along the way.

base and solvent used. We could not find better yielding

conditions. However, the desired products could be sepa-

rated from the dienes, and subsequently transformed into

the desired sulfoximines through copper(II)-mediated im-

ination of the sulfoxide moieties.²⁶Separation of unreact-

Sulfoximines

After being well studied in the late sixties/early seventies, ed 3 from sulfoxides 4a–c and 5a–c proved to be difficult.

and then suffering a fading interest, sulfoximines have Whenever this is the case, the remaining traces of 3 are

once again become popular in organic synthesis,²⁰mainly further separated from the precursors after the imination

because of their role as asymmetric ligands.²¹They con- step (Scheme 2 and Table 1).

stitute also good chiral auxiliaries, complementary to sulf-

Titanium-mediated cyclization of 8a–c and 9a–c yielded

alkylidene pyrrolidines 10a–c in acceptable yields, after

oxides,²²as well as building blocks of new classes of

peptidomimetics.²³To the best of our knowledge, their be-

acidic workup (Scheme 3). Manganese was a better re-

havior in radical chemistry has never been examined out-

ductant than zinc, which led to the formation of some

side our group. We showed that b-sulfoximyl radicals

chlorohydrin byproducts arising from ZnCl₂-mediated

opening of the oxirane. As was the case with TBTH-me-

diated b-elimination from sulfoxides, no endo products

attached to a sp²carbon do not b-eliminate.²⁴Since such

eliminations are comparatively much more difficult than

those featuring only sp³carbons, we thought that the latter

were ever detected.^14b

process could be observed. We wanted to know whether it

could lead to good setereochemical outcomes.

O

Ts

N

ArOS

R¹

O

NHTs

3

ArOS

Br

R⁴

+

R²

R¹or R²

K₂CO₃, DMF, r.t.

ArOS

4a–c Ar = Ph

R³

R¹

5a–c Ar = p-Tol

6a–c Ar = Ph

7a–c Ar = p-Tol

1a–c Ar = Ph

2a–c Ar = p-Tol (S_S)

O

Ts

N

PhINTs, Cu(OTf)₂cat.

MeCN, r.t.

O

R²

S

TsN

R¹

Ar

8a–c Ar = Ph

9a–c Ar = p-Tol (S_S)

Scheme 2 Preparation of the sulfoximine precursors

Table 1 Preparation of Sulfoximine Precursors

Entry

Bromide

R¹

Me

H

R²

Ar

Sulfoxide, yield (%) Diene, yield (%) Sulfoximine, yield (%)

1

2

3

4

5

6

1a

1b

1c

2a

2b

2c

Me

i-Pr

Ph

4a, 20

4b, 77

4c, 60

5a, 44

5b, 48

5c, 45

6a, 42

–

8a, 90^a

8b, 62

8c, 74

9a, 85^b

9b, 68

9c, 78

Ph

-(CH₂)₅-

Ph

6c, 12

7a, 24

–

Me

H

Me

p-Tol

i-Pr

7c, 6

^aContaminated by oxirane 3 (18%).

^bContaminated by oxirane 3 (20%).

Synthesis 2005, No. 9, 1405–1420 © Thieme Stuttgart · New York

PAPER

Radical Intramolecular Vinylations

1407

1. Cp₂TiCl₂

Mn,THF, r.t.

2. aq H₂SO₄

phosphonyl radical eliminations for the synthesis of ke-

tones,³⁵although in both cases the systems were signifi-

cantly biased to favor the elimination pathway. The

former case was a rearomatization, and the latter involved

a highly reactive acylphosphonate, with restoration of a

C=O bond.

Ts

N

O

Ts

N

O

R²

HO

S

R¹

10a–c

TsN

R¹

Ar

8a–c Ar = Ph

9a–c Ar = p-Tol (S_S)

Vinylic derivatives 11 and 12 were reacted with various

aldehydes and ketones in the presence of LDA at –78 °C

to afford allylic alcohols 13a–i in good yields (Scheme 4

and Table 3). Upon reaction with the Me₂S·NBS complex,

alcohols 13a–i led to bromides 14a–i. The procedure had

been introduced by Corey (esters³⁶) and Maignan

(sulfoxides²⁵), but never for phosphorus derivatives. As

was the case for sulfoxides, this method gave only the E-

bromides, except for 14h, which was obtained as an insep-

arable mixture of both diastereoisomers (E/Z ratio was

around 1.4:1; the Z-isomer rearranged relatively rapidly to

the E-isomer). The double bond geometries were deter-

Scheme 3 Cyclization of sulfoximine precursors

Thus, b-sulfoximyl radicals do b-eliminate in the alkyl se-

ries. We could use this new reaction to prepare interesting

building blocks, with a fair degree of functionalization

(Table 2). Unfortunately, when the reaction was carried

out starting from the enantiopure precursors 9a–c, the ee’s

were low (<40%, entries 2, 4, 6).

Table 2 Titanocene-Mediated Vinylation from Sulfoximines

1

Entry

Substrate

8a^b

Product, yield (%)

10a, 53

ee (%)^a

mined by H NMR spectroscopy by looking at the cou-

pling constant between the vinylic hydrogen and the

phosphorus atom: a cis relationship gives a 10–30 Hz cou-

pling constant, while a trans relationship leads to a 30–

60 Hz range. However, in most cases, the bromides were

isolated together with 10% of an unidentified by-product,

and could not be purified further. Nonetheless, the crude

bromides were satisfactorily coupled to oxirane 3 to deliv-

er cleanly substrates 15a–i (the isomers of substrate 15h

were separated). The reactions were smoother than with

sulfoximines 4a–c and 5a–c. Yet, dienes were still formed

as minor secondary products and were not isolated.

1

2

3

4

5

6

–

9a^c

10a, 56

40

–

8b^b

10b, 83

9b^c

10b, 82

40

–

8c^b

10c, 78

9c^c

10c, 75

20

^aDetermined by chiral HPLC (CHIRALPAK AD-H column).

^bRacemic compound.

^cEnantiopure compound.

Because the synthesis of precursors 9a–c was tedious and

the stereoselectivities low, we did not push forward, nor

try to determine the absolute configuration of the prod-

ucts, and decided to concentrate on phosphine oxides.

Phosphine Oxides

Literature involving organophosphorus radicals is wide-

spread.²⁷In particular, the stability of P-centered radicals

has facilitated the use of phosphorus hydrides as tin hy-

dride surrogates.²⁸Furthermore, the addition of phosphi-

nyl,²⁹phosphinoyl,³⁰phosphonyl radicals,³¹and their

sulfur-containing counterparts³²to alkenes is a widely

used method for the preparation of organophosphorus de-

rivatives, and polymers.

Scheme 4 Preparation of precursors 15a–i

We submitted phosphine oxide precursor 15a to the con-

ditions we used previously, i.e. at room temperature, with

a stoichiometric amount of Cp₂TiCl₂, and powdered man-

ganese to reduce the titanium species (Scheme 5 and

Table 4). We were pleased to observe the formation of

exo-isopropylidene pyrrolidine 10a, the desired domino

product, as a sole product, in good isolated yield (entry 1).

In contrast, when we first observed b-elimination of a

phosphinoyl radical, almost nothing was known about the

b-elimination of P-centered radicals, and the use of such

pathways in synthesis. It had been shown that phosphinyl

radical additions were reversible.³³Since our initial publi-

cation, radicals derived from phosphinates have been ex-

ploited for the preparation of aromatic compounds,³⁴and

Synthesis 2005, No. 9, 1405–1420 © Thieme Stuttgart · New York

1408

D. Leca et al.

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Table 3 Preparation of Precursors 15a–i

Entry

R

R¹

Me

H

R²

Alcohol, yield (%) Bromide, yield (%) Precursor, yield (%)

1

2

3

4

5

6

Ph

Me

i-Pr

13a, 61

13b, 45

13c, 40

13d, 68

13e, 50

13f, 68

14a, 93

14b, 67

14c, 40

14d, 75

14e, 50

14f, 58

15a, 90

15b, 69

15c, 75

15d, 50

15e, 58

15f, 66

-(CH₂)₅-

-(CH₂)₄-

-(CH₂)₃-

( )₂

O

( )₂

O

7

Ph

H

Ph

13g, 25

13h, 67

13i, 74

14g, 66

14h, 57^a

14i, 85

15g, 78

15h, 50^a

15i, 85

8

Ph

H

c-Pr

Me

9

OEt

Me

^aE/Z ratio = 1.4:1.

1. Cp₂TiCl₂

Ts

N

Table 4 Titanium-Mediated Cyclizations of Substrates 15a–g

O

Ts

N

Mn,THF, r.t.

2. H⁺

Entry

Substrate

15a

Product,^ayield (%)

10a, 80

O

R²

HO

P

1

2

3

4

5

6

7

8

R¹

10a–g, 16

Ph

R¹

Ph

15a–g

15b

15c

10b, 61

10c, 82

Scheme 5 Titanium-mediated vinylation from phosphine oxides

15d

15e

10d, 58

The reaction exhibits good versatility, allowing access to

tetrasubstituted (entries 1 and 3–7), as well as trisubstitut-

ed (entries 2 and 8) exo-alkylidene pyrrolidines. In the

case of the trisubstituted olefins 10b and 10g, b-elimina-

tion proceeds with retention of configuration as evidenced

by NOE (entry 2). However, in the case of oxirane 15g,

25% of the E-isomer was also observed. This result is puz-

zling. Perhaps some p-stacking with the aromatics on tita-

nium accounts for this outcome. Vinylphosphine oxide

15f led either to 10f or to 16 (Figure 1), depending on the

choice of the workup conditions: stronger acidic hydroly-

sis deprotected the ketal.

10e, 57

15f

10f, 57

15f

16, 60^b

15g

10g, 71^c

^aExcept where otherwise noted, the reaction mixture was hydrolyzed

by 10% aq H₂SO₄.

^bHydrolysis was carried out with aq sat. NH₄Cl solution.

^cE/Z ratio = 1:3.

The reaction of cyclopropyl-substituted precursor 15h led

to the ring-opened product 17 as a single diastereoisomer,

the relative configuration of which was determined by X-

ray crystallography. It is derived from pseudo-chair cy-

clization transition state A, which leads to opening of the

cyclopropyl ring (Scheme 6). This strongly suggests that

the cyclization is radical in nature. While there is no rea-

son for a totally stereoselective ring opening, we did not

observe any Z olefinic product by NMR spectroscopy.

Ts

N

PhSe

E

MeO

O

HO

P

Ph Ph

18

16

O

E = CO₂Me

Figure 1 Structure of adduct 16 and substrate 18

We designed several experiments to gather data on the

elimination step. First, we carried out the TBTH-mediated

cyclization of substrates 18 (Figure 1) and 19

(E = CO₂Me) with triethylborane/oxygen as initiator. Di-

ester 18 gave a cyclopropyl-ring opened cyclopentane ad-

duct in 75% yield as a single diastereoisomer. The relative

Mechanistic Study

Since the titanium(III) reagent is an organometallic com-

pound, we wanted to confirm that the observed products

were being formed via a domino radical reaction pathway.

Synthesis 2005, No. 9, 1405–1420 © Thieme Stuttgart · New York

PAPER

Radical Intramolecular Vinylations

1409

Ts

O

Ts

N

O

Ph

P

Ph

Cp₂TiCl

70%

Ts

O

HO

N

O[Ti]

P(O)Ph₂

P

Ph Ph

15 h

A

17

Scheme 6 Titanium-mediated cyclization of substrate 15h

configuration was assumed to be similar to that of 17, Switching to AIBN as initiator did not dramatically alter

which was further confirmed by NOE studies. This again the outcome of the reaction (entry 2), nor did slow addi-

indicates a radical cyclization, but also that the rate of tion of TBTH (entry 3). In the latter case, efficiency of the

elimination of b-phosphinoyl radical is considerably radical chains became an issue, and the conversion was

slower than that of the sulfinyl leaving group, for in that low. In refluxing benzene, we were able to increase the

latter case we observed no opening of the strained ring.^14bamount of 20 relative to 21, but the combined yield

Hence we concentrated our attention on the substrate 19 dropped (entry 4). Slow addition of TBTH allowed us to

(Scheme 7 and Table 5).

remove any trace of reduced material, but the overall yield

dropped further (entry 5). We next looked for tin-free con-

ditions. The C–Se bond of phenylseleno groups is rather

weak, and can be homolytically broken upon irradiation,

leading to group transfer reactions.³⁷An interesting fea-

ture of this method is that it cannot lead to reduction. In

our case, cycloadduct 20 was obtained in 51% yield (entry

6).

PhSe

E

MeO

conditions

O

P

E = CO₂Me

19

Ph Ph

E

MeO

We finally carried out the titanium-mediated process on

phosphonate derivative 15i and obtained the bicyclic

product 22 (78%, Scheme 8). Previously, we had subject-

ed the corresponding malonate to the classical tin-mediat-

ed reaction and observed the overwhelming formation of

cyclopentane products (i.e., cyclized but not eliminated),

along with a minimal (5%) amount of desired product.

More interestingly, the radical termination step was not a

bimolecular reduction by TBTH, but a dismutation of the

intermediate radical. This seemed to indicate that the ter-

tiary b-phosphono radical is rather long-lived. A similar

outcome to the production of 22 was described recently by

Gansäuer and Trost.³⁸It originates from a Ti–O bond

breaking 5-exo-tet radical cyclization on the oxygen atom

of intermediate B. Gansäuer took advantage of the ‘rela-

tive persistence under reducing conditions (of tertiary rad-

icals) through exclusion of competing radical pathways’.

Together with our previous observations, this constitutes

an important circumstantial evidence that no rapid reduc-

tion by a second equivalent of Ti(III) reagent takes place,

and that in the case of b-phosphinoyl radicals, radical

elimination is observed. If this were not the case, we

would much more likely have observed formation of

structures like 22, especially in the case of tetrasubstituted

olefins. As had been reported by Gansäuer, the prepara-

tion of 22 under catalytic radical conditions was possible.

Thus, upon use of 10 mol% of titanium and collidine hy-

drochloride (2 equiv), 68% of 22 was isolated. Alterna-

tively, collidine/TMSCl can be used instead of collidine

hydrochloride (65%).³⁹

+

O

MeO

P

Ph Ph

20

21

Scheme 7 TBTH-mediated cyclization of malonate 19

When 19 was treated under standard radical conditions at

low temperature, we observed the desired domino product

20. However, it came with roughly an equimolar amount

of malonate 21, which presumably arose from direct re-

duction of 19, without cyclization (entry 1). This behavior

also was different from its sulfoxide counterpart, and can

be rationalized by the increased steric bulk about the het-

eroatom. Nevertheless, the observation of 20 confirmed

that the b-elimination of phosphinoyl radicals was indeed

possible.

Table 5 Radical Cyclization of Malonate 19

Entry

Conditions

Yield of 20

(%)

Yield of 21

(%)

1

2

3

4

5

6

TTMSS, Et₃B/O₂, r.t.

56

36

28

51

43

50

29^b

25

–

TBTH, AIBN, hn, 10 °C

TBTH,^aAIBN, hn, 10 °C

TBTH, AIBN, benzene, D

TBTH,^aAIBN, benzene, D 58

AIBN, hn, 50 °C 51

–

^aSlow addition.

^bStarting material (39%) was isolated.

Synthesis 2005, No. 9, 1405–1420 © Thieme Stuttgart · New York

1410

D. Leca et al.

PAPER

purchased from Strem (99+% pure, 325 mesh) and used without fur-

ther purification. Compound 20 and a general procedure for the

preparation of malonates 18 and 19 have been described.^14b

Ts

N

O

Ts

N

O

P

OEt

conditions

O

P

Allyl Bromides 14a–i; General Procedure 1 (GP1)

O

EtO OEt

To a stirred suspension of NBS (540 mg, 3 mmol, 1.5 equiv) in

CH₂Cl₂(10 mL) in the dark at 0 °C, was added dropwise Me₂S (293

mL, 4 mmol, 2 equiv) followed by the alcohol 13a–i (2 mmol,

1 equiv) in CH₂Cl₂(3 mL). The reaction mixture was allowed to

warm to r.t., and stirred overnight in the dark. It was then diluted in

Et₂O (15 mL), washed with brine (30 mL), and dried (Na₂SO₄). The

crude material was purified by flash chromatography.

15i

22

stoich. Cp₂TiCl₂

Mn, then H⁺, 78%

Ts

N

cat. Cp₂TiCl₂(10%),

Mn (2 equiv),

Coll⋅HCl (2 equiv),

68%

O

P

OEt

O

cat. Cp₂TiCl₂(10%),

Mn (2 equiv),

Coll (4 equiv),

TMSCl (2 equiv),

65%

Epoxysulfoxides 4,5; General Procedure 2 (GP2)

ClCp₂Ti

B

K₂CO₃(46 mg, 0.3 mmol, 1 equiv) and then tosylamine 3 (68 mg,

0.3 mmol, 1 equiv) were added at r.t. to a solution of bromide 1a–c

or 2a–c (0.3 mmol, 1 equiv) in DMF (30 mL). The reaction mixture

was stirred at r.t. for 3 days, quenched with H₂O (20 mL), and

CH₂Cl₂(30 mL) was added. The aqueous phase was extracted with

CH₂Cl₂(3 × 30 mL). The organic layers were combined and

washed with H₂O (30 mL) and brine (30 mL), and dried (Na₂SO₄).

Concentration in vacuo gave a crude oil which was purified over sil-

ica gel.

Scheme 8 Case of a vinylic phosphonate

Conclusion

To conclude, we were able to observe for the first time ti- Epoxyphosphine Oxides 15a–i; General Procedure 3 (GP3)

Bromides 14a–i (1 mmol, 1 equiv) were reacted overnight at 40 °C

with the epoxyamine 3 (239 mg, 1.05 mmol, 1.05 equiv) in the pres-

ence of K₂CO₃(691 mg, 5 mmol, 5 equiv) in anhyd acetone

(10 mL). The solvent was removed in vacuo, and the residue was

dissolved in H₂O (5 mL) and extracted with CH₂Cl₂(3 × 30 mL).

The combined organic phases were washed with aq 10% NaOH,

then with brine, and dried (Na₂SO₄). The crude material was puri-

tanium-mediated intramolecular vinylations based on the

b-elimination of both sulfoximyl and phosphinoyl radi-

cals. The former gave good yields of the desired products,

but the enantioselectivities when enantiopure sulfox-

imines were used were disappointingly low. Still, ours is

the first example of radical elimination of b-sulfoximyl

radicals. The latter reactions have not been reported be- fied by flash chromatography on silica gel.

fore our initial studies. They open the way to promising

Epoxysulfoximines 8,9; General Procedure 4 (GP4)

Sulfoxides 4,5 (0.5 mmol, 1 equiv) were added to a solution of

Cu(OTf)₂(18 mg, 0.05 mmol, 10 mol%) in MeCN (3 mL) at r.t.

PhINTs (205 mg, 0.55 mmol, 1.1 equiv) was then added in one por-

reactivities. Work to examine the full scope and limita-

tions of this method, as well as the development of a cat-

alytic asymmetric version, is currently underway.

tion. The reaction was monitored by the rapid disappearance of the

yellowish powder from the reaction mixture, which turned homoge-

Reactions were carried out under an inert gas, with magnetic stirring

neous and green, generally after 2 min. MeCN was removed in vac-

and redistilled, degassed solvents when necessary. TLC was per-

uo and the crude material was purified by flash chromatography on

formed on Merck 60 F254 silica gel. Merck Geduran SI 60 A silica

gel (35–70 mm) was used for column chromatography. Petroleum

ether (bp 35–60 °C) and EtOAc are abbreviated as PE and EA, re-

spectively. The melting points reported were measured with a Re-

ichert hot stage apparatus and are uncorrected. IR spectra were

silica gel.

Ti-Mediated Cyclization of the Amine Precursors 8,9,15; Gen-

eral Procedure 5 (GP5)

Cp₂TiCl₂(187 mg, 0.75 mmol, 2.5 equiv) and Mn (65 mg, 3 mmol,

10 equiv) were added dropwise at r.t. to a degassed solution of ap-

propriate 8, 9 or 15 (0.3 mmol, 1 equiv) in THF (6 mL). After com-

pletion (generally 2–3 h), the reaction was quenched with

aq 10% H₂SO₄. The mixture was extracted with Et₂O. The organics

were washed with aq sat. NaHCO₃, brine, and dried (Na₂SO₄). The

crude material was purified by flash chromatography on silica gel.

recorded with a Bruker Tensor 27 ATR diamant PIKE spectrome-

1

ter. H NMR (resp. ¹³C NMR) spectra were recorded at r.t. with

200 MHz (resp. 50 MHz) Bruker AC 200 and ARX 200 spectro-

meters, 250 MHz (resp. 62.5 MHz) Bruker ARX 250 and 400 MHz

(resp. 100 MHz) Bruker ARX 400 and AVANCE 400 spectrome-

ters. Chemical shifts are given in ppm, referenced to the residual

proton resonances of the solvents (d = 7.26, resp. 77.0, for CDCl₃).

³¹P NMR was recorded with 162 MHz Bruker ARX 400 and

AVANCE 400 spectrometers. Chemical shifts are given in ppm,

referenced to the external phosphorus resonance of 85% aq H₃PO₄

(0 ppm). Coupling constants (J) are given in Hertz (Hz). Elemental

analyses were performed by the Service Régional de Microanalyse

de l’Université Pierre et Marie Curie and Exact Mass were recorded

at ICSN (CNRS, Gif) on a LCT micromass apparatus (Electrospray

source). X-ray diffraction was recorded at the Laboratoire de chimie

inorganique et matériaux moléculaires (UMR 7071 CNRS, UPMC)

and was deposited at Cambridge (Ref. CCDC 233638). THF was

distilled from Na/benzophenone. Anhyd acetone was purchased

from various retailers and used without further purification. Ben-

zene and toluene were distilled from CaH₂. Cp₂TiCl₂was purchased

from Aldrich (97% pure) and was used as received. Manganese was

4a

Following GP2 from bromide 1a, the epoxysulfoxide 4a was isolat-

ed as an inseparable mixture of two diastereoisomers (PE–THF,

70:30); yield: 25 mg (20%); yellowish oil.

IR (neat): 3061, 1333, 1159, 852 cm^–1.

¹H NMR (400 MHz, CDCl₃): d = 2.16 [s, 3 H, =C(CH₃)Me, one

dia.], 2.18 [s, 3 H, =C(CH₃)Me, one dia.], 2.29 [s, 3 H, =C(Me)CH₃,

one dia.], 2.30 [s, 3 H, =C(Me)CH₃, one dia.], 2.39 (s, 6 H, CH₃of

Ts, two dias.), 2.44–2.49 (m, 2 H, OCHH, two dias.), 2.64–2.69 (m,

2 H, OCHH, two dias.), 2.97–3.04 (m, 4 H, NCHHCH, two dias. +

CHO, one dia. + NCHHCH, one dia.), 3.10–3.14 (m, 1 H, CHO, one

dia.), 3.21–3.26 (m, 1 H, NCHHCH, one dia.), 3.29 (B of AB,

J = 14.2 Hz, 1 H, =CCNHH, one dia.), 3.41 (B of AB, J = 14.2 Hz,

Synthesis 2005, No. 9, 1405–1420 © Thieme Stuttgart · New York

PAPER

Radical Intramolecular Vinylations

1411

1 H, =CCNHH, one dia.), 4.09 (A of AB, J = 14.2 Hz, 1 H, =CCN-

HH, one dia.), 4.16 (A of AB, J = 14.2 Hz, 1 H, =CCNHH, one

dia.), 7.25–7.53 (m, 18 H_arom, two dias.).

¹³C NMR (100 MHz, CDCl₃): d = 21.9 (CH₃of Ts, two dias.), 22.9

[=C(CH₃)Me, one dia.], 23.0 [=C(CH₃)Me, one dia.], 23.2

[=C(Me)CH₃, one dia.], 23.2 [=C(Me)CH₃, one dia.], 43.3

(NCH₂C=, one dia.), 43.6 (NCH₂C=, one dia.), 46.3 (OCH₂, one

dia.), 47.2 (OCH₂, one dia.), 49.5 (CHCH₂N, one dia.), 50.5

(CHCH₂N, one dia.), 50.8 (OCH, one dia.), 51.4 (OCH, one dia.),

124.1 (Ph CH_arom, two dias.), 127.4 (Ts CH_arom, one dia.), 127.5 (Ts

4.17 (A of AB, J = 13.9 Hz, 1 H, =CCHHN, one dia.), 4.22 (A of

AB, J = 13.9 Hz, 1 H, =CCHHN, one dia.), 7.27–7.30 (m, 4 H_arom

two dias.), 7.37–7.41 (m, 4 H_arom, two dias.), 7.45–7.52 (m, 6 H_arom

two dias.), 7.57–7.62 (m, 4 H_arom, two dias.).

,

¹³C NMR (100 MHz, CDCl₃): d = 21.9 (CH₃of Ts, two dias.), 26.4

[one =CCH₂(CH₂)₃, one dia.], 26.5 [one =CCH₂(CH₂)₃, one dia.],

27.7 [(one =CCH₂(CH₂)₃, one dia.], 27.9 [one =CCH₂(CH₂)₃, one

dia.], 28.4 [one =CCH₂(CH₂)₃, one dia.], 28.6 [one =CCH₂(CH₂)₃,

one dia.], 32.6 [=CCH₂(CH₂)₃, two dias.], 42.8 (NCH₂C=, one dia.),

43.0 (NCH₂C=, one dia.), 46.4 (CH₂O, one dia.), 47.6 (CH₂O, one

dia.), 49.6 (CHCH₂N, one dia.), 50.6 (CHCH₂N, one dia.), 51.3

(CHO, one dia.), 51.8 (CHO, one dia.), 124.5 (CH_arom, two dias.),

CH_arom, one dia.), 129.3 (Ph CH_arom, two dias.), 129.9 (Ts CH_arom

,

two dias.), 130.4 (Ph CH_arom, one dia.), 130.6 (Ph CH_arom, one dia.),

132.5 (C=, one dia.), 133.1 (C=, one dia.), 134.8 (C=, two dias.),

127.8 (CH_arom, one dia.), 127.9 (CH_arom, one dia.), 129.5 (CH_arom

,

143.4 (SC_i-arom, one dia.), 143.9 (SC_i-arom, one dia.), 144.1 (SC_i-arom

one dia.), 144.2 (SC_i-arom, one dia.), 152.0 (C=, one dia.), 152.3 (C=,

one dia.).

,

one dia.), 129.6 (CH_arom, one dia.), 130.2 (CH_arom, two dias.), 130.8

[CH_arom(one dia.) + C= (one dia.)], 130.9 [CH_arom(one dia.) + C=

(one dia.)], 134.6 (C=, two dias.), 143.7 (SC_i-arom, one dia.), 144.1

(SC_i-arom, one dia.), 144.2 (SC_i-arom, two dias.), 159.2 (C=, one dia.),

159.3 (C=, one dia.).

Anal. Calcd for C₂₁H₂₅NO₄S₂(419.56): C, 60.12; H, 6.01; N, 3.34.

Found: C, 60.21; H, 6.06; N, 3.30.

5a

4b

Following GP2 from bromide 2a, the epoxysulfoxide 5a was isolat-

ed as an inseparable mixture of two diastereoisomers (PE–EA–

CH₂Cl₂, 50:30:20); yield: 57 mg (44%); yellow oil.

IR (neat): 2924, 1634, 1160, 1072 cm^–1.

Following GP2 from bromide 1b, the epoxysulfoxide 4b was isolat-

ed as an inseparable mixture of two diastereoisomers (PE–THF,

70:30); yield: 100 mg (77%); yellow oil.

IR (neat): 3057, 1158, 886 cm^–1.

¹H NMR (400 MHz, CDCl₃): d = 2.19 [s, 3 H, =C(CH₃)Me, one

dia.], 2.21 [s, 3 H, =C(CH₃)Me, one dia.], 2.31 [s, 3 H, =C(Me)CH₃,

one dia.], 2.33 [s, 3 H, =C(Me)CH₃, one dia.], 2.41 (s, 6 H, CH₃of

p-Tol, two dias.), 2.44 (s, 3 H, CH₃of p-Tol, one dia.), 2.45 (s, 3 H,

CH₃of p-Tol, one dia.), 2.53–2.56 (m, 2 H, OCHH, two dias.),

2.63–2.70 (m, 2 H, OCHH, two dias.), 2.97–3.10 (m, 5 H, NCH-

HCH, two dias. + CHO, two dias. + NCHHCH, one dia.), 3.25–3.30

(m, 1 H, NCHHCH, one dia.), 3.38 (B of AB, J = 13.9 Hz, 1 H,

=CCNHH, one dia.), 3.46 (B of AB, J = 13.9 Hz, 1 H, =CCNHH,

one dia.), 4.15 (A of AB, J = 13.9 Hz, 1 H, =CCNHH, one dia.),

4.21 (A of AB, J = 13.9 Hz, 1 H, =CCNHH, one dia.), 7.26–7.31

(m, 8 H_arom, two dias.), 7.56–7.60 (m, 4 H_arom, two dias.), 7.72–7.75

(m, 4 H_arom, two dias.).

¹³C NMR (100 MHz, CDCl₃): d = 21.4 (CH₃of p-Tol, two dias.),

21.6 (CH₃of p-Tol, two dias.), 22.4 [=C(CH₃)Me, one dia.], 22.5

[=C(CH₃)Me, one dia.], 22.7 [=C(Me)CH₃, one dia.], 22.8

[=C(Me)CH₃, one dia.], 42.7 (NCH₂C=, one dia.), 43.0 (NCH₂C=,

one dia.), 45.1 (OCH₂, one dia.), 46.0 (OCH₂, one dia.), 49.1

(CHCH₂N, one dia.), 50.0 (CHCH₂N, one dia.), 50.8 (OCH, one

dia.), 51.4 (OCH, one dia.), 124.0 (CH_arom, two dias.), 127.0

(CH_arom, two dias.), 127.4 (CH_arom, two dias.), 129.9 (CH_arom, two

dias.), 132.2 (C=, one dia.), 132.8 (C=, one dia.), 134.3 (C=, one

dia.), 134.4 (C=, one dia.), 139.7 (C=, one dia.), 140.2 (C=, one

dia.), 140.7 (C=, one dia.), 140.9 (C=, one dia.), 143.7 (C=, one

dia.), 143.8 (C=, one dia.), 151.1 (C=, one dia.), 151.4 (C=, one

dia.).

¹H NMR (400 MHz, CDCl₃): d = 1.06–1.15 [m, 12 H, CH(CH₃)₂,

two dias.], 2.44 (s, 6 H, CH₃of Ts, two dias.), 2.42–2.46 (m, 1 H,

CHHO, one dia.), 2.53–2.56 (m, 1 H, CHHO, one dia.), 2.71–2.79

(m, 2 H, CHHO, two dias.), 2.95–3.11 [m, 6 H, CHCHHN (two

dias.) + Me₂CH (two dias.) + CHO (two dias.)], 3.27–3.35 (m, 2 H,

CHCHHN, two dias.), 3.66 (B of AB, J = 14.9 Hz, 1 H, =CCHHN,

one dia.), 3.81 (B of AB, J = 14.9 Hz, 1 H, =CCHHN, one dia.),

3.95 (A of AB, J = 14.9 Hz, 1 H, =CCHHN, one dia.), 3.99 (A of

AB, J = 14.9 Hz, 1 H, =CCHHN, one dia.), 6.60 (d, J = 10.6 Hz,

1 H, =CH, one dia.), 6.61 (d, J = 10.6 Hz, 1 H, =CH, one dia.),

7.31–7.75 (m, 18 H_arom, two dias.).

¹³C NMR (100 MHz, CDCl₃): d = 22.0 (CH₃of Ts, two dias.), 22.6

[CH(CH₃)₂, two dias.], 27.9 (Me₂CH, one dia.), 28.1 (Me₂CH, one

dia.), 43.2 (NCH₂C=, one dia.), 43.4 (NCH₂C=, one dia.), 46.4

(OCH₂, one dia.), 46.5 (OCH₂, one dia.), 50.0 (CHCH₂N, one dia.),

50.3 (OCH, one dia.), 50.5 (CHCH₂N, one dia.), 50.6 (OCH, one

dia.), 125.6 (CH_arom, one dia.), 125.9 (CH_arom, one dia.), 127.8

(CH_arom, two dias.), 129.3 (CH_arom, two dias.), 129.9 (CH_arom, two

dias.), 131.6 (CH_arom, one dia.), 131.8 (CH_arom, one dia.), 135.2 (C=,

one dia.), 135.4 (C=, one dia.), 136.9 (C=, one dia.), 137.0 (C=, one

dia.), 142.8 (C=, one dia.), 142.9 (C=, one dia.), 143.9 (C=, one

dia.), 144.0 (C=, one dia.), 146.7 (=CH, one dia.), 148.1 (=CH, one

dia.).

Anal. Calcd for C₂₂H₂₇NO₄S₂(433.58): C, 60.94; H, 6.28; N, 3.23.

Found: C, 61.06; H, 6.32; N, 3.30.

4c

5b

Following GP2 from bromide 1c, the epoxysulfoxide 4c was isolat-

ed as an inseparable mixture of two diastereoisomers (CH₂Cl₂–EA,

90:10); yield: 83 mg (60%), along with oxirane 3 (16 mg, 23%);

yellow oil.

Following GP2 from bromide 2b, the epoxysulfoxide 5b was isolat-

ed as an inseparable mixture of two diastereoisomers (PE–EA–

CH₂Cl₂, 50:30:20); yield: 64 mg (48%); yellow oil.

IR (neat): 3053, 2959, 1158, 886 cm^–1.

IR (neat): 3029, 1219, 1151, 1086, 932 cm^–1.

¹H NMR (400 MHz, CDCl₃): d = 1.06–1.10 [m, 12 H, CH(CH₃)₂,

two dias.], 2.42 (s, 6 H, CH₃of p-Tol, two dias.), 2.44 (s, 6 H, CH₃

of p-Tol, two dias.), 2.42–2.46 (m, 1 H, CHHO, one dia.), 2.53–2.56

(m, 1 H, CHHO, one dia.), 2.65–2.75 (m, 2 H, CHHO, two dias.),

2.95–3.11 [m, 6 H, CHCHHN (two dias.) + Me₂CH (two dias.) +

CHO (two dias.)], 3.27–3.33 (m, 2 H, CHCHHN, two dias.), 3.68

(B of AB, J = 14.9 Hz, 1 H, =CCHHN, one dia.), 3.82 (B of AB,

J = 14.9 Hz, 1 H, =CCHHN, one dia.), 3.92 (A of AB, J = 14.9 Hz,

1 H, =CCHHN, one dia.), 3.96 (A of AB, J = 14.9 Hz, 1 H,

¹H NMR (CDCl₃, 400 MHz):

d = 1.65–1.95 [m, 12 H,

=CCH₂(CH₂)₃, two dias.], 2.45 (s, 6 H, CH₃of Ts, two dias.), 2.56–

2.59 (m, 2 H, CHHO, two dias.), 2.60–2.71 [m, 4 H, =CCH₂(CH₂)₃,

two dias.], 2.72–2.77 (m, 2 H, CHHO, two dias.), 2.82–2.90 [m,

4 H, =CCH₂(CH₂)₃, two dias.], 3.02–3.18 [m, 5 H, CHO (two dias.)

+ CHCHHN (two dias.) + CHCHHN (one dia.)], 3.25–3.28 (m, 1 H,

CHCHHN, one dia.), 3.31 (B of AB, J = 13.9 Hz, 1 H, =CCHHN,

one dia.), 3.41 (B of AB, J = 13.9 Hz, 1 H, =CCHHN, one dia.),

Synthesis 2005, No. 9, 1405–1420 © Thieme Stuttgart · New York

1412

D. Leca et al.

PAPER

=CCHHN, one dia.), 6.58 (d, J = 10.6 Hz, 1 H, =CH, two dias.),

7.28–7.45 (m, 8 H_arom, two dias.), 7.43–7.47 (m, 4 H_arom, two dias.),

7.62–7.67 (m, 4 H_arom, two dias.).

two dias.), 3.12 (B of ABX, J = 15.6, 6.1 Hz, 1 H, CHCHHN, one

dia.), 3.21 (B of ABX, J = 15.6, 6.1 Hz, 1 H, CHCHHN, one dia.),

3.43 (A of ABX, J = 15.6, 6.1 Hz, 1 H, CHCHHN, one dia.), 3.42

(A of ABX, J = 15.6, 6.1 Hz, 1 H, CHCHHN, one dia.), 4.40 (B of

AB, J = 14.9 Hz, 1 H, =CCHHN, one dia.), 4.48 (br s , 2 H, =CH₂N,

one dia.), 4.56 (A of AB, J = 14.9 Hz, 1 H, =CCHHN, one dia.),

7.19–7.21 (m, 4 H_arom, two dias.), 7.34–7.38 (m, 4 H_arom, two dias.),

7.49–7.53 (m, 4 H_arom, two dias.), 7.58–7.62 (m, 2 H_arom, two dias.),

7.70–7.78 (m, 8 H_arom, two dias.), 7.88–7.94 (m, 4 H_arom, two dias.).

¹³C NMR (CDCl₃, 100 MHz): d = 21.9 (CH₃of p-Tol, two dias.),

22.0 (CH₃of p-Tol, two dias.), 24.3 [=C(CH₃)Me, two dias.], 26.1

[=C(Me)CH₃, one dia.], 26.2 [=C(Me)CH₃, one dia.], 46.4 (CH₂O,

one dia.), 46.6 (CH₂O, one dia.), 47.8 (=CCH₂N, one dia.), 48.1

(=CCH₂N, one dia.), 50.8 (CHO, one dia.), 50.9 (CHO, one dia.),

51.2 (CHCH₂N, two dias.), 126.9 (CH_arom, two dias.), 127.9

(CH_arom, one dia.), 128.0 (CH_arom, one dia.), 129.7 (CH_arom, one dia.),

¹³C NMR (100 MHz, CDCl₃): d = 21.5 (CH₃of p-Tol, two dias.),

21.6 (CH₃of p-Tol, two dias.), 22.1 [CH(CH₃)₂, one dia.], 22.2

[CH(CH₃)₂, one dia.], 22.3 [CH(CH₃)₂, one dia.], 22.3 [CH(CH₃)₂,

one dia.], 27.5 (Me₂CH, one dia.), 27.6 (Me₂CH, one dia.), 43.0

(NCH₂C=, one dia.), 43.2 (NCH₂C=, one dia.), 46.0 (OCH₂, one

dia.), 46.1 (OCH₂, one dia.), 49.5 (CHCH₂N, one dia.), 50.0 (OCH,

one dia.), 50.0 (CHCH₂N, one dia.), 50.1 (OCH, one dia.), 125.3

(CH_arom, one dia.), 125.6 (CH_arom, one dia.), 127.4 (CH_arom, two

dias.), 129.9 (CH_arom, two dias.), 135.2 (C=, one dia.), 135.4 (C=,

one dia.), 137.0 (C=, two dias.), 139.5 (C=, one dia.), 139.6 (C=,

one dia.), 141.8 (C=, one dia.), 141.9 (C=, one dia.), 143.9 (C=, one

dia.), 143.9 (C=, one dia.), 145.5 (=CH, one dia.), 146.8 (=CH, one

dia.).

129.8 (CH_arom, one dia.), 129.9 (CH_arom, two dias.), 130.5 (CH_arom

,

Anal. Calcd for C₂₃H₂₉NO₄S₂(447.61): C, 61.72; H, 6.53; N, 3.13.

Found: C, 61.59; H, 6.69; N, 3.05.

two dias.), 130.5 (CH_arom, one dia.), 130.6 (CH_arom, one dia.), 130.9

(=C, two dias.), 134.2 (CH_arom, one dia.), 134.3 (CH_arom, one dia.),

135.2 (=C, one dia.), 135.3 (=C, one dia.), 140.4 (=C, one dia.),

140.6 (=C, one dia.), 141.2 (=C, two dias.), 143.2 (=C, two dias.),

144.6 (=C, one dia.), 144.7 (=C, one dia.), 160.8 (=C, one dia.),

161.0 (=C, one dia.).

5c

Following GP2 from bromide 2c, the epoxysulfoxide 5c was isolat-

ed as an inseparable mixture of two diastereoisomers (PE–EA–

CH₂Cl₂, 60:20:20); yield: 64 mg (45%), along with oxirane 3

(14 mg, 21%); white foam.

Anal. Calcd for C₂₈H₃₂N₂O₆S₃(588.76): C, 57.12; H, 5.48; N, 4.76.

Found: C, 57.28; H, 5.69; N, 4.53.

IR (neat): 2929, 1627, 1597, 1160, 1086 cm^–1.

¹H NMR (CDCl₃, 400 MHz):

d = 1.57–1.88 [m, 12 H,

8b

=CCH₂(CH₂)₃, two dias.], 2.34 (s, 6 H, CH₃of p-Tol, two dias.),

2.36 (s, 6 H, CH₃of p-Tol, two dias.), 2.46–2.48 (m, 2 H, CHHO,

two dias.), 2.54–2.63 [m, 4 H, =CCH₂(CH₂)₃, two dias.], 2.64–2.68

(m, 2 H, CHHO, two dias.), 2.72–2.82 [m, 4 H, =CCH₂(CH₂)₃, two

dias.], 2.95–3.10 [m, 5 H, CHO (two dias.) + CHCHHN (two dias.)

+ CHCHHN (one dia.)], 3.15–3.19 (m, 1 H, CHCHHN, one dia.),

3.24 (B of AB, J = 13.9 Hz, 1 H, =CCHHN, one dia.), 3.33 (B of

AB, J = 13.9 Hz, 1 H, =CCHHN, one dia.), 4.09 (A of AB,

J = 13.9 Hz, 1 H, =CCHHN, one dia.), 4.14 (A of AB, J = 13.9 Hz,

1 H, =CCHHN, one dia.), 7.17–7.22 (m, 12 H_arom, two dias.), 7.49–

7.52 (m, 4 H_arom, two dias.).

¹³C NMR (100 MHz, CDCl₃): d = 21.7 (CH₃of p-Tol, two dias.),

22.0 (CH₃of p-Tol, two dias.), 26.4 [1 × =CCH₂(CH₂)₃, one dia.],

26.5 [1 × =CCH₂(CH₂)₃, one dia.], 27.7 [1 × =CCH₂(CH₂)₃, one

dia.], 27.8 [1 × =CCH₂(CH₂)₃, one dia.], 28.4 [one =CCH₂(CH₂)₃,

one dia.], 28.6 [1 × =CCH₂(CH₂)₃, one dia.], 32.5 [=CCH₂(CH₂)₃,

two dias.], 42.6 (NCH₂C=, one dia.), 43.0 (NCH₂C=, one dia.), 46.4

(CH₂O, one dia.), 47.6 (CH₂O, one dia.), 49.5 (CHCH₂N, one dia.),

50.5 (CHCH₂N, one dia.), 51.3 (CHO, one dia.), 51.8 (CHO, one

dia.), 124.4 (CH_arom, two dias.), 127.8 (CH_arom, one dia.), 127.9

(CH_arom, one dia.), 130.2 (CH_arom, one dia.), 130.3 (CH_arom, one dia.),

130.3 (CH_arom, one dia.), 130.4 (CH_arom, one dia.), 130.9 (C=, two

dias.), 134.6 (C=, two dias.), 140.2 (SC_i-arom, one dia.), 141.0

(SC_i-arom, one dia.), 141.1 (SC_i-arom, one dia.), 141.2 (SC_i-arom, one

dia.), 144.2 (C=, two dias.), 158.7 (C=, one dia.), 158.8 (C=,

one dia.).

Following GP4 from epoxysulfoxide 4b, the sulfoximine 8b was

isolated as an inseparable mixture of two diastereoisomers

(CH₂Cl₂–EA, 90:10); yield: 187 mg (62%); white solid.

IR (neat): 2924, 1634, 1597, 1149, 1088 cm^–1.

¹H NMR (400 MHz, CDCl₃): d = 1.10–1.13 [m, 12 H, CH(CH₃)₂,

two dias.], 2.30–2.34 (m, 2 H, CHHO, two dias.), 2.39 (s, 6 H, CH₃

of p-Tol, two dias.), 2.44 (s, 6 H, CH₃of p-Tol, two dias.), 2.55–

2.59 (m, 2 H, CHHO, two dias.), 2.67–2.80 (m, 3 H, CHO, two dias.

+ CHCHHN, one dia.), 2.88 (B of ABX, J = 15.7, 6.3 Hz, 1 H,

CHCHHN, one dia.), 3.01–3.19 (m, 2 H, Me₂CH, two dias.), 3.14–

3.19 (m, 2 H, CHCHHN, two dias.), 4.16 (B of AB, J = 15.3 Hz,

1 H, =CCHHN, one dia.), 4.22 (B of AB, J = 15.3 Hz, 1 H,

=CCHHN, one dia.), 4.28 (A of AB, J = 15.3 Hz, 1 H, =CCHHN,

one dia.), 4.35 (A of AB, J = 15.3& nbsp;Hz, 1 H, =CCHHN, one

dia.), 7.05 (d, J = 10.9 Hz, 1 H, =CH, one dia.), 7.08 (d,

J = 10.9 Hz, 1 H, =CH, one dia.), 7.23–7.33 (m, 8 H_arom, two dias.),

7.53–7.56 (m, 4 H_arom, two dias.), 7.62–7.66 (m, 6 H_arom, two dias.),

7.79–7.82 (m, 4 H_arom, two dias.), 7.90–7.93 (m, 4 H_arom, two dias.).

¹³C NMR (100 MHz, CDCl₃): d = 21.8 (CH₃, two dias.), 21.9 (CH₃,

two dias.), 22.0 (CH₃, two dias.), 22.1 (CH₃, two dias.), 28.9

(Me₂CH, two dias.), 44.8 (=CCH₂N, two dias.), 46.3 (CH₂O, one

dia.), 46.4 (CH₂O, one dia.), 49.9 (CHO, one dia.), 50.0 (CHO, one

dia.), 51.0 (CHCH₂N, two dias.), 127.0 (CH_arom, two dias.), 127.8

(CH_arom, two dias.), 128.7 (CH_arom, two dias.), 129.7 (CH_arom, two

dias.), 129.9 (CH_arom, two dias.), 130.4 (CH_arom, two dias.), 132.9

(=C, one dia.), 133.0 (=C, one dia.), 134.5 (CH_arom, two dias.), 135.3

(=C, one dia.), 135.4 (=C, one dia.), 140.4 (=C, one dia.), 140.6 (=C,

one dia.), 141.2 (=C, two dias.), 143.2 (=C, two dias.), 144.6 (=C,

one dia.), 144.7 (=C, one dia.), 157.0 (=CH, one dia.), 157.3 (=C,

one dia.).

8a

Following GP4 from epoxysulfoxide 4a, the sulfoximine 8a was

isolated as an inseparable mixture of two diastereoisomers

(CH₂Cl₂–EA, 90:10); yield: 265 mg (90%); yellow oil.

IR (neat): 2923, 1597, 1164, 1086, 938 cm^–1.

Anal. Calcd for C₂₉H₃₄O₆N₂S₃(602.79): C, 57.78; H, 5.69; N, 4.65.

Found: C, 57.17; H, 6.05; N, 4.35.

¹H NMR (400 MHz, CDCl₃): d = 1.95 [s, 3 H, =C(CH₃)Me, one

dia.], 1.98 [s, 3 H, =C(CH₃)Me, one dia.], 2.21 [s, 3 H, =C(Me)CH₃,

one dia.], 2.23 [s, 3 H, =C(Me)CH₃, one dia.], 2.39 (s, 3 H, CH₃of

p-Tol, one dia.), 2.41 (s, 3 H, CH₃of p-Tol, one dia.), 2.47 (s, 6 H,

CH₃of p-Tol, two dias.), 2.45–2.49 (m, 2 H, trans-OCHH, two

dias.), 2.65 (dd, J = 4.5, 4.3 Hz, 1 H, cis-OCHH, one dia.), 2.68 (dd,

J = 4.5, 4.3 Hz, 1 H, cis-OCHH, one dia.), 2.98–3.06 (m, 2 H, CHO,

8c

Following GP4 from epoxysulfoxide 4c, the sulfoximine 8c was

isolated as an inseparable mixture of two diastereoisomers

(CH₂Cl₂–EA, 90:10); yield: 233 mg (74%); white solid.

IR (neat): 3029, 1219, 1152, 1086 cm^–1.

Synthesis 2005, No. 9, 1405–1420 © Thieme Stuttgart · New York

PAPER

Radical Intramolecular Vinylations

1413

¹H NMR (CDCl₃, 400 MHz): d = 1.35–1.45 (m, 6 H, CH₂, two

dias.), 1.50–1.58 (m, 6 H, CH₂, two dias.), 2.30 (s, 3 H, CH₃of p-

Tol, one dia.), 2.32 (s, 3 H, CH₃of p-Tol, one dia.), 2.37 (s, 3 H,

CH₃of p-Tol, one dia.), 2.38 (s, 3 H, CH₃of p-Tol, one dia.), 2.34–

2.44 (m, 6 H, =CCH₂, two dias. + CHHO, two dias.), 2.47–2.56 (m,

6 H, =CCH₂, two dias. + CHHO, two dias.), 2.98–3.01 (m, 2 H,

CHO, two dias.), 3.17 (B of ABX, J = 15.6, 6.0 Hz, 1 H, CHCHHN,

one dia.), 3.18 (B of ABX, J = 15.6, 6.0 Hz, 1 H, CHCHHN, one

dia.), 3.34 (A of ABX, J = 15.6, 6.0 Hz, 1 H, CHCHHN, one dia.),

3.35 (A of ABX, J = 15.6, 6.0 Hz, 1 H, CHCHHN, one dia.), 4.34

(B of AB, J = 15.1 Hz, 1 H, =CCHHN, one dia.), 4.42 (B of AB,

J = 15.1 Hz, 1 H, =CCHHN, one dia.), 4.53 (A of AB, J = 15.1 Hz,

1 H, =CCHHN, one dia.), 4.56 (A of AB, J = 15.1 Hz, 1 H,

=CCHHN, one dia.), 7.08–7.13 (m, 4 H_arom, two dias.), 7.25–7.32

(m, 4 H_arom, two dias.), 7.41–7.48 (m, 4 H_arom, two dias.), 7.51–7.56

(m, 2 H_arom, two dias.), 7.64–7.72 (m, 8 H_arom, two dias.), 7.85–7.90

(m, 4 H_arom, two dias.).

144.2 (=C, one dia.), 145.0 (=C, two dias.), 160.1 (=C, one dia.),

161.2 (=C, one dia.).

Anal. Calcd for C₂₉H₃₄N₂O₆S₃(602.79): C, 57.78; H, 5.69; N, 4.65.

Found: C, 57.28; H, 6.23; N, 4.68.

9b

Following GP4 from epoxysulfoxide 5b, the sulfoximine 9b was

isolated as an inseparable mixture of two diastereoisomers (PE–

CH₂Cl₂–EA, 60:10:30); yield: 210 mg (68%); yellow oil.

IR (neat): 2924, 1634, 1597, 1088 cm^–1.

¹H NMR (400 MHz, CDCl₃): d = 1.00–1.03 [m, 12 H, CH(CH₃)₂,

two dias.], 2.24–2.29 (m, 2 H, CHHO, two dias.), 2.40 (s, 6 H, CH₃

of p-Tol, two dias.), 2.46 (s, 12 H, CH₃of p-Tol, two dias.), 2.45–

2.50 (m, 2 H, CHHO, two dias.), 2.67–2.78 (m, 3 H, CHO, two dias.

+ CHCHHN, one dia.), 2.87 (B of ABX, J = 15.4, 6.3 Hz, 1 H,

CHCHHN, one dia.), 3.01–3.15 (m, 4 H, Me₂CH, two dias. +

CHCHHN, two dias.), 4.04 (B of AB, J = 15.4 Hz, 1 H, =CCHHN,

one dia.), 4.12 (B of AB, J = 15.4 Hz, 1 H, =CCHHN, one dia.),

4.16 (A of AB, J = 15.4 Hz, 1 H, =CCHHN, one dia.), 4.24 (A of

AB, J = 15.4 Hz, 1 H, =CCHHN, one dia.), 6.90 (d, J = 10.9 Hz,

1 H, =CH, one dia.), 6.93 (d, J = 10.9 Hz, 1 H, =CH, one dia.),

7.14-7.25 (m, 12 H_arom, two dias.), 7.55–7.57 (m, 4 H_arom, two dias.),

7.66–7.75 (m, 8 H_arom, two dias.).

¹³C NMR (100 MHz, CDCl₃): d = 21.5 (CH₃of p-Tol, two dias.),

21.6 (CH₃of p-Tol, two dias.), 25.4 [(CH₂)₃, two dias.], 26.9

[(CH₂)₃, two dias.], 28.0 [(CH₂)₃, two dias.], 33.4 (=CCH₂, two

dias.), 34.6 (=CCH₂, two dias.), 46.2 (NCH₂C=, one dia.), 46.4

(NCH₂C=, one dia. + CH₂O, one dia.), 46.8 (CH₂O, one dia.), 50.4

(CHO, one dia.), 50.5 (CHO, one dia.), 50.9 (CHCH₂N, one dia.),

51.0 (CHCH₂N, one dia.), 126.5 (CH_arom, two dias.), 127.1 (CH_arom

,

¹³C NMR (100 MHz, CDCl₃): d = 21.4–21.7 (m, all CH₃, two dias.),

28.3 (Me₂CH, two dias.), 44.3 (=CCH₂N, two dias.), 46.0 (CH₂O,

one dia.), 46.1 (CH₂O, one dia.), 49.6 (CHO, one dia.), 49.7 (CHO,

one dia.), 50.5 (CHCH₂N, one dia.), 50.6 (CHCH₂N, one dia.),

one dia.), 127.2 (CH_arom, one dia.), 127.6 (CH_arom, two dias.), 129.1

(CH_arom, two dias.), 129.2 (CH_arom, one dia.), 129.3 (CH_arom, one

dia.), 130.0 (CH_arom, two dias.), 133.5 (CH_arom, two dias.), 133.5

(=C, two dias.), 133.5 (=C, two dias.), 138.4 (=C, two dias.), 138.5

(=C, two dias.), 140.1 (=C, two dias.), 166.6 (=C, one dia.), 166.9

(=C, one dia.).

126.6 (CH_arom, two dias.), 127.5 (CH_arom, two dias.), 128.4 (CH_arom

,

two dias.), 129.2 (CH_arom, two dias.), 129.9 (CH_arom, two dias.),

130.1 (CH_arom, two dias.), 132.9 (=C, one dia.), 133.0 (=C, one dia.),

134.5 (=C, one dia.), 134.7 (=C, one dia.), 135.1 (=C, two dias.),

140.9 (=C, two dias.), 142.7 (=C, two dias.), 144.1 (=C, two dias.),

145.4 (=C, two dias.), 156.2 (=CH, one dia.), 156.3 (=C, one dia.).

Anal. Calcd for C₃₁H₃₆N₂O₆S₃(628.82): C, 59.21; H, 5.77; N, 4.45.

Found: C, 59.23; H, 5.90; N, 4.01.

9a

Following GP4 from epoxysulfoxide 5a, the sulfoximine 9a was

isolated as an inseparable mixture of two diastereoisomers

(CH₂Cl₂–EA–PE, 50:10:40); yield: 273 mg (85%); yellow oil.

Anal. Calcd for C₃₀H₃₆O₆N₂S₃(616.81): C, 58.42; H, 5.88; N, 4.54.

Found: C, 58.54; H, 5.85; N, 4.39.

IR (neat): 2923, 1597, 1164, 1086, 938 cm^–1.

9c

Following GP4 from epoxysulfoxide 5c, the sulfoximine 9c was

isolated as an inseparable mixture of two diastereoisomers

(CH₂Cl₂–EA, 90:10); yield: 251 mg (78%); yellow oil.

IR (neat): 3029, 1219, 1152, 1086 cm^–1.

¹H NMR (400 MHz, CDCl₃): d = 1.93 [s, 3 H, =C(CH₃)Me, one

dia.], 1.96 [s, 3 H, =C(CH₃)Me, one dia.], 2.20 [s, 3 H, =C(Me)CH₃,

one dia.], 2.21 [s, 3 H, =C(Me)CH₃, one dia.], 2.38 (s, 6 H, CH₃of

p-Tol, two dias.), 2.41 (s, 6 H, CH₃of p-Tol, two dias.), 2.47 (s, 6 H,

CH₃of p-Tol, two dias.), 2.43–2.47 (m, 2 H, trans-OCHH, two

dias.), 2.62–2.68 (m, 2 H, cis-OCHH, two dias.), 2.98–3.06 (m, 2 H,

CHO, two dias.), 3.12 (B of ABX, J = 15.6, 6.1 Hz, 1 H,

CHCHHN, one dia.), 3.21 (B of ABX, J = 15.6, 6.1 Hz, 1 H,

CHCHHN, one dia.), 3.43 (A of ABX, J = 15.6, 4.3 Hz, 1 H,

CHCHHN, one dia.), 3.42 (A of ABX, J = 15.6, 4.3 Hz, 1 H,

CHCHHN, one dia.), 4.38 (B of AB, J = 15.1 Hz, 1 H, =CCHHN,

one dia.), 4.46 (br s, 2 H, =CCH₂N, one dia.), 4.55 (A of AB,

J = 15.1 Hz, 1 H, =CCHHN, one dia.), 7.19–7.21 (m, 4 H_arom, two

¹H NMR (CDCl₃, 400 MHz): d = 1.36–1.45 (m, 6 H, CH₂, two

dias.), 1.61–1.70 (m, 6 H, CH₂, two dias.), 2.30 (s, 6 H, CH₃of p-

Tol, two dias.), 2.34 (s, 6 H, CH₃of p-Tol, two dias.), 2.39 (s, 6 H,

CH₃of p-Tol, two dias.), 2.34–2.44 (m, 6 H, =CCH₂, two dias. +

CHHO, two dias.), 2.45–2.70 (m, 6 H, =CCH₂, two dias. + CHHO,

two dias.), 2.96–3.01 (m, 2 H, CHO, two dias.), 3.17 (B of ABX,

J = 15.6, 6.0 Hz, 1 H, CHCHHN, one dia.), 3.18 (B of ABX,

J = 15.6, 6.0 Hz, 1 H, CHCHHN, one dia.), 3.34 (A of ABX,

J = 15.6, 6.0 Hz, 1 H, CHCHHN, one dia.), 3.35 (A of ABX,

J = 15.6, 6.0 Hz, 1 H, CHCHHN, one dia.), 4.33 (B of AB,

J = 15.1 Hz, 1 H, =CCHHN, one dia.), 4.40 (B of AB, J = 15.1 Hz,

1 H, =CCHHN, one dia.), 4.50 (A of AB, J = 15.1 Hz, 1 H,

=CCHHN, one dia.), 4.52 (A of AB, J = 15.1 Hz, 1 H, =CCHHN,

dias.), 7.24–7.38 (m, 8 H_arom, two dias.), 7.65–7.80 (m, 12 H_arom

two dias.).

,

¹³C NMR (CDCl₃, 100 MHz): d = 21.5 (CH₃of p-Tol, two dias.),

21.6 (CH₃of p-Tol, two dias.), 23.8 [=C(CH₃)Me, two dias.], 25.7

[=C(Me)CH₃, one dia.], 25.7 [=C(Me)CH₃, one dia.], 46.0 (CH₂O,

one dia.), 46.3 (CH₂O, one dia.), 47.4 (=CCH₂N, one dia.), 47.7

(=CCH₂N, one dia.), 50.4 (CHO, one dia.), 50.5 (CHO, one dia.),

one dia.), 7.08–7.13 (m, 4 H_arom, two dias.), 7.25–7.32 (m, 4 H_arom

,

two dias.), 7.41–7.48 (m, 4 H_arom, two dias.), 7.59–7.72 (m,

12 H_arom, two dias.).

¹³C NMR (100 MHz, CDCl₃): d = 21.5 (CH₃of p-Tol, two dias.),

21.6 (CH₃of p-Tol, two dias.), 21.6 (CH₃of p-Tol, two dias.), 25.5

[(CH₂)₃, two dias.], 26.9 [(CH₂)₃, two dias.], 28.0 [(CH₂)₃, two

dias.], 33.3 (=CCH₂, one dia.), 33.4 (=CCH₂, one dia.), 34.5

(=CCH₂, one dia.), 34.6 (=CCH₂, one dia.), 46.2 (NCH₂C=, one

dia.), 46.4 (NCH₂C=, one dia. + CH₂O, one dia.), 46.8 (CH₂O, one

dia.), 50.4 (CHO, one dia.), 50.5 (CHO, one dia.), 50.8 (CHCH₂N,

50.7 (CHCH₂N, two dias.), 126.3 (CH_arom, one dia.), 126.5 (CH_arom

,

one dia.), 127.0 (CH_arom, one dia.), 127.4 (CH_arom, one dia.), 127.5

(CH_arom, one dia.), 127.6 (CH_arom, one dia.), 129.2 (CH_arom, two

dias.), 129.9 (CH_arom, one dia.), 130.0 (CH_arom, one dia.), 130.0

(CH_arom, two dias.), 134.7 (=C, two dias.), 137.1 (=C, two dias.),

140.7 (=C, one dia.), 140.8 (=C, one dia.), 142.7 (=C, two dias.),

143.2 (=C, one dia.), 143.6 (=C, one dia.), 144.1 (=C, one dia.),

Synthesis 2005, No. 9, 1405–1420 © Thieme Stuttgart · New York

1414

D. Leca et al.

PAPER

one dia.), 50.9 (CHCH₂N, one dia.), 126.5 (CH_arom, two dias.), 127.2

(CH_arom, two dias.), 127.6 (CH_arom, two dias.), 129.1 (CH_arom, two

dias.), 129.9 (CH_arom, two dias.), 130.0 (CH_arom, two dias.), 134.9

(=C, two dias.), 135.0 (=C, two dias.), 138.4 (=C, two dias.), 141.2

(=C, two dias.), 142.6 (=C, two dias.), 144.2 (=C, two dias.), 144.8

(=C, two dias.), 166.6 (=C, one dia.), 166.9 (=C, one dia.).

¹H NMR (400 MHz, CDCl₃):

=CCH₂(CH₂)₂], 2.31–2.40 [m, 2 H, =CCH₂(CH₂)₂], 2.50–2.62 [m,

2 H, =CCH₂(CH₂)₂], 3.85 (d, J = 17.2 Hz, 2 H, CH₂Br), 7.35–7.45

(m, 6 H_arom), 7.70–7.75 (m, 4 H_arom).

¹³C NMR (100 MHz, CDCl₃): d = 24.9 [=CCH₂(CH₂)₂], 26.7

[=CCH₂(CH₂)₂], 32.4 (d, J = 17.1 Hz, =CCH₂), 33.6 (d,

J = 11.1 Hz, =CCH₂), 34.5 (d, J = 5.1 Hz, =CCH₂), 120.6 (d,

J = 101.1 Hz, C=CP), 128.4 (d, J = 12.0 Hz, CH_arom), 131.5 (d,

J = 10.3 Hz, CH_arom), 131.8 (d, J = 2.6 Hz, CH_arom), 132.0 (d,

J = 104.0 Hz, PC_arom), 174.0 (d, J = 7.7 Hz, C=CP).

d

=

1.52–1.64 [m, 4 H,

Anal. Calcd for C₃₂H₃₈N₂O₆S₃(642.85): C, 59.79; H, 5.96; N, 4.36.

Found: C, 59.83; H, 6.06; N, 4.40.

14a

Following GP1, the bromide 14a was isolated as a white solid (EA–

PE 40:60); yield: 649 mg (93%); mp 105–107 °C.

³¹P NMR (162 MHz, CDCl₃): d = 30.84.

IR (neat): 2950, 1602, 1436, 1169, 1113, 925 cm^–1.

14e

Following GP1, the bromide 14e was isolated as a yellow oil (EA–

PE, 70:30); yield: 361 mg (50%).

IR (neat): 3053, 2958, 1639, 1436, 1177 cm^–1.

¹H NMR (400 MHz, CDCl₃): d = 2.02 (d, J = 2.8 Hz, 3 H, CH₃),

2.06 (d, J = 2.0 Hz, 3 H, CH₃), 3.91 (d, J = 17.4 Hz, 2 H, CH₂),

7.44–7.51 (m, 6 H_arom) 7.74–7.85 (m, 4 H_arom).

¹³C NMR (100 MHz, CDCl₃): d = 23.5 (d, J = 9.0 Hz, CH₃), 25.7

(d, J = 8.0 Hz, CH₃), 31.7 (d, J = 18.0 Hz, CH₂), 124.6 (d,

J = 100.0 Hz, CP), 128.4 (d, J = 18.0 Hz, CH_arom), 131.7 (d,

J = 4.1 Hz, CH_arom), 133.0 (d, J = 100.0 Hz, PC_arom), 162.0 (d,

J = 8 Hz, C=CP).

³¹P NMR (162 MHz, CDCl₃): d = 32.72.

HRMS: m/z calcd for C₁₇H₁₈BrOP ([M + Na]⁺): 373.0156;

¹H NMR (400 MHz, CDCl₃): d = 1.82–1.90 (m, 2 H, =CCH₂CH₂),

2.38–2.47 (m, 2 H, =CCH₂CH₂), 2.81–2.89 (m, 2 H, =CCH₂CH₂),

3.88 (d, J = 15.4 Hz, 2 H, CH₂Br), 7.31–7.44 (m, 6 H_arom), 7.65–

7.69 (m, 4 H_arom).

¹³C NMR (100 MHz, CDCl₃): d = 16.3 (=CCH₂CH₂), 28.1 (d,

J = 14.6 Hz, =CCH₂), 32.3 (d, J = 13.7 Hz, =CCH₂), 33.2 (d,

J = 7.7 Hz, =CCH₂), 121.8 (d, J = 101.1 Hz, C=CP), 128.3 (d,

J = 12.0 Hz, CH_arom), 131.6 (d, J = 10.3 Hz, CH_arom), 131.6 (d,

J = 2.6 Hz, CH_arom), 132.0 (d, J = 102.8 Hz, PC_arom), 170.5 (d,

J = 7.7 Hz, C=CP).

found: 373.0146.

14b

Following GP1, the bromide 14b was isolated as a colorless oil

(EA–PE, 60:40); yield: 487 mg (67%).

³¹P NMR (162 MHz, CDCl₃): d = 28.14.

14f

IR (neat): 2964, 1621, 1437, 1176, 721 cm^–1.

Following GP1, the bromide 14f was isolated as a white gum (EA–

CH₂Cl₂, 80:20); yield: 519 mg (58%).

IR (neat): 3054, 2953, 2883, 2218, 1597, 1098 cm^–1.

¹H NMR (400 MHz, CDCl₃): d = 1.00 [d, J = 6.6 Hz, 6 H,

CH(CH₃)₂], 2.85–2.93 (m, 1 H, CHMe₂), 4.09 (d, J = 15.6 Hz, 2 H,

CH₂), 6.22 (dd, J = 19.9, 10.3 Hz, 1 H, =CH), 7.38–7.40 (m,

6 H_arom) 7.59–7.71 (m, 4 H_arom).

¹³C NMR (100 MHz, CDCl₃): d = 21.4 (CH₃), 23.8 (d, J = 14.6 Hz,

CHMe₂), 29.0 (d, J = 12.9 Hz, CH₂), 127.5 (d, J = 99.4 Hz, C=CP),

128.4 (d, J = 12 Hz, CH_arom), 131.1 (d, J = 103 Hz, PC_arom), 132.1

(d, J = 10.3 Hz, CH_arom), 132.1 (CH_arom), 159.5 (=CH).

¹H NMR (400 MHz, CDCl₃): d = 1.40–1.44 (m, 2 H, =CCH₂CH₂),

1.82–1.87 (m, 2 H, =CCH₂CH₂), 2.59–2.66 (m, 4 H, =CCH₂CH₂),

3.84–3.95 (m, 6 H, CH₂Br + OCH₂), 7.42–7.55 (m, 6 H_arom), 7.73–

7.85 (m, 4 H_arom).

¹³C NMR (100 MHz, CDCl₃): d = 29.9 (d, J = 11.1 Hz, =CCH₂),

30.4 (d, J = 18.0 Hz, =CCH₂), 31.6 (d, J = 8.6 Hz, =CCH₂), 34.4

(=CCH₂CH₂), 34.9 (=CCH₂CH₂), 64.5 (OCH₂), 107.6 (OCO),

123.9 (d, J = 99.4 Hz, C=CP), 128.6 (d, J = 12.0 Hz, CH_arom), 131.5

(d, J = 10.3 Hz, CH_arom), 131.9 (d, J = 2.6 Hz, CH_arom), 132.8 (d,

J = 102.8 Hz, PC_arom), 165.4 (d, J = 7.7 Hz, C=CP).

³¹P NMR (162 MHz, CDCl₃): d = 32.0.

14c

Following GP1, the bromide 14c was isolated as a yellow oil (EA–

PE, 70:30); yield: 311 mg (40%).

IR (neat): 2929, 1735, 1590, 1436, 1244, 1183, 694 cm^–1.

³¹P NMR (162 MHz, CDCl₃): d = 32.10.

¹H NMR (400 MHz, CDCl₃):

d

=

1.25–1.34 [m, 2 H,

14g

=CCH₂(CH₂)₃], 1.41–1.50 [m, 2 H, =CCH₂(CH₂)₃], 1.62–1.73 [m,

2 H, =CCH₂(CH₂)₃], 2.34–2.49 [m, 4 H, =CCH₂(CH₂)₃], 3.89 (d,

J = 17.2 Hz, 2 H, BrCH₂), 7.29–7.47 (m, 6 H_arom), 7.76–7.81 (m,

4 Harom).

¹³C NMR (100 MHz, CDCl₃): d = 25.6 [=CCH₂(CH₂)₃], 27.1

[=CCH₂(CH₂)₃], 27.7 [=CCH₂(CH₂)₃], 30.6 (d, J = 19.0 Hz,

=CCH₂), 33.2 (d, J = 11 Hz, =CCH₂), 35.2 (d, J = 9.0 Hz, =CCH₂),

122.0 (d, J = 100.3 Hz, C=CP), 128.3 (d, J = 12 Hz, CH_arom), 131.5

(d, J = 9 Hz, CH_arom), 133.6 (d, J = 102.0 Hz, PC_arom), 168.6 (d,

J = 7.7 Hz, C=CP).

Following GP1, the bromide 14g was isolated as a yellow solid

(CH₂Cl₂–EA, 10:90); yield: 524 mg (66%); mp 106–108 °C.

IR (neat): 3033, 1962, 1606, 1436, 1189 cm^–1.

¹H NMR (400 MHz, CDCl₃): d = 4.36 (d, J = 17.2 Hz, 2 H, CH₂Br),

7.30 (d, J = 19.9 Hz, 1 H, =CH), 7.37–7.46 (m, 3 H_arom), 7.47–7.53

(m, 4 H_arom), 7.54–7.61 (m, 4 H_arom), 7.77–7.82 (m, 4 H_arom).

¹³C NMR (100 MHz, CDCl₃): d = 26.5 (d, J = 12.0 Hz, CH₂Br),

128.6 (d, J = 12.0 Hz, CH_arom), 128.9 (CH_arom), 129.7 (CH_arom),

130.6 (d, J = 97.7 Hz, CP), 131.2 (d, J = 103.7 Hz, CP), 132.3

(CH_arom), 132.3 (d, J = 10.3 Hz, CH_arom), 132.3 (d, J = 2.3 Hz,

CH_arom), 134.2 (d, J = 16.3 Hz, C_arom), 147.3 (d, J = 11.1 Hz, =CH).

³¹P NMR (162 MHz, CDCl₃): d = 32.06.

14d

³¹P NMR (162 MHz, CDCl₃): d = 32.9.

Following GP1, the bromide 14d was isolated as a yellow oil (EA–

PE, 60:40); yield: 563 mg (75%).

IR (neat): 2960, 1604, 1437, 1174, 694 cm^–1.

Anal. Calcd for C₂₁H₁₈BrOP (397.24): C, 63.49; H, 4.57. Found:

C, 63.51; H, 4.68.

Synthesis 2005, No. 9, 1405–1420 © Thieme Stuttgart · New York

PAPER

Radical Intramolecular Vinylations

1415

14h

15b

Following GP1, the bromide 14h was isolated as an inseparable

variable E/Z mixture of isomers (usually 1.4:1 to 2:1) (EA–CH₂Cl₂,

80:20); yield: 412 mg (57%); yellow oil. The Z-isomer rearranged

upon standing to the E-isomer within a few hours.

Following GP3 from bromide 14b, the substrate 15b was isolated as

a white solid (EA–PE, 60:40); yield: 350 mg (69%); mp 41–43 °C.

IR (neat): 3051, 1435, 1158 cm^–1.

¹H NMR (400 MHz, CDCl₃): d = 0.99 (d, J = 6.6 Hz, 3 H,

CH₃CHMe), 1.01 (d, J = 6.6 Hz, 3 H, MeCHCH₃), 2.36 (s, 3 H,

ArCH₃), 2.56 (B of ABX, J = 5.1, 2.5 Hz, 1 H, CHHO), 2.68 (A of

ABX, J = 5.1, 4.8 Hz, 1 H, CHHO), 3.10–3.14 (m, 1 H, CHO),

3.31–3.37 (m, 3 H, CHCH₂N + Me₂CH), 3.87 (B of ABX, J = 13.2,

11.2 Hz, 1 H, CHHCP), 4.19 (A of ABX, J = 13.2, 12.6 Hz, 1 H,

CHHCP), 5.91 (dd, J = 21.2, 10.4 Hz, 1 H, = CH), 7.22 (d,

J = 8.1 Hz, 2 H_arom), 7.41–7.62 (m, 12 H_arom).

¹³C NMR (100 MHz, CDCl₃): d = 21.5 (CH₃), 21.6 (CH₃), 21.9

(CH₃), 28.2 (d, J = 14.6 Hz, Me₂CH), 45.0 (d, J = 13.7 Hz, CH₂CP),

46.3 (CH₂O), 50.5 (CHCH₂N), 50.8 (CHO), 125.4 (d, J = 99.4 Hz,

=CP), 127.6 (CH_arom), 128.6 (d, J = 12 Hz, CH_arom), 128.7 (d,

J = 12 Hz, CH_arom), 129.8 (CH_arom), 131.2 (d, J = 102 Hz, PC_arom),

131.4 (d, J = 102 Hz, PC_arom), 131.9–132.1 (m, CH_arom), 134.6

(C_arom), 143.7 (C_arom), 161.0 (d, J = 8.6 Hz, PC=CH).

IR (neat): 3055, 3008, 1617, 1174, 1117 cm^–1.

¹H NMR (400 MHz, CDCl₃): d = 0.55–0.59 (m, 2 H, c-CH₂, Z-iso-

mer), 0.66–0.70 (m, 2 H, c-CH₂, E-isomer), 0.78–0.82 (m, 2 H, c-

CH₂, Z isomer), 1.06–1.10 (m, 2 H, c-CH₂, E-isomer), 1.85–2.01

(m, 2 H, Z- + E-isomers), 3.96 (d, J = 14.9 Hz, 2 H, CH₂Br, Z-iso-

mer), 4.23 (d, J = 15.6 Hz, 2 H, CH₂Br, E-isomer), 5.90 (dd,

J = 18.1, 10.8 Hz, 1 H, E-isomer), 6.10 (dd, J = 32.3, 10.8 Hz, 1 H,

Z-isomer), 7.39–7.58 (m, 6 H_arom, Z- + E-isomers), 7.62–7.88 (m,

4 H_arom, Z- + E-isomers).

¹³C NMR (100 MHz, CDCl₃): d = 9.4 (c-CH₂, Z- + E-isomers), 9.7

(c-CH₂, Z- + E-isomers), 13.1 (d, J = 17.1 Hz, =CCH, E-isomer),

14.5 (d, J = 7.7 Hz, =CCH, Z-isomer), 25.6 (d, J = 15.4 Hz, CH₂Br,

E-isomer), 35.6 (d, J = 15.4 Hz, CH₂Br, Z-isomer), 126.3 (d,

J = 102.8 Hz, C=CP, E-isomer), 126.6 (d, J = 101.0 Hz, C=CP, Z-

isomer), 128.5 (d, J = 12.9 Hz, CH_arom, Z- + E-isomers), 131.2 (d,

J = 103.7 Hz, PC_arom, E-isomer), 131.7–132.0 (m, CH_arom), 132.2 (d,

J = 103.7 Hz, PC_arom, Z-isomer), 158.5 (d, J = 9.4 Hz, =CH, E-iso-

mer), 160.8 (d, J = 6.9 Hz, =CH, Z-isomer).

³¹P NMR (162 MHz, CDCl₃): d = 35.5.

HRMS: m/z calcd for C₂₈H₃₂NO₄PS [M + Na]⁺: 532.1687;

found: 532.1685.

³¹P NMR (162 MHz, CDCl₃): d = 30.8 (Z-isomer), 31.7 (E-isomer).

15c

Following GP3 from bromide 14c, the substrate 15c was isolated as

a white gum (CH₂Cl₂–PE, 60:40); yield: 402 mg (75%).

IR (neat): 3054, 2929, 1595, 1160 cm^–1.

14i

Following GP1, the bromide 14i was isolated as a slightly yellow oil

(EA–PE, 60:40); yield: 485 mg (85%).

¹H NMR (400 MHz, CDCl₃): d = 1.13–1.21 (m, 2 H, CH₂of c-hex-

enylidene), 1.43–1.47 (m, 2 H, CH₂of c-hexenylidene), 1.64–1.70

(m, 2 H, CH₂of c-hexenylidene), 2.18–2.23 (m, 2 H, CH₂of c-hex-

enylidene), 2.34 (s, 3 H, ArCH₃), 2.51 (B of ABX, J = 4.8, 2.5 Hz,

1 H, CHHO), 2.57–2.68 (m, 3 H, CHHO + CH₂of c-hexenylidene),

2.94–2.96 (m, 2 H, CHCH₂N), 3.10–3.14 (m, 1 H, CHO), 3.98–4.02

(m, 2 H, CH₂CP), 7.18 (d, J = 8.3 Hz, 2 H_arom), 7.34–7.42 (m,

6 H_arom), 7.52 (d, J = 8.4 Hz, 2 H_arom), 7.56–7.61 (m, 4 H_arom).

¹³C NMR (100 MHz, CDCl₃): d = 21.4 (ArCH₃), 25.6 (CH₂of c-

hexenylidene), 26.9 (CH₂of c-hexenylidene), 27.8 (CH₂of c-hexe-

nylidene), 33.2 (d, J = 12 Hz, PC=CCH₂), 36.0 (d, J = 9.4 Hz,

PC=CCH₂), 46.4 (CH₂O), 46.8 (d, J = 15.4 Hz, CH₂CP), 49.5

(CHCH₂N), 50.9 (CHO), 117.7 (d, J = 100.3 Hz, =CP), 127.5

(CH_arom), 128.5 (d, J = 12 Hz, CH_arom), 129.7 (CH_arom), 131.3–131.5

(m, CH_arom), 133.8 (C_arom), 133.9 (d, J = 101 Hz, PC_arom), 134.1 (d,

J = 102 Hz, PC_arom), 143.5 (C_arom), 168.5 (d, J = 7.7 Hz, PC=C).

IR (neat): 3051, 2983, 1616, 1268, 1235 cm^–1.

¹H NMR (400 MHz, CDCl₃): d = 1.33 (t, J = 7.1 Hz, 6 H,

OCH₂CH₃), 1.99 (d, J = 2.5 Hz, 3 H, =CCH₃), 2.18 (d, J = 3.3 Hz,

3 H, =CCH₃), 4.04–4.15 (m, 4 H, OCH₂Me), 4.25 (d, J = 17.7 Hz,

2 H, CH₂Br).

¹³C NMR (50 MHz, CDCl₃): d = 16.6 (d, J = 6.7 Hz, OCH₂CH₃),

23.2 (d, J = 17.4 Hz, =CCH₃), 24.8 (d, J = 6.7 Hz, =CCH₃), 30.5 (d,

J = 15.5 Hz, CH₂Br), 62.1 (d, J = 5.4 Hz, OCH₂Me), 121.9 (d,

J = 185.0 Hz, =CP), 160.4 (d, J = 11.0 Hz, C=CP).

³¹P NMR (162 MHz, CDCl₃): d = 19.50.

15a

Following GP3 from bromide 14a, the substrate 15a was isolated as

a white solid (EA–PE, 70:30); yield: 446 mg (90%); mp 62–65 °C.

IR (neat): 3053, 1599, 1160 cm^–1.

¹H NMR (400 MHz, CDCl₃): d = 1.75 [br s, 3 H, =C(CH₃)Me], 2.20

[br s, 3 H, =C(Me)CH₃], 2.38 (s, 3 H, ArCH₃), 2.53 (B of ABX,

J = 5.1, 2.5 Hz, 1 H, CHHO), 2.69 (A of ABX, J = 5.1, 4.8 Hz, 1 H,

CHHO), 2.99 (B of ABX, J = 15.8, 4.9 Hz, CHOCHHN), 3.06 (A

of ABX, J = 15.8, 4.4 Hz, CHOCHHN), 3.10–3.12 (m, 1 H, CHO),

3.99 (B of ABX, J = 12.6, 12.6 Hz, NCHHCP), 4.02 (A of ABX,

J = 12.6, 12.6 Hz, NCHHCP), 7.21 (d, J = 8.1 Hz, 2 H_arom), 7.37–

7.40 (m, 7 H_arom), 7.52–7.64 (m, 5 H_arom).

³¹P NMR (162 MHz, CDCl₃): d = 30.6.

HRMS: m/z calcd for C₃₀H₃₄NO₄PS [M + Na]⁺: 558.1844;

found: 558.1844.

15d

Following GP3 from bromide 14d, the substrate 15d was isolated as

a colorless oil (EA–PE, 50:50); yield: 261 mg (50%).

IR (neat): 3054, 2957, 2884, 1610, 1158 cm^–1.

¹³C NMR (100 MHz, CDCl₃): d = 21.6 (ArCH₃), 24.4 [d, J = 13 Hz,

=C(CH₃)Me], 26.3 [d, J = 8 Hz, =C(Me)CH₃], 46.6 (CH₂O), 47.9

(d, J = 15 Hz, CH₂CP), 49.6 (CHCH₂N), 50.9 (CHO), 120.3 (d,

J = 101 Hz, = CP), 127.6 (CH_arom), 128.7 (d, J = 11.6 Hz, CH_arom),

129.8 (CH_arom), 131.4–131.7 (m, CH_arom), 133.6 (d, J = 102 Hz,

PC_arom), 133.9 (C_arom), 143.7 (CSO₂), 161.2 (PC=C).

³¹P NMR (162 MHz, CDCl₃): d = 30.6.

HRMS: m/z calcd for C₂₇H₃₀NO₄PS [M + Na]⁺: 518.1531;

¹H NMR (400 MHz, CDCl₃): d = 1.51–1.53 (m, 2 H, CH₂of c-pen-

tenylidene), 1.62–1.67 (m, 2 H, CH₂of c-pentenylidene), 1.91–1.94

(m, 2 H, CH₂of c-pentenylidene), 2.36 (s, 3 H, ArCH₃), 2.52 (B of

ABX, J = 4.9, 2.1 Hz, 1 H, CHHO), 2.68 (A of ABX, J = 4.9,

4.2 Hz, 1 H, CHHO), 2.81–2.89 (m, 2 H, CH₂of c-pentenylidene),

3.06–3.17 (m, 3 H, CHO + CHCH₂N), 3.95–4.13 (m, 2 H, CH₂CP),

7.22 (d, J = 8.4 Hz, 2 H_arom), 7.40–7.49 (m, 6 H_arom), 7.56–7.62 (m,

6 H_arom).

found: 518.1525.

¹³C NMR (100 MHz, CDCl₃): d = 21.5 (ArCH₃), 25.3 (CH₂of c-

pentenylidene), 26.8 (CH₂of c-pentenylidene), 34.7–35.5 (m,

=CCH₂), 46.4 (CH₂O), 48.7 (d, J = 14.6 Hz, CH₂CP), 49.9

1416

D. Leca et al.

PAPER

(CHCH₂N), 50.9 (CHO), 116.5 (d, J = 102 Hz, =CP), 127.5

(CH_arom), 128.5–128.8 (m, CH_arom), 129.8 (CH_arom), 131.6–132.4

(m, CH_arom), 132.9 (d, J = 102 Hz, PC_arom), 133.3 (d, J = 102 Hz,

PC_arom), 134.4 (C_arom), 143.6 (C_arom), 172.0 (d, J = 7.7 Hz, PC=C).

³¹P NMR (162 MHz, CDCl₃): d = 30.9.

HRMS: m/z calcd for C₂₉H₃₂NO₄PS [M + Na]⁺: 544.1687;

¹H NMR (400 MHz, CDCl₃): d = 2.39 (s, 3 H, ArCH₃), 2.39–2.41

(m, 1 H, CHHO), 2.54 (A of ABX, J = 5.1, 4.0 Hz, 1 H, CHHO),

2.74–2.75 (m, 1 H, CHO), 3.18–3.21 (m, 2 H, CHCH₂N), 4.34 (B

of ABX, J = 14.6, 13.9 Hz, 1 H, CHHCP), 4.44 (A of ABX,

J = 14.6, 12.9 Hz, 1 H, CHHCP), 7.09 (d, J = 21.7 Hz, 1 H, =CH),

7.16 (d, J = 8.6 Hz, 2 H_arom), 7.28–7.32 (m, 2 H_arom), 7.41–7.50 (m,

11 H_arom), 7.78–7.85 (m, 4 H_arom).

¹³C NMR (100 MHz, CDCl₃): d = 21.5 (ArCH₃), 45.2 (d, J = 11 Hz,

CH₂CP), 46.3 (CH₂O), 49.8 (CHO), 51.2 (CHCH₂N), 127.6

(CH_arom), 128.5 (CH_arom), 128.6 (CH_arom), 128.7 (CH_arom), 129.0

(CH_arom), 129.5 (CH_arom), 129.6 (CH_arom), 131.0 (d, J = 97.7 Hz,

=CP), 131.4 (d, J = 102.8 Hz, =CP), 131.6 (d, J = 103.7 Hz, =CP),

132.2 (CH_arom), 132.2 (CH_arom), 132.3 (CH_arom), 132.3 (CH_arom),

134.7 (C_arom), 134.9 (C_arom), 143.5 (C_arom), 147.8 (d, J = 12 Hz,

PC=_CH).

found: 544.1661.

15e

Following GP3 from bromide 14e, the substrate 15e was isolated as

a white solid (EA–PE, 70:30); yield: 294 mg (58%); mp 57–59 °C.

IR (neat): 3054, 2956, 1733, 1646, 1116 cm^–1.

¹H NMR (400 MHz, CDCl₃):

d

=

1.85–1.91 (m, 2 H,

2 H of CH₂CH₂CH₂), 2.05–2.11 (m, 2 H, 2 H of CH₂CH₂CH₂), 2.34

(s, 3 H, ArCH₃), 2.53 (B of ABX, J = 5.1, 2.5 Hz, 1 H, CHHO),

2.68 (A of ABX, J = 5.1, 4.2 Hz, 1 H, CHHO), 3.06–3.10 (m, 1 H,

CHO), 3.16–3.24 (m, 3 H, CHCHHN + 2 H of CH₂CH₂CH₂), 3.33

(A of ABX, J = 15.5, 4.3 Hz, 1 H, CHCHHN), 3.90 (B of ABX,

J = 13.9, 10.4 Hz, 1 H, CHHCP), 4.11 (A of ABX,

J = 14.6, 12.9 Hz, 1 H, CHHCP), 7.20 (d, J = 8.1 Hz, 2 H_arom),

7.40–7.51 (m, 6 H_arom), 7.57–7.65 (m, 6 H_arom).

³¹P NMR (162 MHz, CDCl₃): d = 35.6.

HRMS: m/z calcd for C₃₁H₃₀NO₄PS [M + Na]⁺: 566.1531;

found: 566.1536.

15h

Following GP3 from bromide 14h, the substrate 15h was isolated as

a colorless oil (EA–PE, 50:50 to 90:10); yield: 254 mg (50%).

IR (neat): 3054, 1626, 1175 cm^–1.

¹³C NMR (100 MHz, CDCl₃): d = 16.8 (CH₂CH₂CH₂), 21.5

(ArCH₃), 33.6–33.8 (m, CH₂CH₂CH₂), 46.2 (CH₂O), 46.9 (d,

J = 13 Hz, CH₂CP), 50.5 (CHCH₂N), 50.5 (CHO), 118.2 (d,

J = 101 Hz, =CP), 127.4 (CH_arom), 128.6–128.9 (m, CH_arom), 129.7

(CH_arom), 131.7–132.3 (m, CH_arom), 132.4 (d, J = 96 Hz, PC_arom),

132.8 (d, J = 103 Hz, PC_arom), 135.2 (C_arom), 143.5 (C_arom), 168.4 (d,

J = 9.4 Hz, PC=C).

¹H NMR (400 MHz, CDCl₃): d = 0.44–0.48 (m, 2 H, c-CH₂), 1.01–

1.07 (m, 2 H, c-CH₂), 2.38 (s, 3 H, ArCH₃), 2.36–2.40 (m, 1 H, c-

CH), 2.60 (B of ABX, J = 4.8, 2.5 Hz, 1 H, CHHO), 2.69 (A of

ABX, J = 4.8, 4.2 Hz, 1 H, CHHO), 3.12–3.14 (m, 1 H, CHO), 3.24

(B of ABX, J = 15.4, 4.8 Hz, 1 H, CHCHHN), 3.37 (A of ABX,

J = 15.4, 5.3 Hz, 1 H, CHCHHN), 4.02 (B of ABX, J = 12.6,

12.6 Hz, NCHHCP), 4.24 (A of ABX, J = 12.6, 12.6 Hz, NCHH-

CP), 5.44 (dd, J = 19.8, 10.7 Hz, 1 H, =CH), 7.24 (d, J = 8.4 Hz,

2 H_arom), 7.42–7.64 (m, 12 H_arom).

³¹P NMR (162 MHz, CDCl₃): d = 29.0.

HRMS: m/z calcd for C₂₈H₃₀NO₄PS [M + Na]⁺: 530.1531;

found: 530.1497.

¹³C NMR (100 MHz, CDCl₃): d = 9.3 (c-CH₂), 9.5 (c-CH₂), 12.5 (d,

J = 18 Hz, c-CH), 21.6 (ArCH₃), 45.6 (d, J = 13.7 Hz, CH₂CP),

46.7 (CH₂O), 50.0 (CHCH₂N), 51.0 (CHO), 124.2 (d, J = 102.8 Hz,

=CP), 127.5 (CH_arom), 128.6 (d, J = 5.1 Hz, CH_arom), 128.7 (d,

J = 5.1 Hz, CH_arom), 129.9 (CH_arom), 131.3 (d, J = 103 Hz, PC_arom),

131.4 (d, J = 104 Hz, PC_arom), 131.9–132.1 (m, CH_arom), 134.8

(C_arom), 143.8 (C_arom), 159.2 (d, J = 11 Hz, =CH).

15f

Following GP3 from bromide 14f, the substrate 15f was isolated as

a white solid (EA–CH₂Cl₂, 80:20); yield: 392 mg (66%), mp 75–

77 °C.

IR (neat): 3056, 2931, 2884, 1598, 1162 cm^–1.

¹H NMR (400 MHz, CDCl₃): d = 1.21–1.35 (m, 2 H, =CCH₂CH₂),

1.70–1.85 (m, 2 H, =CH₂CH₂), 2.32 (m, 5 H, ArCH₃+ =CCH₂),

2.48 (B of ABX, J = 4.8, 2.5 Hz, 1 H, CHHO), 2.65–2.67 (m, 1 H,

CHHO), 2.70–2.77 (m, 1 H, =CCHH), 2.84–2.90 (m, 2 H, =CCHH

+ CHCHHN), 3.04 (A of ABX, J = 15.6, 4.3 Hz, 1 H, CHCHHN),

3.09–3.12 (m, 1 H, CHO), 3.78–3.83 (m, 4 H, OCH₂CH₂O), 3.92–

4.07 (m, 2 H, CH₂CP), 7.17 (d, J = 8.1 Hz, 2 H_arom), 7.31–7.41 (m,

6 H_arom), 7.51–7.59 (m, 6 H_arom).

¹³C NMR (100 MHz, CDCl₃): d = 21.4 (ArCH₃), 29.8 (d, J = 12 Hz,

=CCH₂), 32.3 (d, J = 8.6 Hz, =CCH₂), 34.2 (=CCH₂CH₂), 34.8

(=CCH₂CH₂), 46.4 (CH₂O), 46.9 (d, J = 14.6 Hz, CH₂CP), 49.7

(CHCH₂N), 50.9 (CHO), 64.3 (OCH₂CH₂O), 107.4 (OCO), 119.4

(d, J = 99.4 Hz, =CP), 127.5 (CH_arom), 128.5 (d, J = 12 Hz, CH_arom),

129.6 (CH_arom), 131.1–131.6 (m, CH_arom), 133.5 (C_arom), 133.6 (d,

J = 101 Hz, PC_arom), 134.1 (d, J = 102 Hz, PC_arom), 143.6 (C_arom),

164.7 (d, J = 8.6 Hz, PC=C).

³¹P NMR (162 MHz, CDCl₃): d = 4.8.

HRMS: m/z calcd for C₂₈H₃₀NO₄PS [M + Na]⁺: 530.1531;

found: 530.1519.

15i

Following GP3 from bromide 14i, the substrate 15i was isolated as

a colorless oil (EA–EP 60:40); yield: 367 mg (85%).

IR (neat): 2982, 1617, 1598, 1018 cm^–1.

¹H NMR (400 MHz, CDCl₃): d = 1.25 (td, J = 7.1, 2.2 Hz, 6 H,

CH₂CH₃), 2.10 [d, J = 2.2 Hz, 3 H, =C(CH₃)Me], 2.14 [d,

J = 2.8 Hz, 3 H, =C(Me)CH₃], 2.41 (s, 3 H, ArCH₃), 2.54–2.55 (m,

1 H, CHHO), 2.68–2.69 (m, 1 H, CHHO), 3.02 (B of ABX,

J = 14.8, 5.6 Hz, 1 H, CHCHHN), 3.06–3.09 (m, 1 H, CHO), 3.24

(A of ABX, J = 14.8, 4.0 Hz, 1 H, CHCHHN), 3.97–4.11 (m, 6 H,

CH₂Me + NCH₂CP), 7.30 (d, J = 8.1 Hz, 2 H_arom), 7.69 (d,

J = 8.1 Hz, 2 H_arom).

¹³C NMR (100 MHz, CDCl₃): d = 16.3 (d, J = 6 Hz, CH₂CH₃), 21.5

(ArCH₃), 23.8 [d, J = 18 Hz, =C(CH₃)Me], 24.9 [d, J = 7.7 Hz,

=C(Me)CH₃], 46.8 (CHCH₂O), 48.1 (d, J = 16.3 Hz, NCH₂CP),

49.6 (CHCH₂N), 50.6 (CHO), 61.7 (d, J = 4.2 Hz, CH₂Me), 117.7

(d, J = 184 Hz, PC=C), 127.8 (CH_arom), 129.8 (CH_arom), 134.8

(C_arom), 143.6 (C_arom), 161.8 (d, J = 10 Hz, PC=C).

³¹P NMR (162 MHz, CDCl₃): d = 30.5.

HRMS: m/z calcd for C₃₂H₃₆NO₆PS [M + H]⁺: 594.2079;

found: 594.2081.

15g

Following GP3 from bromide 14g, the substrate 15g was isolated as

a white solid (CH₂Cl₂–PE, 60:40); yield: 424 mg (78%); mp 57–

59 °C.

IR (neat): 2923, 1596, 1116 cm^–1.

³¹P NMR (162 MHz, CDCl₃): d = 20.2.

PAPER

Radical Intramolecular Vinylations

1417

10a

J = 13.6 Hz, 1 H, NCHHC=), 7.33 (d, J = 8.3 Hz, 2 H_arom), 7.71 (d,

J = 8.3 Hz, 2 H_arom).

Following GP5 from substrate 15a, the cycloadduct 10a was isolat-

ed as a yellow oil (PE–EA, 80:20); yield: 177 mg (80%).

IR (neat): 3522, 2922, 1598 cm^–1.

¹³C NMR (100 MHz, CDCl₃): d = 21.6 (ArCH₃), 26.4 (CH₂CH₂=),

26.7 (CH₂CH₂=), 31.0 (CH₂CH₂=), 31.3 (CH₂CH₂=), 45.0

(CHCH₂O), 50.6 (CH₂N), 50.8 (CH₂N), 62.4 (CH₂O), 124.5 (C=C),

128.0 (CH_arom), 129.7 (CH_arom), 132.4 (C_arom), 138.6 (C=C), 143.7

(C_arom).

¹H NMR (400 MHz, CDCl₃): d = 1.55 [s, 3 H, =C(CH₃)Me], 1.65

[s, 3 H, =C(Me)CH₃], 2.43 (s, 3 H, ArCH₃), 2.91–2.96 (m, 2 H, CH

+ CHCHHN), 3.41–3.51 (m, 3 H, CH₂O + NCHHC=), 3.66 (A of

AB, J = 8.6 Hz, 1 H, CHCHHN), 3.91 (A of AB, J = 13.4 Hz, 1 H,

NCHHC=), 7.33 (d, J = 8.1 Hz, 2 H_arom), 7.71 (d, J = 8.1 Hz,

2 H_arom).

¹³C NMR (100 MHz, CDCl₃): d = 20.7 [=C(CH₃)Me], 21.0

[=C(Me)CH₃], 21.5 (ArCH₃), 43.8 (CH), 50.2 (CH₂N), 50.3

(CH₂N), 62.7 (CH₂O), 127.2 (C), 127.8 (CH_arom), 128.0 (C), 129.6

(CH_arom), 132.2 (C_arom), 143.6 (C_arom).

10e

Following GP5 from substrate 15e, the cycloadduct 10e was isolat-

ed as a white solid (PE–EA, 70:30); yield: 131 mg (57%); mp 99–

101 °C.

IR (neat): 3449, 2919, 1597 cm^–1.

¹H NMR (400 MHz, CDCl₃):

d

=

1.91–1.99 (m, 2 H,

2 H of CH₂CH₂CH₂), 2.42 (s, 3 H, ArCH₃), 2.45–2.71 (m, 4 H, 4

H of CH₂CH₂CH₂), 2.75–2.83 (m, 1 H, CHCH₂O), 3.17 (B of ABX,

J = 9.8, 6.8 Hz, 1 H, CHCHHN), 3.39–3.44 (m, 2 H, CHCHHN +

CHHO), 3.50 (A of ABX, J = 10.7, 5.4 Hz, 1 H, CHHO), 3.53 (br-

B of AB, J = 13.4 Hz, 1 H, NCHHC=), 3.67 (br-A of AB,

J = 13.4 Hz, 1 H, NCHHC=), 7.32 (d, J = 8.1 Hz, 2 H_arom), 7.69 (d,

J = 8.1 Hz, 2 H_arom).

¹³C NMR (100 MHz, CDCl₃): d = 17.4 (CH₂CH₂CH₂), 21.7

(ArCH₃), 30.0 (=CH₂), 30.2 (=CH₂), 43.6 (CHCH₂O), 49.6 (CH₂N),

50.9 (CH₂N), 62.8 (CH₂O), 124.9 (C=C), 128.0 (CH_arom), 129.8

(CH_arom), 132.4 (C=C), 135.9 (C_arom), 143.8 (C_arom).

Anal. Calcd for C₁₅H₂₁NO₃S (295.40): C, 60.99; H, 7.17; N, 4.74.

Found: C, 60.82; H, 7.37; N, 4.59.

10b

Following GP5 from substrate 15b, the cycloadduct 10b was isolat-

ed as a yellow oil (PE–EA, 60:40); yield: 142 mg (61%).

IR (neat): 3521, 2922, 1151 cm^–1.

¹H NMR (400 MHz, CDCl₃): d = 0.93 (d, J = 6.7 Hz, 3 H,

CH₃CHMe), 0.94 (d, J = 6.7 Hz, 3 H, MeCHCH₃), 2.20–2.26 (m,

1 H, MeCHMe), 2.43 (s, 3 H, ArCH₃), 2.75–2.79 (m, 1 H,

CHCH₂O), 3.24–3.31 (m, 2 H, CHCH₂N), 3.53 (d, J = 6.8 Hz, 2 H,

CH₂O), 3.70 (B of AB, J = 14 Hz, 1 H, NCHHC=), 3.83 (A of AB,

J = 14 Hz, 1 H, NCHHC=), 5.16 (dd, J = 9.6, 1.8 Hz, 1 H, =CH),

7.33 (d, J = 8.1 Hz, 2 H_arom), 7.69 (d, J = 8.1 Hz, 2 H_arom).

¹³C NMR (100 MHz, CDCl₃): d = 21.5 (ArCH₃), 22.5 (CH₃MeCH),

22.9 (MeCH₃CH), 29.3 (Me₂CH), 45.3 (CHCH₂O), 49.3

(NCH₂C=), 50.5 (CHCH₂N), 63.9 (CH₂O), 127.9 (CH_arom), 129.8

(CH_arom), 132.1 (=CH), 132.3 (C_arom), 132.6 (C=CH), 143.8 (C_arom).

Anal. Calcd for C₁₆H₂₁NO₃S (307.41): C, 62.51; H, 6.89; N, 4.56.

Found: C, 62.76; H, 7.13; N, 4.42.

10f

Following modified GP5 (filtration on Celite, hydrolysis by aq sat.

NH₄Cl instead of dil. H₂SO₄) from substrate 15f, the cycloadduct

10f was isolated as a colorless oil (EA–PE, 60:40); yield: 168 mg

(57%).

IR (neat): 3449, 2925, 1597 cm^–1.

¹H NMR (400 MHz, CDCl₃):

d = 1.61–1.66 (m, 4 H of

=CCH₂CH₂), 2.06–2.10 (m, 2 H, 2 H of =CCH₂CH₂), 2.23–2.28 (m,

2 H, 2 H of =CCH₂CH₂), 2.43 (s, 3 H, ArCH₃), 2.94–2.99 (m, 2 H,

CH + CHCHHN), 3.43–3.55 (m, 3 H, CH₂O + NCHHC=), 3.51 (d,

J = 8.6 Hz, 1 H, CHCHHN), 3.97 (br s, 4 H, OCH₂CH₂O), 3.98 (A

of AB, J = 13.6 Hz, 1 H, NCHHC=), 7.34 (d, J = 8.1 Hz, 2 H_arom),

7.74 (d, J = 8.1 Hz, 2 H_arom).

10c

Following GP5 from substrate 15c, the cycloadduct 10c was isolat-

ed as a yellow oil (PE–EA, 70:30); yield: 206 mg (82%).

IR (neat): 3443, 2925, 1597 cm^–1.

¹H NMR (400 MHz, CDCl₃): d = 1.38–1.56 (m, 6 H, CH₂of c-

Hex), 1.85–2.13 (m, 4 H, CH₂of c-Hex), 2.43 (s, 3 H, ArCH₃),

2.89–2.93 (m, 2 H, CH + CHCHHN), 3.40–3.49 (m, 3 H, CH₂O +

NCHHC=), 3.66 (d, J = 8.3 Hz, 1 H, CHCHHN), 3.93 (A of AB,

J = 13.4 Hz, 1 H, NCHHC=), 7.33 (d, J = 8.3 Hz, 2 H_arom), 7.70 (d,

J = 8.3 Hz, 2 H_arom).

¹³C NMR (100 MHz, CDCl₃):

d

=

21.7 (ArCH₃), 28.0

(CH₂CH₂C=), 28.5 (CH₂CH₂C=), 35.0 (CH₂CH₂C=), 35.6

(CH₂CH₂C=), 43.7 (CHCH₂O), 49.8 (CH₂N), 50.0 (CH₂N), 63.3

(CH₂OH), 64.5 (OCH₂CH₂O), 108.5 (OCO), 126.6 (C=C), 128.0

(CH_arom), 129.8 (CH_arom), 132.5 (C_arom), 132.6 (C=C), 143.9 (C_arom).

¹³C NMR (100 MHz, CDCl₃):

d

=

21.7 (ArCH₃), 26.3

(CH₂CH₂CH₂), 27.4 (CH₂CH₂CH₂), 28.0 (CH₂CH₂CH₂), 31.4

(CH₂CH₂C=), 31.9 (CH₂CH₂C=), 43.4 (CHCH₂O), 49.8 (CH₂N),

50.3 (CH₂N), 63.3 (CH₂O), 124.7 (C=C), 128.0 (CH_arom), 129.8

(CH_arom), 132.4 (C=C), 135.4 (C_arom), 143.8 (C_arom).

Anal. Calcd for C₂₀H₂₇NO₅S (393.50): C, 61.05; H, 6.92; N, 3.56.

Found: C, 60.79, H, 7.29; N, 3.21.

Anal. Calcd for C₁₈H₂₄NO₃S (335.46): C, 64.45; H, 7.51; N, 4.18.

Found: C, 64.48; H, 7.55; N, 4.23.

16

Following GP5 from substrate 15f, the cycloadduct 16 was isolated

as a white gum (EA–PE, 70:30); yield: 157 mg (60%).

IR (neat): 3410, 2953, 1708, 1597 cm^–1.

¹H NMR (400 MHz, CDCl₃): d = 2.34–2.42 (m, 8 H, CH₂CH₂C=),

2.43 (s, 3 H, ArCH₃), 2.94–2.99 (m, 2 H, CHCH₂O + CHCHHN),

3.49–3.53 (m, 3 H, CH₂O + NCHHC=), 3.71 (d, J = 8.3 Hz, 1 H,

CHCHHN), 3.99 (A of AB, J = 13.6 Hz, 1 H, NCHHC=), 7.34 (d,

J = 8.1 Hz, 2 H_arom), 7.70 (d, J = 8.1 Hz, 2 H_arom).

10d

Following GP5 from substrate 15d, the cycloadduct 10d was isolat-

ed as a yellow oil (EA–PE, 70:30); yield: 140 mg (58%).

IR (neat): 3449, 2940, 2867, 1597 cm^–1.

¹H NMR (400 MHz, CDCl₃): d = 1.48–1.70 (m, 4 H, CH₂of c-

Pent.), 1.95–2.09 (m, 2 H, CH₂of c-Pent.), 2.10–2.21 (m, 2 H, CH₂

of c-Pent.), 2.42 (s, 3 H, ArCH₃), 2.75–2.83 (m, 1 H, CHCH₂O),

3.01 (B of ABX, J = 9.6, 6.3 Hz, 1 H, CHCHHN), 3.41–3.47 (m,

2 H, NCHHC= + CHHO), 3.51–3.55 (m, 1 H, CHHO), 3.58 (A of

ABX, J = 9.6, 1.5 Hz, 1 H, CHCHHN), 3.80 (A of AB,

¹³C NMR (100 MHz, CDCl₃):

d

=

21.7 (ArCH₃), 28.1

(CH₂CH₂C=), 28.4 (CH₂CH₂C=), 39.6 (CH₂CH₂C=), 40.1

(CH₂CH₂C=), 43.9 (CHCH₂O), 50.1 (CH₂N), 50.5 (CH₂N), 63.0

(CH₂O), 128.0 (CH_arom), 129.5 (C=C), 129.5 (CH_arom), 132.1

(C_arom), 144.0 (C_arom), 211.2 (C=O).

1418

D. Leca et al.

PAPER

HRMS: m/z calcd for C₁₈H₂₃NO₄S [M + Na]⁺: 372.1245;

found: 372.1256.

(MeCOCH₃), 33.2 (d, J = 12.3 Hz, H₂C=C), 35.5 (CH₂CHSe), 49.6

(Me₂COCH₃), 51.3 (CHSe), 52.5 (CO₂CH₃), 52.7 (CO₂CH₃), 57.2

(CCO₂Me), 79.2 (Me₂COMe), 126.1 (d, J = 100 Hz, PC=), 126.7–

132.1 (m, CH_arom), 132.3 (d, J = 100 Hz, PC_arom), 132.4 (SeC_arom),

132.5 (d, J = 100 Hz, PC_arom), 156.8 (d, J = 12.9 Hz, =CH), 171.6

(CO₂Me), 171.9 (CO₂Me).

³¹P NMR (162 MHz, CDCl₃): d = 35.2.

HRMS: m/z calcd for C₃₅H₄₁O₆PSe + Na [M + Na]⁺: 691.1704;

10g

Following GP5 from substrate 15g, the cycloadduct 10g was isolat-

ed as a 3:1 mixture of two diastereoisomers (CH₂Cl₂–EA, 95:5).

Only the major diastereoisomer could be isolated pure as a white

solid; yield: 183 mg (71%); mp 117–119 °C.

IR (neat): 3277, 2922, 2853, 1598 cm^–1.

found: 691.1702.

¹H NMR (400 MHz, CDCl₃): d = 2.43 (s, 3 H, ArCH₃), 2.96–3.04

(m, 1 H, CHCH₂O), 3.28 (B of ABX, J = 9.6, 6.8 Hz, 1 H,

CHCHHN), 3.42 (A of ABX, J = 9.6, 5.8 Hz, 1 H, CHCHHN),

3.60–3.69 (m, 2 H, CH₂O), 4.02 (br-B of AB, J = 14.6 Hz, 1 H,

NCHHC=), 4.22 (br-A of AB, J = 14.4 Hz, 1 H, NCHHC=), 6.37

(br s, 1 H, =CH), 7.14–7.16 (m, 2 H_arom), 7.26–7.39 (m, 5 H_arom),

7.71–7.73 (m, 2 H_arom).

¹³C NMR (100 MHz, CDCl₃): d = 21.6 (ArCH₃), 47.5 (CHCH₂O),

49.3 (CHCH₂N), 50.8 (NCH₂C=), 63.9 (CH₂O), 124.7 (=CH), 127.3

(CH_arom), 127.8 (CH_arom), 128.2 (CH_arom), 128.6 (CH_arom), 129.8

(CH_arom), 132.3 (C), 136.2 (C), 136.9 (C), 143.9 (C).

19

EA–PE (70:30); yield: 509 mg (86%); white solid; mp 73–74 °C.

IR (neat): 2946, 1727, 1435, 1177 cm^–1.

¹H NMR (250 MHz, CDCl₃): d = 1.01 (s, 3 H, CH₃COMe), 1.04 (s,

3 H, MeCOCH₃), 1.88 [d, J = 3 Hz, 3 H, =C(CH₃)Me], 2.05 (m,

1 H, CHHCHSe), 2.12 [d, J = 2.5 Hz, 3 H, =C(Me)CH₃], 2.82 (A of

AB, J = 14 Hz, 1 H, CHHCHSe), 3.15 (s, 3 H, Me₂COCH₃), 3.37–

3.72 (m, 3 H, CHCSe + CH₂C=), 3.74 (s, 3 H, CO₂CH₃), 3.80 (s,

3 H, CO₂CH₃), 7.31–7.41 (m, 2 H_arom), 7.52–7.70 (m, 9 H_arom),

7.78–7.88 (m, 4 H_arom).

¹³C NMR (62.5 MHz, CDCl₃): d = 21.6 (CH₃COMe), 23.3

(MeCOCH₃), 24.2 [d, J = 20.4 Hz, =C(CH₃)Me], 26.1 [d,

J = 15.7 Hz, =C(Me)CH₃], 34.7 (d, J = 19 Hz, CH₂C=), 36.2

(CH₂CHSe), 49.5 (Me₂COCH₃), 50.7 (CHSe), 52.2 (CO₂CH₃),

52.4 (CO₂CH₃), 57.9 (CCO₂Me), 79.1 (Me₂COMe), 124.5 (d,

J = 100 Hz, PC=), 126.9 (CH_arom), 128.5–129.2 (m, CH_arom), 131.1–

132.7 (m, CH_arom), 134.9 (d, J = 100 Hz, PC_arom), 135.5 (d,

J = 100 Hz, PC_arom), 155.8 (d, J = 14.1 Hz, PC=C), 171.2 (CO₂Me),

171.5 (CO₂Me).

17

Following GP5 from substrate 15h, the cycloadduct 17 was isolated

as colorless crystals (CH₂Cl₂–EA, 70:30); yield: 268 mg (70%); mp

188–190 °C.

IR (neat): 3328, 3006, 1346, 1597, 1165 cm^–1.

¹H NMR (400 MHz, CDCl₃): d = 0.70 (t, J = 7.3 Hz, 3 H, CH₂CH₃),

1.89–1.92 (m, 2 H, CH₂Me), 2.39 (s, 3 H, ArCH₃), 2.45–2.53 (m,

1 H, CHCH₂O), 2.73 (B of ABX, J = 9.8, 9.8 Hz, 1 H, CHCHHN),

3.25 (A of ABX, J = 9.8, 7.7 Hz, 1 H, CHCHHN), 3.34 (B of ABX,

d, J = 11.6, 10.9, 2.8 Hz, 1 H, CHHO), 3.43 (A of ABX, J = 12.1,

10.1 Hz, 1 H, NCHHCP), 3.62 (A of ABX, J = 11.6, 9.6 Hz, 1 H,

CHHO), 3.89 (A of ABX, J = 10.1, 1.5 Hz, 1 H, NCHHCP), 5.45–

5.53 (m, 1 H, PCH=CH), 5.68 (dd, J = 15.9, 8.1 Hz, 1 H,

PCH=CH), 5.89 (d, J = 10.9 Hz, 1 H, OH), 7.18 (d, J = 8.3 Hz,

2 H_arom), 7.40–7.58 (m, 8 H_arom), 7.63–7.75 (m, 4 H_arom).

¹³C NMR (100 MHz, CDCl₃): d = 13.3 (CH₂CH₃), 21.4 (ArCH₃),

26.1 (CH₂Me), 47.2 (d, J = 4.5 Hz, CHCH₂O), 47.6 (CHCH₂N),

51.6 (d, J = 68.4 Hz, PC_alkyl), 52.8 (d, J = 9 Hz, NCH₂CP), 58.1

(CH₂O), 120.9 (PCH=CH), 127.2 (CH_arom), 128.0 (d, J = 100.0 Hz,

PC_arom), 128.5 (d, J = 100.2 Hz, PC_arom), 128.6 (d, J = 12 Hz,

CH_arom), 128.7 (d, J = 12 Hz, CH_arom), 129.8 (CH_arom), 131.7 (d,

J = 9.4 Hz, CH_arom), 132.4 (d, J = 13 Hz, CH_arom), 132.5 (d,

J = 12 Hz, CH_arom), 133.0 (d, J = 8.4 Hz, CH_arom), 133.1 (C_arom),

137.9 (d, J = 10 Hz, PCH=CH), 143.5 (C_arom).

³¹P (162 MHz, CDCl₃): d = 31.5.

HRMS: m/z calcd for C₃₄H₄₁O₆PSe [M + Na]⁺: 679.1704;

found: 679.1711.

21

To a solution of malonate 19 (328 mg, 0.5 mmol, 1 equiv) in toluene

(11 mL) were added TBTH (200 mL, 0.75 mmol, 1.5 equiv) and tri-

ethylborane (2.5 mL, 1 M solution in hexanes, 2.5 mmol, 5 equiv)

under argon at r.t. Air was injected through the solution every

30 min. After 2 h, the same quantities of TBTH and triethylborane

were added and air was injected again, if necessary. After comple-

tion of the reaction, the mixture was diluted with Et₂O (10 mL), and

washed with brine (2 ×). The organic layer was dried (Na₂SO₄), fil-

tered, and concentrated in vacuo. The residue was purified by silica

gel chromatography (pentane–EA, 70:30) to afford 20 (84 mg,

56%) and 21 (108 mg, 43%). Compound 21 was isolated (R_f0.27)

as a slightly yellow oil.

³¹P NMR (162 MHz, CDCl₃): d = 40.9.

Anal. Calcd for C₂₈H₃₂NO₄PS (509.60): C, 65.99; H, 6.33; N, 2.75.

Found: C, 65.82; H, 6.52; N, 2.58.

IR (neat): 2951, 1729, 1115 cm^–1.

¹H NMR (400 MHz, CDCl₃): d = 0.86 [s, 6 H, (CH₃)₂COMe], 1.28

(m, 2 H, CH₂CH₂), 1.53 [d, J = 2.3 Hz, 3 H, =C(CH₃)Me], 1.64 (m,

2 H, CH₂CH₂), 1.84 [d, J = 2.3 Hz, 3 H, =C(Me)CH₃], 2.97 (s, 3 H,

Me₂COCH₃), 3.27 (d, J = 16.4 Hz, 2 H, =CCH₂), 3.61 (s, 6 H,

CO₂CH₃), 7.30–7.45 (m, 6 H_arom), 7.58–7.68 (m, 4 H_arom).

18

EA–PE (60:40); yield: 467 mg (70%); white solid; mp 57–59 °C.

IR (neat): 2947, 1728, 1614, 1578, 1182 cm^–1.

¹H NMR (400 MHz, CDCl₃): d = 0.31–0.35 (m, 2 H, c-CH₂CH₂),

0.81–0.85 (m, 2 H, c-CH₂CH₂), 1.20 (s, 3 H, CH₃COMe), 1.25 (s,

3 H, MeCOCH₃), 1.73-1.78 (m, 1 H, c-CH), 2.06 (B of ABX,

J = 15.4, 11.1 Hz,1 H, CHHCHSe), 2.85 (A of ABX, J = 15.4, 1.5

Hz, 1 H, CHHCHSe), 3.03 (s, 3 H, Me₂COCH₃), 3.27 (B of ABX,

J = 15.7, 15.7 Hz, 1 H, CHHC=), 3.48 (A of ABX, J = 17.7,

15.7 Hz, 1 H, CHHC=), 3.52 (s, 3 H, CO₂CH₃), 3.65 (s, 3 H,

CO₂CH₃), 3.67–3.69 (m, 1 H, CHSe), 5.20 (dd, J = 21.6, 10.5 Hz,

1 H, =CH), 7.15–7.17 (m, 3 H_arom), 7.39–7.65 (m, 12 H_arom).

¹³C NMR (100 MHz, CDCl₃):

d = 24.1 [d, J = 13.1 Hz,

=C(CH₃)Me], 24.9 [s, (CH₃)₂COMe], 26.7 [d, J = 9.5 Hz,

=C(Me)CH₃], 29.2 (CH₂CH₂), 33.4 (d, J = 11.6 Hz, =CCH₂), 33.5

(CH₂CH₂), 48.9 (Me₂COCH₃), 52.3 (CO₂CH₃), 58.7 (CCO₂CH₃),

74.4 (Me₂COMe), 123.3 (d, J = 98.2 Hz, PC=), 128.4 (d,

J = 12.4 Hz, CH_arom), 131.3 (d, J = 2.2 Hz, CH_arom), 132.0 (d,

J = 10.2 Hz, CH_arom), 134.8 (d, J = 99.7 Hz, PC_arom), 155.6 (d,

J = 9.5 Hz, =CMe₂), 172.0 (CO₂Me).

³¹P NMR (162 MHz, CDCl₃): d = 30.6.

HRMS: m/z calcd for C₂₈H₃₇O₆P [M + Na]⁺: 523.2225; found:

¹³C NMR (100 MHz, CDCl₃): d = 8.87 (c-CH₂CH₂), 9.14 (c-

CH₂CH₂), 12.8 (d, J = 18.9 Hz, c-CH), 22.9 (CH₃COMe), 23.4

523.2221.

PAPER

Radical Intramolecular Vinylations

1419

22

(3) (a) Miyamoto, N.; Fukuoka, D.; Utimoto, K.; Nozaki, H.

Bull. Chem. Soc. Jpn. 1974, 47, 503. (b) Russell, G. A.;

Ngoviwatchai, P.; Tashtoush, H. I. Organometallics 1988, 7,

696. (c) Russell, G. A.; Tashtoush, H.; Ngoviwatchai, P. J.

Am. Chem. Soc. 1984, 106, 4622.

Cyclization of substrate 15i following GP5 afforded deoxygenated

product (EA–EP, 60:40; 37 mg, 12%) and cycloadduct 22 (EA–EP,

50:50; 252 mg, 78%); colorless oil.

IR (neat): 2982, 1598, 1163 cm^–1.

¹H NMR (400 MHz, CDCl₃): d = 1.24 (td, J = 7.1, 2.2 Hz, 6 H,

CH₂CH₃), 1.32 (s, 3 H, CH₃CMe), 1.34 (s, 3 H, MeCCH₃), 2.43 (s,

3 H, ArCH₃), 3.14 (B of AB, J = 9.8 Hz, 1 H, CHCHHN), 3.22–

3.26 (m, 2 H, OCHHCH + CH), 3.33 (B of ABX, J = 20.5, 10.4 Hz,

1 H, NCHHCP), 3.47 (A of ABX, J = 9.8, 6.2 Hz, 1 H, CHCHHN),

3.62 (A of ABX, J = 16.7, 10.4 Hz, 1 H, NCHHCP), 3.99–4.12 (m,

5 H, CH₂Me + OCHHCH), 7.31 (d, J = 8.2 Hz, 2 H_arom), 7.69 (d,

J = 8.2 Hz, 2 H_arom).

(4) Bertrand, F.; Quiclet-Sire, B.; Zard, S. Z. Angew. Chem. Int.

Ed. 1999, 38, 1943.

(5) (a) Xiang, J.; Fuchs, P. L. J. Am. Chem. Soc. 1996, 118,

11986. (b) Xiang, J.; Jiang, W.; Gong, J.; Fuchs, P. L. J. Am.

Chem. Soc. 1997, 119, 4123.

(6) Clark, A. J.; Rooke, S.; Sparey, T. J.; Taylor, P. C.

Tetrahedron Lett. 1996, 37, 909.

(7) Huval, C. C.; Singleton, D. A. Tetrahedron Lett. 1993, 34,

3041.

¹³C NMR (50 MHz, CDCl₃): d = 16.4 (d, J = 5.5 Hz, CH₂CH₃), 21.6

(ArCH₃), 23.8 (CH₃CMe), 25.3 (MeCCH₃), 46.1 (CH), 51.0

(NCH₂CP), 53.3 (CHCH₂N), 58.3 (d, J = 149 Hz, CP), 62.4 (d,

J = 6.7 Hz, CH₂Me), 62.5 (d, J = 7.7 Hz, CH₂Me), 70.4 (d,

J = 12 Hz, OCH₂CH), 85.5 (d, J = 11 Hz, MeCMe), 127.6 (CH_arom),

129.8 (CH_arom), 133.3 (C_arom), 143.8 (C_arom).

(8) (a) Yao, C.-F.; Chu, C.-M.; Liu, J.-T. J. Org. Chem. 1998,

63, 719. (b) Jang, Y.-J.; Yan, M.-C.; Lin, Y.-F.; Yao, C.-F.

J. Org. Chem. 2004, 69, 3961.

(9) Takami, K.; Yorimitsu, H.; Oshima, K. Org. Lett. 2004, 6,

4555.

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³¹P NMR (162 MHz, CDCl₃): d = 28.8.

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H]⁺).

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Alternative Procedure 1 (Coll·HCl): Collidine hydrochloride (40

mg, 0.23 mmol, 2.0 equiv), Cp₂TiCl₂(2.9 mg, 0.02 mmol,

0.1 equiv) and Mn powder (12.6 mg, 0.23 mmol, 2.0 equiv) were

suspended under argon in degassed THF (2 mL). The resulting sus-

pension was stirred at r.t. until the reaction mixture turned green

(10 min). After addition of a degassed 15i (50 mg, 0.12 mmol) so-

lution in THF (2 mL), the reaction was left at r.t. for 14 h, then

quenched by addition of 2 M HCl (3 mL). The mixture was extract-

ed with Et₂O (30 mL). The organics were washed with aq sat.

NaHCO₃, brine and dried (Na₂SO₄). The crude material was puri-

fied by flash chromatography to yield 22 (34 mg, 68%).

1998, 63, 6764.

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Alternative Procedure

2 (Coll·TMSCl): Cp₂TiCl₂(2.9 mg,

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0.02 mmol, 0.1 equiv) and Mn powder (12.6 mg, 0.23 mmol,

2.0 equiv) were suspended under argon in degassed THF (2 mL).

The resulting suspension was stirred at r.t. until the reaction mixture

turned green (10 min). After addition of a degassed mixture of 15i

(50 mg, 0.12 mmol), collidine (61 mL, 0.46 mmol, 4.0 equiv) and

TMSCl (37 mL, 0.29 mmol, 2.5 equiv) in THF (2 mL), the reaction

was left at r.t. for 14 h, then quenched by addition of 2 M HCl. The

mixture was extracted with Et₂O (30 mL). The organics were

washed with aq sat. NaHCO₃, brine and dried (Na₂SO₄). The crude

material was purified by flash chromatography to yield 22 (32 mg,

64%).

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M. Angew. Chem. Int. Ed. 1999, 38, 2909. (b) Gansäuer,

A.; Bluhm, H.; Rinker, B.; Narayan, S.; Schick, M.;

Lauterbach, T.; Pierobon, M. Chem. Eur. J. 2003, 9, 531.

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Acknowledgment

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Tetrahedron Lett. 1996, 37, 3985. (b) Bolm, C.; Simic, O. J.

Am. Chem. Soc. 2001, 123, 3830.

We gratefully acknowledge financial support from UPMC, CNRS,

and Institut Universitaire de France, of which M.M. is a senior

member. D.L. and K.S. thank the Ministère de la Jeunesse, de

l’Education Nationale et de la Recherche for a fellowship. M.A.

thanks CNRS for a fellowship.

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Titanocene-mediated intramolecular radical vinylations

DOI: 10.1055/s-2005-865357

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