Chameleon reactivity of the allene bond of 4-vinylidene-2-oxazolidinone: Novel through-space conjugative nucleophilic addition of electron-rich alkenes and hetero-nucleophiles

DOI: 10.1002/chem.200700691

Chameleon Reactivity of the Allene Bond of 4-Vinylidene-2-oxazolidinone:

Novel Through-Space Conjugative Nucleophilic Addition of Electron-Rich

Alkenes and Hetero-Nucleophiles

Masanari Kimura,^[b]Yoshikazu Horino,^[c]Masahiko Mori,^[b]and Yoshinao Tamaru*^[a]

Abstract: The Ca=Cb double bond of

allene carbamates 1 serves as an elec-

tron acceptor similar to the double

bond of conjugated enones by means

of a through-space interaction with the

alkoxy-5-sulfonyltetrahydropyridines 2

and 2-silylmethyl-5-sulfonyltetrahydro-

pyridines 3, respectively, with high

regio- and stereoselectivity and reten-

tion of configuration of the double

bonds of these electron-rich alkenes; 2)

silanes (R_nSiH_4ꢀn, n=1–3)and thiols

deliver the hydride and the thiolate at

the Cb carbon and promote the 1,3-sul-

fonyl migration, followed by protona-

tion of the thus-formed carbamate

anion (Z)-III to provide, for example,

(Z)-4a and (Z)-4j, respectively; 3)al-

cohols simply add to the Ca=Cb

double bond and provide (E)-6. Usual-

ly, the reaction with alcohols is accom-

panied by the second pathway, giving

rise to, for example, (Z)-4b in addition

to (E)-6b. Phenol engages in the third

pathway and provides (E)-6g exclu-

sively. Heteroaromatics, such as furans

and benzofurans follow the first path-

way, however, in a different regioselec-

tivity from enol ethers and allylsilanes,

delivering the oxygen atom at the 3-po-

sition of 5-sulfonyltetrahydropyridines

(2g and 2h). Indoles, on the other

hand, show a dichotomy, equally enjoy-

ing the first and the third pathways and

provide mixtures of (E)-7 and (E)-8,

respectively.

ꢀ

N SO₂bond; the carbamate double

bond is thus subject to nucleophilic ad-

dition for a wide variety of nucleo-

philes, which proceeds under mild con-

ditions by heating at 70–1008C. De-

pending on the kind of nucleophiles, 1

displays three different reaction

modes: 1)Typically enol ethers and al-

lylsilanes promote 1,3-sulfonyl migra-

tion of 1 and undergo the inverse elec-

tron demand Diels–Alder reaction with

the 1-aza-1,3-butadiene intermediates

II thus formed to furnish bicyclic 2-

Keywords: allenes

·

Diels–Alder

reactions · enols · indoles · sulfona-

mides

Introduction

of terminal alkynes and alkenes under strictly thermal acti-

vation conditions (80–1008C, Scheme 1)undergoing [2 +2]

cycloaddition though in potential violation of the Wood-

ward–Hoffmann rule and the Fukui frontier orbital theor-

y.^[1a,b]Alkynes and alkenes provided 3-substituted (Z)-meth-

ylenecyclobutenes A and 3-substituted methylenecyclobu-

tanes B, respectively, in good to excellent yields. The [2+2]

cycloaddition was concluded to proceed via a concerted

[(p_2s+p_2s)_allene+p_2s] Hückel transition state. Enones and ni-

trile oxides, on the other hand, reacted with 1 selectively at

the internal allene C4=Ca double bond and underwent

[4+2] and [3+2] cycloaddition reactions to give spiro com-

pounds C and D, respectively.

In this article, we disclose that the allene carbamates 1

behave like a chameleon dramatically changing the reaction

patterns depending on the reaction partners.^[2]That is, in

sharp contrast to the reactions with alkenes and alkynes

mentioned above, the Ca=Cb double bond of 1 behaves like

an electron-deficient double bond of enones and is subject

to nucleophilic addition at the Cb carbon when exposed to a

We report that the allene bond of 4-vinylidene-2-oxazolidi-

nones 1 significantly deviated from linearity (173–1768)and

that the terminal allene Ca=Cb bond reacted with a variety

[a] Prof. Y. Tamaru

Department of Applied Chemistry, Faculty of Engineering

Nagasaki University, 1-14 Bunkyo-Machi

Nagasaki 852-8521 (Japan)

E-mail: tamaru@net.nagasaki-u.a

[b] Dr. M. Kimura, Dr. M. Mori

Graduate School of Science and Technology, Nagasaki University

1-14 Bunkyo-machi, Nagasaki 852-8521 (Japan)

[c] Dr. Y. Horino

Department of Applied Chemistry

Graduate School of Science and Engineering

University of Toyama, 3190 Gohuku, Toyama 930-8555 (Japan)

Supporting information for this article is available on the WWW

under http://www.chemeurj.org/ or from the author: H NMR spectra

for all previously unreported compounds.

1

9686

ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Chem. Eur. J. 2007, 13, 9686 – 9702

FULL PAPER

necessitated.^[6]In sharp contrast to this, 1.5–2.0 equivalents

of alcohols are sufficient to complete the addition to 1. Fur-

thermore, the reaction is completed at a temperature as low

as 808C under neutral conditions even diluted with a sol-

vent. 2)Nucleophilic addition ordinarily takes place at the

central carbon of allenes,^[7]while the reaction of 1 with alco-

hols and other nucleophiles takes place exclusively at the

terminal allene carbon of 1. It has been reported sporadical-

ly that allenyl amides,^[8]allenyl alkoxides,^[9]and allenyl thio-

lates^[10]undergo intramolecular nucleophilic attack at the

allene terminal carbons to furnish pyrrole, furan, and thio-

phene derivatives, respectively. To the best our knowledge,

however, the reactions indicated in Scheme 1 with thick

arrows are the first examples that nucleophilic addition even

proceeds at the allene terminal carbons in an intermolecular

fashion. 3)The sulfonamide bond is so strong that, in order

ꢀ

to break the SO₂N bond, generally either strong nucleo-

philes or strong reducing agents under harsh conditions are

required.^[11]In contrast, the Ca carbanion, generated by ad-

dition of electronically neutral carbo- and hetero-nucleo-

philes to the Cb position of 1, is capable of cleaving the sul-

fonamide bond. All these unique reactivity associated with 1

may be ascribed to a through-space interaction in a transi-

Scheme 1. Chameleon reactivity of the allene double bond of 1, providing

seven different products depending on reaction partners. For the reac-

tions giving A ꢁD, see ref. [1a,b]. R = CO₂Me, CN, phenyl, vinyl; X =

OR’’, SR’’, H; Y = Me₃, Ph₃

tion state between the p*ACHTERUGN(Ca=Cb)and s*CAHTRE(UGN N-SO₂)orbitals,

which makes the Ca=Cb double bond as a good electrophile

variety of carbon nucleophiles (enol ethers, allylsilanes,

furans, benzofurans, indoles)and hetero nucleophiles (alco-

hols, thiols, silanes R_nSiH_4ꢀn, n=1–3).

for a variety of nucleophiles.

Interestingly, these nucleophilic addition reactions are ac-

companied with an intramolecular migration of the sulfonyl

group from N to Ca as can be seen explicitly, for example,

for the conversion of 1 to 4 (Scheme 1). Ethers and sulfides

4, with a Z structure with respect to the tetrasubstituted en-

amine double bonds, are produced stereoselectively in excel-

lent yields for the reactions with alcohols and thiols, respec-

tively. Silanes (R_nSiH_4ꢀn, n=1–3)react in a way similar to

alcohols and thiols, delivering a hydride in place of RO or

RS.

The reactions with enol ethers and allylsilanes are also

triggered by nucleophilic attack at the Cb carbon accompa-

nied by the 1,3-sulfonyl shift; however, the reaction feature

has changed dramatically. In these reactions, bicyclic tetra-

hydropyridine derivatives 2 and 3 are formed in good to ex-

cellent yields, where the double bonds of enol ethers and al-

lylsilanes are incorporated as the C2–C3 component of the

tetrahydropyridine ring regio- and stereoselectively with re-

tention of configuration at the double bond. The other tetra-

hydropyridine components (N, C4, C5, C6)originate from 1.

The unique reactivity of 1 may be apparent by taking the

following aspects into consideration: 1)Usually, allenes are

susceptible to electrophilic addition^[3]to both the central^[4]

and the terminal carbons.^[5]In contrast, they are robust to

nucleophilic attack. For example, addition of alcohols to al-

lenes at the central sp carbon is an important industrial pro-

cess to produce enol ethers. For this purpose, activation of

an alcohol as the metal alkoxide in a vast excess amount of

the alcohol as well as high temperatures (170–2508C)are

Results and Discussion

Reaction of 1 with enol ethers derived from aldehydes, ke-

tones, and esters: Table 1 summarizes the reactions of allene

carbamates 1a and 1b with a wide range of enol ethers. The

reaction was usually performed by stirring a mixture of 1

(0.5 mmol)and an excess amount of an enol ether in neat or

as a solution in dioxane at 70–1008C under nitrogen. Table 1

shows that a wide structural variety of enol ethers, encom-

passing those derived from aldehydes, ketones, and esters,

provide 5-tosyltetrahydropyridines 2 in good to excellent

yields.

The structure of 2 was elucidated by means of spectro-

scopic (FT-IR, ¹H and ¹³C NMR)and analytical (HRMS,

combustion)methods. In addition, in some cases, the struc-

ture was determined unequivocally by means of the single-

crystal X-ray diffraction methods (see below).^[12]The struc-

ture of 2 indicates that the reaction involves migration of

the sulfonyl group from N to Ca as a key step.

Among the results in Table 1, run 7 is especially notewor-

thy. Despite its aromaticity, furan acts as a 4p component in

the Diels–Alder reaction when exposed to electron-deficient

alkenes^[13]and allenes.^[14,15]For the reaction with 1a, howev-

er, furan behaved just like other enol ethers and served as a

2p component to give rise to 2g in reasonable yield. Benzo-

furan displayed a reactivity similar to furan (run 8). It

should be noted that furan and benzofuran furnish the posi-

tional isomers and introduce the oxygen atoms at the 3-posi-

tion of the tetrahydropyridine ring (runs 7 and 8), although

Chem. Eur. J. 2007, 13, 9686 – 9702

ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemeurj.org

9687

Y. Tamaru et al.

Table 1. Thermal [4+2] cycloaddition of 2a,b and enol ethers.^[a]

Table 1. (Continued)

Run Alene 1 Vinyl ether

T [8C]/t

[h]

Product (% isolated

yield)

Run Alene 1 Vinyl ether

T [8C]/t

[h]

Product (% isolated

yield)

[equiv]

1

100/8

12

13

1b

80/33

80/23

2

1a

100/22

3

4

1a

70/23

14

1b

80/57

100/24

15

16

1b

100/26

80/12

5

1a

80/12

6

7

1a

80/6

[a] A mixture of 1 (0.5 mmol), and an enol ether was heated at the tem-

perature and for the period of time indicated under nitrogen. The reac-

tion asterisked was undertaken as a dioxane solution (1 mL). [b] At start,

Z/E 17:1; at end, Z/E 1.3:1.0. [c] At start, Z/E 10:1; at end, Z/E 2.2:1.0

80/48

dihydrofuran and all other enol ethers provide tetrahydro-

pyridines bearing the oxygen atoms at the 2-position.

Enol ethers derived from ketones and esters create qua-

ternary carbon centers at the 2-position of tetrahydropyri-

dine ring (runs 9–11 and 14–16). The quaternary carbon cen-

ters are sterically congested and bear two or three electron-

donating hetero atom substituents. Accordingly, these prod-

ucts were expected to be rather unstable and to decompose

owing to heterolytic cleavage of these substituents. Contrary

to our expectation, however, they turned out to be very

stable. The high stability of 2j’, 2o’, and 2q is remarkable;

2j’ and 2o’ exist as a hemiaminal and do not undergo ring

opening to give a keto imine (or a keto enamine)form. The

orthoester 2q is stable and withstands purification by

column chromatography over silica gel and recrystallization,

and forms a nice crystalline solid suitable for X-ray crystal-

lographic analysis.^[12]

8

1q

1a

100/23

80/48

80/24

9

10

In the light of the fact that methyl acrylate and methyl a-

methoxyacrylate selectively react with 1 to give [2+2] cyclo-

addition products [e.g. B-1, Eq. (1)],^[1a,b]it is quite surprising

that methyl trans-b-methoxyacrylate reacts with 1b to pro-

vide a tetrahydropyridine product 2l exclusively as a single

diastereomer. A similar, but a more exciting result was ob-

served for the reaction of 1b and methyl (E)-3-silyloxy-2-

butenoate (run 15), where 2p was obtained exclusively with

11

80/85

9688

www.chemeurj.org

ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Chem. Eur. J. 2007, 13, 9686 – 9702

Conjugative Nucleophilic Addition

FULL PAPER

complete retention of configuration of the double bond of

the trisubstituted enol ether.

Further contrasting results were observed for the reaction

of dienyl ethers [Eq. (2)]. A wide variety of 1,3-dienes, in-

cluding 1- and 2-siloxy-1,3-butadienes uniformly undergo

[2+2] cycloaddition exclusively and provide 3-vinylmethyle-

[1a,b]

necyclobutanes (e.g., B-2)in excellent yields.

2-Siloxy-

1,3-cyclohexadiene, on the other hand, underwent formal

[4+2] (four-component from 1b and two from an enol

ether)cycloaddition to give rise to a tricyclic compound 2r

in reasonable yield.

product, B-4, was obtained exclusively in excellent yield.

This suggests that a phenyl group is more influential than an

alkoxy group to determine the course of reactions.

As for the reaction mechanism, two routes, pathways A

and B giving rise to intermediates s-trans-II and (Z)-III, re-

spectively, which pass through a sulfurane oxide I as a

common intermediate, are conceivable as illustrated in

Scheme 2 using 1a and a (Z)-enol ether as the starting ma-

terials. The intermediacy of four-membered sulfurane oxide

I that might be formed via intramolecular addition of Ca

carbanion to S, the anion being generated by nucleophilic

addition of vinyl ether upon Cb, relies on a four-membered

aminodioxysulfuran oxide I’ of structural similarity, which is

isolated as crystals.^[16]The intermediate I would be unstable

owing to greater ring strain and zwitterionic nature placing

anionic charge on O, hence would react to give either s-

trans-II (path A)or a zwitterionic intermediate ( Z)-III

(path B). The zwitterionic intermediate (Z)-III might either

fragment to give a mixture of s-trans-II and an enol ether

(path C)or isomerize to ( E)-III, which is ready to cyclize to

give 2 (path D).

These contrasting results [Eqs. (1)and (2)] may be ration-

alized on the basis of steric repulsion in the imaginary [2+2]

cycloaddition products with enol ethers bearing substituents

on the b carbon, as is illustrated in Equation (3)using 2-

siloxy-1,3-cyclohexadiene as an example. The allylic methyl-

ene group of cyclobutane syn to Ts is subject to an allylic

strain against the Ts group (indicated with a dotted double-

headed arrow); hence, there might be no room to accommo-

date substituents on the same carbon any more (indicated

by a double-headed arrow).

During the isomerization of 1a to II (path A and paths

B–C), the enol ether might lose its geometrical integrity,

that is, in these processes, the enol ether serves as a catalyst

for the isomerization of 1a to II at the expense of its geo-

metrical purity.

The high stereoselectivity, giving rise to 2b, 2c 2l, and 2p

with complete retention of configuration of the starting

alkene geometries [runs 2, 3, and 15, Table 1 and Eq. (1)],

may be rationalized by the route involving an intermediate

II.

Equation (4)indicates that the [2 +2] versus [4+2] selec-

tivity depends on a subtle difference in the electronic nature

of enol ethers; an enol ether bearing a phenyl group at the

a-position behaves like styrene, providing [2+2] cycloaddi-

tion product B-3 exclusively,^[1a,b]while an enol ether bearing

a methyl group in place of a phenyl group provides a [4+2]

cycloaddition product 2s exclusively.

In good agreement with this, the [2+2] cycloaddition with

styrene proceeded much faster than the [4+2] cycloaddition

with dihydropyran [Eq. (5)], where only [2+2] cycloaddition

The 1-azabutadiene intermediate s-cis-II is nicely assem-

bled as an enophile for the inverse electron demand Diels–

Alder reaction,^[17]possessing a highly polarized structure

with a partial negative charge on N and a partial positive

charge on the terminal carbon. The polar nature of II is en-

hanced by the CO on N and the Ts on the C₃carbon of 1-

aza-1,3-diene unit. Accordingly, it should react with enol

ethers as soon as formed.^[17j,k]

According to pathway D (Scheme 2), a faster rotation

ꢀ

about the C C single bond bearing R and OR’ as compared

Chem. Eur. J. 2007, 13, 9686 – 9702

ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemeurj.org

9689

Y. Tamaru et al.

neither Et₃N (1 equiv)nor PPh (1 equiv)had nothing to do

3

with the reactions in the presence and absence of dihydro-

pyran. Interestingly, DBU (1,8-diazabicycloACHTREU[NG 5.4.0]undec-7-

ene)caused facile and complete decomposition of 1b in the

presence and absence of dihydropyran even at room temper-

ature and provided an intractable black tarry mixture of

products.

The generation of 2 indicates that a strong sulfonamide

bond^[11]of 1 is cleaved under such mild conditions as heating

at 70–1008C with weak neutral nucleophiles. This may

sound rather unreasonable, and alternative pathways, for ex-

ample, a pathway that involves radical intermediates should

be taken into consideration: 1)a single electron transfer

ꢀ

from an enol ether to 1; 2)a homolytic SO N bond cleav-

2

age of the radical anion of 1 to give a carbamate anion and

an SO₂Tol radical;^[19]3)recombination of the carbamate

anion and the SO₂Tol radical at the Ca position; and 4)an

inverse electron transfer from the radical anion II to the

enol ether radical cation.

However, this is probably not the case. As shown in

Equation (6), N-methanesulfonylallene carbamate 1c be-

haves just like N-toluenesulfonylallene carbamates 1a and

1b, providing 2t in reasonable yield. Provided that a radical

species like methanesulfonyl radical were involved as an in-

termediate, 1c should provide some desulfonylated products.

The life-time of alkylsulfonyl radicals is much shorter than

that of arylsulfonyl radicals. By virtue of the ready extrusion

of SO₂, alkylsulfonyl radials, and never arylsulfonyl radicals,

have been utilized as efficient alkyl radical carriers for a

wide range of radical chain reactions of synthetic impor-

tance.^[20]

Scheme 2. 1,3-Migration of toluenesulfonyl group promoted by a (Z)-

vinyl ether via a four-membered sulfurane oxide I as a common inter-

mediate: path A: N!C sulfonyl shift giving rise to an s-trans-1-aza-1,3-

butadine II accompanying vinyl ether isomerization. Path B: N!C sulfo-

nyl shift giving rise to a zwitterionic intermediate (Z)-III. Path C: elimi-

nation of a mixture of (E)- and (Z)-vinyl ether giving rise to s-trans-II.

C^ꢀ

ꢀ

with a rotation around the C4 Ca bond that has a higher

bond order should result in a formation of stereoisomeric

mixtures of 2. Apparently this is not the case and the path-

way D might be ruled out.

In accord with the proposed mechanism, enol ethers

turned out to isomerize to a considerable extent; (Z)-b-me-

thoxystyrene (Z/E 17:1, at start)was recovered as a mixture

of 1.3:1.0 after completion of reaction (run 2, Table 1), and

1-siloxy-1-butene (Z/E 10:1, at start)as a mixture of 2.2:1.0

(run 12). It was established independently that these enol

ethers were geometrically stable and, in the absence of 1, no

isomerization took place under the reaction conditions. Ac-

cordingly, the exclusive and selective formation of cis-2b

(run 2)and cis-2m (run 12), respectively, might be attribut-

ed to an easier access of II to the (Z)-enol ethers than to

the (E)-isomers just from steric reasons. (E)-b-Methoxy ac-

rylate (run 3)and ( E)-b-siloxy-2-butenoate (run 15)were re-

covered without any isomerization after the reaction with 1.

As expected from a rate-determining formation of zwitter-

ionic I, all the reactions examined in polar solvents showed

reasonable reaction rates and yields: for example, 2e; 95%

at 808C for 8 h in DMSO; 93% at 808C for 8 h in acetoni-

trile, 89% at 808C for 12 h in dioxane (run 5, Table 1),

while 62% at 808C for 20 h in benzene.

The catalytic role of enol ethers for the isomerization of 1

to II is reminiscent of the role that amines and phosphines

play in the Baylis–Hillman reaction;^[18]these Lewis bases

promote a kind of aldol addition of unsaturated carbonyl

compounds to aldehydes to provide the same unsaturated

carbonyl compounds, the H on the Ca being replaced with

1-hydroxyalkyl groups. Accordingly, we examined a variety

of Lewis bases in order to isolate or detect the intermediate

II, or to accelerate the present [4+2] cycloaddition reaction.

However, no positive results were obtained. For example,

The carbamates 1a,b form stable crystalline solid, while

the carbamate 1c is a heavy oil and rather unstable decom-

posing gradually during storage in a refrigerator. Further-

more, 1c was less reactive compared with 1a,b and necessi-

tated heating at 808C using dihydropyran as a solvent (cf.

runs 5 and 13, Table 1). The comparably low yield of 2t may

be ascribed to these factors.

Enol ethers with low electron density on the double

bonds, such as [1,3]dioxol-2-one and vinyl acetate, as well as

vinylamines and vinylamides, such as N-vinylimidazole and

N-vinyl-g-butyrolactam, were unreactive, and 1 was recov-

ered. Ketene dithioacetal^[21]turned out to be reactive

enough and provided 2u in moderate yield [Eq. (7)].

9690

www.chemeurj.org

ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Chem. Eur. J. 2007, 13, 9686 – 9702

Conjugative Nucleophilic Addition

FULL PAPER

The tetrahydropyridine structure of 2 was determined un-

equivocally by the X-ray crystallographic analyses of 2a, 2e,

2i, 2l, 2o, 2q, and 2t.^[12]They showed standard values of

coupling constants (³J)of cyclohexenes with respect to the

substitution patterns of the C2 and C3 positions. For exam-

ple, the C3-H_eqof 2l resonates at d 2.99 ppm and splits into

dt (J = 5.7 and 2.2 Hz), which are ascribed to the couplings

with C4-H_axand C4-H_eqand C2-H_eq, respectively. The sub-

stitution pattern of other 2 was determined on the same

grounds. For example, the axial orientation of the CO₂Me

group of 2p was determined on the basis of the similarity of

the coupling pattern of C3-H (dd, J=6.2, 1.8 Hz)to that of

2l. The axial C2-OMe and the equatorial C3-Ph orientations

of 2b are also deduced on the basis of their coupling pat-

tern: C2-H_eq(d=5.15 ppm, d, J=2.3 Hz)and C3-H

2.78 ppm, ddd, J=2,3, 4.1, 13.2 Hz).

(d=

ax

The regioisomeric attachment of the oxygen atom on the

tetrahydropyridine ring observed for 2g and 2h could be de-

1

termined by comparing the H and ¹³C NMR chemical shifts

at the C2 and C3 positions of relevant reference compounds.

Typical examples are illustrated in Figure 1. NOE experi-

ments also support the structure of 2h.

Figure 2. Chem3D X-ray structures for products 2, 3, 4, and 6. For clarity,

all hydrogens, carbons of tolyl group (replaced for Me), and alkyl groups

ꢀ

on Si are omitted. Ethereal C O bond lengths are shown in .

quasi-axial position. This is apparently due to an allylic

strain that quasi-equatorial substituents might experience

against the oxazolidinone carbonyl oxygen. In those cases

where C2 bears both O and C substituents, as in 2i, 2o, and

2p, the oxygen substituents monopolize a quasi-axial posi-

tion, suggesting that the electrostatic C9=O···O-C2 repulsion

is decisively influential over the van der Waals repulsion be-

tween C9=O and alkyl-C2.

Figure 1. Chemical shifts of ¹H (400 MHz)and ¹³C (100 MHz, in italic)

NMR for 2d and 2h (d in ppm). Relevant coupling constants and NOE

increments (%)are also shown.

The essential bond lengths and dihedral angles of 2 of in-

terest are summarized in Table 2, which indicate that, except

2q, C5, C6, N, and C2 lie almost in a plane and C3 and C4

move either up and down (2a, 2e, 2l, 2o, 2q), or down and

up (2i)to a similar extent to each other from the plane. The

tricyclic compound 2q is unique, in which the C2 bears two

Figure 2 shows the Chem 3D presentation of the struc-

tures of 2 of interest determined by the single-crystal X-ray

diffraction methods, along with the structures of the other

products 3, 4 and 6,^[12]which will be referred to later in this

article.

ꢀ

The short C2 O bond lengths

observed for 2a, 2l and 2q, as

Table 2. Selected bond lengths [] and dihedral angles [8] of 2, 3 and 4.

compared with the standard

ꢀ

C_sp₃O_sp₃values, 1.42–1.45 ,

may suggest polarization of the

ꢀ

N C2 bond of the tetrahydro-

pyridine ring in a way of N^dꢀ

2a

2e

2i

2l

2o

2q

3a

3h

(Z)-4c

ꢀ

C2^d+, though apparent length-

ening of the N C2 bonds is not

observed (Table 2). Similar

shortening of the C2 O bond

lengths was observed for 2e, 2i,

2o and 2t.^[12]Another common

structural feature of 2 is that

the C2 substituents occupy a

ꢀ

d O8 C9

d C9=0

1.349

1.196

1.372

1.468

1.326

2.5

1.345

1.201

1.375

1.378

1.451

1.335

ꢀ0.5

1.343

1.191

1.395

1.385

1.470

1.336

1.6

1.369

1.183

1.342

1.435

1.513

1.269

1.0

1.332

1.195

1.388

1.403

1.480

1.349

ꢀ2.2

1.330

1.197

1.392

1.393

1.487

1.348

ꢀ14.3

42.5

1.334

1.209

1.370

1.385

1.465

1.340

ꢀ2.0

1.343

1.202

1.374

1.383

1.466

1.345

ꢀ2.9

1.338

1.196

1.369

1.370

ꢀ

d C9 N

ꢀ

d N C6

ꢀ

d N C2

ꢀ

d C5 C6

1.348

a C5-C6-N-C2

a C6-N-C2-C3

a N-C2-C3-C4

20.0

ꢀ53.8

27.0

ꢀ50.2

ꢀ23.6

30.0

ꢀ59.4

34.4

ꢀ57.8

32.5

ꢀ56.0

31.6

ꢀ55.5

48.5

ꢀ57.9

Chem. Eur. J. 2007, 13, 9686 – 9702

ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemeurj.org

9691

Y. Tamaru et al.

Table 3. Thermal cycloaddition of allylsilanes and -stannanes toward

oxygen substituents and the tetrahydropyran oxygen atom is

forced to locate in a quasi-equatorial position in a distance

(2.788 )to the carbonyl oxygen, much shorter than the

sum of the van der Waals radius of oxygen (1.75 )

(Figure 2). This may correspond to an unusually large dihe-

dral angle, C5-C6-N-C2 ꢀ14.38.

1b.^[a]

Run

Allyl-X

T [8C]/t [h]

Isolated yield [%]

Reaction of 1 with allylsilanes: Allylsilanes are a rather

poor nucleophile as compared with enol ethers, yet they

belong to a unique class of compounds in that the double

bonds display versatile nucleophilic reactivities; they serve

not only as an allylating agent toward carbonyl compounds,

but also as a two- and three-carbon component for [2+2]

and [2+3] cycloaddition reactions with compounds possess-

ing highly polarized C=C double bonds.^[22]

In order to shed more light on the mechanistic aspects of

the unique 1,3-sulfonyl rearrangement (Scheme 2), we ex-

amined the reaction of allylsilanes as a probe in expectation

that an intermediate (Z)-III’ (corresponding to (Z)-III in

Scheme 2)might possibly undergo either desilylation to pro-

vide (Z)-E or isomerization to (E)-III’ to give (E)-E and/or

F (via 1,2-silyl migration, Scheme 3).

3

5

1

2

3

4

5

X=SiMe₃

80/25

80/12

80/10

80/24

3a: 56

3b: 48

3c: 40

0^[b]

5: 20

5: 19

5: 10

0^[b]

X=Si

X=SiPh₃

X=Si(OEt)₃

X=SnMe₃

A

H

80/98 then 100/21

0^[b]

[a] 1b (0.5 mmol)and allyl-X (5 mmol)in dry dioxane (1 mL)under N

[b] Decomposition of 1b. No detection of characteristic spots ascribable

to 3 and 5.

.

2

amount of water, present as a contaminant in the reaction

mixture; however, this seems to be improbable; the reaction

was undertaken several times with great care under rigor-

ously dry conditions, but the results were reproducible. Fur-

thermore, an independent reaction undertaken in the pres-

ence of two equivalents of water added deliberately did not

give 5 at all and 1b was recovered cleanly.

We next examined allylsilanes with higher migratory apti-

tude^[22](runs 2 and 3, Table 3)in an attempt to detect the

type of product F; however, allyltriisopropyl- and allyltri-

phenylsilanes reacted in a way similar to allyltrimethylsilane.

Allyltriethoxysilane caused decomposition of 1b (run 4).

The reaction feature turned out to depend significantly on

the substitution pattern of the allylic moiety of allylsilanes

[Eq. (9)]. b-Methylallyl(trimethyl)silane reacted as usual to

give a [4+2] product 3d, though under rather harsh condi-

tions, while b-phenylallyl(trimethyl)silane underwent [2+2]

cycloaddition exclusively and provided B-5 in excellent yiel-

d.^[1a,b]These results well correspond to those described in

Equation (4).

Scheme 3. Possible routes that an imaginary intermediate III’ might un-

dergo.

As seen in run 1 of Table 3, however, when 1b and allyl-

trimethylsilane were heated in dry dioxane at 808C under

N₂, no trace amounts of (Z)-E, (E)-E, and F were detected;

instead, a formal [4+2] addition product 3a was isolated in

56% yield [Eq. (8)]. Strangely, in addition to 3a, a bis-allyl

ether 5 was also isolated in a considerable amount (20%).

The yield of 5 is calculated on the mole base of 5 and

should be doubled to estimate the material balance of the

reaction. This treatment indicates that the reaction is quanti-

tative with respect to 1b. The structures of 3a and 5 were

determined by the X-ray crystallographic analyses.^[12]Chem

3D drawing of the structure of 3a is shown in Figure 2.

The reaction was also examined in the presence of LiCl in

order to stabilize the ionic intermediate III’, and at the same

time, to help desilylation by an attack by the chloride ion on

silicon; however, there were no appreciable changes in the

presence and absence of LiCl.

All these results clearly indicate that the conjugation of a

phenyl and a vinyl group is decisively more influential than

the allylic conjugation with silicone to determine the course

of the reaction.

It may be worth noting that the relative reactivity order

observed for [4+2] cycloaddition among allylsilanes

At present, the mechanism for the generation of 5 is not

clear. One suggested route is the reaction of 1b with a trace

[(iPr)₃Si

ACHTRE(UNG allyl), Ph₃SiACHERT(UNG allyl) > Me₃SiACHTRE(NUG allyl) > Me₃Si(b-meth-

ylallyl)], estimated roughly on the basis of the reaction

9692

www.chemeurj.org

ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Chem. Eur. J. 2007, 13, 9686 – 9702

Conjugative Nucleophilic Addition

FULL PAPER

times and temperatures required for completion of reaction,

seems to be reversely correlated to “the scales of nucleophi-

licity”, proposed by Mayr et al. [Me₃Si(a-methylallyl) @

did not take place at all even by heating the mixture under

harsh reaction conditions [Eq. (11)]. On the other hand, in

the presence of trimethoxyvinylsilane, the [4+2] cycloaddi-

tion of 1b and allylbenzene did proceed to give 3 f, albeit in

low yield [Eq. (12)]. Homoallylsilanes might be regarded as

a simple, non-activated alkene, since the orbital interaction

(allyl)].^[23]

(iPr)₃SiACHTREUNG(allyl), Me₃SiACHERTUNG(allyl) > Ph₃SiACHTRENUG

In accord with this, allyltrimethylstannane, expected to be

by far more reactive as a nucleophile than allylsilanes,^[23]

turned out to be reluctant to undergo cycloaddition to 1

(run 5, Table 3). Thus, 1b was recovered almost quantita-

tively when heated with allyltrimethylstannane at 808C for

10–20 h. Prolonged heating at higher temperatures only re-

sulted in the decomposition of 1b.

ꢀ

between the p-bond and the C Si bond is negligibly

small.^[24]However, homoallyltrimethylsilane did undergo cy-

cloaddition and provided 3g, though again albeit in low

yield [Eq. (13)].

These results suggest that some factors other than nucleo-

philicity, such as Lewis acidity of silicone, might operate to

promote the [4+2] cycloaddition. That is, the silicone of al-

lylsilanes coordinates to the sulfonamide oxygen so as to fa-

cilitate the formation of I.

Bearing this in mind, we examined the reaction of (Z)-3-

hexyloxyl-2-propenyl(trimethyl)silane and 1b [Eq. (10)] in

expectation that intramolecular coordination of the silicon

to the ether oxygen might render an intermolecular coordi-

nation of the silicon to the sulfonamide oxygen of 1b inef-

fective and hence retard the [4+2] cycloaddition. Indeed,

almost no reaction proceeded when the mixture was heated

under the usual conditions (808C, 21 h). For the reaction to

proceed at a reasonable rate, heating at a higher tempera-

ture was required (1008C, 12 h). Taking into consideration

the fact that the enol ethers of a similar structural type (e.g.,

runs 11 and 12, Table 1)are reactive enough at 80 8C, the

sluggish reaction of this enol ether may be attributed to in-

tramolecular coordination of the oxygen to the silicone,

which decreases the electron donation ability of the oxygen

atom to the enol double bond.

During examination of silicone compounds as a promoter

of 1,3-sulfonyl shift, we found by chance that some silicone

ꢀ

compounds possessing an Si H bond promote a reductive

1,3-sulfonyl shift and deliver the hydrogens at the Cb posi-

tion of 1 to provide 2-oxazolidinones 4 in reasonable yields

(Table 4). Among silanes, tris(trimethylsilyl)silane gave the

cleanest results and provided (Z)-4a as a single product in

Table 4. Reductive 1,3-tosyl migration induced by silanes.^[a]

The reaction displayed interesting regio- and stereoselec-

tivity; the product 3e possesses an opposite regiochemistry

to 3a–d, locating the trimethylsilylmethyl group at the C3

position of the tetrahydropyridine ring. This result clearly

indicates that (Z)-3-hexyloxyl-2-propenyl(trimethyl)silane

displays the reactivity as an enol ether rather than an allylsi-

lane. The reaction proceeded with complete retention of

configuration as generally observed for enol ethers

(Table 1). The structure of cis-3e was determined on the

basis of NOE experiments: a large increment of the area in-

tensity of C3H (9.0%)and a small enhancement of the area

intensity of one of the diastereotopic methylene protons of

the trimethylsilylmethyl group (3.8%)by the irradiation

upon C2H.

Run

Silane

(TMS)₃SiH

PhSiH₃

Et₃SiH

Et₂SiH₂

T [8C])/t [h]

Isolated yield [%]

(Z)-4a

(E)-4a

1

2

3

4

G

80/33

80/23

80/60

50/118

70

60

26

40

0

4

31

0

Further supporting results that silane serves as a promoter

for 1,3-sulfonyl shift were obtained in the following experi-

ments [Eqs. (11–13)]. The reaction of 1b and allylbenzene

[a] 1b (0.5 mmol)and a silane (5 mmol)in dry dioxane (1 mL)under ni-

trogen.

Chem. Eur. J. 2007, 13, 9686 – 9702

ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemeurj.org

9693

Y. Tamaru et al.

70% isolated yield just by heating a mixture of the silane

(10 equiv)and 1b in dry dioxane at 808C for 33 h. With

some other silanes, (Z)-4a was produced together with (E)-

4a (runs 2 and 3).

Interestingly, despite the presence of acidic NH, these tet-

rasubstituted enamines, (Z)- and (E)-4a, did not isomerize

to each other. Independent heating at 808C for over 40 h of

each of the isolated pure isomers (E)- and (Z)-4a in dioxane

did not cause isomerization and each isomer was recovered

quantitatively. The geometrical stability seems to be reflect-

The ratio of 4 to 6 seems to depend on the steric bulk and

the acidity of alcohols; roughly, the bulkier and the higher

the acidity, the higher is the proportion of 6. Phenol is one

extreme that provides (E)-6g exclusively in good yield (run

6, Table 5).

Thiols, on the other hand, displayed a general trend to

provide 4 either exclusively (run 7)or highly selectively (run

8). The product distribution slightly depends on the kind of

1, and the reaction of 1d and thiophenol provided (Z)-4j

exclusively [Eq. (16)]. The relatively high proportion of 4 to

6 for the reactions with thiols as compared with alcohols

may be attributed to the higher nucleophilicity of thiols. Re-

agents with poor nucleophilicity like alcohols may be unable

to supply a sufficient anionic charge to the allene Ca carbon

to displace the sulfonyl group and end up with providing

(E)-6 just via simple addition to the Ca=Cb double bond.

In these reactions, the products (E)-4 were only produced

in the reaction with thiols and it may be reasonable to attri-

bute their formation to a thiyl radical-mediated isomeriza-

tion of the primary products (Z)-4.^[25]

ꢀ

ed in the bond lengths of C9 N, N C6, and C5 C6, which

are almost identical for 2, 3, and 4 (Table 2).

The geometric stability of 4 indicates that the E and Z

isomers were produced either via different routes independ-

ently or more likely via an isomerization of (Z)-4a to (E)-

4a promoted by some unknown catalysts that might be pro-

duced in the reaction mixture. The exclusive (runs 1 and 4)

and the selective formation of (Z)-4a (run 2)suggests the

reaction most probably proceeds via a bicyclic transition

state IV. A sulfurane oxide intermediate V is electronically

neutral, as opposed to the zwitterionic intermediate I

ꢀ

(Scheme 2)and possesses a strong Si O bond. Accordingly,

V [Eq. (14)] is expected to be stable enough to be isolated.

Despite our careful examination, however, no V was detect-

1

ed in the reaction mixture (crude H NMR and TLC).

Reaction of 1 with hetero-nucleophiles: Encouraged by the

smooth nucleophilic reductive 1,3-sulfonyl shift promoted

by silanes, we examined hetero-nucleophiles as reaction

partners. To our pleasant surprise, alcohols and thiols

smoothly reacted with 1, and the reactions completed even

by exposure to a small excess amount of alcohols and thiols

(1.5–2.0 equiv, as opposed to 10 equiv of silanes)under neu-

tral conditions. The reaction feature, however, was some-

what different to the one observed for silanes; in addition to

1,3-sulfonyl migration products (Z)-4, were produced non-

sulfonyl migration products (E)-6 [Eq. (15)] in considerable

amounts (Table 5).

Surprisingly, in sharp contrast to alcohols and thiols, sec-

ondary amines, such as N-methylaniline and dipropylamine,

were definitively unreactive under the usual conditions and

the starting 1b was recovered quantitatively. Among secon-

dary amines examined, indole was one exception and served

as a C-nucleophile rather than an N-nucleophile and provid-

ed a mixture of (E)-7a and (E)-8a in comparable amounts

and in a reasonable combined isolated yield [Eq. (17)]. N-

Methylindole displayed almost parallel results [Eq. (18)].

We also examined Meldrumꢁs acid and diethyl malonate

as a typical soft carbon nucleophile; however, all attempts

either in the presence or absence of a base [Et₃N, NaH, po-

tassium bis(trimethylsilyl)amide] were unsuccessful and re-

sulted in the formation of intractable mixtures of products.

The electrophilic reactivity of the allene Ca=Cb double

bond of 1 is very specific to the kind of nucleophiles, and at

present it is difficult to give a rationale for the distinct dif-

ference of reactivities that nucleophiles display; alcohols,

thiols, and indoles are allowed to react with 1, while amines

Table 5. Addition of alcohols and thiols to the allene terminal double

bond of 1b with and without 1,3-tosyl migration.^[a]

Run Alcohol [equiv]

T [8C]/t [h]

Isolated yield [%]

(Z)-4 (E)-4 (E)-6

1

2

3

4

5

6

7

8

MeOH (2)80/22

PhCH₂OH (2)80/22

CH₂=CMeCH₂OH (1.5)80/22

iPrOH (2)80/12

CH₂=CHCHMeOH (1.5)80/41

PhOH (3)80/24

4b: 47

4c: 48

4d: 11

4e: 34

4 f: 14

4g: 0

0

31

12

6b: 35

6c: 35

6d: 61

6e: 44

6 f: 60

6g: 70

6h: 0

C₁₆H₃₃SH (2)80/21

PhSH (2)80/42

4h: 5

4i: 72

6i: 15

[a] 1b (0.5 mmol)and an alcohol or a thiol (indicated amount)in dry di-

oxane (1 mL)under N .

2

9694

www.chemeurj.org

ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Chem. Eur. J. 2007, 13, 9686 – 9702

Conjugative Nucleophilic Addition

FULL PAPER

and soft carbon nucleophiles like malonates are not. Howev-

er, for the reactions that show positive results [Table 5 and

Eqs. (16–18)], the mechanism seems to be rationalized ac-

cording to Scheme 2.

Alcohols and thiols are able to form such a stable and

+

ꢀ

strong oxonium Cb O bond (or neutral Cb O bond by de-

+

ꢀ

protonation)and sulfonium C b S bond (or neutral Cb S

bond by deprotonation), respectively, that pathway B might

be favored over pathway A and the thus-formed zwitterionic

intermediates (non-vinylogous analogue of (Z)-III)would

immediately undergo proton exchange to give the final

products 4. Protonation at the Ca leads to (E)-6. The selec-

tive formation of (Z)-4 and (E)-6, the structures of which

have been determined firmly on the basis of NOE experi-

ments, lends further support to the reaction mechanism

passing through pathway B; through pathway A, that is, via

the Michael addition of alcohols and thiols to a 1-aza-1,3-

butadiene intermediate II, random mixtures of (E)- and

(Z)-4 should result.

Scheme 4. A plausible mechanism for the reaction of 1 and indoles (R=

H or Me).

cially 2q (Table 1), display. The structure of 7 and 8 was de-

termined unequivocally on the basis of NOE experiments

(Figure 3).

The nucleophilic addition of indoles providing (E)-8 [Eqs.

(17 and 18)], in a sense, might be regarded as electrophilic

aromatic substitution of 1; that is, despite the fact that 1 is a

neutral species, it is even capable of undergoing the Friedel–

Crafts type electrophilic aromatic substitution in the absence

of any Lewis acid catalysts (path D, Scheme 4). Electrophilic

addition of 1 to indoles and aromatization by deprotonation

would provide (E)-8.

The exclusive formation of (E)-7 can hardly be explained

according to pathway B followed by aromatization leading

(Z)-7. Like 4, the exocyclic enamide double bond of (Z)-7 is

expected to be geometrically stable and would not isomerize

to (E)-7. Furthermore, there seems to be no such strong

thermodynamic bias to cause complete isomerization from

(Z)-7 to (E)-7. Instead, pathway A or pathway C that fol-

lows pathway B seems to be more likely, where a tetracyclic

intermediate VI, formed by the inverse electron demand

Diels–Alder reaction of II and indole,^[17n]would readily un-

dergo dehydroamination to give rise to (E)-7. That is, a di-

chotomy exists for the reaction of 1 and indoles; one is elec-

trophilic substitution (path D)and the other is a sequential

1,3-sulfonyl shift and the inverse electron demand Diels–

Alder reaction (path A or paths B–C), followed by ring

Figure 3. NOE increments (%)in area intensities for 1b–indole adducts

7 and 8.

It should be noted that indole and benzofuran undergo

the inverse electron demand Diels–Alder reaction in an op-

posite direction, placing N and O at the C2 and C3 positions

of tetrahydropyridine ring, respectively, which is in good

accord with precedents.^[17l,m,27]

ꢀ

opening. Strain relief, significant N1 C2 bond weakening by

The unique electrophilic reactivity associated with the

allene Ca=Cb bond of 1 is reminiscent of the reactivity of

the double bond of unsaturated carbonyl compounds and

suggests a strong through-space orbital interaction between

electron-donation by N3, and, in particular, aromatization

stabilization of indole^[26]would contribute to a facile conver-

sion of VI to (E)-7. The second and the third factors are

crucial to rationalize the contrasting stability that the inter-

mediate VI (R=H, Me)and a series of compounds 2, espe-

ꢀ

the Ca=Cb double bond and the N SO₂single bond

(Figure 4).

Chem. Eur. J. 2007, 13, 9686 – 9702

ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemeurj.org

9695

Y. Tamaru et al.

nyl-migration, delivering a hydride at the Cb position of 1,

and furnish 4-(1-sulfonylethylidene)oxazolidin-2-ones 4 ex-

clusively. Alcohols react in a way similar to hydrosilanes, de-

livering alkoxy groups at the Cb position (4, X=OR). How-

ever, in this case, simple addition to the Ca=Cb bond con-

comitantly takes place to give 6 in comparable amounts.

Phenol is one exception and provides 6 exclusively. Thiols,

on the other hand, selectively provide the type of product 4.

An interesting dichotomy exists for the reaction of indoles

and 1; indoles behave like enol ethers yielding II as an inter-

mediate (Scheme 4)as well as like phenols giving rise to the

addition products at the Ca=Cb double bond of 1 without

accompanying 1,3-sulfonyl shift.

Figure 4. Through-space orbital interaction of the Ca=Cb double bond

ꢀ

and the N SO₂single bond of 1a.

We envisage that a p*

makes the LUMO (Ca=Cb)low in energy and the double

bond an excellent electron acceptor. Furthermore, a p(Ca=

(N-SO₂)interaction weakens the N SO₂bond so that

ACHRTU(NEG Ca=Cb)-s*CAHTRE(UGN N-SO₂)interaction

AHCTREUNG

ꢀ

Cb)-s*ACHTREUNG

the novel 1,3-sulfonyl migration even proceeds by treatment

with some weak nucleophiles.

Thus, allene carbamates 1 may be referred to as a chame-

leon compound that dramatically alters its reaction features,

giving rise to 2--8 and also AꢁD^[1a,b][Scheme 1 and Eqs.

(17,18)].

Conclusion

The exocyclic allene Ca=Cb bond of 1 serves as a potential

electron acceptor and undergoes nucleophilic addition of a

wide variety of nucleophiles, encompassing enol ethers, al-

lylsilanes, hydrosilanes (R_nSiH_4ꢀn, n=1–3), alcohols, thiols,

and some aromatic compounds, such as furans, benzofurans,

and indoles. The reaction proceeds readily just by heating a

mixture of 1 and a nucleophile at about 70–1008C.

Experimental Section

Reactions employed oven-dried glassware unless otherwise noted. Thin-

layer chromatography (TLC)employed glass 0.25 mm silica gel plates

with UV indicator (Merck, Silica gel 60F254). Flash chromatography col-

umns were packed with 230–400 mesh silica gel as a slurry in hexane.

Gradient flash chromatography was conducted eluting with a continuous

gradient from hexane to the indicated solvent. Melting points were deter-

mined on a Yanaco apparatus and are uncorrected. Boiling points refer

to the Kugelrohr oven temperatures. Proton and carbon NMR data were

obtained with a JEOL-GX400 with tetramethylsilane as an internal stan-

dard (see Supporting Information for ¹H NMR spectra for all previously

unreported compounds.). Chemical shift values were given in ppm down-

field from the internal standard. Infrared spectra were recorded with a

JASCO A-100 FT-IR spectrophotometer. High resolution mass spectra

(HRMS)were measured with a JEOL JMS-DX303. Combustion analyses

were performed by the Instrumental Analysis Center of Nagasaki Uni-

versity. Analysis agreed with the calculated values within +0.4%.

The unique reaction behavior of the allene Ca=Cb bond

is primarily due to a through-space interaction of the Ca=

ꢀ

Cb p-orbital and the N SO₂s-orbital, which renders the

LUMO (Ca=Cb)low in energy and electrophilic in nature.

The interaction was evidenced by a 1,3-sulfonyl shift from N

to Ca in the reactions with nucleophiles. The reactions of 1

and enol ethers derived from aldehydes, ketones and esters,

all provided 2-alkoxy-5-sulfonyltetrahydropyridines

2 in

good to excellent yields. Furans and benzofurans were ex-

ceptional and furnished 3-alkoxy-5-sulfonyltetrahydropyri-

dines 2g,h. Enol ethers, irrespective of their structure, were

incorporated in the products with complete retention of con-

figuration of the double bond. Based on these results, a

mechanism relying on enol ether promoted isomerization of

1 to 1-azabutadienes II, followed by the inverse electron

demand Diels–Alder reaction, was proposed (Scheme 2).

Allylsilanes reacted with 1 in a way similar to enol ethers

and provided 2-silylmethyl-5-sulfonyltetrahydropyridines 3.

The interesting reaction feature of allylsilanes is that it is a

Lewis acid-base promoted reaction, that is, the nucleophilic-

ity of the double bond brought about by allylic conjugation

Solvents and reagents: 1,4-Dioxane was dried and distilled from sodium

prior to use under nitrogen atmosphere. Enol ethers^[28]and allylsilanes^[29]

were prepared according to the literature.

General procedure for the reaction of

1 with nucleophiles (run 3,

Table 1): A mixture of 1a (0.5 mmol, R_f=0.57, hexane/ethyl acetate 2:1)

and methyl b-methoxyacrylate (20 mmol, E/Z >99:1, Aldrich)was

heated at 708C for 23 h under N₂. After completion of the reaction, the

ester was removed in vacuo. The resultant sticky mixture was purified by

column chromatography over silica gel (hexane/ethyl acetate 2:1)to give

2c (R_f=0.23)as a white solid in 70% isolated yield.

5-Ethoxy-8-(p-toluenesulfonyl)-1,5,6,7-tetrahydro-oxazoloACTHRE[UNG 3,4-a]pyridin-

3-one (2a): CCDC-181727; m.p. 133.7–134.18C (CH₂Cl₂/hexane);

¹H NMR (400 MHz, CDCl₃): d=1.14 (t, J=7.0 Hz, 3H), 1.44 (ddt, J=

2.3, 13.6, 9.4 Hz, 1H), 2.12 (ddt, J=2.3, 13.6, 3.5 Hz, 1H), 2.21 (dd, J=

3.5, 9.4 Hz, 2H), 2.44 (s, 3H), 3.65 (q, J=7.0 Hz, 2H), 5.24 (t, J=2.3 Hz,

1H), 7.34 (d, J=7.7 Hz, 2H), 7.72 ppm (d, J=7.7 Hz, 2H); ¹³C NMR

(100 MHz, CDCl₃): d=15.1, 17.1, 21.6, 25.9, 65.0, 68.2, 77.5, 108.5, 127.2,

129.9, 137.5, 141.3, 144.5, 155.5 ppm; IR (KBr): n˜ = 1800 (vs), 1680 (vs),

1420 (s), 1380 (s), 1300 (s), 1160 (s), 1140 (s), 1080 (s), 1020 cm^ꢀ1(s); ele-

mental analysis calcd (%)for C ₁₆H₁₉NO₅S: C 56.92, H 5.68, N 4.15, S

9.48; found: C 56.54, H 5.56, N 4.31, S, 9.66.

ꢀ

with the C Si bond is merely one of the factors for promot-

ing [4+2] cycloaddition; silicone plays an important role as

a Lewis acid; coordination of silicone to the sulfonyl oxygen

facilitates the formation of four-membered sulfurane oxide

I. This conclusion is based on many observations. For exam-

ple, 1)silicone compounds promote the [4 +2] cycloaddition

of simple, non-functionalized alkenes, which are otherwise

unreactive. 2)Allylstannanes are more nucleophilic than al-

lylsilanes, yet they are absolutely reluctant to reaction with

1. Hydrosilanes (R₄SiH_4ꢀn, n=1–3)nicely promote 1,3-sulfo-

cis-5-Methoxy-6-phenyl-8-(p-toluenesulfonyl)-1,5,6,7-tetrahydro-oxazolo-

AHCTRE[UNG 3,4-a]pyridin-3-one (cis-2b): M.p. 238.0–238.58C (CH₂Cl₂/hexane);

¹H NMR (400 MHz, CDCl₃): d=2.44 (s, 3H), 2.44 (ddm, J=4.1, 16.0 Hz,

1H), 2.72 (ddt, J=13.2, 16.0, 3.3 Hz, 1H), 2.84 (ddd, J=2.3, 4.1, 13.2 Hz,

1H), 3.31 (s, 3H), 5.15 (d, J=2.3 Hz, 1H), 5.56 (dm, J=3.3 Hz, 2H),

7.33–7.56 (m, 5H), 7.32 (d, J=8.1 Hz, 2H), 7.73 ppm (d, J=8.1 Hz, 2H);

9696

www.chemeurj.org

ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Chem. Eur. J. 2007, 13, 9686 – 9702

Conjugative Nucleophilic Addition

FULL PAPER

¹³C NMR (100 MHz, CDCl₃): d=21.6, 23.2, 42.7, 58.0, 68.2, 82.6, 108.8,

127.3, 127.7, 128.3, 128.6, 130.1, 137.4, 137.8, 141.0, 144.6, 155.2 ppm; IR

(KBr): n˜ = 1780 (s), 1670 (s), 1300 (s), 1240 (s), 1140 (s), 1130 (s), 1080

(s), 820 (s), 750 cm^ꢀ1(s); elemental analysis calcd (%) for C ₂₁H₂₁NO₅S: C

63.14, H 5.30, N 5.30, S 8.03; found: C 63.24, H 5.56, N 5.31, S, 8.66.

(m), 800 cm^ꢀ1(m); HRMS: m/z (%): calcd for C₁₆H₁₅NO₅S: 333.0671,

found: 333.0652 (100)[ M]⁺.

4-(p-Toluenesulfonyl)-3,5,5a,10b-tetrahydro-2,6-dioxa-10c-aza-cyclopen-

ta[c]fluoren-1-one (2h): M.p. 56.0–57.28C (CH₂Cl₂/hexane); ¹H NMR

(400 MHz, CDCl₃): d=2.46 (s, 3H), 2.65–2.76 (m, 2H), 5.06 (dt, J=7.0,

4.6 Hz, 1H), 5.21 (d, J=7.0 Hz, 1H), 5.38 (dm, J=16.5 Hz, 1H), 5.53

(dm, J=16.5 Hz, 1H), 6.77 (d, J=8.2 Hz, 1H), 6.93 (brt, J=8.2 Hz, 1H),

7.25 (brt, J=8.2 Hz, 1H), 7.34 (d, J=8.2 Hz, 2H), 7.69 (d, J=8.2 Hz,

1H), 7.43 ppm (d, J=8.2 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃): d=21.6,

24.8, 54.9, 68.3, 78.2, 103.3, 110.8, 121.6, 125.4, 127.3, 128.0, 130.0, 131.2,

137.3, 143.7, 144.7, 155.0, 158.8; IR (KBr): n˜ =2341 (m), 1778 (s), 1665

(s), 1076 (s), 818 (m), 675 cm^ꢀ1(s); HRMS: m/z (%): calcd for

C₂₀H₁₇NO₅S: 383.0827, found: 383.0818 (100)[ M]⁺, 266 (10).

trans-5-Methoxy-3-oxo-8-(p-toluenesulfonyl)-1,5,6,7-tetrahydro-oxazolo-

ACHTREUNG[3,4-a]pyridine-6-carboxylic acid methyl ester (trans-2c): M.p. 142.5–

143.58C (CH₂Cl₂/hexane); ¹H NMR (400 MHz, CDCl₃): d=2.45 (s, 3H),

2.58 (brd, J=15.0 Hz, 1H), 2.68 (brd, J=15.0 Hz, 1H), 3.07 (brs, 1H),

3.33 (s, 3H), 3.47 (s, 3H), 5.40 (s, 1H), 5.46 (d, J=18.5 Hz, 1H), 5.51 (d,

J=18.5 Hz, 1H), 7.35 (d, J=7.8 Hz, 2H), 7.71 ppm (d, J=7.8 Hz, 2H);

IR (KBr): n˜ = 1800 (s), 1720 (s), 1640 (s), 1600 (m), 1370 (s), 1310 (s),

1290 (s), 1220 (m), 1150 (s), 1120 (m), 1100 (s), 1080 cm^ꢀ1(s); elemental

analysis calcd (%)for C ₁₇H₁₉NO₇S: C 53.53, H 5.02, N 3.67, S 8.41;

found: C 53.42, H 5.21, N 3.41, S 8.53.

4-(p-Toluenesulfonyl)-8a-trimethylsiloxy-5,5a,6,7,8,8a-hexahydro-3H-2-

oxa-8b-aza-as-indacen-1-one (2i): CCDC-181723; m.p. 162.0–162.18C

(CH₂Cl₂/hexane); ¹H NMR (400 MHz, CDCl₃): d=0.01 (s, 9H), 0.86 (m,

1H), 1.29–1.55 (m, 2H), 1.55–1.78 (m, 2H), 2.04–2.28 (m, 3H), 2.34 (s,

3H), 3.19 (m, 1H), 5.29 (brd, J=18.3 Hz, 1H), 5.33 (brd, J=18.3 Hz,

1H), 7.22 (d, J=8.0 Hz, 2H), 7.62 ppm (d, J=8.0 Hz, 2H); ¹³C NMR

(100 MHz, CDCl₃): d=1.4, 19.0, 21.5, 21.6, 24.2, 33.4, 44.6, 66.7, 91.2,

106.1, 127.1, 129.9, 137.7, 142.1, 144.4, 154.0 ppm; IR (KBr): n˜ =1786 (s),

1665 (s), 1597 (m), 1389 (s), 1344 (s), 1286 (s), 1250 (s), 1167 (s), 1080 (s),

833 (s), 762 cm^ꢀ1(m); HRMS: m/z (%): calcd for C₂₀H₂₇NO₅SSi:

421.1379, found: 421.1378 (100)[ M]⁺; elemental analysis calcd (%)for

C₂₀H₂₇NO₅SSi: C 56.98, H 6.46, N 3.32, S 7.61; found: C 56.73, H 6.46, N

3.41, S 7.58.

5-(p-Toluenesulfonyl)-2,3,3a,4,6,8b-hexahydro-1,7-dioxa-8a-aza-as-inda-

cen-8-one (2d): M.p. 223.2–224.08C (CH₂Cl₂/hexane); ¹H NMR

(400 MHz, CDCl₃): d=1.82 (dddd, J=2.9, 5.2, 7.3, 12.1 Hz, 1H), 1.93

(ddt, J=8.8, 15.4, 2.9 Hz, 1H), 2.21 (m, 1H), 2.31 (m, 1H), 2.45 (s, 3H),

2.48 (ddm, J=6.5, 15.8 Hz, 1H), 3.94 (dd, J=6.5, 8.4 Hz, 1H), 3.97 (dd,

J=5.2, 8.4 Hz, 1H), 5.36 (d, J=4.0 Hz, 1H), 5.45 (ddd, J=1.8, 2.9,

16.9 Hz, 1H), 5.55 (ddd, J=1.8, 2.9, 16.9 Hz, 1H), 7.35 (d, J=8.1 Hz,

2H), 7.71 ppm (d, J=8.1 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃): d=21.6,

23.5, 29.6, 33.5, 64.7, 68.1, 81.2, 106.7, 127.2, 130.1, 137.4, 141.7, 144.7,

154.7ppm; IR (KBr): n˜ = 1790 (s), 1670 (s), 1290 (m), 1240 (m), 1200

(m), 1150 (m), 1050 (m), 990 (m), 945 cm^ꢀ1(m); elemental analysis calcd

(%)for C ₁₆H₁₇NO₅S: C 57.29, H 5.12, N 4.18, S 9.54; found: C 57.18, H

5.03, N 4.11, S 9.68.

4-(p-Toluenesulfonyl)-9a-trimethylsiloxy-3,5,5a,6,7,8,9,9a-octahydro-

oxazoloCAHTRE[UNG 3,4-a]quinolin-1-one (2j, a mixture with 2j’ in a ratio of 3.5:1):

m.p. 39.5–40.58C (CH₂Cl₂/hexane); ¹H NMR (400 MHz, CDCl₃): d=0.03

(s, 9H), 0.92 (m, 1H), 1.12–2.03 (m, 8H), 2.13 (brd, J=14.5 Hz, 1H,

minor), 2.44 (s, 3H), 2.53 (m, 1H), 3.22 (brd, J=12.5 Hz, 1H, minor),

3.45 (d, J=12.8 Hz, 1H), 5.31–5.48 (m, 2H), 7.34 (d, J=7.7 Hz, 2H),

7.72 ppm (d, J=7.7 Hz, 2H). ¹³C NMR (100 MHz, CDCl₃): d=0.6, 20.7,

22.7, 23.8, 24.0, 27.6, 33.9, 41.1, 65.7, 85.0, 106.9, 126.2, 129.0, 136.9, 140.9,

143.5, 153.2 ppm; IR (KBr): n˜ =1790 (s), 1668 (s), 1381 (m), 1340 (m),

1250 (m), 1148 (m), 845 cm^ꢀ1(m); HRMS: m/z (%): calcd for

C₂₁H₂₉NO₅SSi: 435.1536, found: 435.1516 (49)[ M]⁺, 280 (100).

4-(p-Toluenesulfonyl)-3,5,5a,7,8,9a-hexahydro-6H-2,9-dioxa-9b-aza-cyclo-

penta[a]naphthalen-1-one (2e): CCDC-181562; M.p. 199.5–200.08C

(CH₂Cl₂/hexane); ¹H NMR (400 MHz, CDCl₃): d=1.37 (dd, J=2.3,

13.4 Hz, 1H), 1.74 (m, 1H, coalescing to dq, J=4.8, 13.4 Hz by irradia-

tion at 3.98), 1.84–1.98 (m, 3H), 2.18 (dd, J=4.0, 16.0 Hz, 1H), 2.40

(ddm, J=12.1, 16.0 Hz, 1H), 2.45 (s, 3H), 3.65 (dt, J=2.3, 12.1 Hz, 1H),

3.98 (dd, J=4.8, 12.1 Hz, 1H), 5.06 (d, J=1.1 Hz, 1H), 5.43 (ddd, J=1.1,

3.1, 16.5 Hz, 1H), 5.50 (ddd, J=1.1, 3.1, 16.5 Hz, 1H), 7.35 (d, J=8.2 Hz,

2H), 7.71 ppm (d, J=8.2 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃): d=20.1,

21.4, 21.6, 26.1, 30.6, 68.0, 68.2, 78.2, 107.3, 127.2, 130.0, 137.5, 141.3,

144.6, 154.2 ppm; IR (KBr): n˜ = 1790 (s), 1670 (s), 1410 (s), 1380 (m),

1360 (m), 1300 (m), 1240 (m), 1210 (m), 1050 cm^ꢀ1(m); HRMS: m/z

(%): calcd for C₁₇H₁₉O₅NS: 349.4076, found: 349.09840 (22)[ M]⁺, 194

(100); elemental analysis calcd (%) for C ₁₇H₁₉NO₅S: C 58.44, H 5.48, N

4.01, S 9.18; found: C 58.48, H 5.50, N 3.98, S 9.20.

9a-Hydroxy-4-(p-toluenesulfonyl)-3,5,5a,6,7,8,9,9a-octahydro-oxazoloACHTREUNG[3,4-

a]quinolin-1-one (2j’): M.p. 224.0–224.28C (CH₂Cl₂/hexane); ¹H NMR

(400 MHz, CDCl₃): d1.24- 1.78 (m, 8H), 1.97 (ddt, J=15.4, 18.7, 3.3 Hz,

1H), 2.22 (dd, J=4.2, 15.4 Hz, 1H), 2.44 (s, 3H), 3.01 (brs, 1H), 3.23

(brd, J=12.8 Hz, 1H), 5.31 (dm, J=14.7 Hz, 1H), 5.45 (dm, J=14.7 Hz,

1H), 7.34 (d, J=8.25 Hz, 2H), 7.72 ppm (d, J=8.25 Hz, 2H); ¹³C NMR

(100 MHz, CDCl₃): d=21.0, 24.0, 24.3, 27.3, 32.8, 65.6, 84.5, 108.0, 129.1,

137.1, 141.6, 153.0 ppm; IR (KBr): n˜ =3260 (m), 1790 (s), 1660 (s), 1600

(m), 1380 (m), 1320 (m), 1220 (m), 1150 (m), 1080 (w), 1030 cm^ꢀ1(w); el-

emental analysis calcd (%)for C ₁₈H₂₁NO₅S: C 59.49, H 5.82, N 3.85, S

8.82; found: C 59.39, H 5.76, N 3.67, S 8.80.

8-Methoxy-4-(p-toluenesulfonyl)-3,5,5a,7,8,9a-hexahydro-6H-2,9-dioxa-

9b-aza-cyclopenta[a]naphthalen-1-one (2 f): M.p. 203.0–203.58C (CH₂Cl₂/

hexane); ¹H NMR (400 MHz, CDCl₃): d=1.55 (dd, J=4.8, 13.9 Hz, 1H),

1.61 (ddt, J=4.8, 13.9, 2.4 Hz, 1H), 1.75 (ddt, J=3.3, 4.8, 13.9 Hz, 1H),

1.87 (m, 1H), 2.15 (ddd, J=1.5, 5.5, 15.8 Hz, 1H), 2.24 (tt, J=4.8,

13.9 Hz, 1H), 2.38 (ddt, J=15.8, 12.8, 3.3 Hz, 1H), 2.45 (s, 3H), 3.48 (s,

3H), 4.71 (brd, J=3.3 Hz, 1H), 5.45 (ddd, J=1.5, 3.3, 16.5 Hz, 1H), 5.51

(d, J=2.2 Hz, 1H), 5.52 (ddd, J=1.5, 3.3, 16.5 Hz, 1H), 7.34 (d, J=

8.1 Hz, 2H), 7.71 ppm (d, J=8.1 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃):

d=15.3, 21.0, 21.2, 21.6, 23.9, 29.7, 55.2, 65.9, 68.2, 70.9, 76.8, 77.1, 77.4,

99.8, 107.1, 127.2, 130.1, 137.5, 141.4, 144.6, 154.2 ppm; IR (KBr): n˜

=1775 (s), 1660 (s), 1410 (s), 1375 (w), 1295 (w), 1190 (w), 1130 (w),

1070 (w), 1025 (w), 980 cm^ꢀ1(s); HRMS: m/z (%): calcd for

C₁₈H₂₁NO₆S: 379.1090, found: 379.1069 (100)[ M]⁺; elemental analysis

calcd (%)for C ₁₈H₂₁NO₆S: C 56.98, H 5.58, N 3.69; found: C 56.59, H

5.52, N 3.55.

3,3-Dimethyl-4-(p-toluenesulfonyl)-10b-triisopropylsiloxy-5,5a,6,10b-tet-

rahydro-3H-2-oxa-10c-aza-cyclopenta[c]fluoren-1-one (2k): M.p. 169.0–

170.08C (CH₂Cl₂/hexane); ¹H NMR (400 MHz, CDCl₃): d=0.77–1.09 (m,

21H), 1.18–1.25 (m, 2H), 1.60–1.70 (m, 2H), 2.30 (m, 1H), 2.47 (s, 3H),

2.60 (m, 1H), 2.83 (m, 1H), 5.36 (ddd, J=1.7, 3.3, 15.4 Hz, 1H), 7.16–

7.27 (m, 4H), 7.36 (d, J=8.1 Hz, 2H), 7.75 ppm (d, J=8.1 Hz, 2H); IR

(KBr): n˜ =1810 (s), 1675 (s), 1380 (m), 1320 (m), 1260 (m), 1215 (m),

1160 (s), 1115 (m), 1080 (m), 1040 (w), 920 cm^ꢀ1(m); elemental analysis

calcd (%)for C ₃₁H₄₁NO₅SSi: C 65.57, H 7.28, N 2.47; found: C 65.35, H

7.27, N 2.43.

trans-5-Methoxy-1,1-dimethyl-3-oxo-8-(p-toluenesulfonyl)-1,5,6,7-tetrahy-

4-(p-Toluenesulfonyl)-3,5,5a,8a-tetrahydro-2,6-dioxa-8b-aza-as-indacen-1-

one (2g): M.p. 186.2–187.08C (CH₂Cl₂/hexane); ¹H NMR (400 MHz,

CDCl₃): d=2.45 (s, 3H), 2.56 (brddd, J=3.1, 5.1, 16.9 Hz, 1H), 2.79 (dd,

J=16.9, 1.3 Hz, 1H), 4.60 (dd, J=2.6, 7.7 Hz, 1H), 4.90 (ddd, J=2.6, 5.1,

7.7 Hz, 1H), 5.46 (dd, J=3.1, 1.3 Hz, 2H), 5.57 (t, J=2.6 Hz, 1H), 6.40

(d, J=2.6 Hz, 1H), 7.35 (d, J=8.4 Hz, 2H), 7.72 ppm (d, J=8.4 Hz, 2H);

¹³C NMR (100 MHz, CDCl₃): d=21.6, 24.1, 55.4, 68.5, 77.6, 101.9, 102.7,

127.2, 130.0, 137.3, 144.0, 144.6, 150.1 ppm; IR (KBr): n˜ =1780 (s), 1670

(s), 1360 (m), 1300 (m), 1260 (m), 1160 (m), 1140 (m), 1120 (m), 1020

dro-oxazoloACHTREU[NG 3,4-a]pyridine-6-carboxylic acid methyl ester (2l): CCDC-

181552; m.p. 193.0–193.38C (CH₂Cl₂/hexane); ¹H (400 MHz, CDCl₃): d=

1.94 (s, 3H), 1.99 (s, 3H), 2.45 (s, 3H), 2.52 (dd, J=5.7, 16.5 Hz, 1H),

2.66 (ddd, J=1.1, 2.2, 16.5 Hz, 1H), 2.99 (dt, J=5.7, 2.2 Hz, 1H), 3.42 (s,

3H), 3.45 (s, 3H), 5.39 (dd, J=1.1, 2.2 Hz, 1H), 7.35 (d, J=8.4 Hz, 2H),

7.75 ppm (d, J=8.4 Hz, 2H); IR (KBr): n˜ =1800 (s), 1720 (s), 1640 (s),

1600 (m), 1370 (s), 1310 (s), 1290 (s), 1220 (m), 1150 (s), 1120 (m), 1100

(s), 1080 (s), 960 cm^ꢀ1(m); elemental analysis calcd (%) for C ₁₉H₂₃NO₇S:

C 55.73, H 5.66, N 3.42, S 7.83; found: C 55.42, H 5.61, N 3.31, S 7.43.

Chem. Eur. J. 2007, 13, 9686 – 9702

ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemeurj.org

9697

Y. Tamaru et al.

6-Ethyl-1,1-dimethyl-8-(p-toluenesulfonyl)-5-triisopropylsiloxy-1,5,6,7-tet-

rahydro-oxazolo[3,4-a]pyridin-3-one (cis-2m): M.p. 186.2–187.08C

144.0, 150.0, 150.7 pppm; IR (KBr): n˜ =1782 (s), 1626 (s), 1337 (m), 1317

(s), 883 (m), 756 cm^ꢀ1(m); HRMS: m/z (%): calcd for

C₂₈H₄₃NO₆SSiꢀiPr: 506.2033, found: 506.2030 (100)[ MꢀiPr]⁺.

ACHTREUNG

(CH₂Cl₂/hexane); ¹H NMR (400 MHz, CDCl₃): d=0.91–0.99 (m, 21H),

1.05–1.14 (m, 3H), 1.32 (dq, J=14.3, 7.4 Hz, 1H), 1.44 (m, 1H), 1.50 (dq,

J=14.3, 7.4 Hz, 1H), 1.87 (dd, J=12.3, 15.9 Hz, 1H), 2.41 (dd, J=4.8,

15.9 Hz, 1H), 5.53 (d, J=1.5 Hz, 1H), 7.29 (d, J=8.1 Hz, 2H), 7.71 ppm

(d, J=8.1 Hz, 2H); trans-2m: d=0.73 (t, J=7.0 Hz, 3H), 0.91–0.99 (m,

21H), 1.05–1.14 (m, 3H), 1.26–1.55 (m, 3H), 1.87 (dd, J=12.3, 15.9 Hz,

1H), 2.41 (dd, J=4.8, 15.9 Hz, 1H), 5.37 (d, J=1.8 Hz, 1H), 7.30 (d, J=

8.6 Hz, 2H), 7.73 ppm (d, J=8.6 Hz, 2H); IR (KBr): n˜ =1770 (s), 1630

(s), 1325 (m), 1305 (s), 1260 (m), 1220 (m), 1170 (m), 1140 (s), 1080 (s),

1055 (m), 995 (m), 960 (m), 940 (m), 870 (m), 840 (m), 800 cm^ꢀ1(m);

HRMS: m/z (%): calcd for C₂₇H₄₃NO₅SSiꢀiPr: 478.2083, found: 478.2074

(100)[ MꢀiPr]⁺; elemental analysis calcd (%)for C ₂₇H₄₃NO₅SSi: C 62.15,

H 8.31, N 2.68; found: C 62.08, H 8.20, N 2.70.

9a-Hydroxy-3,3-dimethyl-4-(toluene-4-sulfonyl)-3,5,5a,6,7,9a-hexahydro-

oxazoloACHTRE[UNG 3,4-a]quinolin-1-one (2r): M.p. 61.0–62.08C (CH₂Cl₂/hexane);

¹H NMR (400 MHz, CDCl₃): d=1.06 (s, 3H), 1.45 (s, 3H), 1.47 (m, 1H),

1.85 (m, 1H), 1.98 (m, 1H), 2.30–2.44 (m, 2H), 2.40 (s, 3H), 2.85 (dd, J=

2.8, 15.2 Hz, 1H), 2.94 (d, J=15.2 Hz, 1H), 3.80 (brs, 1H), 5.80 (m, 1H),

5.82 (m, 1H), 7.31 (d, J=8.3 Hz, 2H), 7.85 ppm (d, J=8.3 Hz, 2H);

¹³C NMR (100 MHz, CDCl₃): d=18.6, 21.7, 25.2, 26.6, 44.6, 53.7, 67.3,

85.2, 121.2, 128.9, 129.7, 129.8, 130.4, 130.8, 146.0, 152.3 ppm; IR (KBr): n˜

=3400 (s), 1786 (s), 1281 (s), 1267 (s), 1177 (s), 1088 (m), 937 cm^ꢀ1(m);

elemental analysis calcd (%)for C ₂₀H₂₃NO₅S: C 61.68, H 5.95, N 3.60; O,

20.54, S 8.23; found: C 61.70, H 5.61, N 3.31, S 8.53.

5-Methoxy-5-methyl-8-(p-toluenesulfonyl)-1,5,6,7-tetrahydro-oxazoloACHTREUNG[3,4-

3,3-Dimethyl-4-(p-toluenesulfonyl)-3,5,5a,7,8,9a-hexahydro-6H-2,9-dioxa-

9b-azacyclopenta[a]naphthalen-1-one (2n): M.p. 224.0–225.08C (CH₂Cl₂/

hexane); ¹H NMR (400 MHz, CDCl₃): d=1.33 (dm, J=13.4 Hz, 1H),

1.68 (ttm, J=4.4, 13.4 Hz, 1H), 1.79–2.06 (m, 3H), 1.97 (s, 3H), 1.98 (s,

3H), 2.16 (ddm, J=4.8, 15.8 Hz, 1H), 2.43 (dm, J=15.8 Hz, 1H), 2.45 (s,

3H), 3.63 (dm, J=12.1 Hz, 1H), 3.98 (dd, J=4.8, 12.1 Hz, 1H), 5.07 (brs,

1H), 7.35 (d, J=8.2 Hz, 2H), 7.73 ppm (d, J=8.2 Hz, 2H); ¹³C NMR

(100 MHz, CDCl₃): d=20.0, 21.6, 23.5, 26.0, 26.3, 26.9, 30.1, 68.0, 78.2,

86.8, 107.8, 127.5, 130.0, 137.5, 144.3, 147.7, 152.9 ppm; IR (KBr): n˜

=1786 (s), 1634 (s), 1333 (s), 1294 (s), 1267 (s), 1148 (s), 847 (m),

762 cm^ꢀ1(m); elemental analysis calcd (%) for C ₁₉H₂₃NO₅S: C 60.46, H

6.14, N 3.71, S 8.50; found: C 59.96, H 6.07, N 3.71, S 8.62.

a]pyridin-3-one (2s): M.p. 133.0–133.18C (CH₂Cl₂/hexane); ¹H NMR

(400 MHz, CDCl₃): d=1.57 (m, 1H), 1.88 (s, 3H), 2.02 (ddd, J=2.6, 4.8,

13.6 Hz, 1H), 2.29 (m, 2H), 2.45 (s, 3H), 3.29 (s, 3H), 5.44 (ddd, J=1.7,

3.3, 14.5 Hz, 1H), 5.45 (ddd, J=1.7, 3.3, 14.5 Hz, 1H), 7.34 (d, J=8.1 Hz,

2H), 7.72 ppm (d, J=8.1 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃): d=18.4,

20.5, 21.6, 34.9, 51.1, 66.9, 85.2, 109.1, 127.2, 130.0, 137.7, 142.6, 144.5,

193.9 ppm; IR (KBr): n˜ =1780 (s), 1670 (s), 1380 (s), 1300 (s), 1160 (s),

1140 (s), 1080 (s), 1020 (s), 760 cm^ꢀ1(m); HRMS: m/z (%): calcd for

C₁₆H₁₉NO₅S: 337.0984, found: 337.0988 (100)[ M]⁺; elemental analysis

calcd (%)for C ₁₆H₁₉NO₅S: C 56.96, H 5.68, N 4.15, S 9.50; found: C

56.86, H 5.78, N 4.10, S 9.48.

4-Methanesulfonyl-3,5,5a,7,8,9a-hexahydro-6H-2,9-dioxa-9b-aza-cyclo-

penta[a]naphthalene-1-one (2t): CCDC-188831; m.p. 201.5–202.08C

(CH₂Cl₂/hexane); ¹H NMR (400 MHz, CDCl₃): d=1.47 (dm, J=15.8 Hz,

1H), 1.80–2.07 (m, 4H), 2.39 (tm, J=15.4 Hz, 1H), 2.95 (s, 3H), 3.73

(dtm, J=2.6, 11.5 Hz, 1H), 4.10 (ddm, J=4.8, 11.5 Hz, 1H), 5.12 (brs,

1H), 5.30 (dm, J=17.7 Hz, 1H), 5.35 ppm (dm, J=17.7 Hz, 1H);

¹³C NMR (100 MHz, CDCl₃): d=20.2, 21.7, 26.2, 30.7, 42.2, 67.8, 68.4,

78.2, 106.1, 142.1, 154.1 pp,; IR (KBr): n˜ =2862 (m), 1788 (s), 1665 (s),

1298 (s), 1020 (s), 783 cm^ꢀ1(m); HRMS: m/z (%): calcd for C₁₁H₁₃NO₃S:

273.0671, found: 273.0652 (95)[ M]⁺, 214 (100), 194 (28), 193 (73).

3,3-Dimethyl-4-(p-toluenesulfonyl)-9a-trimethylsiloxy-3,5,5a,6,7,8,9,9a-

octahydrooxazoloACHTREUNG[3,4-a]quinolin-1-one (2o): CCDC-181722; m.p. 117.0–

118.08C (CH₂Cl₂/hexane); ¹H NMR (400 MHz, CDCl₃): d=0.05 (s, 9H),

1.06–1.45 (m, 5H), 1.53–1.78 (m, 3H), 1.93 (s, 3H), 1.95 (s, 3H), 1.96 (m,

1H), 2.41 (s, 3H), 2.48 (dd, J=5.5, 15.9 Hz, 1H), 3.54 (brd, J=15.9 Hz,

1H), 7.31 (d, J=8.5 Hz, 2H), 7.70 ppm (d, J=8.5 Hz, 2H); IR (KBr): n˜

=1780 (s), 1640 (s), 1370 (m), 1350 (m), 1290 (s), 1250 (m), 1160 (s),

1130 (s), 1110 (s), 1070 (m), 950 cm^ꢀ1(m); elemental analysis calcd (%)

for C₂₃H₃₃NO₅SSi: C 59.58, H 7.17, N 3.02; found: C 59.39, H 7.16, N

2.67.

5,5-Bis-methylsulfanyl-8-(p-toluenesulfonyl)-1,5,6,7-tetrahydro-oxazolo-

AHCTRE[UGN 3,4-a]pyridin-3-one (2u): M.p. 231.0–231.28C (CH₂Cl₂/hexane);

9a-Hydroxy-3,3-dimethyl-4-(toluene-4-sulfonyl)-3,5,5a,6,7,8,9,9a-octahy-

dro-oxazoloACHTREUNG[3,4-a]quinolin-1-one (2o’): M.p. 217.5–218.08C (CH₂Cl₂/

¹H NMR (400 MHz, CDCl₃): d=2.23 (brd, J=6.4 Hz, 2H), 2.26 (s, 6H),

2.42 (tt, J=2.4, 6.4 Hz, 2H), 2.46 (s, 3H), 5.43 (t, J=2.4 Hz, 2H), 7.35 (d,

J=8.1 Hz, 2H), 7.72 ppm (d, J=8.1 Hz, 2H); ¹³C NMR (100 MHz,

CDCl₃): d=14.3, 20.3, 21.6, 34.6, 66.7, 72.8, 108.6, 127.1, 130.1, 137.4,

142.2, 144.7. 153.2 ppm; IR (KBr): n˜ =1780 (s), 1660 (s), 1380 (s), 1300

(s), 1290 (s), 740 cm^ꢀ1(s); HRMS: m/z (%): calcd for C₁₆H₁₉NO₄S₃:

385.0476, found: 385.0477 (1)[ M]⁺, 338 (100).

hexane); ¹H NMR (400 MHz, CDCl₃): d=1.18–1.80 (m, 8H), 1.92 (s,

3H), 1.94 (m, 1H), 1.98 (s, 3H), 2.20–2.39 (m, 2H), 2.45 (s, 3H), 4.42

(brs, 1H), 7.34 (d, J=7.0 Hz, 2H), 7.72 (d, J=7.0 Hz, 2H); IR (KBr): n˜

=3470 (m), 1760 (s), 1650 (s), 1370 (w), 1300 (m), 1150 (m), 1100 cm^ꢀ1

(w); HRMS: m/z (%): calcd for C₂₀H₂₅NO₅S: 391.1453, found: 391.1470

(50)[ M]⁺, 236 (100); elemental analysis calcd (%) for C ₂₀H₂₅NO₅S: C

61.36, H 6.44, N 3.58, S 8.19; found: C 60.39, H 6.77, N 3.67, S 8.48.

6-Aza-5-(trimethylsilylmethyl)-9,9-dimethyl-2-(p-toluenesulfonyl)-8-

oxabicycloACHTREU[NG 4.3.0]non-1-en-7-one (3a): CCDC-139284; m.p. 173.0–

1,1,5-Trimethyl-3-oxo-8-(p-toluenesulfonyl)-5-triisopropylsilanyloxy-

1,5,6,7-tetrahydro-oxazoloACTHRE[UNG 3,4-a]pyridine-6-carboxylic acid methyl ester

173.58C (CH₂Cl₂/hexane); ¹H NMR (400 MHz, CDCl₃): d=0.05 (s, 9H),

0.69 (dd, J=10.3, 14.5 Hz, 1H), 0.94 (dm, J=14.5 Hz, 1H), 1.57 (dm, J=

13.6 Hz, 1H), 1.80 (dm, J=13.6 Hz, 1H), 1.94 (s, 3H), 1.98 (s, 3H), 2.15

(dm, J=16.7 Hz, 1H), 2.30 (dm, J=16.7 Hz, 1H), 2.45 (s, 3H), 4.20

(brquint, J=4.2 Hz, 1H), 7.34 (d, J=8.2 Hz, 2H), 7.73 ppm (d, J=

8.2 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃): d = ꢀ1.1, 19.8, 21.3, 21.6,

25.1, 26.3, 26.7, 47.3, 86.4, 106.1, 127.3, 129.8, 137.9, 144, 149.7,

153.4 ppm; IR (KBr): n˜ = 1770 (s), 1630 (s), 1390 (m), 1370 (m), 1320

(m), 1290 (s), 1240 (m), 1160 (m), 1140 (s), 1090 (m), 960 cm^ꢀ1(m);

HRMS: m/z (%): calcd for C₂₀H₂₁NO₄SSi: 407.1587, found: 407.1595

(100)[ M]⁺; elemental analysis calcd (%)for C ₂₀H₂₁NO₄SSi: C 58.93, H

7.17, N 3.44; found: C 58.47, H 7.03, N 3.42.

(2p): M.p. 132.0–132.28C (CH₂Cl₂/hexane); ¹H NMR (400 MHz, CDCl₃):

d=0.92–1.06 (m, 21H), 1.97 (s, 6H), 2.02 (s, 3H), 2.43 (s, 3H), 2.50 (dd,

J=1.8, 16.5 Hz, 1H), 2.64 (dd, J=6.2, 16.5 Hz, 1H), 2.77 (dd, J=1.8,

6.2 Hz, 1H), 3.49 (s, 3H), 7.32 (d, J=7.8 Hz, 2H), 7.72 ppm (d, J=

7.8 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃): d=13.2, 18.1, 18.2, 21.5, 24.3,

25.0, 26.5, 26.9, 49.5, 51.8, 82.2, 84.3, 106.3, 127.7, 129.7, 137.7, 144.0,

150.1, 152.4, 170.1 ppm; IR (KBr): n˜ =1782 (s), 1741 (s), 1618 (s), 1350

(m), 1332 (m), 1294 (s), 1144 (s), 962 (m), 760 cm^ꢀ1(m); HRMS: m/z

(%): calcd for C₂₈H₄₃NO₇SSiꢀiPr: 522.1982, found: 522.1985 (100)

[MꢀiPr]⁺.

3,3-Dimethyl-4-(p-toluenesulfonyl)-9a-triisopropylsiloxy-3,5,5a,7,8,9a-

hexahydro-6H-2,9-dioxa-9b-aza-cyclopenta[a]naphthalen-1-one

CCDC-181725; m.p. 110.5–110.98C (CH₂Cl₂/hexane);

(2q):

¹H NMR

6-Aza-5-(triisopropylsilylmethyl)-9,9-dimethyl-2-(p-toluenesulfonyl)-8-

oxabicycloCATHRE[UNG 4.3.0]non-1-en-7-one (3b): M.p. 177.0–177.58C (CH₂Cl₂/

(400 MHz, CDCl₃): d=0.95 (d, J=1.8 Hz, 9H), 0.97 (d, J=1.8 Hz, 9H),

1.05–1.28 (m, 4H), 1.46 (m, 1H), 1.55 (m, 1H), 1.65 (m, 1H), 1.81 (m,

1H), 1.95 (s, 3H), 1.98 (s, 3H), 2.18 (dd, J=1.8, 16.3 Hz, 1H), 2.43 (s,

3H), 2.53 (dd, J=5.9, 16.3 Hz, 1H), 3.58 (dt, J=2.6, 12.5 Hz, 1H), 3.99

(dd, J=5.1, 12.5 Hz, 1H), 7.31 (d, J=8.4 Hz, 2H), 7.71 ppm (d, J=

8.4 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃): d=0.3, 12.9, 18.1, 21.6, 24.4,

26.0, 26.6, 27.5, 29.2, 39.2, 65.6, 83.6, 102.8, 106.6, 127.5, 129.8, 138.0,

hexane); ¹H NMR (400 MHz, CDCl₃): d=0.91–1.11 (m, 21H), 1.53 (d,

J=1.8 Hz, 2H), 1.56 (dm, J=16.5 Hz, 1H), 1.85 (dm, J=16.5 Hz, 1H),

1.96 (s, 3H), 1.97 (s, 3H), 2.22 (dm, J=16.5 Hz, 1H), 2.33 (dm, J=

16.5 Hz, 1H), 2.43 (s, 3H), 4.34 (tm, J=1.8 Hz, 1H), 7.32 (d, J=8.4 Hz,

2H), 7.73 ppm (d, J=8.4 Hz, 2H); IR (KBr): n˜ =1800 (s), 1780 (s), 1680

(s), 1210 (s), 1150 (s), 1140 (s), 1090 (m), 1070 (w), 1060 (w), 960 cm^ꢀ1

9698

www.chemeurj.org

ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Chem. Eur. J. 2007, 13, 9686 – 9702

Conjugative Nucleophilic Addition

FULL PAPER

(m); elemental analysis calcd (%) for C ₂₆H₄₁NO₄SSi: C 63.50, H 8.40, N

2.85; found: C 63.20, H 8.72, N 2.92.

154.9 ppm; IR (KBr): n˜ =3497 (w), 3192 (m), 3134 (m), 1771 (s), 1757

(s), 1636 (s), 1300 (s), 1288 (m), 1126 (m), 1078 (m), 810 (m), 658 cm^ꢀ1

(m); HRMS: m/z (%): calcd for C₁₄H₁₇NO₄S: 295.0878, found: 295.0873

(100)[ M]⁺.

6-Aza-5-(triphenylsilylmethyl)-9,9-dimethyl-2-(p-toluenesulfonyl)-8-

oxabicycloACHTREUNG[4.3.0]non-1-en-7-one (3c): M.p. 223.5–224.58C (CH₂Cl₂/

hexane); ¹H NMR (400 MHz, CDCl₃): d=1.42–1.52 (m, 2H), 1.89 (dm,

J=16.9 Hz, 1H), 1.94 (s, 3H), 1.95 (s, 3H), 1.98 (dm, J=16.9 Hz, 1H),

2.44 (s, 3H), 4.41 (dm, J=12.1 Hz, 1H), 7.31–7.44 (m, 11H), 7.54 (dm,

J=8.4 Hz, 6H), 7.67 ppm (d, J=8.4 Hz, 2H); IR (KBr): n˜ =1769 (s),

1620 (s), 1427 (m), 1396 (m), 1366 (s), 1352 (m), 1292 (s), 1148 (s), 1111

(m), 729 cm^ꢀ1(s); HRMS: m/z (%): calcd for C₃₅H₃₅O₄NSSiꢀPh:

516.1665, found: 516.1661 (100)[ MꢀPh]⁺; elemental analysis calcd (%)

for C₃₅H₃₅O₄NSSi: C 70.79, H 5.94, N 2.36; found: C 70.85, H 6.03, N

2.34.

Ether connected at C-2’ of (E)-4-Ethylidene-5,5-dimethyl-3-(p-toluene-

sulfonyl)oxazolidin-2-one (5): CCDC-139285; m.p. 160.3–161.38C

(CH₂Cl₂/hexane); ¹H NMR (400 MHz, CDCl₃): d = 1.56 (s, 6H), 2.46 (s,

3H), 4.10 (d, J=7.7 Hz, 2H), 6.23 (t, J=7.7 Hz, 1H), 7.37 (d, J=8.2 Hz,

2H), 7.94 ppm (J=8.2 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃): d = 21.8,

27.2, 64.7, 82.7, 104.2, 128.2, 129.9, 134.5, 140.9, 146.2, 150.0 ppm; IR

(KBr): n˜ =1790 (s), 1690 (s), 1390 (m), 1340 (m), 1280 (m), 1180 (m),

1110 (m), 1090 (m), 810 (m), 750 cm^ꢀ1(m); elemental analysis calcd (%)

for C₂₈H₃₂N₂O₉S₂: C 55.61, H 5.33, N 4.63, S 10.61; found: C 55.77, H

5.41, N 4.69, S 10.58.

6-Aza-5-methyl-5-(trimethylsilylmethyl)-9,9-dimethyl-2-(p-toluenesulfon-

yl)-8-oxabicycloACHTREUNG[4.3.0]non-1-en-7-one (3d): M.p. 164.5–165.18C (CH₂Cl₂/

(Z)-4-[2-Methoxy-1-(p-toluenesulfonyl)ethylidene]-5,5-dimethyloxazoli-

din-2-one [(Z)-4b]: M.p. 106.1–107.08C (hexane/CH₂Cl₂); ¹H NMR

(400 MHz, CDCl₃): d=1.67 (s, 6H), 2.44 (s, 3H), 3.17 (s, 2H), 4.11 (s,

2H), 7.33 (d, J=8.4 Hz, 2H), 7.76 (d, J=8.4 Hz, 2H), 9.50 ppm (brs,

1H); IR (KBr): n˜ =3364 (m), 1782 (s), 1639 (s), 1302 (m), 1078 (m), 1007

(m), 899 (m), 816 cm^ꢀ1(m); HRMS: m/z (%): calcd for C₁₅H₁₉NO₅S:

325.0984, found: 325.0981 (72)[ M]⁺, 91 (100).

hexane); ¹H NMR (400 MHz, CDCl₃): d=0.03 (s, 9H), 1.36 (d, J=

14.7 Hz, 1H), 1.46 (d, J=14.7 Hz, 1H), 1.49 (s, 3H), 1.59 (ddd, J=5.1,

8.1, 13.9 Hz, 1H), 1.72 (ddd, J=5.1, 7.3, 13.9 Hz, 1H), 1.94 (s, 6H), 2.16

(ddd, J=5.1, 7.3, 16.5 Hz, 1H), 2.25 (ddd, J=5.1, 8.4, 16.5 Hz, 1H), 2.45

(s, 3H), 7.34 (d, J=8.2 Hz, 2H), 7.73 ppm (d, J=8.2 Hz, 2H); IR (KBr):

n˜ =1774 (s), 1629 (s), 1375 (m), 1366 (m), 1335 (m), 1310 (s), 1304 (s),

1248 (m), 1213 (m), 1150 (m), 1143 (s), 1099 (m), 1078 (m), 1057 (m),

966 cm^ꢀ1(m); HRMS: m/z (%): calcd for C₂₁H₃₁NO₄SSi: 421.1743,

found: 421.1738 (40)[ M]⁺, 406 (100).

(E)-4-(2-Methoxyethylidene)-5,5-dimethyl-3-(p-toluenesulfonyl)oxazoli-

din-2-one [(E)-6b]: CCDC-181556; m.p. 102.3–103.18C (hexane/CH₂Cl₂);

¹H NMR (400 MHz, CDCl₃): d = 1.53 (s, 6H), 2.45 (s, 3H), 3.37 (s, 3H),

4.01 (d, J=7.6 Hz, 2H), 6.22 (t, J=7.6 Hz, 1H), 7.36 (d, J=8.2 Hz, 2H),

7.94 ppm (d, J=8.2 Hz, 2H); IR (KBr): n˜ =1790 (s), 1682 (s), 1655 (w),

1381 (s), 1273 (s), 1084 (s), 1016 (w), 914 (w), 816 cm^ꢀ1(m); HRMS: m/z

(%): calcd for C₁₅H₁₉NO₅S: 325.0984, found: 325.0989 (12)[ M]⁺, 91

(100).

5-Hexyloxy-1,1-dimethyl-8-(p-toluenesulfonyl)-6-trimethylsilylmethylhex-

ahydro-oxazoloACHTREUNG[3,4-a]pyridin-3-one (3e): M.p. 86.5–87.58C (CH₂Cl₂/

hexane); ¹H NMR (400 MHz, CDCl₃): d = ꢀ0.06 (s, 9H), 0.60 (dd, J=

8.4, 15.0 Hz, 1H), 0.69 (dd, J=6.2, 15.0 Hz, 1H), 0.89 (t, J=7.0 Hz, 3H),

1.18–1.31 (m, 6H), 1.43–1.52 (m, 2H), 1.60 (m, 1H), 1.95 (s, 3H), 1.98

(m, 1H), 2.01 (s, 3H), 2.17 (dd, J=5.0, 10.3 Hz, 1H), 2.44 (s, 3H), 3.50–

3.60 (m, 2H), 4.96 (d, J=2.6 Hz, 1H), 7.33 (d, J=8.2 Hz, 2H), 7.71 ppm

(d, J=8.2 Hz, 2H); IR (KBr): n˜ =1776 (s), 1634 (s), 1344 (m), 1300 (s),

1144 (s), 1113 (s), 841 cm^ꢀ1(m); HRMS: m/z (%): calcd for

C₂₆H₄₁NO₅SSi: 507.2475, found: 504.2490 (100)[ M]⁺, 318 (87), 274 (58),

73 (29).

(Z)-4-[2-Benzyloxy-1-(p-toluenesulfonyl)ethylidene]-5,5-dimethyloxazoli-

din-2-one [(Z)-4c]: CCDC-186252; m.p. 139.9–140.68C (hexane/CH₂Cl₂);

¹H NMR (400 MHz, CDCl₃): d=1.61 (s, 6H), 2.41 (s, 3H), 4.17 (s, 2H),

4.35 (s, 2H), 7.07 (brd, J=2.2 Hz, 1H), 7.09 (brd, J=3.7 Hz, 1H), 7.27–

7.30 (m, 5H), 7.73 (d, J=8.4 Hz, 2H), 9.53 ppm (brs, 1H); IR (KBr): n˜

=3317 (w), 1780 (s), 1626 (s), 1302 (m), 1148 (m), 1061 (m), 935 (w),

812 cm^ꢀ1(w); HRMS: m/z (%): calcd for C₂₁H₂₃NO₅S - CH₂Ph: 310.0749,

found: 310.0777 (9)[ MꢀCH₂Ph]⁺, 296 (14), 251 (66), 139 (46), 107 (32),

95 (57), 91 (100).

5-Benzyl-1,1-dimethyl-8-(p-toluenesulfonyl)-1,5,6,7-tetrahydrooxazolo-

ACHTREUNG

[3,4-a]pyridin-3-one (3 f): M.p. 168.5–169.08C (CH₂Cl₂/hexane); ¹H NMR

(400 MHz, CDCl₃): d=1.42 (tt, J=4.9, 13.2 Hz, 1H), 1.80 (dm, J=

13.2 Hz, 1H), 1.99 (s, 3H), 2.00 (s, 3H), 2.16 (ddd, J=4.8, 13.2, 16.9 Hz,

1H), 2.33 (brdd, J=4.9, 16.9 Hz, 1H), 2.46 (s, 3H), 2.52 (dd, J=9.9,

13.4 Hz, 1H), 2.94 (dd, J=4.8, 13.4 Hz, 1H), 4.26 (dt, J=9.9, 4.8 Hz,

1H), 7.13 (d, J=7.0 Hz, 2H), 7.20–7.30 (m, 3H), 7.35 (d, J=8.4 Hz, 2H),

7.73 ppm (d, J=8.4 Hz, 2H); IR (KBr): n˜ =1776 (s), 1632 (s), 1375 (s),

1292 (s), 1170 (m), 1142 (s), 1063 (m) cm^ꢀ1; HRMS: m/z (%): calcd for

C₂₃H₂₅NO₄S: 411.1504, found: 411.1511 (100).

(E)-4-(2-Benzyloxyethylidene)-5,5-dimethyl-3-(p-toluenesulfonyl)oxazoli-

din-2-one [(E)-6c]: ¹H NMR (400 MHz, CDCl₃): d = 1.46 (s, 6H), 2.45

(s, 3H), 4.07 (d, J=7.7 Hz, 2H), 4.55 (s, 2H), 6.26 (t, J=7.7 Hz, 1H),

7.30–7.39 (m, 7H), 7.94 ppm (d, J=8.4, 2H); IR (neat): n˜ = 1790 (s),

1375 (m), 1273 (m), 1177 (s), 1088 (m), 1070 (m), 912 (w), 915 cm^ꢀ1(w).

(Z)-4-[2-Allyloxy-1-(p-toluenesulfonyl)ethylidene]-5,5-dimethyloxazoli-

din-2-one [(Z)-4d]: M.p. 129.5–130.58C (CH₂Cl₂/hexane); ¹H NMR

(400 MHz, CDCl₃): d=1.58 (s, 3H), 1.68 (s, 6H), 2.43 (s, 3H), 3.72 (brs,

2H), 4.13 (s, 2H), 4.75 (brs, 1H), 4.82 (brs, 1H), 7.30 (d, J=8.2 Hz, 2H),

7.77 (d, J=8.2 Hz, 2H), 9.50ppm (brs, 1H); IR (KBr): n˜ =3306 (m),

1774 (s), 1734 (w), 1639 (s), 1308 (s), 1288 (s), 1146 (m), 1124 (m), 1082

(m), 1009 (m), 894 cm^ꢀ1(m); HRMS: m/z (%): calcd for C₁₈H₂₃NO₅S:

365.1297, found: 365.1320 (12)[ M]⁺, 310 (14), 294 (88), 210 (100).

6-Aza-5-(trimethylsilylethyl)-9,9-dimethyl-2-(p-toluenesulfonyl)-8-

oxabicyloACHTREUNG[4.3.0]non-1-en-7-one (3g): M.p. 139.5–140.08C (CH₂Cl₂/

hexane); ¹H NMR (400 MHz, CDCl₃): d=ꢀ 0.07 (s, 9H), 0.37 (dt, J=

4.8, 13.9 Hz, 1H), 0.45 (dt, J=4.8, 13.9 Hz, 1H), 1.16 (ddt, J=4.4, 8.8,

8.8 Hz, 1H), 1.44–1.53 (m, 2H), 1.96 (s, 3H), 1.99 (s, 3H), 1.92–2.04 (m,

2H), 2.32 (dm, J=15.7 Hz, 1H), 2.44 (s, 3H), 3.96 (quint, J=4.7 Hz,

1H), 7.33 (d, J=8.2 Hz, 2H), 7.71 ppm (d, J=8.2 Hz, 2H); IR (KBr): n˜

=1765 (s), 1622 (s), 1334 (m), 1302 (s), 1292 (s), 1250 (m), 1207 (m),

1143 (s), 1110 (m), 964 cm^ꢀ1(m); HRMS: m/z (%): calcd for

C₂₁H₃₁NO₄SSi: 421.1743, found: 421.1731 (100)[ M]⁺.

(E)-5,5-Dimethyl-4-[2-(2-methylallyloxy)ethylidene]-3-(p-toluenesulfonyl)-

AHCTREUNG

oxazolidin-2-one [(E)-6d]: M.p. 76.5–78.08C (CH₂Cl₂/hexane); ¹H NMR

(400 MHz, CDCl₃): d=1.52 (s, 6H), 1.76 (s, 3H), 2.45 (d, 3H), 3.91 (brs,

2H), 4.03 (d, J=7.7 Hz, 2H), 4.94 (brs, 1H), 4.98 (brs, 1H), 6.23 (t, J=

7.7 Hz, 1H), 7.35 (d, J=8.3 Hz, 2H), 7.93 ppm (d, J=8.3 Hz, 2H); IR

(KBr): n˜ =1788 (s), 1684 (s), 1369 (s), 1275 (s), 1191 (m), 1178 (s), 1088

(s), 978 cm^ꢀ1(m); HRMS: m/z (%): calcd for C₁₈H₂₃NO₅S: 365.1297,

found: 365.1294 (2)[ M]⁺, 310 (2), 294 (15), 210 (91), 91 (100).

(Z)-5,5-Dimethyl-4-[1-(p-toluenesulfonyl)ethylidene]oxazolidin-2-one

[(Z)-4a]: M.p. 188.2–189.18C (CH₂Cl₂/hexane); ¹H NMR (400 MHz,

CDCl₃): d=1.63 (s, 6H), 1.84 (s, 3H), 2.46 (s, 3H), 7.35 (d, J=8.2 Hz,

2H), 7.72 (d, J=8.2 Hz, 2H), 9.51 ppm (brs, 1H); ¹³C NMR (400 MHz,

CDCl₃): d=12.2, 21.6, 25.3, 85.2, 102.8, 127.3, 130.1, 136.9, 144.9, 149.6,

153.3 ppm; IR (KBr): n˜ =3323 (m), 1805 (brs), 1653 (s), 1298 (s), 1277

(m), 1126 (m), 1078 (m), 820 (m), 658 cm^ꢀ1(m); HRMS: m/z (%): calcd

for C₁₄H₁₇NO₄S: 295.0878, found: 295.0909 (100)[ M]⁺.

(Z)-4-[2-Isopropoxy-1-(p-toluenesulfonyl)ethylidene]-5,5-dimethyl-oxazo-

lidin-2-one [(Z)-4e]: M.p. 109.5–110.58C (hexane/CH₂Cl₂); ¹H NMR

(400 MHz, CDCl₃): d = 0.98 (d, J=6.1 Hz, 6H), 1.69 (s, 6H), 2.44 (s,

3H), 3.44 (hept, J=6.1 Hz, 1H), 4.13 (s, 2H), 7.32 (d, J=7.9 Hz, 2H),

7.77 (d, J=7.9 Hz, 2H), 9.49ppm (brs, 1H); IR (KBr): n˜ =3350 (w),

1784 (s), 1636 (s), 1373 (m), 1302 (m), 1055 (m), 1018 (m), 897 (m),

818 cm^ꢀ1(m); HRMS: m/z (%): calcd for C₁₇H₂₃NO₅S: 353.1297, found:

353.1291 (69)[ M]⁺, 310 (100).

(E)-5,5-Dimethyl-4-[1-(p-toluenesulfonyl)-ethylidene]-oxazolidin-2-one

[(E)-4a]: M.p. 202.0–202.58C (THF/hexane); ¹H NMR (400 MHz,

CDCl₃): d=1.53 (s, 3H), 2.01 (s, 6H), 2.44 (s, 3H), 7.33 (d, J=8.6 Hz,

2H), 7.72 (d, J=8.6 Hz, 2H), 7.94 ppm (brs, 1H); ¹³C NMR (400 MHz,

CDCl₃): d=15.3, 21.6, 26.7, 89.25, 106.6, 127.6, 129.9, 137.6, 144.3, 150.2,

Chem. Eur. J. 2007, 13, 9686 – 9702

ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemeurj.org

9699

Y. Tamaru et al.

(E)-4-(2-Isopropoxyethylidene)-5,5-dimethyl-3-(p-toluenesulfonyl)oxazo-

lidin-2-one [(E)-6e]: M.p. 70.9–71.98C (hexane/CH₂Cl₂); ¹H NMR

(400 MHz, CDCl₃): d=1.19 (d, J=6.2 Hz, 6H), 1.54 (s, 6H), 2.45 (s, 3H),

3.64 (hept, J=6.2 Hz, 1H), 4.03 (d, J=7.7 Hz, 2H), 6.21 (t, J=7.7 Hz,

1H), 7.36 ppm (d, J=8.3 Hz, 2H), 7.94 (d, J=8.3 Hz, 2H); IR (KBr): n˜

=1782 (s), 1749 (m), 1682 (s), 1655 (w), 1379 (s), 1263 (s), 1086 (s), 1016

(w), 914 (m), 817 cm^ꢀ1(s); HRMS: m/z (%): calcd for C₁₇H₂₃NO₅S:

353.1297, found: 353.1314 (6)[ M]⁺, 139 (8), 91 (100).

¹H NMR (400 MHz, CDCl₃): d=1.66–1.71 (m, 2H), 1.85–1.89 (m, 2H),

2.13–2.19 (m, 2H), 2.25–2.32 (m, 2H), 2.46 (s, 3H), 3.75 (s, 2H), 7.21–

7.30 (m, 5H), 7.34 (d, J=8.4 Hz, 2H), 7.81 (d, J=8.4 Hz, 2H), 9.62 ppm

(brs, 2H); ¹³C NMR (100 MHz, CDCl₃): d=21.7, 25.3, 25.6, 32.5, 39.6,

40.3, 95.5, 104.6, 127.3, 127.7, 129.2, 129.9, 130.6, 136.0, 138.1, 145.1,

152.8, 153.1ppm; IR (KBr): n˜ =1784 (s), 1290 (s), 1130 (s), 741 (m),

654 cm^ꢀ1(m); HRMS: m/z (%): calcd for C₂₂H₂₃NO₄S₂: 429.1068, found:

429.1071 (6)[ M]⁺, 320 (100).

(Z)-5,5-Dimethyl-4-[2-(1-methylallyloxy)-1-(p-toluenesulfonyl)ethylide-

ne]oxazolidin-2-one [(Z)-4 f]: M.p. 100.5–101.58C (CH₂Cl₂/hexane);

¹H NMR (400 MHz, CDCl₃): d=1.00 (d, J=6.2 Hz, 1H), 1.66 (s, 3H),

1.67 (s, 3H), 2.44 (s, 3H), 3.67 (brquint, J=6.2 Hz, 1H), 3.98 (d, J=

12.3 Hz, 1H), 4. 16 (d, J=12.3 Hz, 1H), 5.11 (dm, J=10.3 Hz, 1H), 5.13

(dm, J=16.9 Hz, 1H), 5.52 (ddd, J=6.2, 10.3, 12.3 Hz, 1H), 7.32 (d, J=

7.3 Hz, 2H), 7.77 (d, J=7.3 Hz, 2H), 9.53 ppm (brs, 1H); IR (KBr): n˜

=3321 (m), 1782 (s), 1634 (s), 1375 (m), 1300 (s), 1279 (s), 1150 (s), 1124

(m), 1076 (s), 1040 (m), 1011 (m), 950 cm^ꢀ1(w); HRMS: m/z (%): calcd

for C₁₈H₂₃NO₅S: 365.1297, found: 365.1267 (26)[ M]⁺, 294 (57), 210

(100).

5,5-Dimethyl-4-[2-(1H-indol-3-yl)-1-(p-toluenesulfonyl)ethylidene]oxazo-

lidin-2-one [(E)-7a]: ¹H NMR (400 MHz, CDCl₃): d=2.05 (s, 6H), 2.42

(s, 3H), 3.62 (brs, 2H), 6.78 (brs, 1H), 6.81 (brs, 1H), 7.12 (brt, J=

8.1 Hz, 1H), 7.22 (brt, J=8.1 Hz, 1H), 7.30 (d, J=8.2 Hz, 2H), 7.34 (d,

J=8.1 Hz, 1H), 7.48 (d, J=8.1 Hz, 1H), 7.78 (d, J=8.2 Hz, 2H),

8.02 ppm (brs, 1H); ¹³C NMR (100 MHz, CDCl₃): d=21.6, 25.8, 26.7,

88.9, 109.5, 111.6, 118.2, 120.2, 121.8, 123.1, 126.4, 127.9, 130.0, 136.6,

137.7, 144.4, 152.2, 153.1, 193.9 ppm; IR (neat): n˜ = 1763 (s), 1632 (s),

1020 (s), 660 cm^ꢀ1(s); HRMS: m/z (%): calcd for C₂₂H₂₂N₂O₄S: 410.1300,

found: 410.1315 (59)[ M]⁺, 254 (100), 225 (12), 210 (13), 209 (41).

5,5-Dimethyl-3-(p-toluenesulfonyl)-4-[2-(1H-indol-3-yl)-ethylidene]oxa-

zolidin-2-one [(E)-8a]: ¹H NMR (400 MHz, CDCl₃): d=1.58 (s, 6H),

2.44 (s, 3H), 3.58 (brd, J=8.1 Hz, 2H), 6.36 (t, J=8.1 Hz, 1H), 6.97 (brs,

1H), 7.14 (brt, J=8.1 Hz, 1H), 7.23 (brt, J=8.1 Hz, 1H), 7.35 (d, J=

8.2 Hz, 2H), 7.39 (d, J=8.1 Hz, 1H), 7.55 (d, J=8.1 Hz, 1H), 7.89 (d, J=

8.2 Hz, 2H), 8.06 ppm (brs, 1H); ¹³C NMR (100 MHz, CDCl₃): d=21.8,

23.2, 26.9, 29.7, 82.9, 107.5, 111.4, 114.2, 119.6, 121.6, 122.4, 128.1, 129.9,

134.8, 136.5, 137.1, 145.8, 150.5, 193.3ppm; IR (neat): n˜ = 1782 (s), 1086

(s), 739 cm^ꢀ1(m); HRMS: m/z (%): calcd for C₂₂H₂₂N₂O₄S: 410.1300,

found: 410.1317 (100)[ M]⁺, 293 (7), 282 (11), 281 (28).

(E)-5,5-Dimethyl-4-[2-(1-methylallyloxy)ethylidene]-3-(p-toluenesulfonyl)-

ACHTREUNG

oxazolidin-2-one [(E)-6 f]: M.p. 66.5–67.08C (CH₂Cl₂/hexane); ¹H NMR

(400 MHz, CDCl₃): d=1.27 (d, J=6.6 Hz, 3H), 1.51 (s, 6H), 2.43 (s, 3H),

3.89 (brquint, J=6.6 Hz, 3H), 3.91 (dd, J=7.7, 11.7 Hz, 1H), 4.08 (dd,

J=7.7, 11.7 Hz, 1H), 5.18 (dm, J=17.2 Hz, 1H), 5.22 (dm, J=10.3 Hz,

1H), 5.73 (ddd, J=6.6, 10.3, 17.2 Hz, 1H), 6.21 (t, J=7.7 Hz, 1H), 7.35

(d, J=8.6 Hz, 2H), 7.93 ppm (d, J=8.6 Hz, 2H); IR (KBr): n˜ =3321 (m),

1782 (s), 1634 (s), 1375 (m), 1300 (s), 1279 (s), 1192 (w), 1150 (s), 1124

(m), 1076 (s), 1040 (m), 1011 (m), 950 cm^ꢀ1(w); HRMS: m/z (%): calcd

for C₁₈H₂₃NO₅S: 365.1297, found: 365.1295 (10)[ M]⁺, 91 (100).

5,5-Dimethyl-4-[2-(1-methyl-1H-indol-3-yl)-1-(p-toluenesulfonyl)ethyli-

1

(E)-4-(2-Phenoxyethylidene)-5,5-dimethyl-3-(p-toluenesulfonyl)-oxazoli-

dene]-oxazolidin-2-one [(E)-7b]: H NMR (400 MHz, CDCl₃): d=2.16 (s,

1

din-2-one [(E)-6g]: H NMR (400 MHz, CDCl₃): d=1.55 (s, 6H), 2.45 (s,

6H), 2.43 (s, 3H), 3.59 (s, 2H), 3.69 (s, 3H), 6.62 (s, 1H), 6.81 (brs, 1H),

7.09 (m, 1H), 7.24 (m, 1H), 7.26 (m, 1H), 7.31 (d, J=8.1 Hz, 2H), 7.45

(dt, J=1.1, 8.1 Hz, 1H), 7.78 ppm (d, J=8.1 Hz, 2H); ¹³C NMR

(100 MHz, CDCl₃): d=21.6, 25.7, 26.7, 32.8, 88.8, 107.7, 109.2, 118.2,

119.7, 122.5, 126.5, 126.8, 127.2, 127.9, 129.9, 137.4, 137.8, 144.3, 152.1,

153.1 ppm; IR (neat): n˜ = 1784 (s), 1277 (s), 1090 (m), 743 cm^ꢀ1(m);

HRMS: m/z (%): calcd for C₂₃H₂₄N₂O₄S: 424.1457, found: 424.1434 (100)

[M]⁺.

3H), 4.59 (d, J=7.7 Hz, 2H), 6.40 (t, J=7.7 Hz, 1H), 6.91 (dd, J=1.1,

8.6 Hz, 2H), 7.00 (tt, J=1.1, 7.3 Hz, 1H), 7.25–7.35 (m, 4H), 7.91 ppm

(d, J=8.6 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃): d=21.8, 27.1, 62.6,

82.9, 103.5, 115.0, 121.5, 128.2, 129.7, 129.9, 134.5, 141.6, 146.1, 150.1,

158.1 ppm; IR (neat): n˜ = 1790 (s), 1599 (s), 1177 (s), 1088 (s), 667 cm^ꢀ1

(s); HRMS: m/z (%): calcd for C₂₀H₂₁NO₅S: 387.1140, found: 387.1137

(100)[ M]⁺, 294 (51).

5,5-Dimethyl-4-[2-hexadecylsulfanyl-1-(p-toluenesulfonyl)ethylidene]oxa-

zolidin-2-one (4h): a mixture of two isomers in a ratio of 7:1 (E/Z);

¹H NMR (400 MHz, CDCl₃, major isomer): d=0.88 (t, J=6.8 Hz, 3H),

1.26 (s, 24H), 1.40–1.50 (m, 4H), 2.00 (s, 6H), 2.37 (t, J=7.5 Hz, 2H),

2.44 (s, 3H), 3.31 (s, 2H), 7.34 (d, J=8.1 Hz, 2H), 7.73 (d, J=8.1 Hz,

2H), 8.29 ppm (brs, 1H); ¹³C NMR (100 MHz, CDCl₃, major isomer):

d=14.4, 21.6, 22.7, 26.5, 28.8, 29.2, 29.4, 29.5, 29.7, 30.8, 32.0, 89.1, 106.8,

127.8, 129.9, 137.7, 144.5, 153.4, 154.2 ppm; IR (KBr): n˜ =2853 (s), 1784

(s), 1628 (s), 1298 (s), 1080 (m), 656 cm^ꢀ1(m); HRMS: m/z (%): calcd

for C₃₀H₄₉NO₅S: 551.3103, found: 551.3123 (100)[ M]⁺, 396 (16).

5,5-Dimethyl-3-(p-toluenesulfonyl)-4-[2-(1-methyl-1H-indol-3-yl)-ethyli-

dene]oxazolidin-2-one [(E)-8b]: M.p. 136.5–137.08C (CH₂Cl₂/hexane);

¹H NMR (400 MHz, CDCl₃): d=1.58 (s, 6H), 2.45 (s, 3H), 3.57 (brd, J=

8.1 Hz, 2H), 3.77 (s, 3H), 6.33 (t, J=8.1 Hz, 1H), 6.80 (s, 1H), 7.12 (dt,

J=1.1, 8.1 Hz, 1H), 7.26 (dt, J=1.1, 8.1 Hz, 1H), 7.31 (d, J=8.3 Hz,

2H), 7.32 (d, J=8.1 Hz, 1H), 7.53 (d, J=8.1 Hz, 1H), 7.90 ppm (d, J=

8.3 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃): d=21.8, 23.1, 27.0, 32.7, 82.8,

107.5, 109.4, 112.6, 118.6, 119.0, 120.0, 126.4, 127.3, 128.1, 129.8, 134.9,

137.0, 137.3, 145.8, 150.4 ppm; IR (KBr): n˜ =1786 (s), 1178 (s), 739 cm^ꢀ1

(s); HRMS: m/z (%): calcd for C₂₃H₂₄N₂O₄S: 424.1457, found: 424.1454

(100)[ M]⁺.

5,5-Dimethyl-4-[2-phenylsulfanyl-1-(p-toluenesulfonyl)ethylidene]oxazo-

lidin-2-one (4i): a mixture of two isomers in a ratio of 6:1 (Z:E);

¹H NMR (400 MHz, CDCl₃, major isomer): d=1.69 (s, 6H), 2.45 (s, 3H),

3.85 (s, 2H), 7.20–7.30 (m, 5H), 7.33 (d, J=8.3 Hz, 2H), 7.79 (d, J=

8.3 Hz, 2H), 9.59 ppm (brs, 1H); ¹³C NMR (100 MHz, CDCl₃, major

isomer): d=21.7, 26.4, 32.3, 85.9, 104.9, 127.2, 127.5, 129.2, 129.9, 130.3,

135.9, 138.1, 145.1, 152.8, 153.5 ppm; IR (KBr): n˜ =1769 (s), 1300 (s),

1016 (s), 740 (s), 656 cm^ꢀ1(s); HRMS: m/z (%): calcd for C₂₀H₂₁NO₄S₂:

403.0912, found: 403.0889 (100)[ M]⁺.

Acknowledgements

We thank Mr. Y. Ohhama (NMR measurements, Nagasaki Univ.), Dr. H.

Kawano and Mrs. J. Nagaoka (X-ray structure analyses, NU), and Mr. Y.

Wakamiya, Mr. K. Odaka, and Mr. K. Iwata (NU)for their technical as-

sistance. We also thank Dr. T. Okajima (Department of Chemistry, Facul-

ty of Culture and Education, Saga University)for his helpful theoretical

discussion. This research has been supported by the Ministry of Educa-

tion, Science, Sports and Culture, Japanese Government, Grant-in-Aid

for Scientific Research B and Scientific Research on Priority Areas “Ad-

vanced Molecular Transformations of Carbon Resources”.

(E)-4-(2-Phenylsulfanylethylidene)-5,5-dimethyl-3-(p-toluenesulfonyl)-ox-

azolidin-2-one [(E)-6i]: ¹H NMR (400 MHz, CDCl₃): d=1.40 (s, 6H),

2.46 (s, 3H), 3.57 (d, J=8.4 Hz, 2H), 6.20 (t, J=8.4 Hz, 1H), 7.26–7.32

(m, 3H), 7.34 (d, J=8.3 Hz, 2H), 7.39–7.44 (m, 2H), 7.84 ppm (d, J=

8.3 Hz, 2H); ¹³C NMR (100 MHz, CDCl₃): d=21.7, 27.0, 32.3, 82.5, 104.4,

127.3, 127.6, 128.1, 129.1, 129.9, 132.0, 134.6, 139.1, 146.0, 150.0,

154.6ppm; IR (neat): n˜ = 1790 (s), 1271 (s), 1177 (s), 746 (s), 671 cm^ꢀ1

(s); HRMS: m/z (%): calcd for C₂₀H₂₁NO₄S₂: 403.0912, found: 403.0883

(100)[ M]⁺.

[1] a)Y. Horino, M. Kimura, S. Tanaka, T. Okajima, Y. Tamaru, Chem.

Eur. J. 2003 , 9 , 241 9 –2 438; b)M. Kimura, Y. Horino, Y. Wakamiya,

T. Okajima, Y. Tamaru, J. Am. Chem. Soc. 1997 , 119 , 1086 9 –1 0870.

4-[2-Phenylsulfanyl-1-(p-toluenesulfonyl)ethylidene]-1-oxa-3-aza-spiro-

ACHTREUNG[4.4]nonan-2-one [(Z)-4j]: M.p. 174.5–175.58C (CH₂Cl₂/hexane);

9700

www.chemeurj.org

ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Chem. Eur. J. 2007, 13, 9686 – 9702

Conjugative Nucleophilic Addition

FULL PAPER

For recent development in the intramolecular [2+2] cycloaddition of

allenes and alkenes (or alkynes), see: c) H. Ohno, T. Mizutani, Y.

Kadoh, K. Miyamura, T. Tanaka, Angew. Chem. 2005 , 117 , 524 3 –

5245; Angew. Chem. Int. Ed. 2005 , 44 , 511 3 –5 115; d)C. H. Oh,

A. K. Gupta, D. I. Park, N. Kim, Chem. Commun. 2005 , 567 0 –5 672;

e)B. Alcaide, P. Almendros, C. Aragonicillo, Org. Lett. 2003 , 5 ,

379 5 –3 798.

dron Lett. 1999, 40, 5009–5012; d)V. Breuil-Desvergnes, P. Com-

pain, J.-M. Vatele, J. Gore, Tetrahedron Lett. 1999, 40, 8789–8792.

[9] a)S. Ma, Z. Zheng, X. Jiang, Org. Lett. 2007 , 9 , 52 9 –5 32; b)B. Al-

caide, P. Almendros, T. M. del Campo, Angew. Chem. 2006 , 118 ,

461 3 –4 616; Angew. Chem. Int. Ed. 2006 , 45 , 450 1 –4 504; c)S. Ma,

Z. Gu, J. Am. Chem. Soc. 2005 , 127 , 618 2 –6 183; d)A. Al-Harrasi,

H.-U. Reißig, Angew. Chem. 2005 , 117 , 638 3 –6 387; Reißig, Angew.

Chem. 2005, 117, 6383–6387; Angew. Chem. Int. Ed. 2005 , 44 , 622 7 –

6231; e)M. Helms, W. Schade, R. Pulz, T. Watanabe, A. Al-Harrasi,

L. Fisera, I. Hlobilovµ, G. Zahn, H.-U. Reißig, Eur. J. Org. Chem.

2005 , 100 3 –1 019; f)S. W. Youn, Y. H. Kim, J.-W. Hwang, Y. Do,

Chem. Commun. 2001 , 99 6 –9 97.

[2] Preliminary communications: a)Y. Horino, M. Kimura, Y. Waka-

miya, T. Okajima, Y. Tamaru, Angew. Chem. 1999 , 111 , 12 3 –1 26;

Angew. Chem. Int. Ed. 1999 , 38 , 12 1 –1 23; b)Y. Horino, M. Kimura,

M. Naito, S. Tanaka, Y. Tamaru, Tetrahedron Lett. 2000 , 41 , 342 7 –

3431.

[10] C.-F. Lee, L.-M. Yang, T.-Y. Hwu, A.-S. Feng, J.-C. Tseng, T.-Y. Luh,

[3] W. Smadja, Chem. Rev. 1983 , 83 , 26 3 –3 20.

J. Am. Chem. Soc. 2000 , 122 , 499 2 –4 993, and references therein.

[4] a)I. Kadota, L. M. Lutete, A. Shibuya, Y. Yamamoto, Tetrahedron

Lett. 2001 , 42 , 620 7 –6 210; b)R. Grigg, I. Kçppen, M. Rasparini, V.

Sridharan, Chem. Commun. 2001 , 96 4 –9 65; c)A. V. Kel ’in, A. W.

Sromek, V. Gevorgyan, J. Am. Chem. Soc. 2001, 123, 2074–2075;

d)S. Ma, S. Zhao, J. Am. Chem. Soc. 2001 , 123 , 557 8 –5 579; e)B. M.

Trost, A. B. Pinkerton, D. Kremzow, J. Am. Chem. Soc. 2000 , 122 ,

1200 7 –1 2008; f)C. Jonasson, A. Horvath, J.-E. Bäckwall, J. Am.

Chem. Soc. 2000 , 122 , 960 0 –9 609; g)S. Ma, S. Zhao, Org. Lett. 2000 ,

2 , 249 5 –2 497; h)S. Ma, L. Li, Org. Lett. 2000 , 2 , 94 1 –9 44; i)B. M.

Trost, A. B. Pinkerton, J. Am. Chem. Soc. 1999 , 121 , 406 8 –4 069;

j)S. Ma, Z. Shi, Z. Yu, Tetrahedron Lett. 1999 , 40 , 239 3 –2 396; k)M.

Anzai, A. Toda, H. Ohno, Y. Takemoto, N. Fujii, T. Ibuka, Tetrahe-

dron Lett. 1999 , 40 , 739 3 –7 397; l)V. M. Arredondo, S. Tian, F. E.

McDonald, T. J. Marks, J. Am. Chem. Soc. 1999 , 121 , 363 3 –3 639;

m)F. P. J. T. Rutjes, K. C. M. F. Tjen, L. B. Wolf, W. F. J. Karstens,

H. E. Schoemaker, H. Hiemstra, Org. Lett. 1999 , 1 , 71 7 –7 20;

n)R. C. Larock, Y. He, W. W. Leong, X. Han, M. D. Refvik, J. M.

Zenner, J. Org. Chem. 1998 , 63 , 215 4 –2 160; o)R. C. Larock, C. Tu,

P. Pace, J. Org. Chem. 1998 , 63 , 685 9 –6 866; p)M. Al-Masum, Y. Ya-

mamoto, J. Am. Chem. Soc. 1998 , 120 , 380 9 –3 810; q)B. M. Trost,

P.-Y. Michellys, V. J. Gerusz, Angew. Chem. 1997 , 109 , 183 7 –1 839;

Angew. Chem. Int. Ed. Engl. 1997 , 36 , 175 0 –1 753; r)J. A. Marshall,

M. A. Wolf, E. M. Wallace, J. Org. Chem. 1997 , 62 , 36 7 –3 71; s)Y.

Tamaru, M. Kimura, Synlett 1997 , 74 9 –7 57.

ꢀ

[11] Cleavage of N SO₂bond by reduction: a)T. Hosaka, Y. Torisawa,

M. Nakagawa, Tetrahedron Lett. 1997 , 38 , 353 5 –3 538; b)D. J.

Ramon, G. Guillena, D. Seebach, Helv. Chim. Acta 1996, 79, 875–

894. By alkaline hydrolysis: c)Z. Xu, X. Lu, Tetrahedron Lett. 1997 ,

38 , 346 1 –3 464; d)S. B. Sobolov, J. Sun, B. A. Cooper, Tetrahedron

Lett. 1998 , 39 , 568 5 –5 688. By acid hydrolysis: e)W. J. Drury III, D.

Ferraris, C. Cox, B. Young, T. Lectka, J. Am. Chem. Soc. 1998 , 120 ,

1100 6 –1 1007; f)G. Li, K. B. Sharpless, Acta Chem. Scand. 1996, 50,

649–651; g)J. M. Wood, P. S. Hinchliffe, S. Paul S. A. M. Davis, R. P.

Austin, M. I. Page, Chem. Commun. 2002 , 77 2 –7 73. Current devices

ꢀ

for the N SO₂bond cleavage under mild conditions: h)G. M.

Sammis, E. C. Flamme, H. Xie, D. M. Ho, E. J. Sorensen, J. Am.

Chem. Soc. 2005 , 127 , 861 2 –8 6613; i)A. Yasuhara, T. Sakamoto,

Tetrahedron Lett. 1998 , 39 , 59 5 –5 96; j)A. Fürstner, H. Szillatt, B.

Gabor, R. Mynott, J. Am. Chem. Soc. 1998, 120, 8305–8314; k)T.

Fukuyama, M. Cheung, C.-K. Jow, Y. Hidai, T. Kan, Tetrahedron

Lett. 1997 , 38 , 583 1 –5 835; l)S. M. Weinreb, D. M. Demko, T. A.

Lessen, Tetrahedron Lett. 1986 , 27 , 209 9 –2 102.

[12] CCDC-181727 (2a), -181562 (2e), -181723 (2i), -181552 (2l),

-181722 (2o), -181725 (2q), -188831 (2t), -139284 (3a), -139285 (5),

-181556 (E-6b), -186252 (Z-4c)contain the supplementary crystal-

lographic data for this paper. These data can be obtained free of

charge from The Cambridge Crystallographic Data Centre via

www.ccdc.cam.ac.uk/data_request/cif.

[5] a)J. S. Johnson, R. G. Bergman, J. Am. Chem. Soc. 2001 , 123 , 292 3 –

2924; b)M. V. Chevliakov, J. Montgomery, J. Am. Chem. Soc. 1999 ,

121 , 1113 9 –1 1143; c)O. Kitagawa, T. Suzuki, H. Fujiwara, T. Tagu-

chi, Tetrahedron Lett. 1999 , 40 , 254 9 –2 552; d)B. W. G. van Hene-

gouwen, R. M. Fieseler, F. P. J. T. Rutjes, H. Hiemstra, Angew.

Chem. 1999, 111, 2351–2355; Angew. Chem. Int. Ed. 1999, 38, 2214–

2217; e)W. F. J. Karstens, M. Stol, F. P. J. T. Rutjes, H. Hiemstra,

Synlett 1998 , 112 6 –1 128; f)A. Ogawa, A. Kudo, T. Hirao, Tetrahe-

dron Lett. 1998 , 39 , 521 3 –5 216; g)A. Stephen, K. Hashimi, Angew.

Chem. 1995, 107, 1749–1751; Angew. Chem. Int. Ed. Engl. 1995, 34,

1581–1583.

[13] a)D. Graham, A, Enright, Curr. Org. Synth. 2006 , 3 , 9 –1 7; b)M.

Shoji, J. Yamaguchi, H. Kakeya, H. Osada, Y. Hayashi, Angew.

Chem. 2002 , 114 , 332 4 –3 326; Angew. Chem. Int. Ed. 2002 , 41 , 319 2 –

3194; c)V. O. Rogatchov, H. Bernsmann, P. Schwab, R. Frohlich, B.

Wibbeling, P. Metz, Tetrahedron Lett. 2002 , 43 , 475 3 –4 756; d)A.

Padwa, M. Dimitroff, B. Liu, Org. Lett. 2000 , 2 , 323 3 –3 235; e)B. A.

Keay, I. R. Hunt, Adv. Cycloaddit. 1999, 6, 173–210.

[14] a)F. Algi, R. Ozen, M. Balci, Tetrahedron Lett. 2002 , 43 , 312 9 –

3131; b)M. Nendel, L. M. Tolbert, L. E. Herring, M. N. Islam, K. N.

Houk, J. Org. Chem. 1999 , 64 , 97 6 –9 83; c)I. Ikeda, A. Gondo, M.

Shiro, K. Kanematsu, Heterocycles 1993, 36, 2669–2672; d)S. G.

Cauwberghs, P. J. De Clercq, Tetrahedron Lett. 1988 , 29 , 650 1 –6 504;

e)P. Missiaen, P. J. De Clercq, Bull. Soc. Chim. Belg. 1987, 96, 105–

113.

[6] K. Breuer, J. H. Teles, D. Demuth, H. Hibst, A. Schäfer, S. Brode,

H. Domgçrgen, Angew. Chem. 1999 , 111 , 149 7 –1 502; Angew. Chem.

Int. Ed. 1999 , 38 , 140 1 –1 405, and references therein.

[7] a)H. Hamaguchi, S. Kosaka, H. Ohno, T. Tanaka, Angew. Chem.

2005 , 117 , 153 7 –1 541; Angew. Chem. Int. Ed. 2005 , 44 , 151 3 –1 517;

b)S. Ma, W. Gao, Synlett 2002, 65–68; c)N. Waizumi, T. Itoh, T. Fu-

kuyama, Tetrahedron Lett. 1998 , 39 , 601 5 –6 018; d)Z. Xu, X. Lu, J.

Org. Chem. 1998 , 63 , 503 1 –5 041; e)S. Ma, Z. Shi, L. Li, J. Org.

Chem. 1998 , 63 , 452 2 –4 523; f)H. Urabe, T. Takeda, D. Hideura, F.

Sato, J. Am. Chem. Soc. 1997 , 119 , 1129 5 –1 1305; g)S. Yamanoi, T.

Imai, T. Matsumoto, K. Suzuki, Tetrahedron Lett. 1997 , 38 , 303 1 –

3034; h)G. Zhu, Z. Chen, Q. Jiang, D. Xiao, P. Cao, X. Zhang, J.

Am. Chem. Soc. 1997 , 119 , 383 6 –3 837; i)K. Banert, C. Toth, Angew.

Chem. 1995 , 107 , 177 6 –1 778; Angew. Chem. Int. Ed. Engl. 1995 , 34 ,

162 7 –1 629.

[8] a)Z. Zhang, C. Liu, R. E. Kinder, X. Han, H. Qian, R. A. Widen-

foefer, J. Am. Chem. Soc. 2006 , 128 , 906 6 –9 073; b)P. H. Lee, H.

Kim, K. Lee, M. Kim, K. Noh, H. Kim, D. Seomoon, Angew. Chem.

2005 , 117 , 187 4 –1 877; Angew. Chem. Int. Ed. 2005 , 44 , 184 0 –1 843;

c)V. Breuil-Desvergnes, P. Compain, J.-M. Vatele, J. Gore, Tetrahe-

[15] Strained allenes: a)F. Algi, R. Ozen, M. Balci, Tetrahedron Lett.

2002 , 43 , 312 9 –3 131; b)M. Nendel, L. M. Tolbert, L. E. Herring,

M. N. Islam, K. N. Houk, J. Org. Chem. 1999 , 64 , 97 6 –9 83.

[16] a)K. Okuma, Y. Tanaka, H. Ohta, J. Am. Chem. Soc. 1981 , 103 ,

597 6 –5 977. For five-membered sulfurane oxides, see: b)K. Ohkata,

M. Ohnishi, K. Yoshinaga, K. Akiba, J. C. Rongione, J. C. Martin, J.

Am. Chem. Soc. 1991 , 113 , 927 0 –9 276; c)J. C. Rongione, J. C.

Martin, J. Am. Chem. Soc. 1990 , 112 , 163 7 –1 638.

[17] a)K. A. Jorgensen, Asym. Synth, 2007, 191–195; b)K. A. Jorgensen,

Eur. J. Org. Chem. 2004, 2093–2102; c)L. F. Tietze, N. Rackelmann,

Pure Appl. Chem. 2004, 76, 1967–1983; d)G. J. Bodwell, J. Li,

Angew. Chem. 2002 , 114 , 339 5 –3 396; Angew. Chem. Int. Ed. 2002 ,

41 , 326 1 –3 262; e)M. Largeron, A. Neudorffer, M. Vuilhorgne, E.

Blattes, M.-B. Fleury, Angew. Chem. 2002 , 114 , 85 2 –8 55; Angew.

Chem. Int. Ed. 2002 , 41 , 82 4 –8 27; f)E. R. Bilbao, M. Alvarado,

C. F. Masaguer, E. Ravina, Tetrahedron Lett. 2002 , 43 , 355 1 –3 554;

g)K. C. Nicolaou, K. Sugita, P. S. Baran, Y.-L. Zhong, Angew.

Chem. Eur. J. 2007, 13, 9686 – 9702

ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemeurj.org

9701

Y. Tamaru et al.

Chem. 2001 , 113 , 21 3 –2 16; Angew. Chem. Int. Ed. 2001 , 40 , 20 7 –

210; h)D. L. Boger, J. Hong, J. Am. Chem. Soc. 2001 , 123 , 851 5 –

8519; i)R. Nomak, J. K. Snyder, Tetrahedron Lett. 2001 , 42 , 792 9 –

7933; j)O. A. Attanasi, L. D. Crescentini, P. Fillippone, F. Fringuelli,

F. Mantellini, O. Piermatti, M. Matteucco, F. Pizzo, Helv. Chim.

Acta 2001 , 84 , 51 3 –5 25; k)R. C. Boruah, S. Ahmed, U. Sharma, J. S.

Sandhu, J. Org. Chem. 2000 , 65 , 92 2 –9 25; l)L. Balazs, I. Kadas, L.

Toke, Tetrahedron Lett. 2000, 41, 7583–7587; m)M.-F. Hsieh, P. D.

Rao, C.-C. Liao, Chem. Commun. 1999 , 144 1 –1 442; n)L. Lee, J. K.

Snyder, Adv. Cycloaddit. 1999, 6, 119–171.

[22] a)C. Rernandez-Rivas, M. Mendez, C. Nieto-Oberhuber, A. M. Es-

chavarren, J. Org. Chem. 2002, 67, 5197–5201; b)V. Nair, C. Rajesh,

R. Dhanya, N. P. Rath, Org. Lett. 2002 , 4 , 95 3 –9 55; c)S. Giese, L.

Kastrup, D. Stiens, F. G. West, Angew. Chem. 2000 , 112 , 204 6 –2 049;

Angew. Chem. Int. Ed. 2000 , 39 , 197 0 –1 973; d)H.-J. Knoelker, N.

Foitzik, C. Gabler, R. Graf, Synthesis 1999, 145–151, and references

therein.

[23] H. Mayr, T. Bug, M. F. Gotta, N. Hering, B. Irrgang, B. Janker, B.

Kempf, R. Loos, A. R. Ofial, G. Remennikov, H. Schimmel, J. Am.

Chem. Soc. 2001 , 123 , 950 0 –9 512.

[18] a)S. M. Weinreb, R. K. Orr, Synthesis 2005 , 120 5 –1 227; b)T. Katao-

ka, H. Kinoshita, Eur. J. Org. Chem. 2005 , 4 5 –5 8; c)J. J. Li, Name

Reactions, Springer, Berlin, 2002.

[19] a)S. Caddick, D. Hamza, S. N. Wadman, Tetrahedron Lett. 1999 , 40 ,

728 5 –7 288; b)C. Wang, G. A. Russell, J. Org. Chem. 1999 , 64 ,

234 6 –2 352; c)D. C. Craig, G. L. Edwards, C. A. Muldoon, Synlett

1997 , 144 1 –1 443; d)S. Caddick, C. L. Shering, S. N. Wadman, Tetra-

hedron Lett. 1997 , 38 , 624 9 –6 250.

[20] a)C. Ollivier, P. Renaud, J. Am. Chem. Soc. 2001 , 123 , 471 7 –4 727;

b)Y.-L. Wu, C.-P. Chuang, P.-Y. Lin, Tetrahedron 2000 , 56 , 620 9 –

6217; c)R. Nouguier, S. Gastaldi, D. Stien, M. Bertrand, P. Renaud,

Tetrahedron Lett. 1999 , 40 , 337 1 –3 374; d)B. Sire, S. Seguin, S. Z.

Zard, Angew. Chem. 1998, 110, 3056–3058; Angew. Chem. Int. Ed.

1998, 37, 2864–2866; e)S. Kim, J.-Y. Yoon, J. Am. Chem. Soc. 1997 ,

119 , 598 2 –5 983; f)B. Quiclet-Sire, S. Z. Zard, J. Am. Chem. Soc.

1996 , 118 , 120 9 –1 210.

[24] a)M. Sugawara, Y. Yoshida, Bull. Chem. Soc. Jpn, 2000, 73, 1253–

1257; b)M. Sugawara, J. Yoshida, Tetrahedron 2000 , 56 , 468 3 –4 689,

and references therein. c)O. Andrey, C. Glanzmann, Y. Landais, L.

Parra-Rapado, Tetrahedron 1997 , 53 , 283 5 –2 854.

[25] D. M. Graham, R. L. Mieville, C. Sivertz, Can. J. Chem. 1964 , 42 ,

223 9 –2 249.

[26] Z. Zhou, R. G. Parr, J. Am. Chem. Soc. 1989 , 111 , 737 1 –7 379.

[27] There has been reported one exception that shows that indole^[17k]

shows the same regioselectivity as that of furan and benzofuran

toward inverse electron demand Diels–Alder reaction.

[28] P. Cazeau, F. Duboudin, F. Moulines, O. Babot, J. Dunogues, Tetra-

hedron 1987 , 43 , 208 9 –2 100.

[29] A. Hosomi, M. Saito, H. Sakurai, Tetrahedron Lett. 1979, 20, 429–

432.

[21] K. Narasaka, Y. Hayashi, H. Shimadzu, S. Niihata, J. Am. Chem.

Soc. 1992 , 114 , 886 9 –8 885.

Received: May 7, 2007

Published online: September 4, 2007

9702

www.chemeurj.org

ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Chem. Eur. J. 2007, 13, 9686 – 9702

Article Doi

Chameleon reactivity of the allene bond of 4-vinylidene-2-oxazolidinone: Novel through-space conjugative nucleophilic addition of electron-rich alkenes and hetero-nucleophiles

DOI: 10.1002/chem.200700691

Source and publish data:

Authors:

Article abstract of DOI:10.1002/chem.200700691

Full text of DOI:10.1002/chem.200700691

Products guided by the article

R&D Labs maybe for 1001080-44-9

Relevant to this article

Hot Product