Photocycloaddition and Rearrangement Reactions in a Putative Route to the Skeleton of Plicamine-Type Alkaloids

SYNTHESIS

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2015, 47, 2869–2884

paper

2869

K.-H. Rimböck et al.

Paper

Synthesis

Photocycloaddition and Rearrangement Reactions in a Putative

Route to the Skeleton of Plicamine-Type Alkaloids

Karl-Heinz Rimböck

TBSO

O

Alexander Pöthig

4a

TBSO

O

Y

Thorsten Bach*

X

N

5a

R

NH

N

Department Chemie and Catalysis Research Center (CRC),

Technische Universität München,

Lichtenbergstr. 4, 85747 Garching, Germany

thorsten.bach@ch.tum.de

NH

X

O

[2+2] photocycloaddition

products (Y = CH₂)

meta-photocycloaddition

by-product

rearrangement:

migration of C5a

Received: 13.04.2015

Accepted: 16.04.2015

Published online: 26.06.2015

DOI: 10.1055/s-0034-1380756; Art ID: ss-2015-z0241-op

were mainly used in their work, which culminated in the

first total syntheses of (+)-plicamine,^5a,b(+)-plicane, and

(–)-obliquine.^5c

OMe

Abstract Two isoquinolones were prepared, to which an allenyl side

chain was linked at position C4 via a stereogenic silyloxy-substituted

carbon atom. Intramolecular [2+2] photocycloaddition reactions of

these substrates proceeded with high diastereoselectivity and delivered

the respective cyclobutanes with an exocyclic methylene group (83%

and 49% yield). With the 5,6-dioxoloisoquinolone precursor an unprec-

edented meta-photocycloaddition was observed as a significant side re-

action, which occurred at positions C4 and C8a of the isoquinolone

skeleton. The cyclobutane products were, after N-alkylation and trans-

formation into the respective cyclobutanones (22–57%), subjected to

various rearrangement reactions. In detail, a direct photochemical rear-

rangement, thermal and photochemical Beckmann rearrangements,

and Baeyer–Villiger oxidation reactions were studied. In all cases, prod-

ucts were found, which resulted from cleavage of the amino-substitut-

ed cyclobutane bond, but not from the desired cleavage of the alterna-

tive alkyl-substituted cyclobutane bond.

4a

1

N

11

O

12b

6a

12a

O

N

8

O

A

1

OH

4a

TBSO

11b

5a

5

NH

Key words alkaloids, cycloaddition, heterocycles, isoquinolones, pho-

tochemistry, rearrangements

O

2

Figure 1 Structure of (+)-plicamine (1), the tetracyclic skeleton A of

plicamine-type alkaloids, and the intramolecular [2+2] photocycloaddi-

tion product 2

Plicamine (1), first isolated from Galanthus plicatus sub-

sp. byzantinus (Amaryllidaceae),¹and structurally related

natural products with a decahydroindolo[3,3a-c]isoquino-

line skeleton (A)²are unique among the Amaryllidaceae al-

kaloids, because they contain two nitrogen atoms as op-

posed to the large majority of these alkaloids, which exhibit

only a single nitrogen atom (Figure 1).

Biosynthetically, it is assumed that the second nitrogen

atom stems from a tyramine, which intercepts a norbella-

dine-derived key intermediate,³which is known to lead to

alkaloids of the crinine and tazettine type.⁴Extensive syn-

thetic work on plicamine-type alkaloids has been per-

formed by Ley and co-workers, who developed a concise ac-

cess to skeleton A by an oxidative aromatic coupling be-

tween positions C12a and C12b.⁵Polymer-based reagents

We became interested in plicamine-type alkaloids as

synthetic targets in connection with recent work on the

[2+2] photocycloaddition reaction of isoquinolones.⁶Most

notably, we found that product 2 with an octahydro-1H-

benzo[2,3]cyclobuta[1,2-c]isoquinoline core could be readi-

ly accessed by a diastereoselective intramolecular isoquino-

lone [2+2] photocycloaddition, in which the bonds between

carbon atoms C4a/C11b and C5/C5a were established.^6aIt

seemed promising to attempt a ring expansion of the cy-

clobutane to a pyrrolidine ring by 1,2-migration of carbon

atom C4a to an electron-deficient nitrogen atom, which

was to be installed at carbon atom C5.

2870

K.-H. Rimböck et al.

Paper

Synthesis

Br

HO

•

MeLi, LiBr (THF); t-BuLi;

X

O

•

4

NH

O

3a

3b

(X,X = H,H)

(X,X = OCH₂O)

36–71%

25–43%

5a

5b

TBSO

•

TBSOTf, 2,6-lutidine

(DMF)

X

93%

76%

NH

6a

6b

O

Scheme 1 Synthesis of allenic irradiation precursors 6 from 4-bromoisoquinolones 3

In this paper, we provide full details on the synthesis of

appropriate precursors for the attempted ring expansion

reaction. For the [2+2] photocycloaddition, allenes were

used to generate products with a functionalization at car-

bon atom C5. Unexpectedly, one of the allenyl-substituted

precursors led to a photocycloaddition product, which for-

mally resulted from a yet unprecedented meta-addition to

the isoquinolone core. The attempted rearrangement reac-

tions were performed thermally (Beckmann rearrange-

ment) or photochemically. In all cases, a preference for mi-

gration of carbon atom C5a versus C4a was found resulting

in the formation of the decahydroisoindolo[1,7a-c]isoquin-

oline skeleton, which is regioisomeric to skeleton A.

The synthetic work commenced with the preparation of

the starting materials 6 from the respective 4-bromoiso-

quinolones 3⁷(Scheme 1). In the first step, deprotonation

and a subsequent bromine–lithium exchange reaction gen-

erate a putative dianion, which can be trapped with suit-

able electrophiles.^6a,7While reactions with simple alde-

hydes and with DMF gave good results, the reaction with

aldehyde 4⁸turned out to be capricious and yields were

variable. Protection of the resulting secondary alcohols

with a tert-butyldimethylsilyl (TBS) group was facile if the

respective triflate (OTf) was used as silylating agent. Al-

though other methods for the construction of compounds 6

were tested, the brevity of the depicted route was consid-

ered a significant benefit and led us eventually to perform

the synthesis of irradiation precursors 6 consistently by this

route.⁹

In line with our previous work on the intramolecular

[2+2] photocycloaddition of olefins to isoquinolones,^6athe

reaction of allenic substrate 6a proceeded smoothly and de-

livered the expected product 7a in good yields (Scheme 2).

While the straight isomer clearly prevailed, minor amounts

of the crossed regiosiosmer were detected. For solubility

reasons the reaction was performed in acetonitrile as the

solvent (c = 25 mM). At the chosen concentration, the prod-

uct precipitated and could be easily separated from its re-

gioisomer and from unreacted starting material by filtra-

tion. The diastereoselectivity of the [2+2] photocycloaddi-

tion was perfect and is explained by 1,3-allylic strain¹⁰

operating between the aryl group and the substituents at

the stereogenic center. The relative configuration of product

7a was unambiguously established by its crystal structure.

Scheme 2 Diastereoselective intramolecular [2+2] photocycloaddition of isoquinolone 6a to product 7a (left); proof of relative configuration for 7a by

single-crystal X-ray crystallography (right)

2871

K.-H. Rimböck et al.

Paper

Synthesis

It has been shown for intermolecular [2+2] photocyc-

loaddition reactions of isoquinolones that substituents at

the isoquinolone do not alter the reaction course of the re-

action with olefins.^6cThe substitution of the isoquinolone

ring in substrate 6b seemed therefore to be a minor modifi-

cation and was not expected to influence the outcome of

the photochemical reaction. It was the more surprising that

– upon irradiation at λ = 366 nm – a second product accom-

panied the desired [2+2] photocycloaddition product 7b in

significant amounts. The formation of the by-product could

be suppressed at the expense of total yield, if the reaction

was performed in chlorinated solvents (Table 1, entries 1–

3). These conditions allowed us to isolate the desired prod-

uct essentially free from other isomers. In acetone (entry 4)

and other solvents (entries 5–7), however, the undesired re-

action pathway competed successfully with the [2+2] pho-

tocycloaddition reaction. The by-product 8 could be sepa-

rated by column chromatography and was obtained in pure

form. It was proven to be a constitutional isomer of 7b, but

the aromatic ring of the isoquinolone was no longer intact.

NMR data suggested that compound 8 was the product

of an intramolecular meta-photocycloaddition, but final

proof for its constitution and relative configuration could

only be obtained by single-crystal X-ray crystallography

(Scheme 3). Apparently, the allene adds with its terminal

double bond across the isoquinolone ring, forming carbon–

carbon bonds to the former isoquinolone carbon atoms C4

and C8a, while the former carbon atoms C4a and C3 of the

isoquinolone ring establish a cyclopropane bond. To the

best of our knowledge, this type of meta-photocycloaddi-

tion¹²has not yet been reported. In order to illustrate the

reaction course the reaction is depicted stepwise via 9 and

10 but it is mechanistically not clear whether it occurs on

the singlet or triplet hypersurface.

Further exploratory experiments with other isoquino-

lone derivatives revealed that the isoquinolone meta-pho-

tocycloaddition reaction requires the presence of the 1,3-

dioxole ring and of a tethered allene. If either one of them is

absent the normal [2+2] photocycloaddition mode is ob-

served.¹³

With the more readily accessible product 7a, initial

studies regarding a potential rearrangement were under-

taken. The required para-hydroxyphenethyl chain was at-

tached to the nitrogen atom by alkylation with bromide 11

(Scheme 4). The resulting product 12 was subjected to oxi-

dative cleavage of the double bond. Dihydroxylation with N-

methylmorpholine-N-oxide (NMO) was followed by oxida-

tive diol cleavage¹⁴to generate the desired cyclobutanone

13 in moderate yields. There was no precedence for

Beckmann rearrangement reactions^15,16at cyclobutanones

of this type. However, it had been reported that α,α-dichlo-

rocyclobutanones underwent the desired rearrangement

reaction upon treatment with the Tamura reagent,¹⁷O-me-

sitylenesulfonylhydroxylamine (MSH).¹⁸In these examples,

it was not the chloro-substituted alkyl group, which under-

went the migration but the other ketone substituent. We

hoped that the amino-substituted alkyl group would be-

have similarly and would allow for a preferred migration of

the secondary alkyl group. Initially, we were pleased to

note that exposure of cyclobutanone 13 to MSH led in high

yields to a single rearrangement product, which was shown

to be a γ-lactam (pyrrolidinone).

Table 1 Irradiation Products 7b and 8 Obtained under Various Conditions from Isoquinolone 6b

TBSO

hν (λ), r.t.

TBSO

(solvent)

O

6b

+

NH

O

7b

8

Entry

Solvent

c (mM)

λ (nm)^a

Time (h)^b

Yield (%)^c

7b/8

89:11

r.r.^d

>95:5

1

2

3

4

5

6

7

1,2-DCE^e

1,3-DCP^f

acetone

benzene

toluene

Et₂O

5

366

350

366

16

17

14

6

41

49

39

48

65

58

60

>99:1

93:7

>95:5

94:6

10

5

77:23

58:42

60.40

61:39

>95:5

85:15

84:16

87:13

5

18

19

17

5

^aEmission maximum of the fluorescent light source.¹¹

^bTime for complete conversion at the indicated conditions.

^cCombined yield for isolated products 7b and 8.

^dThe regioisomeric ratio (r.r.) refers to the ratio of product 7b to its regioisomer, which was formed in minor amounts and which was not separable from 7b.

^e1,2-Dichloroethane.

^f1,3-Dichloropropane.

2872

K.-H. Rimböck et al.

Paper

Synthesis

Scheme 3 Stepwise mechanism for the formation of product 8 from substrate 6b (left); proof of constitution and configuration for 8 by single-crystal

X-ray crystallography (right)

Attempts to elucidate the structure of rearrangement

product 14 by NMR led to some ambiguities and we there-

fore strived to prove the structure by X-ray crystallography.

After N-methylation of the γ-lactam core, a crystalline ma-

terial was obtained, and its structure could be unequivocal-

ly elucidated (Scheme 5).

Disappointingly, the structure of product 15 revealed

that the undesired migration pathway had been taken with

the amino-substituted alkyl group migrating instead of the

desired secondary alkyl group. We speculated that the ob-

served migration was due to the fact that oxime formation

at ketone 13 had for steric reasons occurred in favor of the

E-diastereoisomer (relative to the amino-substituted alkyl

NaH, (DMF)

TBSO

Br

1. NMO [OsO₄]

(CH₂Cl₂/H₂O)

2. NaIO₄(acetone/H₂O)

N

11

Oi-Pr

7a

O

52%

53%

12

Oi-Pr

O

TBSO

1. MSH (CH₂Cl₂)

2. Al₂O₃(MeOH)

O

NH

N

92%

O

13

14

Oi-Pr

Scheme 4 Preparation of cyclobutanone 13 from [2+2] photocycloaddition product 7a and Beckmann rearrangement to product 14

Scheme 5 N-Methylation of amide 14 (left) and proof of constitution and configuration for 15 by single-crystal X-ray crystallography (right)

2873

K.-H. Rimböck et al.

Paper

Synthesis

1. NMO [OsO₄]

(CH₂Cl₂/H₂O)

2. NaIO₄

TBSO

Me₃OBF₄

Cs₂CO₃

(CH₂Cl₂)

O

(acetone/H₂O)

N

7a

98%

84%

OMe

16

17

Scheme 6 Synthesis of cyclobutanone 17 from [2+2] photocycloaddition product 7a

group). As a consequence, the typical anti-specific migra-

tion pathway invoked for the Beckmann rearrangement¹⁶

would account for the observed regioselectivity. Attempts

were therefore undertaken to minimize the steric bulk at

the lactam site of the cyclobutanone. In a first set of experi-

ments, lactam 7a was converted into the respective imidate

by treatment with Meerwein salt.¹⁹Product 16 was subse-

quently converted into cyclobutanone 17 by the established

sequence of dihydroxylation/diol cleavage (Scheme 6). Ap-

plication of the MSH protocol to this substrate did not pro-

vide any meaningful results and led only to unidentifiable

products. It was possible to convert ketone 17 into the re-

spective oxime by treatment with hydroxylamine and pyri-

dine in CH₂Cl₂–MeOH (10:1). Despite extensive experimen-

tal efforts, conditions for a successful Beckmann rearrange-

ment of the oxime could not be found.

Attempts to convert lactams 7a and 7b into the respec-

tive cyclobutanones without prior N-protection suffered

from the instability of the products, which prohibited their

isolation. Due to the reluctance of imidate 17 to undergo a

Beckmann rearrangement, it was planned to attach a meth-

yl group to the lactam nitrogen atom and study the regiose-

lectivity of the Beckmann rearrangement with this sub-

strate class. To this end, lactams 7a,b were N-methylated

(Scheme 7) under standard conditions.²⁰The resulting

products 18 were converted into cyclobutanones 19, which

in turn were submitted to the Tamura conditions of the

Beckmann rearrangement. Disappointingly, the only isol-

able products in both cases were the undesired rearrange-

ment products 20. Their constitution was proven upon N-

methylation of the pyrrolidinone nitrogen atom by compar-

ison of their NMR spectra with the spectra of product 15. In

the Beckmann rearrangement of substrate 19b, a second re-

gioisomer was detected in the crude mixture in a ratio of

1:10 relative to the major product. It is likely that this prod-

uct was the desired regioisomer but it could not be isolated.

Starting from cyclobutanone 19a, stoichiometric oxime for-

mation was possible under the conditions given above for

17. The oxime was formed as a 2:1 mixture of diastereoiso-

mers but – like the former oxime – it could not be forced to

undergo the desired rearrangement.

When preparing cyclobutanone 19b under oxidative

conditions from the respective diol (Scheme 7) we surpris-

ingly found – apart from the desired product (52% yield) –

the respective lactone 22b (Figure 2) as a by-product (30%

yield), which appears to be the product of a Baeyer–Villiger-

type oxidation. Indeed, it could be shown that the more sta-

ble cyclobutanone 19a underwent a clean Baeyer–Villiger

oxidation^21,22to lactone 22a upon treatment with meta-

chloroperbenzoic acid (m-CPBA) and sodium bicarbonate in

CH₂Cl₂(97% yield).²³Expectedly, the more nucleophilic

group migrated in the course of the rearrangement as prov-

en by the crystal structure of γ-lactone 22a.

1. NMO [OsO₄]

(CH₂Cl₂/H₂O)

2. NaIO₄(acetone/H₂O)

NaH

MeI

(DMF)

TBSO

X

7a (X,X = H,H)

7b (X,X = OCH₂O)

N

a: 88%

b: 42%

a: 65%

b: 52%

X

O

18

O

TBSO

X

TBSO

N

1. MSH (CH₂Cl₂)

2. Al₂O₃(MeOH)

O

R

X

N

X

N

a: 96%

b: 77%

X

O

NaH

MeI

(DMF)

R = H

20

21

O

19

R = Me

a: 81%, b: 62%

Scheme 7 Synthesis of cyclobutanones 19 from [2+2] photocycloaddition products 7 and Beckmann rearrangement to products 20

2874

K.-H. Rimböck et al.

Paper

Synthesis

context of this work, further mechanistic studies were not

undertaken but it appears – based on the results of stoi-

chiometric oxime formation – that oxime formation from

cyclobutanone 19a is not selective (vide supra). Under the

conditions of the MSH-initiated rearrangement E- and Z-

oximes might equilibrate and eventually the higher migra-

tory aptitude of the amino-substituted alkyl group (as seen

in the Baeyer–Villiger oxidation, cf. Figure 2) could be deci-

sive for selective product formation.

A final photochemical experiment was performed with

cyclobutanone 19a. A solution in methanol was irradiated

at λ = 300 nm to initiate a Norrish type I cleavage. The reac-

tion has been successfully applied to natural product total

synthesis²⁷and it was expected to lead to an acetal via an

oxacarbene intermediate.²⁸The major product, however,

turned out to be ester 24, which was isolated in 52% yield

(Scheme 9). A by-product was obtained in 12% yield, to

which acetal structure 25 was tentatively assigned based on

its analytical data. In both cases, it is again the bond be-

tween carbon atoms C5a and C5, which is preferentially

broken. Formation of compound 24 can be explained by

Norrish type I cleavage of this bond and subsequent car-

bon–carbon bond fission between C4a and C11 (Figure 1) in

the intermediate 1,4-diradical.²⁹The resulting ketene is

trapped by the solvent. Formation of acetal 25 can be ex-

plained by invoking the same intermediate, which closes to

the five-membered oxacarbene, which in turn forms the

acetal upon reaction with MeOH. The latter reaction has

been suggested to occur on the singlet hypersurface.²⁸

Figure 2 Structure of Baeyer–Villiger oxidation products 22 (left) and

proof of constitution and configuration for 22a by single-crystal X-ray

crystallography (right)

Since thermal variants of the Beckmann rearrangement

had led either to the formation of the undesired regioiso-

mer or had not proceeded at all, our interest shifted to a

photochemical variant of the Beckmann rearrangement.^24,25

In this sequence, an oxaziridine is photochemically rear-

ranged to the respective lactam. Consequently, cyclobuta-

none 19a was first condensed with N-methylamine to the

respective Schiff base. Without isolation, the solution of the

imine was added at –40 °C to a solution of m-CPBA in

CH₂Cl₂to generate the required oxaziridine 23. The reaction

mixture was taken without workup into the photochemical

step, which included a room temperature irradiation at λ =

300 nm. The three-step sequence delivered a single Beck-

mann-type rearrangement product, which turned out to be

identical to the previous product 21a (Scheme 8). In addi-

tion, indicating that the imine formation had been incom-

plete, lactone 22a was isolated in 16% yield as result of a

Baeyer–Villiger oxidation.

TBSO

OMe

TBSO

hν (λ = 300 nm)

(MeOH)

O

19a

N

COOMe

N

52%

1. H₂NMe, MS 3 Å

O

hν (λ = 300 nm)

(CH₂Cl₂)

TBSO

24

25

O

N

(CH₂Cl₂)

2. m-CPBA (CH₂Cl₂)

21a

19a

Scheme 9 Irradiation of cyclobutanone 19a leads mainly to ester 24 as

product of an α-cleavage with subsequent ketene formation; minor

amounts of the oxacarbene rearrangement product 25 were obtained

53% overall

N

O

23

Scheme 8 Preparation of oxaziridine 23 and photochemical rearrange-

ment to product 21a

In summary, we have shown in the first part of this

study that intramolecular [2+2] photocycloaddition reac-

tions of allenes to isoquinolones lead diastereoselectively to

products with an octahydro-1H-benzo[2,3]cyclobuta[1,2-

c]isoquinoline core. For substrate 6b an unusual by-product

was observed, which was shown to be the product of a yet

unknown meta-photocycloaddition variant.

Attempts to rearrange the tetracyclic product skeleton

to the decahydroindolo[3,3a-c]isoquinoline skeleton of pli-

camine-type alkaloids by migration of carbon atom C4a re-

mained futile. Migration and carbon–carbon bond fission at

the amino-substituted carbon atom C5a were preferred in

all cases and led to the formation of undesired regioiso-

mers. Baeyer–Villiger rearrangement product 22b (Figure 2)

could be of relevance to the synthesis of the plicamine-type

The outcome of the photochemical Beckmann rear-

rangement was surprising because the reaction has been

employed previously to obtain products, which are re-

giochemically complimentary to the products of the ther-

mal Beckmann rearrangement.^24a,eIndeed, it has been

shown that for stereoelectronic reasons there is a migration

preference for the group which is trans to the free electron

pair at the oxaziridine nitrogen atom.²⁶In our case, the out-

come of the rearrangement suggests that the oxaziridine is

derived from a Z-configured imine, while the outcome of

the thermal Beckmann rearrangement (Scheme 7) suggests

that oxime formation occurred with E-selectivity. In the

2875

K.-H. Rimböck et al.

Paper

Synthesis

alkaloid seco-plicamine.¹The latter compound exhibits a

similar spiro skeleton but lacks the γ-lactam unit. Instead, it

carries an amino group at C4a and a carbonyl group at C6a.

It is apparent that these structural elements could be readi-

ly established from product 22b.

3 × 18 cm, CH₂Cl₂–MeOH, 95:5) to give 5a as a colorless solid; yield:

315 mg (1.23 mmol, 68%); mp 129–130 °C; R_f<0.10 (CH₂Cl₂–MeOH,

95:5) [UV/CAM].

IR (ATR): 3423 (m), 3146 (w), 3050 (w), 2904 (m), 1959 (w), 1632

(vs), 1605 (s), 1070 (m), 801 (vs), 689 cm^–1(s).

¹H NMR (360 MHz, CDCl₃): δ = 10.00 (br s, 1 H, NH), 8.48 (dd, ³J = 8.2

Hz, ⁴J = 1.4 Hz, 1 H, C8-H), 7.87 (d, ³J = 8.2 Hz, 1 H, C5-H), 7.73 (virt. td,

³J ≅ 7.7 Hz, ⁴J = 1.4 Hz, 1 H, C6-H), 7.55 (virt. t, ³J ≅ 7.7 Hz, 1 H, C7-H),

7.24 (d, J = 4.0 Hz, 1 H, C3-H), 5.12 (virt. quint, ³J ≅ ⁴J = 6.7 Hz, 1 H, C5′-

H), 5.04 (td, ³J = 7.9 Hz, J = 4.0 Hz, 1H, C1′-H), 4.67 (dt, ⁴J = 6.7 Hz, ⁵J =

General:³⁰All reactions involving water-sensitive chemicals were

carried out in flame-dried glassware under positive pressure of argon

with magnetic stirring. Tetrahydrofuran, dichloromethane, and dieth-

yl ether were purified using a SPS-800 solvent purification system

(M. Braun). Triethylamine was distilled over calcium hydride. All oth-

er chemicals were either commercially available or prepared accord-

ing to the cited references. For photochemical reactions, the reaction

mixture was degassed by purging with argon in an ultrasonicating

bath. Subsequently, the solution was transferred into Duran tubes (di-

ameter: 1 cm, volume: 10 mL) and irradiated in a Rayonet RPR100 re-

actor, equipped with 16 fluorescent lamps (for emission spectra, see

refs.¹¹and the Supporting Information). The reactor was cooled with

an internal fan, the operating temperature for photochemical reac-

tions was ca. 35 °C. Thin-layer chromatography (TLC) was performed

on silica-coated glass plates (silica gel 60 F₂₅₄) with detection by UV

(λ = 254 nm) or KMnO₄(0.5% in water) with subsequent heating.

Flash chromatography was performed on silica gel 60 (Merck, 230–

400 mesh) with the indicated eluent. Common solvents for chroma-

tography [dichloromethane (CH₂Cl₂), pentane (P), ethyl acetate

(EtOAc), methanol (MeOH)] were distilled prior to use. IR spectra

were recorded on a JASCO IR-4100 (ATR) or Perkin-Elmer 1600 FT/IR.

MS / HRMS measurements were performed on a Finnigan MAT 8200

or Thermo Fisher DFS (EI) / Finnigan LSQ classic or Thermo Fisher LTY

Orbitrap XL (ESI). ¹H and ¹³C NMR were recorded in CDCl₃at 303 K on

a Bruker AV-250, Bruker AVHD-300, Bruker AV-360, Bruker AVHD-

400, Bruker AV-500, or a Bruker AVHD-500 instrument. Chemical

shifts are reported relative to CHCl₃(δ = 7.26 ppm). Apparent multi-

plets that occur as a result of the accidental equality of coupling con-

stants to those of magnetically non-equivalent protons are marked as

virtual (virt.). The multiplicities of the ¹³C NMR signal were deter-

mined by DEPT experiments, assignments are based on COSY, HMBC

and HMQC experiments.

3

5

3.2 Hz, 2H, C7′-H), 2.10 (virt. qt, J ≅ 6.9 Hz, J = 3.2 Hz, 2 H, C4′-H₂),

2.05–1.83 (m, 2 H, C2′-H₂), 1.80–1.46 (m, 2 H, C3′-H₂).

¹³C NMR (91 MHz, CDCl₃): δ = 208.5 (s, C6′), 163.8 (s, C1), 136.2 (s,

C4a), 132.5 (d, C6), 127.9 (d, C8a), 126.6 (s, C8), 125.9 (d, C7), 124.9 (d,

C3), 123.1 (s, C5), 119.5 (d, C4), 89.6 (d, C5′), 75.0 (d, C1′), 69.8 (t, C7′),

36.4 (t, C2′), 27.9 (t, C4′), 25.5 (t, C3′).

MS (EI, 70 eV): m/z (%) = 237 (100, [M⁺– H₂O]), 222 (65), 208 (27),

195 (12), 184 (25), 158 (21), 128 (11), 115 (10), 77 (12).

HRMS (EI): m/z [(M

–

H₂O)⁺] calcd for C₁₆H₁₅NO: 237.1148;

found: 237.1150.

4-{1-[(tert-Butyldimethylsilyl)oxy]hepta-5,6-dien-1-yl)isoquino-

lin-1(2H)-one (6a)

A solution of 5a (1.02 g, 4.00 mmol, 1.00 equiv) in DMF (22 mL) was

cooled to 0 °C. After addition of 2,6-lutidine (1.40 mL, 1.29 g, 12.0

mmol, 3.00 equiv) and stirring for 5 min, t-BuMe₂SiOTf (1.40 mL, 1.61

g, 6.09 mmol, 1.52 equiv) was added dropwise at 0 °C and the reac-

tion mixture was warmed to r.t. overnight. Sat. aq NH₄Cl (35 mL) and

CH₂Cl₂(100 mL) were added and the layers were separated. The aque-

ous layer was extracted with CH₂Cl₂(3 × 100 mL). The combined or-

ganic layers were subsequently washed with H₂O (4 × 100 mL) and

brine (50 mL), and dried (Na₂SO₄). After filtration, the solvent was re-

moved in vacuo and the crude product was purified by flash chroma-

tography (SiO₂, 3.5 × 20 cm, P–EtOAc, 1:1) to give 6a as a colorless res-

in, which partially solidified upon storage in the refrigerator at 4 °C;

yield: 1.38 g (3.72 mmol, 93%); mp 77–79 °C; R_f= 0.52 (P–EtOAc, 1:1)

[UV/CAM].

IR (ATR): 3168 (w br), 3032 (w), 2926 (m), 2854 (m), 2360 (w), 2342

(w), 1955 (w), 1663 (vs), 1641 (s), 1607 (m), 1347 (m), 1248 (m),

1076 (m), 831 (vs), 767 (vs), 541 cm^–1(m).

¹H NMR (500 MHz, CDCl₃): δ = 9.67 (br s, 1 H, NH), 8.48 (dd, ³J = 8.1

Hz, ⁴J = 1.0 Hz, 1 H, C8-H), 7.88 (d, ³J = 8.1 Hz, 1 H, C5-H), 7.70 (virt. t,

³J ≅ 7.7 Hz, 1 H, C6-H), 7.52 (virt. t, ³J ≅ 7.7 Hz, 1 H, C7-H), 7.14 (d, J =

4.8 Hz, 1 H, C3-H), 5.05 (virt. quint, ³J ≅ ⁴J = 6.6 Hz, 1 H, C5′-H), 4.92 (t,

CAUTION: O-Mesitylenesulfonylhydroxylamine (MSH)¹⁷is a potential

explosive and appropriate safety measures should be taken when

working with this compound.

4-(1-Hydroxyhepta-5,6-dien-1-yl)isoquinolin-1(2H)-one (5a)

To a suspension of 4-bromoisoquinolin-1(2H)-one (3a;⁷407 mg, 1.82

mmol, 1.00 equiv) in THF (20 mL) at 0 °C was added dropwise a solu-

tion of MeLi·BrLi (2.2 M in Et₂O, 910 μL, 218 mg, 2.00 mmol, 1.10

equiv). After stirring for 10 min, the reaction mixture was cooled to

–78 °C and a solution of t-BuLi (1.6 M in pentane, 2.50 mL, 256 mg,

4.00 mmol, 2.20 equiv) was added dropwise and the mixture stirred

at –78 °C for 20 min. Subsequently hepta-5,6-dienal (4;⁸400 mg, 3.63

mmol, 2.00 equiv) was added quickly in one portion whereupon the

cooling bath was removed. The temperature was adjusted to –40 °C

with another cooling bath. The mixture was stirred for 2 h at –40 °C.

Subsequently, the reaction was quenched with sat. aq NH₄Cl (7 mL)

and the resulting slurry was warmed to r.t. After addition of H₂O (7

mL) and CH₂Cl₂(40 mL), the layers were separated and the aqueous

layer was extracted with CH₂Cl₂(3 × 50 mL). The combined organic

layers were dried (Na₂SO₄), filtered, and the solvent was removed in

vacuo. The crude product was purified by flash chromatography (SiO₂,

4

5

³J = 6.0 Hz, 1 H, C1′-H), 4.61 (dt, J = 6.6 Hz, J = 3.2 Hz, 2 H, C7′-H₂),

3

5

2.00 (virt. qt, J ≅ 6.8 Hz, J = 3.2 Hz, 2 H, C4′-H₂), 1.89–1.82 (m, 2 H,

C2′-H₂), 1.61–1.40 (m, 2 H, C3′-H₂), 0.90 [s, 9 H, SiC(CH₃)₃], 0.09 (s, 3

H, SiCH₃), –0.10 (s, 3 H, SiCH₃).

¹³C NMR (126 MHz, CDCl₃): δ = 208.6 (s, C6′), 162.5 (s, C1), 136.9 (s,

C4a), 132.7 (d, C6), 132.5 (s, C8a), 127.8 (d, C8), 126.9 (d, C7), 123.8 (d,

C3), 123.4 (d, C5), 117.0 (s, C4), 89.2 (d, C5′), 77.2 (d, C1′), 75.3 (t, C7′),

32.5 (t, C2′), 27.9 (t, C4′), 25.64 (t, C3′), 25.63 [q, SiC(CH₃)₃], 18.0 [s,

SiC(CH₃)₃], –3.6 (q, SiCH₃).

MS (EI, 70 eV): m/z (%) = 369 (5, [M⁺]), 312 (28, [M⁺– t-Bu]), 294 (11,

[M⁺– C₂H₇OSi]), 288 (46, [M⁺– C₆H₉]), 241 (11), 185 (10), 167 (18),

149 (44), 75 (100, [C₂H₇OSi⁺]), 57 (42, [t-Bu⁺]), 43 (43).

HRMS (EI): m/z [M⁺] calcd for C₂₂H₃₁NO₂Si: 369.2119;

found: 369.2125.

2876

K.-H. Rimböck et al.

Paper

Synthesis

1-[(tert-Butyldimethylsilyl)oxy]-5-methylene-1,2,3,4,4a,5,5a,6-oc-

tahydro-7H-benzo[2,3]cyclobuta[1,2-c]isoquinolin-7-one (7a)

(3 × 40 mL). The combined organic layers were washed with sat. aq

NaHCO₃(30 mL) and brine (30 mL), dried (Na₂SO₄), filtered, and the

solvent was removed in vacuo. The crude product was purified by

flash chromatography (SiO₂, 3.5 × 19 cm, EtOAc) to give 5b as a color-

less solid; yield: 133 mg (443 μmol, 43%); mp 192–194 °C; R_f= 0.27

(CH₂Cl₂–MeOH, 95:5) [UV/CAM].

A solution of 6a (1.74 g, 4.72 mmol) in anhydrous MeCN (189 mL) was

purged with argon in an ultrasound bath for 20 min. After irradiation

(λ = 366 nm) at r.t. for 26 h, the crystalline product was collected by

filtration and successive concentration of the filtrate gave 7a as a col-

orless crystalline solid; total yield: 1.45 g (3.92 mmol, 83%); mp 186–

189 °C; R_f= 0.20 (CH₂Cl₂–MeOH, 99:1) [UV/CAM].

IR (ATR): 3401 (m), 2911 (m), 1953 (w), 1645 (vs), 1461 (s), 1262 (s),

1038 (s), 852 cm^–1(s).

¹H NMR (500 MHz, DMSO-d₆): δ = 11.11 (d, ³J = 5.9 Hz, 1 H, NH), 7.55

IR (ATR): 3189 (w br), 3071 (w), 2935 (s), 2879 (m), 2853 (m), 1673

(s), 1600 (m), 1460 (m), 1353 (s), 1085 (s), 857 (vs), 780 (vs), 751

cm^–1(s).

(s, 1 H, C4-H), 7.33 (s, 1 H, C-9H), 6.98 (d, ³J = 5.9 Hz, 1 H, C7-H), 6.16

3

4

(s, 2 H, OCH₂O), 5.22–5.09 (m, 1 H, OH), 5.16 (virt. quint, J ≅ J = 6.5

3

¹H NMR (500 MHz, CDCl₃): δ = 8.11 (dd, ³J = 7.9 Hz, ⁴J = 1.4 Hz, 1 H,

C8-H), 7.54 (virt. td, ³J ≅ 7.6 Hz, ⁴J = 1.4 Hz, 1 H, C10-H), 7.34 (virt. td,

³J ≅ 7.6 Hz, ⁴J = 1.2 Hz, 1 H, C9-H), 7.28 (dd, ³J = 7.9 Hz, ⁴J = 1.2 Hz, 1 H,

C11-H), 6.30 (br s, 1 H, NH), 4.93 (s, 1 H, C5-CHH), 4.78–4.70 (m, 1 H,

Hz, 1 H, C5′-H), 4.74–4.67 (m, 3 H, C1′-H, C7′-H₂), 1.97 (virt. tdd, J ≅

9.8 Hz, ³J = 6.1 Hz, ⁵J = 2.6 Hz, 2 H, C4′-H₂), 1.79–1.68 (m, 1 H, C2′-HH),

1.68–1.59 (m, 1 H, C2′-HH), 1.56–1.38 (m, 2 H, C3′-H₂).

¹³C NMR (126 MHz, DMSO-d₆): δ = 207.9 (s, C6′), 160.7 (s, C5), 151.3

(s, C9a), 146.7 (s, C3a), 133.3 (s, C8a), 124.2 (d, C7), 121.4 (s, C4a),

118.4 (s, C8), 104.6 (d, C4), 101.9 (d, C9), 101.8 (t, C2), 89.8 (d, C5′),

75.3 (d, C1′), 68.1 (t, C7′), 36.4 (t, C2′), 27.5 (t, C4′), 25.2 (t, C3′).

3

C5a-H), 4.73 (s, 1 H, C5-CHH), 3.84 (dd, J = 10.9 Hz, J = 5.8 Hz, 1 H,

C1-H), 2.83 (virt. t, ³J ≅ 9.0 Hz, 1 H, C4a-H), 2.18–2.05 (m, 1 H, C4-HH),

1.99–1.94 (m, 1 H, C2-HH)), 1.86–1.76 (m, 1 H, C3-HH), 1.56–1.44 (m,

1 H, C2-HH), 1.41–1.28 (m, 2 H, C3-HH, C4-HH), 0.69 [s, 9 H,

SiC(CH₃)₃], –0.24 (s, 3 H, SiCH₃), –0.65 (s, 3 H, SiCH₃).

MS (EI, 70 eV): m/z (%) = 299 (2, [M⁺]), 281 (14), 266 (6), 218 (11), 202

(7), 189 (100, [M⁺– C₇H₁₀O]), 131 (17), 103 (9), 76 (12).

¹³C NMR (126 MHz, CDCl₃): δ = 164.2 (s, C7), 152.7 (s, C5), 145.8 (s,

C11a), 132.6 (d, C10), 129.1 (s, C7a), 127.3 (d, C8), 127.2 (d, C11),

126.7 (d, C9), 104.4 (t, C5=CH₂), 76.5 (d, C1), 52.6 (d, C5a), 51.0 (d,

C4a), 46.3 (s, C11b), 32.0 (t, C2), 28.8 (t, C4), 25.5 [q, SiC(CH₃)₃], 22.4

(t, C3), 17.6 [s, SiC(CH₃)₃], –5.1 (q, SiCH₃), –5.9 (q, SiCH₃).

HRMS (EI): m/z [M⁺] calcd for C₁₇H₁₇NO₄: 299.1158; found: 299.1152.

8-{1-[(tert-Butyldimethylsilyl)oxy]hepta-5,6-dien-1-yl}[1,3]dioxo-

lo[4,5-g]isoquinolin-5(6H)-one (6b)

A solution of 5b (61.3 mg, 205 μmol, 1.00 equiv) in DMF (2 mL) was

cooled to 0 °C. After addition of 2,6-lutidine (94.5 μL, 87.2 mg, 814

μmol, 3.97 equiv) and stirring for 5 min, t-BuMe₂SiOTf (94.3 μL, 108

mg, 409 μmol, 2.00 equiv) was added dropwise at 0 °C and the reac-

tion mixture was warmed to r.t. overnight. Sat. aq NH₄Cl (15 mL), H₂O

(10 mL), and Et₂O (40 mL) were added, and the layers were separated.

The aqueous layer was extracted with Et₂O (5 × 50 mL) and the com-

bined organic layers were dried (Na₂SO₄), filtered, and the solvent

was removed in vacuo. The crude product was purified by flash chro-

matography (SiO₂, 3 × 10 cm, EtOAc) to give 6b as a colorless solid;

yield: 66.9 mg (162 μmol, 79%); mp 178–180 °C (dec.); R_f= 0.78

(CH₂Cl₂–MeOH, 9:1) [UV/CAM].

MS (EI, 70 eV): m/z (%) = 354 (3, [M⁺– CH₃]), 312 (100, [M⁺– t-Bu]),

294 (7, [M⁺– C₂H₇OSi]), 236 (5), 209 (4), 147 (4), 115 (4, [C₆H₁₅Si⁺]), 84

(14), 75 (19, [C₂H₇OSi⁺]).

HRMS (EI): m/z [(M

–

CH₃)⁺] calcd for C₂₁H₂₈NO₂Si: 354.1884;

found: 354.1885.

X-ray Crystal Data³¹

Formula: C₂₂H₃₁NO₂Si; M_r= 369.57; crystal color and shape: colorless

prism, crystal dimensions = 0.11 × 0.22 × 0.35 mm; crystal system:

triclinic; space group P-1 (no. 2); a = 7.8533(1), b = 9.8450(2), c =

13.2681(2) Å, α = 94.7210(8), β = 101.3000(7), γ = 90.7474(8); V =

1002.09(3) Å³; μ(Mo_Kα) = 0.133 mm^–1; ρ_calcd=1.225 g cm^–3; θ-range =

1.57–25.51°; data collected: 42364; independent data [I_o>2σ(I_o)/all

IR (ATR): 2924 (w), 2853 (m), 1955 (w), 1655 (vs), 1476 (s), 1258 (s),

1035 (s), 831 (s), 772 cm^–1(m).

data/R_int]:

3706/0/240; R1 [I_o>2σ(I_o)/all data]: 0.0324/0.0405; wR2 [I_o>2σ(I_o)/all

data]: 0.0804/0.0850; GOF = 1.026; Δρ_max/min: 0.33/–0.26 e Å^–3

3193/3706/0.0311;

data/restraints/parameters:

¹H NMR (500 MHz, DMSO-d₆): δ = 11.13 (d, ³J = 5.8 Hz, 1 H, NH), 7.54

(s, 1 H, C9-H), 7.44 (s, 1 H, C4-H), 7.02 (d, ³J = 5.8 Hz, 1 H, C7-H), 6.18

(d, ²J = 1.0 Hz, 1 H, OCHHO), 6.15 (d, ²J = 1.0 Hz, 1 H, OCHHO), 5.14

(virt. quint, ³J ≅ ⁴J = 6.7 Hz, 1 H, C5′-H), 4.86 (t, ³J = 6.2 Hz, 1 H, C1′-H),

4.69 (dt, ⁴J = 6.7 Hz, ²J = 3.3 Hz, 2 H, C7′-H₂), 1.95 (m, 2 H, C4′-H₂),

1.82–1.65 (m, 2 H, C2′-H₂), 1.52–1.42 (m, 1 H, C3′-HH), 1.41–1.30 (m,

1 H, C3′-HH), 0.84 [s, 9 H, SiC(CH₃)₃], 0.06 [s, 3 H, Si(CH₃)(CH₃)], –0.14

[s, 3 H, Si(CH₃)(CH₃)].

¹³C NMR (126 MHz, DMSO-d₆): δ = 207.9 (s, C6′), 160.7 (s, C5), 151.2

(s, C9a), 146.7 (s, C3a), 132.8 (s, C8a), 124.8 (d, C7), 121.5 (s, C4a),

117.5 (s, C8), 104.6 (d, C4), 102.1 (d, C9), 101.9 (t, OCH₂O), 89.7 (d,

C5′), 75.3 (t, C7′), 37.5 (t, C2′), 27.2 (t, C4′), 25.7 [q, SiC(CH₃)₃], 25.0 (t,

C3′), 17.8 [s, SiC(CH₃)₃], –4.8 [q, Si(CH₃)(CH₃)], –5.0 [q, Si(CH₃)(CH₃)].

.

8-(1-Hydroxyhepta-5,6-dien-1-yl)[1,3]dioxolo[4,5-g]isoquinolin-

5(6H)-one (5b)

To a suspension of 8-bromo[1,3]dioxolo[4,5-g]isoquinolin-5(6H)-one

(3b;^7,32276 mg, 1.03 mmol, 1.00 equiv) in THF (12 mL) at 0 °C was

added dropwise a solution of MeLi·BrLi complex (2.2 M in Et₂O, 520

μL, 123 mg, 1.13 mmol, 1.10 equiv). After stirring for 10 min, the reac-

tion mixture was cooled to –78 °C and a solution of t-BuLi (1.6 M in

pentane, 1.12 mL, 146 mg, 2.28 mmol, 2.20 equiv) was added drop-

wise and the mixture was stirred at –78 °C for 20 min. Subsequently

hepta-5,6-dienal (4;⁸228 mg, 2.07 mmol, 2.00 equiv) was added

dropwise whereupon the cooling bath was removed and the mixture

slowly warmed to r.t. The reaction was quenched with sat. aq NH₄Cl

(5 mL). After addition of H₂O (5 mL) and CH₂Cl₂(30 mL), the layers

were separated, and the aqueous layer was extracted with CH₂Cl₂

MS (EI, 70 eV): m/z (%) = 413 (7, [M⁺]), 356 (11), 332 (36), 281 (10),

189 (100, [M⁺– C₁₃H₂₅OSi]), 131 (18), 75 (61).

HRMS (EI): m/z [M⁺] calcd for C₂₃H₃₁NO₄Si: 413.2022;

found: 413.2019.

2877

K.-H. Rimböck et al.

Paper

Synthesis

1-[(tert-Butyldimethylsilyl)oxy]-5-methylene-1,2,3,4,4a,5,5a,6-oc-

HRMS (ESI): m/z [(M

+

H)⁺] calcd for C₂₃H₃₂NO₄Si: 414.2101;

tahydro-7H-benzo[2,3]cyclobuta[1,2-c][1,3]dioxolo[4,5-g]isoquin-

olin-7-one (7b) and 5-[(tert-Butyldimethylsilyl)oxy]-6,7,8,10-

tetrahydro-4aH,5H-4b,10a-(methanoiminomethano)cyclohep-

ta[1,2]indeno[5,6-d][1,3]dioxol-12-one (8)

found: 414.2099.

X-ray Crystal Data³¹

Formula: C₂₃H₃₁NO₄Si; M_r= 413.58; crystal color and shape: yellow

fragment, crystal dimensions = 0.23 × 0.33 × 0.64 mm; crystal system:

trigonal; space group R –3 (no. 148); a = b = 26.8583(10), c =

A solution of 6b (18.0 mg, 43.5 μmol) in anhydrous benzene (8.7 mL)

was purged with argon in an ultrasound bath for 20 min. After irradi-

ation (λ = 366 nm) at r.t. for 18 h, the solvent was removed in vacuo.

The crude product was purified by flash chromatography (SiO₂,

2 × 10 cm, P–EtOAc, 5:1 → 4:1 → 3:1) to give the [2+2] photocycload-

dition product 7b and the meta-photocycloaddition product 8 as col-

orless solids.

17.0912(7) Å; V = 10677.3(10) Å³; μ(Mo_Kα) = 0.125 mm^–1; ρ_calcd

=

1.158 g cm^–3; θ-range = 1.48–25.35°; data collected: 34010; indepen-

dent data [I_o>2σ(I_o)/all data/R_int]: 3668/4347/0.0497; data/

restraints/parameters:

0.0402/0.0501; wR2 [I_o>2σ(I_o)/all data]: 0.0934/0.0990; GOF = 1.036;

Δρ_max/min: 0.32/–0.35 e Å^–3

4347/0/267;

R1

[I_o>2σ(I_o)/all

data]:

.

[2+2] Photocycloaddition Product 7b

Yield: 6.8 mg (16.4 μmol, 38%); mp 158–160 °C; R_f= 0.74 (P–

EtOAc, 1:1) [UV/CAM].

1-[(tert-Butyldimethylsilyl)oxy]-6-(4-isopropoxyphenethyl)-5-

methylene-1,2,3,4,4a,5,5a,6-octahydro-7H-benzo[2,3]cyclobu-

ta[1,2-c]isoquinolin-7-one (12)

IR (ATR): 3203 (w), 3076 (w), 2929 (vs), 2856 (s), 1671 (vs), 1471 (m),

1247 (m), 835 cm^–1(w).

NaH (60% dispersion in mineral oil, 32.7 mg, 818 μmol, 1.20 equiv)

was added to a solution of isoquinolone 7a (252 mg, 682 μmol,

1.00 equiv) in DMF (10 mL) and the resulting suspension was stirred

for 45 min. A solution of 1-(2-bromoethyl)-4-isopropoxybenzene

(11;³³348 mg, 1.43 mmol, 2.10 equiv) in DMF (2 mL) was added and

the reaction mixture was stirred at r.t. for 24 h. H₂O (20 mL) and

EtOAc (25 mL) were added and the layers were separated. The aque-

ous layer was extracted with EtOAc (5 × 25 mL) and the combined or-

ganic layers were subsequently washed with H₂O (5 × 15 mL) and

brine (2 × 15 mL), and dried (Na₂SO₄). After filtration, the solvent was

removed in vacuo and the crude product was purified by flash chro-

matography (SiO₂, 2 × 20 cm, P–EtOAc, 10:1 → 5:1) to give the N-al-

kylated isoquinolone 12 as a colorless resin; yield: 187 mg (352 μmol,

52%); R_f= 0.63 (P–EtOAc, 5:1) [UV/CAM].

¹H NMR (500 MHz, CDCl₃): δ = 7.53 (s, 1 H, C8-H), 6.66 (s, 1 H, C12-H),

6.53 (d, ³J = 5.3 Hz, 1 H, NH), 6.00 (d, ²J = 1.4 Hz, 1 H, OCHHO), 5.97 (d,

²J = 1.4 Hz, 1 H, OCHHO), 4.92–4.89 (m, 1 H, C5-CHH), 4.74–4.71 (m, 1

H, C5-CHH), 4.69 (virt. dq, ³J = 5.3 Hz, ⁴J = 2.4 Hz, 1 H, C5a-H), 3.75 (dd,

³J = 10.9 Hz, ³J = 5.8 Hz, 1 H, C1-H), 2.77 (virt. t, ³J ≅ 8.5 Hz, 1 H, C4a-

H), 2.13–2.04 (m, 1 H, C4-HH), 1.97–1.88 (m, 1 H, C2-HH), 1.81–1.72

(m, 1 H, C3-HH), 1.52–1.40 (m, 1 H, C2-HH), 1.28 (m, 2 H, C3-HH, C4-

HH), 0.70 [s, 9 H, SiC(CH₃)₃], –0.22 [s, 3 H, Si(CH₃)(CH₃)], –0.55 [s, 3 H,

Si(CH₃)(CH₃)].

¹³C NMR (126 MHz, CDCl₃): δ = 164.0 (s, C7), 153.0 (s, C5), 151.3 (s,

C11a), 146.8 (s, C8a), 141.3 (s, C12a), 124.0 (s, C7a), 107.0 (d, C8),

106.7 (d, C12), 104.3 (t, C5=CH₂), 101.6 (t, OCH₂O), 76.2 (d, C1), 52.6

(d, C5a), 51.1 (d, C4a), 46.7 (s, C12b), 32.1 (t, C2), 28.9 (t, C4), 25.6 [q,

SiC(CH₃)₃], 22.5 (t, C3), 17.7 [s, SiC(CH₃)₃], –4.9 [q, Si(CH₃)(CH₃)], –5.5

(q, Si(CH₃)(CH₃)].

IR (ATR): 2928 (br s), 2855 (m), 1659 (m), 1509 (vs), 1477 (s), 1242 (s),

1036 cm^–1(s).

¹H NMR (500 MHz, CDCl₃): δ = 8.15 (d, ³J = 7.8 Hz, 1 H, C8-H), 7.51

(virt. t, ³J ≅ 7.5 Hz, 1 H, C10-H), 7.34 (virt. t, ³J ≅ 7.6 Hz, 1 H, C9-H),

7.24 (virt. d, J = 8.3 Hz, 2 H, C2′′-H, C6′′-H), 6.86 (virt. d, J = 8.3 Hz, 2 H,

C3′′-H, C5′′-H), 4.85 (s, 1 H, C5-CHH), 4.75 (s, 1 H, C5a-H), 4.67 (s, 1 H,

C5-CHH), 4.53 [sept, ³J = 6.1 Hz, 1 H, OCH(CH₃)₂], 3.84 (dd, ³J = 11.1 Hz,

³J = 5.8 Hz, 1 H, C1-H), 3.82–3.68 (m, 2 H, C1′-H₂), 3.01–2.88 (m, 2 H,

C1′-H₂), 2.80 (virt. t, ³J ≅ 8.7 Hz, 1 H, C4a-H), 2.12 (virt. t, ³J ≅ 9.1 Hz, 1

H, C4-HH), 2.02–1.92 (m, 1 H, C2-HH), 1.87–1.77 (m, 1 H, C3-HH),

1.62–1.48 (m, 1 H, C2-HH), 1.34 [d, ³J = 6.1 Hz, 6 H, OCH(CH₃)₂], 1.43–

1.21 (m, 2 H, C3-HH, C4-HH), 0.65 [s, 9 H, SiC(CH₃)₃], –0.28 (s, 3 H,

SiCH₃), –0.62 (s, 3 H, SiCH₃).

MS (ESI): m/z = 414 [(M + H)⁺].

HRMS (ESI): m/z [(M

+

H)⁺] calcd for C₂₃H₃₂NO₄Si: 414.2101;

found: 414.2099.

meta-Photocycloaddition Product 8

Yield: 4.9 mg (11.9 μmol, 27%); mp 168 °C (dec.); R_f= 0.20 (CH₂Cl₂–

MeOH, 99:1) [UV/CAM].

IR (ATR): 3204 (w), 3073 (w), 2927 (vs), 2855 (s), 1666 (s), 1470 (s),

1252 (m), 1039 (m), 835 (w), 775 cm^–1(w).

¹H NMR (500 MHz, CDCl₃): δ = 6.59 (s, 1 H, NH), 5.90 (ddd, ³J = 6.6 Hz,

The ¹H NMR signal for C11-H was covered by the residual proton sig-

nal of the solvent. Measurement in CD₃OD resulted in the following

¹H NMR signal:

4

³J = 4.4 Hz, J = 2.5 Hz, 1 H, C5-H), 5.55 (d, ²J = 0.8 Hz, 1 H, OCHHO),

5.49 (d, ²J = 0.8 Hz, 1 H, OCHHO), 5.32 (d, ⁵J = 0.9 Hz, 1 H, C11-H), 5.15

(d, ⁵J = 0.9 Hz, 1 H, C7-H), 4.23 (dd, ³J = 8.7 Hz, ³J = 4.1 Hz, 1 H, C1-H),

3.61 (s, 1 H, C12-H), 2.91 (virt. dq, ²J = 13.4 Hz, ⁴J ≅ 2.5 Hz, 1 H, C6-

HH), 2.72 (d, ²J = 13.4 Hz, 1 H, C6-HH), 2.14–1.96 (m, 3 H, C4-HH, C4-

HH, C2-HH), 1.83–1.60 (m, 2 H, C2-HH, C3-HH), 1.54–1.39 (m, 1 H,

C3-HH), 0.90 [s, 9 H, SiC(CH₃)₃], 0.10 [s, 3 H, Si(CH₃)(CH₃)], 0.10 [s, 3 H,

Si(CH₃)(CH₃)].

3

4

¹H NMR (500 MHz, CD₃OD): δ = 7.45 (dd, J = 7.9 Hz, J = 1.4 Hz, 1 H,

C11-H).

¹³C NMR (126 MHz, CDCl₃): δ = 162.5 (s, C7), 156.4 (s, C4′′), 152.4 (s,

C5), 144.7 (s, C11a), 131.9 (d, C10), 131.0 (s, C1′′), 130.2 (s, C7a), 129.8

(d, C2′′, C6′′), 127.6 (d, C8), 126.8 (d, C11), 126.7 (d, C9), 115.9 (d, C3′′,

C5′′), 104.0 (t, C5-CH₂), 76.5 (d, C1), 69.9 [d, OCH(CH₃)₂], 58.4 (d, C5a),

50.6 (d, C4a), 49.8 (t, C1′), 46.4 (s, C11b), 34.1 (t, C2′), 31.9 (t, C2), 28.6

(t, C4), 25.6 [q, SiC(CH₃)₃], 22.5 (t, C3), 22.1 [q, OCH(CH₃)₂], 17.7 [s,

SiC(CH₃)₃], –5.3 (q, SiCH₃), –5.7 (q, SiCH₃).

¹³C NMR (126 MHz, CDCl₃): δ = 183.1 (s, C14), 145.2 (s, C10a), 144.3

(s, C7a), 133.6 (s, C5a), 126.7 (d, C5), 99.0 (t, OCH₂O), 91.5 (d, C11),

90.2 (d, C7), 70.7 (d, C1), 59.1 (t, C6), 54.7 (s, C6a), 50.6 (s, C12a), 45.9

(s, C11a), 45.8 (d, C12), 39.4 (t, C2), 28.4 (t, C4), 26.2 [q, SiC(CH₃)₃],

23.3 (t, C3), 18.2 [s, SiC(CH₃)₃], –3.8 [q, Si(CH₃)(CH₃)], –3.8 [q,

Si(CH₃)(CH₃)].

MS (ESI): m/z = 532 [(M + H)⁺].

HRMS (ESI): m/z [(M

+

H)⁺] calcd for C₃₃H₄₆NO₃Si: 532.3247;

MS (ESI): m/z = 414 [(M + H)⁺]

found: 532.3238.

2878

K.-H. Rimböck et al.

Paper

Synthesis

1-[(tert-Butyldimethylsilyl)oxy]-7-(4-isopropoxyphenethyl)-

2,3,4,4a,6a,7-hexahydroisoindolo[1,7a-c]isoquinoline-5,8(1H,6H)-

dione (14) via 1-[(tert-Butyldimethylsilyl)oxy]-6-(4-isopropoxy-

phenethyl)-2,3,4,4a,5a,6-hexahydro-1H-benzo[2,3]cyclobuta[1,2-

c]isoquinoline-5,7-dione (13)

IR (ATR): 3229 (br w), 2928 (vs), 2856 (s), 1708 (s), 1654 (s), 1508 (m),

1479 (w), 1462 (w), 1241 (s), 1095 (m), 836 cm^–1(s).

¹H NMR (500 MHz, CDCl₃): δ = 8.14 (dd, ³J = 7.8 Hz, ⁴J = 1.5 Hz, 1 H,

C9-H), 7.53 (virt. td, ³J ≅ 7.6 Hz, ⁴J = 1.5 Hz, 1 H, C11-H), 7.37 (virt. td,

³J ≅ 7.5 Hz, ⁴J = 1.1 Hz, 1 H, C10-H), 7.31 (dd, ³J = 7.9, ⁴J = 1.1 Hz, 1 H,

C12-H), 7.20 (virt. d, J = 8.6 Hz, 2 H, C2′′-H, C6′′-H), 6.87 (virt. d, J = 8.6

Hz, 2 H, C3′′-H, C5′′-H), 5.25 (s, 1 H, C6a-H), 5.10 (s, 1 H, NH), 4.52

[sept, ³J = 6.1 Hz, 1 H, OCH(CH₃)₂], 4.27–4.16 (m, 1 H, C1′-HH), 3.77

(dd, ³J = 11.3 Hz, ³J = 4.6 Hz, 1 H, C1-H), 3.54–3.34 (m, 1 H, C1′-HH),

3.07 (virt. dt, ²J = 13.7 Hz, ³J ≅ 8.2 Hz, 1 H, C2′-HH), 2.93 (ddd, ²J = 13.7

Hz, ³J = 8.0 Hz, ³J = 4.7 Hz, 1 H, C2′-HH), 2.81 (dd, ³J = 12.2 Hz, ³J = 6.4

Hz, 1 H, C4a-H), 2.18–2.08 (m, 1 H, C4-HH), 1.99–1.84 (m, 2 H, C2-HH,

C3-HH), 1.67–1.53 (m, 1 H, C2-HH), 1.55–1.42 (m, 1 H, C3-HH), 1.32

[d, ³J = 6.1 Hz, 6 H, OCH(CH₃)₂], 1.32–1.27 (m, 1 H, C4-HH), 0.67 [s, 9 H,

SiC(CH₃)], –0.32 (s, 3 H, SiCH₃), –0.67 (s, 3 H, SiCH₃).

¹³C NMR (126 MHz, CDCl₃): δ = 175.1 (s, C5), 162.5 (s, C8), 156.8 (s,

C4′′), 141.0 (s, C12a), 132.7 (d, C11), 130.6 (s, C8a), 129.8 (d, C2′′, C6′′),

129.8 (s, C1′′), 128.0 (d, C9), 127.6 (d, C10), 125.8 (d, C12), 116.3 (d,

C3′′, C5′′), 77.7 (d, C1), 70.5 (d, C6a), 70.0 [d, OCH(CH₃)₂], 51.5 (t, C1′),

50.9 (s, C12b), 50.4 (d, C4a), 34.0 (t, C2′), 31.9 (t, C2), 26.6 (t, C4), 25.6

[q, SiC(CH₃)₃], 22.7 (t, C3), 22.03 [q, OCH(CH₃)₂], 17.7 [s, SiC(CH₃)₃],

–5.8 (q, SiCH₃).

A solution of the N-alkylated isoquinolone 12 (184 mg, 345 μmol,

1.00 equiv) in CH₂Cl₂(10 mL) was treated with NMO monohydrate

(140 mg, 1.04 mmol, 3.00 equiv) and aq 4% OsO₄(110 μL, 4.39 mg,

17.3 μmol, 0.05 equiv). The reaction mixture was stirred for 37 h at r.t.

The reaction was quenched by the addition of sat. aq Na₂S₂O₃(5 mL)

and stirred for 1 h. The solvents were removed in vacuo and the re-

maining residue was extracted with EtOAc (5 × 25 mL). The EtOAc

solution of the crude product was dried (Na₂SO₄) and filtered over a

short pad of silica gel. Removal of the solvent in vacuo furnished the

respective diol of modest purity. The crude diol (158 mg, 279 μmol,

1.00 equiv) was dissolved in acetone (16 mL) and treated with aq

NaIO₄(0.21 M, 179 mg, 837 μmol, 3.00 equiv). The reaction mixture

was stirred for 12 h at r.t. and then filtered through a short pad of

Celite. The solvent was removed in vacuo and the residue was redis-

solved in a mixture of EtOAc (40 mL) and H₂O (20 mL). The layers

were separated and the aqueous layer was extracted with EtOAc

(3 × 15 mL). The combined organic layers were washed with brine (20

mL), dried (Na₂SO₄), filtered, and the solvent was removed in vacuo.

The crude product was purified by flash chromatography [SiO₂,

2 × 20 cm, P–EtOAc, 5:1 (2% Et₃N)] to give 13 as a colorless resin;

yield: 97.6 mg (183 μmol, 53% over two steps); R_f= 0.83 [P–EtOAc, 5:1

(2% Et₃N)] [UV/CAM]. Due to the high reactivity of the cyclobutanone

only NMR spectra were recorded.

¹H NMR (500 MHz, CDCl₃): δ = 8.17 (dd, ³J = 7.9 Hz, ⁴J = 1.4 Hz, 1 H,

C8-H), 7.54 (virt. td, ³J ≅ 7.6 Hz, ⁴J = 1.4 Hz, 1 H, C10-H), 7.38 (virt. td,

³J ≅ 7.6 Hz, ⁴J = 1.2 Hz, 1 H, C9-H), 7.30 (dd, ³J = 7.8 Hz, ⁴J = 1.2 Hz, 1 H,

C11-H), 7.22 (virt. d, J = 8.5 Hz, 2 H, C2′′-H, C-6′′-H), 6.85 (virt. d, J =

8.5 Hz, 2 H, C3′′-H, C5′′-H), 5.07 (d, ⁴J = 2.3 Hz, 1 H, C5a-H), 4.52 [sept,

³J = 6.1 Hz, 1 H, OCH(CH₃)₂], 4.12 (dd, ³J = 10.5 Hz, ³J = 5.5 Hz, 1 H, C1-

H), 4.04 (ddd, ²J = 13.4 Hz, ³J = 10.3 Hz, ³J = 6.7 Hz, 1 H, C1′-HH), 3.45

(ddd, ²J = 13.4 Hz, ³J = 10.3 Hz, ³J = 6.7 Hz, 1 H, C1′-HH), 3.13 (virt. td,

³J₁≅ 10.0 Hz, ⁴J = 2.3 Hz, 1 H, C4a-H), 3.04–2.90 (m, 2 H, C2′-H₂), 2.13–

2.08 (m, 1 H, C4-HH), 2.09–2.00 (m, 1 H, C2-HH), 1.99–1.90 (m, 1 H,

C3-HH), 1.62–1.50 (m, 1 H, C2-HH), 1.51–1.40 (m, 2 H, C3-HH, C4-

HH), 1.33 [d, ³J = 6.1 Hz, 6 H, OCH(CH₃)₂], 0.67 [s, 9 H, SiC(CH₃)₃], –0.23

(s, 3 H, SiCH₃), –0.62 (s, 3 H, SiCH₃).

MS (ESI): m/z = 549 [(M + H)⁺].

HRMS (ESI): m/z [(M + H)⁺] calcd for C₃₂H₄₅N₂O₄Si: 549.3149;

found: 549.3145.

1-[(tert-Butyldimethylsilyl)oxy]-7-(4-isopropoxyphenethyl)-6-

methyl-2,3,4,4a,6a,7-hexahydroisoindolo[1,7a-c]isoquinoline-

5,8(1H,6H)-dione (15)

NaH (60% dispersion in mineral oil, 3.0 mg, 74.8 μmol, 1.20 equiv)

was added to a solution of γ-lactam 14 (34.2 mg, 62.3 μmol, 1.00

equiv) in DMF (2 mL) and the resulting suspension was stirred for

45 min. MeI (12 μL, 26.5 mg, 187 μmol, 3.00 equiv) was added and the

reaction mixture was stirred at r.t. for 13 h. Sat. aq NH₄Cl (10 mL), H₂O

(5 mL), Et₂O (20 mL) were added and the layers were separated. The

aqueous layer was extracted with Et₂O (3 × 20 mL). The combined or-

ganic layers were washed with brine (40 mL), dried (Na₂SO₄), filtered,

and the solvent was removed in vacuo. The crude product was puri-

fied by flash chromatography [SiO₂, 2 × 10 cm, EtOAc (2% Et₃N)] to

give the N-alkylated γ-lactam 15 as a colorless solid; yield: 32.5 mg

(57.7 μmol, 93%); mp 184 °C; R_f= 0.59 (P–EtOAc, 1:1) [UV/CAM].

¹³C NMR (126 MHz, CDCl₃): δ = 204.3 (s, C5), 161.6 (s, C7), 156.4 (s,

C4′′), 142.3 (s, C11a), 132.5 (d, C10), 131.0 (s, C7a), 129.8 (s, C1′′),

129.8 (d, C2′′, C6′′), 128.4 (d, C8), 127.7 (d, C9), 126.9 (d, C11), 115.9

(d, C3′′, C5′′), 76.0 (d, C1), 69.9 [d, OCH(CH₃)₂], 69.6 (d, C5a), 64.5 (d,

C4a), 49.8 (t, C1′), 41.4 (s, C11b), 33.6 (t, C2′), 31.2 (t, C2), 25.5 [q,

SiC(CH₃)₃], 23.3 (t, C4), 22.9 (t, C3), 22.1 [q, OCH(CH₃)₂], 17.6 [s,

SiC(CH₃)₃], –5.2 (s, SiCH₃), –5.8 (s, SiCH₃).

IR (ATR): 2930 (br s), 2857 (s), 1698 (s), 1653 (vs), 1508 (m), 1478 (m),

1462 (m), 1239 (s), 1089 (s), 835 cm^–1(s).

¹H NMR (360 MHz, CDCl₃): δ = 8.14 (dd, ³J = 7.8 Hz, ⁴J = 1.5 Hz, 1 H,

C9a-H), 7.54 (virt. td, ³J ≅ 7.8 Hz, ⁴J = 1.6 Hz, 1 H, C11-H), 7.43–7.33

(m, 2 H, C10-H, C12-H), 7.23–7.17 (m, 2 H, C2′′-H, C6′′-H), 6.94–6.81

(m, 2 H, C3′′-H, C5′′-H), 5.44 (s, 1 H, C6a-H), 4.62–4.52 (m, 1 H, C1′-

HH), 4.52 [sept, ³J = 6.1 Hz, 1 H, OCH(CH₃)₂], 3.87 (dd, ³J = 11.4 Hz, ³J =

A solution of the cyclobutanone 13 (97.6 mg, 183 μmol, 1.00 equiv) in

CH₂Cl₂(2 mL) was treated with a solution of MSH¹⁷(41.2 mg, 192

μmol, 1.05 equiv) in CH₂Cl₂(2 mL) at 0 °C (CAUTION! For precautions

when working with MSH, see the general remarks section and the lit-

erature^17b). The resulting mixture was stirred for 1 h at 0 °C whereup-

on the solvent was removed in vacuo at r.t. (!). The residue was redis-

solved in a mixture of benzene (3.6 mL) and MeOH (1.2 mL) and add-

ed to a suspension of activated basic Al₂O₃(activity I, 1.15 g) in MeOH

(3 mL). The suspension was stirred for 14 h and then filtered through

a pad of Celite. After removal of the solvents in vacuo, the crude prod-

uct was purified by flash chromatography [SiO₂, 3.5 × 15 cm, P–EtOAc,

1:1 (1% Et₃N) → 0:1 (1% Et₃N)] to give the γ-lactam 14 as a colorless

solid; yield. 92.8 mg (169 μmol, 92%); mp 210 °C; R_f= 0.59 [EtOAc (1%

Et₃N)] [UV/CAM].

3

4.5 Hz, 1 H, C1-H), 3.27–3.07 (m, 2 H, C1′-HH, C2′-HH), 2.96 (dd, J =

12.2 Hz, ³J = 6.3 Hz, 1 H, C4a-H), 2.92–2.83 (m, 1 H, C2′-HH), 2.70 (s, 3

H, NCH₃), 2.26–2.11 (m, 1 H, C4-HH), 2.10–1.92 (m, 2 H, C2-HH, C3-

HH), 1.71 (virt. qd, ²J ≅ ³J = 11.4 Hz, ³J = 2.7 Hz, 1 H, C2-HH), 1.63–1.47

3

(m, 1 H, C3-HH), 1.43–1.25 (m, 1 H, C4-HH), 1.33 [d, J = 6.1 Hz, 6 H,

OCH(CH₃)₂], 0.65 [s, 9 H, SiC(CH₃)₃], –0.37 [s, 3 H, Si(CH₃)(CH₃)], –0.47

[s, 3 H, Si(CH₃)(CH₃)].

¹³C NMR (91 MHz, CDCl₃): δ = 173.1 (s, C5), 162.9 (s, C8), 156.6 (s,

C4′′), 141.1 (s, C12a), 132.7 (d, C11), 130.5 (s, C2′′, C6′′), 129.9 (s, C1′′),

129.6 (s, C8a), 128.1 (d, C9), 127.6 (d, C10), 125.4 (d, C12), 116.0 (d,

C3′′, C5′′), 78.0 (d, C1), 73.2 (d, C6a), 69.9 [d, OCH(CH₃)₂], 51.4 (t, C1′),

2879

K.-H. Rimböck et al.

Paper

Synthesis

50.1 (d, C4a), 49.5 (s, C12b), 33.9 (t, C2′), 31.9 (t, C2), 26.3 (t, C4), 26.1

(q, NCH₃), 25.8 [q, SiC(CH₃)₃], 23.0 (t, C3), 22.1 [q, OCH(CH₃)₂], 18.0 [s,

SiC(CH₃)₃], –5.3 [q, Si(CH₃)(CH₃)], –5.7 [q, Si(CH₃)(CH₃)].

MS (ESI): m/z = 563 [(M + H)⁺].

HRMS (ESI): m/z [(M + H)⁺] calcd for C₃₃H₄₇N₂O₄Si: 563.3305;

found: 563.3301.

1-[(tert-Butyldimethylsilyl)oxy]-7-methoxy-2,3,4,4a-tetrahydro-

1H-benzo[2,3]cyclobuta[1,2-c]isoquinolin-5(5aH)-one (17)

A solution of the methyl imidate 16 (323 mg, 842 μmol, 1.00 equiv) in

CH₂Cl₂(24 mL) was treated with NMO monohydrate (341 mg, 2.53

mmol, 3.00 equiv) and aq 4% OsO₄(326 μL, 12.9 mg, 50.2 μmol, 0.06

equiv). The reaction mixture was stirred for 23 h at r.t. The reaction

was quenched by the addition of sat. aq Na₂S₂O₃(2 mL) and the re-

sulting mixture was stirred for 1 h. The solvents were removed in vac-

uo and the remaining residue was washed with CH₂Cl₂(3 × 30 mL)

and the combined CH₂Cl₂solution of the crude product was dried

(Na₂SO₄). Filtration and removal of the solvent in vacuo furnished the

respective crude diol. The crude diol was dissolved in acetone (10 mL)

and treated with aq NaIO₄(0.67 M, 360 mg, 1.68 mmol, 2.00 equiv).

The reaction mixture was stirred for 30 min at r.t. and then filtered

over a short pad of Celite. The solvent was removed in vacuo and the

residue was partitioned between CH₂Cl₂(100 mL) and brine (40 mL).

The layers were separated and the organic layer was washed with

brine (40 mL), dried (Na₂SO₄), filtered and the solvent was removed in

vacuo. The crude product was purified by flash chromatography

(SiO₂, 3.5 × 13 cm, P–EtOAc, 5:1) to give the cyclobutanone 17 as a

colorless resin; yield: 272 mg (705 μmol, 84%); R_f= 0.92 (CH₂Cl₂–

MeOH, 95:5) [UV/CAM].

X-ray Crystal Data³¹

Formula: C₃₃H₄₆N₂O₄Si; M_r= 562.81; crystal color and shape: colorless

fragment, crystal dimensions = 0.05 × 0.12 × 0.46 mm; crystal system:

orthorhombic; space group P b c a (no. 61); a = 13.8133(12), b =

9.9083(9), c = 46.649(4) Å; V = 6384.7(10) Å³; μ(Mo_Kα) = 0.111 mm^–1

;

ρ_calcd= 1.171 g cm^–3; θ-range = 1.71–25.34°; data collected: 15738;

independent data [I_o>2σ(I_o)/all data/R_int]: 3580/5754/0.0669; data/

restraints/parameters:

0.0567/0.1054; wR2 [I_o>2σ(I_o)/all data]: 0.1167/0.1359; GOF = 1.014;

Δρ_max/min: 0.38/–0.28 e Å^–3

5754/0/369;

R1

[I_o>2σ(I_o)/all

data]:

.

1-[(tert-Butyldimethylsilyl)oxy]-7-methoxy-5-methylene-

2,3,4,4a,5,5a-hexahydro-1H-benzo[2,3]cyclobuta[1,2-c]isoquino-

line (16)

Cs₂CO₃(8.39 g, 25.8 mmol, 25.0 equiv) was added to a solution of

[2+2] photocycloaddition product 7a (380 mg, 1.03 mmol, 1.00 equiv)

in CH₂Cl₂(30 mL) at 0 °C and the solution stirred for 5 min. Subse-

quently, Me₃OBF₄(762 mg, 5.15 mmol, 5.00 equiv) was added at 0 °C

in portions (ca. 100 mg every 2 min). After the addition was com-

plete, the reaction mixture was warmed to r.t. over 3.5 h. Ice-water

(80 mL) was added to quench the reaction. The layers were separated

and the aqueous layer was extracted with CH₂Cl₂(3 × 60 mL). The

combined organic layers were washed with brine (60 mL), dried

(Na₂SO₄), filtered, and the solvent was removed in vacuo. The crude

product was purified by flash chromatography (SiO₂, 3.5 × 10 cm, P–

EtOAc, 5:1) to give the methyl imidate 16 as a colorless resin; yield:

386 mg (1.01 mmol, 98%); R_f= 0.90 (P–EtOAc, 5:1) [UV/CAM].

IR (ATR): 2946 (vs), 2931 (vs), 2855 (s), 1783 (s), 1652 (s), 1462 (w),

1438 (w), 1313 (s), 1087 cm^–1(s).

¹H NMR (500 MHz, CDCl₃): δ = 7.74 (d, ³J = 7.8 Hz, 1 H, C8-H), 7.48

3

4

3

(virt. td, J ≅ 7.8 Hz, J = 1.3 Hz, 1 H, C10-H), 7.34 (d, J = 7.8 Hz, 1 H,

C11-H), 7.27 (virt. t, ³J ≅ 7.8 Hz, 1 H, C9-H), 5.64 (d, ⁴J = 1.6 Hz, 1 H,

C5a-H), 4.01 (dd, ³J = 10.9 Hz, ³J = 5.4 Hz, 1 H, C1-H), 3.85 (s, 3 H,

OCH₃), 3.15 (virt. td, ³J ≅ 10.2 Hz, ⁴J = 1.6 Hz, 1 H, C4a-H), 2.16–2.04

(m, 1 H, C4-HH), 1.99–1.85 (m, 2 H, C2-HH, C-3-HH), 1.69–1.37 (m, 3

H, C2-HH, C3-HH, C4-HH), 0.67 [s, 9 H, SiC(CH₃)₃], –0.20 [s, 3 H,

Si(CH₃)(CH₃)], –0.68 [s, 3 H, Si(CH₃)(CH₃)].

¹³C NMR (126 MHz, CDCl₃): δ = 207.3 (s, C5), 160.2 (s, C7), 143.5 (s,

C11a), 132.1 (d, C10), 127.7 (s, C7a), 127.3 (d, C8), 126.1 (d, C11),

124.9 (d, C9), 76.5 (d, C1), 71.3 (d, C5a), 66.7 (d, C4a), 53.2 (q, OCH₃),

39.4 (s, C11b), 30.9 (t, C2), 25.5 [q, SiC(CH₃)₃], 23.9 (t, C4), 23.0 (t, C3),

17.7 [s, SiC(CH₃)₃], –4.6 [q, Si(CH₃)(CH₃)], –6.1 [q, Si(CH₃)(CH₃)].

IR (ATR): 2930 (br vs), 2856 (s), 1658 (m), 1460 (w), 1438 (w), 1308

(w), 1255 (w), 1088 cm^–1(m).

¹H NMR (360 MHz, CDCl₃): δ = 7.71 (dd, ³J = 7.5 Hz, ⁴J = 1.3 Hz, 1 H,

C8-H), 7.45 (virt. td, ³J ≅ 7.5 Hz, ⁴J = 1.3 Hz, 1 H, C10-H), 7.27 (dd, ³J =

7.5 Hz, ⁴J = 1.2 Hz, 1 H, C11-H), 7.23 (virt. td, ³J ≅ 7.5 Hz, ⁴J = 1.2 Hz, 1

H, C9-H), 5.18 (virt. q, ²J ≅ ⁴J = 2.7 Hz, 1 H, C5=CHH), 4.86 (virt. t, ⁴J ≅

2.1 Hz, 1 H, C5a-H), 4.64 (dd, ²J = 2.7 Hz, ⁴J = 1.2 Hz, 1 H, C5=CHH),

3.85 (s, 3 H, OCH₃), 3.72 (dd, ³J = 11.0 Hz, ³J = 5.8 Hz, 1 H, C1-H), 2.85

(virt. t, ³J ≅ 9.1 Hz, 1 H, C4a-H), 2.16–2.05 (m, 1 H, C4-HH), 1.96–1.70

(m, 2 H, C2-HH, C3-HH) 1.56 (virt. qd, ²J ≅ ³J = 11.0 Hz, ³J = 2.5 Hz, 1 H,

C2-HH), 1.48–1.27 (m, 2 H, C3-HH, C4-HH), 0.66 [s, 9 H, SiC(CH₃)₃],

–0.23 [s, 3 H, Si(CH₃)(CH₃)], –0.72 [s, 3 H, Si(CH₃)(CH₃)].

¹³C NMR (126 MHz, CDCl₃): δ = 159.3 (s, C7), 155.0 (s, C5), 145.9 (s,

C7a), 131.5 (s, C11a), 127.5 (d, C10), 126.2 (d, C8), 125.9 (d, C11),

124.1 (d, C9), 103.1 (t, C5=CH₂), 76.9 (d, C1), 57.9 (d, C5a), 52.9 (s,

C11b), 52.2 (d, C4a), 43.9 (q, OCH₃), 31.4 (t, C2), 29.4 (t, C4), 25.4 [q,

SiC(CH₃)₃], 22.5 (t, C3), 17.5 [s, SiC(CH₃)₃], –4.8 [q, Si(CH₃)(CH₃)], –6.2

[q, Si(CH₃)(CH₃)].

MS (ESI): m/z = 386 [(M + H)⁺].

HRMS (ESI): m/z [(M

+

H)⁺] calcd for C₂₂H₃₂NO₃Si: 386.2152;

found: 386.2150.

1-[(tert-Butyldimethylsilyl)oxy]-6-methyl-5-methylene-

1,2,3,4,4a,5,5a,6-octahydro-7H-benzo[2,3]cyclobuta[1,2-c]iso-

quinolin-7-one (18a)

NaH (60% dispersion in mineral oil, 77.0 mg, 1.93 mmol, 1.57 equiv)

was added to a solution of [2+2] photocycloaddition product 7a (456

mg, 1.23 mmol, 1.00 equiv) in DMF (46 mL) and the resulting suspen-

sion was stirred for 45 min. MeI (278 μL, 631 mg, 4.44 mmol,

3.60 equiv) was added and the reaction mixture was stirred at r.t. for

18 h. Sat. aq NH₄Cl (30 mL), H₂O (10 mL), and Et₂O (50 mL) were add-

ed and the layers were separated. The aqueous layer was extracted

with Et₂O (3 × 50 mL). The combined organic layers were washed

with brine (30 mL), dried (Na₂SO₄), filtered, and the solvent was re-

moved in vacuo. The crude product was purified by flash chromatog-

raphy (SiO₂, 3.5 × 14 cm, P–EtOAc, 5:1) to afford the N-alkylated iso-

quinolone 18a as a colorless solid; yield: 414 mg (1.08 mmol, 88%);

mp 82 °C; R_f= 0.49 (P–EtOAc, 2:1) [UV/CAM].

MS (ESI): m/z = 384 [(M + H)⁺].

HRMS (ESI): m/z [(M

+

H)⁺] calcd for C₂₃H₃₄NO₂Si: 384.2359;

found: 384.2356.

IR (ATR): 2928 (vs), 2855 (s), 1651 (vs), 1089 (m), 835 cm^–1(w).

2880

K.-H. Rimböck et al.

Paper

Synthesis

¹H NMR (500 MHz, CDCl₃): δ = 8.13 (dd, ³J = 7.9 Hz, ⁴J = 1.5 Hz, 1 H,

C8-H), 7.49 (virt. td, ³J ≅ 7.6 Hz, ⁴J = 1.5 Hz, 1 H, C10-H), 7.31 (ddd, ³J ≅

7.9 Hz, ³J = 7.3, ⁴J = 1.2 Hz, 1 H, C9-H), 7.23 (dd, ³J = 7.6 Hz, ⁴J = 1.2 Hz,

1 H, C11-H), 4.87–4.83 (m, 1 H, C5-CHH), 4.70–4.63 (m, 1 H, C5-CHH),

4.62 (d, ⁴J = 2.4 Hz, 1 H, C5a-H), 3.82 (dd, ³J = 10.9 Hz, ³J = 5.9 Hz, 1 H,

C1-H), 3.24 (s, 3 H, NCH₃), 2.86–2.75 (m, 1 H, C4a-H), 2.20–2.07 (m, 1

H, C4-HH), 2.00–1.89 (m, 1 H, C2-HH), 1.85–1.77 (m, 1 H, C3-HH),

1.50 (m, 1 H, C2-HH), 1.41–1.27 (m, 2 H, C3-HH, C4-HH), 0.68 [s, 9 H,

SiC(CH₃)₃], –0.24 [s, 3 H, Si(CH₃)(CH₃)], –0.70 [s, 3 H, Si(CH₃)(CH₃)].

¹³C NMR (126 MHz, CDCl₃): δ = 162.8 (s, C7), 152.8 (s, C5), 145.1 (s,

C11a), 132.0 (d, C10), 127.7 (d, C8), 127.0 (d, C11), 126.8 (d, C9), 104.1

(t, C5=CH₂), 76.3 (d, C1), 59.7 (d, C5a), 51.0 (d, C4a), 46.3 (s, C11b),

35.4 (q, NCH₃), 32.1 (t, C2), 28.9 (t, C4), 25.6 [q, SiC(CH₃)₃], 22.5 (t, C3),

17.7 [s, SiC(CH₃)₃], –4.9 [q, Si(CH₃)(CH₃)], –5.8 [q, Si(CH₃)(CH₃)]; de-

spite prolonged acquisition time, the signal for carbon atom C7a was

not detected.

HRMS (ESI): m/z [(M

found: 386.2151.

+

H)⁺] calcd for C₂₂H₃₂NO₃Si: 386.2152;

1-[(tert-Butyldimethylsilyl)oxy]-7-methyl-2,3,4,4a,6a,7-hexahy-

droisoindolo[1,7a-c]isoquinoline-5,8(1H,6H)-dione (20a)

A solution of cyclobutanone 19a (64.6 mg, 168 μmol, 1.00 equiv) in

CH₂Cl₂(2 mL) was treated with a solution of MSH¹⁷(54.1 mg, 251

μmol, 1.50 equiv) in CH₂Cl₂(2 mL) at 0 °C (CAUTION! For precautions

when working with MSH, see the general remarks section and the lit-

erature^17b). The resulting mixture was stirred for 1 h at 0 °C whereup-

on the solvent was removed in vacuo at r.t. (!). The residue was redis-

solved in a mixture of benzene (2.4 mL) and MeOH (0.8 mL) and add-

ed to a suspension of activated basic Al₂O₃(activity I, 500 mg) in

MeOH (2 mL). The suspension was stirred for 19 h and then filtered

through a pad of Celite. After removal of the solvents in vacuo, the

crude product was purified by flash chromatography [SiO₂, 2 × 15 cm,

EtOAc (1% Et₃N)] to provide the γ-lactam 20a as a colorless resin;

yield: 64.6 mg (161 μmol, 96%); R_f= 0.42 (EtOAc) [UV/CAM].

MS (ESI): m/z = 384 [(M + H)⁺].

HRMS (ESI): m/z [(M

+

H)⁺] calcd for C₂₃H₃₄NO₂Si: 384.2359;

IR (ATR): 2926 (s), 2855 (m), 1714 (s), 1654 (vs), 1092 (m), 837 cm^–1

(w).

found: 384.2356.

¹H NMR (500 MHz, CDCl₃): δ = 8.13 (dd, ³J = 7.7 Hz, ⁴J = 1.5 Hz, 1 H,

C9-H) 7.54 (virt. td, ³J ≅ 7.9 Hz, ⁴J = 1.5 Hz, 1 H, C11-H), 7.37 (virt. td,

³J ≅ 7.7 Hz, ⁴J = 1.1 Hz, 1 H, C10-H), 7.33 (dd, ³J = 7.9 Hz, ⁴J = 1.1 Hz, 1

H, C12-H), 7.05 (s, 1 H, N6-H), 5.34 (s, 1 H, C6a-H), 3.80 (dd, ³J = 11.2

Hz, ³J = 4.6 Hz, 1 H, C1-H), 3.20 (s, 3 H, N7-CH₃), 2.87 (dd, ³J = 12.0 Hz,

³J = 6.5 Hz, 1 H, C4a-H), 2.22–2.15 (m, 1 H, C4-HH), 1.96–1.89 (m, 2 H,

C2-HH, C3-HH), 1.63–1.44 (m, 2 H, C2-HH, C3-HH), 1.39–1.30 (m, 1 H,

C4-HH), 0.67 [s, 9 H, SiC(CH₃)₃], –0.27 [s, 3 H, Si(CH₃)(CH₃)], –0.75 [s, 3

H, Si(CH₃)(CH₃)].

¹³C NMR (126 MHz, CDCl₃): δ = 175.7 (s, C5), 162.7 (s, C8), 141.5 (s,

C12a), 132.9 (d, C11), 129.4 (s, C8a), 128.2 (d, C9), 127.8 (d, C10),

126.2 (d, C12), 77.9 (d, C1), 71.0 (d, C6a), 51.0 (d, C4a), 50.8 (s, C12b),

35.4 (q, N7-CH₃), 32.1 (t, C2), 27.1 (t, C4), 25.7 [q, SiC(CH₃)₃], 22.7 (t,

C3), 17.7 [s, SiC(CH₃)₃], –5.4 (q, SiCH₃), –5.9 [q, Si(CH₃)(CH₃)].

1-[(tert-Butyldimethylsilyl)oxy]-6-methyl-2,3,4,4a,5a,6-hexahy-

dro-1H-benzo[2,3]cyclobuta[1,2-c]isoquinoline-5,7-dione (19a)

A solution of the N-alkylated isoquinolone 18a (296 mg, 772 μmol,

1.00 equiv) in CH₂Cl₂(20 mL) was treated with NMO monohydrate

(320 mg, 2.37 mmol, 3.08 equiv) and aq 4% OsO₄(256 μL, 10.2 mg,

40.1 μmol, 0.05 equiv). The reaction mixture was stirred for 16 h at r.t.

The reaction was quenched by the addition of sat. aq Na₂S₂O₃(1 mL)

and the resulting mixture was stirred for 1 h. The solvents were re-

moved in vacuo and the remaining residue was washed with CH₂Cl₂

(75 mL). The CH₂Cl₂solution of the crude product was dried (Na₂SO₄),

filtered, and the solvent was removed in vacuo to furnish the respec-

tive crude diol. The crude diol was dissolved in acetone (48 mL) and

treated with aq NaIO₄(0.20 M, 522 mg, 2.44 mmol, 3.17 equiv). The

reaction mixture was stirred for 2 h at r.t. and then filtered over a

short pad of Celite. The solvent was removed in vacuo and the residue

was partitioned between EtOAc (150 mL) and brine (40 mL). The lay-

ers were separated and the organic layer was washed with brine (40

mL), dried (Na₂SO₄), filtered, and the solvent was removed in vacuo.

The crude product was purified by flash chromatography (SiO₂,

3.5 × 15 cm, P–EtOAc, 4:1) to give the cyclobutanone 19a as a color-

less solid; yield: 192 mg (790 μmol, 65%); mp 127 °C; R_f= 0.96 (P–

EtOAc, 1:1) [UV/CAM].

MS (ESI): m/z = 401 [(M + H)⁺].

HRMS (ESI): m/z [(M + H)⁺] calcd for C₂₂H₃₂N₂O₃Si: 401.2260;

found: 401.2257.

1-[(tert-Butyldimethylsilyl)oxy]-6,7-dimethyl-2,3,4,4a,6a,7-hexa-

hydroisoindolo[1,7a-c]isoquinoline-5,8(1H,6H)-dione (21a)

By Methylation of γ-Lactam 20a

IR (ATR): 2929 (s), 2856 (s), 1786 (vs), 1651 (vs), 1253 (m), 834 cm^–1

(w).

NaH (60% dispersion in mineral oil, 9.5 mg, 239 μmol, 1.64 equiv) was

added to a solution of γ-lactam 20a (58.5 mg, 146 μmol, 1.00 equiv)

in DMF (6 mL) and the resulting suspension was stirred for 45 min.

MeI (40.0 μL, 90.8 mg, 640 μmol, 4.38 equiv) was added and the reac-

tion mixture was stirred at r.t. for 19 h. Sat. aq NH₄Cl (10 mL), H₂O (5

mL), and Et₂O (20 mL) were added, and the layers were separated. The

aqueous layer was extracted with Et₂O (3 × 20 mL). The combined or-

ganic layers were washed with brine (40 mL), dried (Na₂SO₄), filtered,

and the solvent was removed in vacuo. The crude product was puri-

fied by flash chromatography (SiO₂, 2 × 15 cm, EtOAc) to give the N-

alkylated γ-lactam 21a as a colorless resin; yield: 48.8 mg (118 μmol,

81%).

¹H NMR (500 MHz, CDCl₃): δ = 8.14 (dd, ³J = 7.8 Hz, ⁴J = 1.4 Hz, 1 H,

C8-H), 7.54 (virt. td, ³J ≅ 7.8 Hz, ⁴J = 1.4 Hz, 1 H, C10-H), 7.37 (virt. td,

³J ≅ 7.8 Hz, ⁴J = 1.2 Hz, 1 H, C9-H), 7.29 (dd, ³J = 7.8 Hz, ⁴J = 1.2 Hz, 1 H,

C11-H), 4.99 (d, ⁴J = 2.3 Hz, 1 H, C5a-H), 4.09 (dd, ³J = 10.7 Hz, ³J = 5.7

Hz, 1 H, C1-H), 3.23 (s, 3 H, NCH₃), 3.13 (virt. td, ³J ≅ 9.9 Hz, ⁴J = 2.3 Hz,

1 H, C4a-H), 2.14–2.07 (m, 1 H, C4-HH), 2.07–2.00 (m, 1 H, C2-HH),

1.96–1.91 (m, 1 H, C3-HH), 1.58–1.50 (m, 1 H, C2-HH), 1.50–1.43 (m,

2

H, C3-HH, C4-HH), 0.68 [s,

9 H, SiC(CH₃)₃], –0.20 [s, 3 H,

Si(CH₃)(CH₃)], –0.68 [s, 3 H, Si(CH₃)(CH₃)].

¹³C NMR (126 MHz, CDCl₃): δ = 204.8 (s, C5), 162.1 (s, C7), 142.6 (s,

C11a), 132.7 (d, C10), 129.7 (s, C7a), 128.4 (d, C8), 127.8 (d, C11),

127.1 (d, C9), 75.9 (d, C1), 70.6 (d, C5a), 65.0 (d, C4a), 41.5 (s, C11b),

35.4 (q, NCH₃), 31.4 (t, C2), 25.6 [q, SiC(CH₃)₃], 23.4 (t, C4), 22.9 (t, C3),

17.7 [s, SiC(CH₃)₃], –4.9 [q, Si(CH₃)(CH₃)], –5.9 [q, Si(CH₃)(CH₃)].

By the Photochemical Beckmann Rearrangement of Cyclobuta-

none 19a via Oxaziridine 23

A solution of cyclobutanone 19a (30.0 mg, 77.8 μmol, 1.00 equiv) in

CH₂Cl₂(5 mL) over activated molecular sieves (3Å, 300 mg) was treat-

ed with MeNH₂(2.0 M in THF, 470 μL, 29.0 mg, 934 μmol, 12.0 equiv).

MS (ESI): m/z = 386 [(M + H)⁺].

2881

K.-H. Rimböck et al.

Paper

Synthesis

The resulting mixture was stirred for 23 h at 40 °C. Upon cooling to

r.t., the reaction mixture was filtered over a short pad of Celite under

argon atmosphere. The solvents were removed in vacuo. The residue

was redissolved in CH₂Cl₂(3 mL) and cooled to –40 °C. A suspension

of m-CPBA (70%, 20.1 mg, 81.7 mg, 1.05 equiv) and MgSO₄(60 mg) in

CH₂Cl₂(2 mL) was filtered via a syringe filter to remove the solid com-

ponents. The obtained solution of the dried peracid was also cooled

down to –40 °C. Under exclusion of light (!), the MeNH₂solution was

added dropwise to the solution of the peracid in CH₂Cl₂. After the ad-

dition was complete, the reaction mixture was stirred for 20 h at

–40 °C under exclusion of light (!). Under an argon atmosphere, the

mixture was quickly transferred into a photo tube and irradiated (λ =

300 nm) at r.t. for 8 h. After removal of the solvent in vacuo, the crude

product was purified by flash chromatography (SiO₂, 2 × 13 cm, P–

EtOAc, 2:1 → 1:1 → 0:1) to give the γ-lactam 21a as a colorless resin;

yield: 17.1 mg (41.2 μmol, 53%); R_f= 0.46 (EtOAc) [UV/CAM].

¹³C NMR (126 MHz, CDCl₃): δ = 174.2 (s, CO₂CH₃), 162.4 (s, C1), 135.1

(s, C4a), 131.9 (d, C6), 130.0 (d, C7), 128.5 (d, C5), 126.7 (d, C8), 126.1

(s, C8a), 122.9 (d, C3), 119.3 (s, C4), 71.1 (d, C1′), 51.6 (q, CO₂CH₃), 38.7

(t, C2′), 37.3 (q, NCH₃), 34.1 (t, C5′), 25.9 [q, SiC(CH₃)₃], 25.4 (t, C3′),

24.9 (t, C4′), 18.3 [s, SiC(CH₃)₃], –4.5 [q, Si(CH₃)(CH₃)], –4.9 (q,

Si(CH₃)(CH₃)].

MS (ESI): m/z = 418 [(M + H)⁺].

HRMS (ESI): m/z [(M

+

H)⁺] calcd for C₂₃H₃₆NO₄Si: 418.2414;

found: 418.2407.

Acetal 25

Acetal 25 was contaminated with unseparable traces of lactone 22a

and starting material 19a; yield: 4.31 mg (10.3 μmol, 12%); R_f= 0.77

(P–EtOAc, 1:1) [UV/CAM].

IR (ATR): 2929 (s), 2856 (s), 1786 (vs), 1651 (vs), 1253 (m), 834 cm^–1

(w).

IR (ATR): 2948 (s), 2929 (s), 2857 (m), 1699 (s), 1654 (vs), 1091 (m),

836 cm^–1(m).

¹H NMR (500 MHz, CDCl₃): δ = 8.15 (dd, ³J = 7.8 Hz, ⁴J = 1.5 Hz, 1 H,

C9-H), 7.51 (virt. td, ³J ≅ 7.6 Hz, ⁴J = 1.5 Hz, 1 H, C11-H), 7.34–7.27 (m,

2 H, C10-H, C12-H), 5.53 (s, 1 H, C6a-H), 4.53 (s, 1 H, C5-H), 3.91 (dd,

³J = 11.1 Hz, ³J = 4.7 Hz, 1 H, C1-H), 3.28 (s, 3 H, NCH₃), 2.88 (s, 3 H,

OCH₃), 2.72 (dd, ³J = 12.5 Hz, ³J = 6.3 Hz, 1 H, C4a-H), 1.96–1.90 (m, 1

H, C4-HH), 1.89–1.84 (m, 2 H, C2-HH, C3-HH), 1.52–1.41 (m, 1 H, C2-

HH, C3-HH), 1.31–1.20 (m, 1 H, C4-HH), 0.65 [s, 9 H, SiC(CH₃)₃], –0.25

[s, 3 H, Si(CH₃)(CH₃)], –0.80 [s, 3 H, Si(CH₃)(CH₃)].

¹³C NMR (126 MHz, CDCl₃): δ = 162.9 (s, C8), 144.5 (s, C12a), 132.1 (d,

C11), 128.4 (s, C8a), 127.6 (d, C9), 126.4 (d, C10), 125.5 (d, C12), 107.7

(d, C5), 91.7 (d, C6a), 78.7 (d, C1), 54.0 (q, OCH₃), 53.5 (d, C4a), 50.0 (s,

12b), 34.9 (NCH₃), 31.5 (t, C2), 26.9 (t, C4), 25.6 [s, SiC(CH₃)₃], 22.4 (t,

C3), 17.6 [s, SiC(CH₃)₃], –5.1 [q, Si(CH₃)(CH₃)], –6.1 [q, Si(CH₃)(CH₃)].

¹H NMR (500 MHz, CDCl₃): δ = 8.11 (dd, ³J = 7.8 Hz, ⁴J = 1.5 Hz, 1 H,

C9-H), 7.53 (virt. td, ³J = 7.6 Hz, ⁴J = 1.5 Hz, 1 H, C11-H), 7.39–7.32 (m,

2 H, C10-H, C12-H), 5.21 (s, 1 H, C6a-H), 3.84 (dd, ³J = 11.1 Hz, ³J = 4.7

Hz, 1 H, C1-H), 3.34 (s, 3 H, N7-CH₃), 2.97–2.91 (m, 1 H, C4a-H), 2.76

(s, 3 H, N6-CH₃), 2.23–2.14 (m, 1 H, C4-HH), 1.99–1.88 (m, 2 H, C2-

HH, C3-HH), 1.70–1.45 (m, 2 H, C2-HH, C3-HH), 1.29–1.18 (m, 1 H,

C4-HH), 0.69 [s, 9 H, SiC(CH₃)₃], –0.28 [s, 3 H, Si(CH₃)(CH₃)], –0.70 [s, 3

H, Si(CH₃)(CH₃)].

¹³C NMR (126 MHz, CDCl₃): δ = 173.4 (s, C5), 163.3 (s, C8), 141.8 (s,

C12a), 132.9 (d, C11), 129.6 (s, C8a), 128.1 (d, C9), 127.7 (d, C10),

125.8 (d, C12), 77.8 (d, C1), 75.7 (d, C6a), 50.5 (d, C4a), 49.3 (s, C12b),

37.0 (q, N7-CH₃), 32.3 (t, C2), 26.7 (t, C4), 26.5 (q, N6-CH₃), 25.8 [q,

SiC(CH₃)₃], 22.8 (t, C3), 17.8 [s, SiC(CH₃)₃], –5.6 [q, Si(CH₃)(CH₃)], –5.7

[q, Si(CH₃)(CH₃)].

MS (ESI): m/z = 418 [(M + H)⁺].

HRMS (ESI): m/z [(M

+

H)⁺] calcd for C₂₃H₃₆NO₄Si: 418.2414;

MS (ESI): m/z = 415 [(M + H)⁺].

HRMS (ESI): m/z [(M + H)⁺] calcd for C₂₃H₃₅N₂O₃Si: 415.2417;

found: 418.2411.

found: 415.2418.

1-[(tert-Butyldimethylsilyl)oxy]-7-methyl-2,3,4,4a,6a,7-hexahy-

dro-8H-isobenzofuro[1,7a-c]isoquinoline-5,8(1H)-dione (22a)

Methyl 6-[(tert-Butyldimethylsilyl)oxy]-6-(2-methyl-1-oxo-1,2-di-

hydroisoquinolin-4-yl)hexanoate (24) and 1-[(tert-Butyldimethyl-

silyl)oxy]-5-methoxy-7-methyl-1,2,3,4,4a,5,6a,7-octahydro-8H-

isobenzofuro[1,7a-c]isoquinolin-8-one (25)

A solution of cyclobutanone 19a (30.0 mg, 77.8 μmol, 1.00 equiv) in

CH₂Cl₂(2 mL) was treated with NaHCO₃(13.1 mg, 156 μmol, 2.00

equiv). The mixture was cooled to 0 °C and m-CPBA (70%, 38.4 mg,

156 μmol, 2.00 equiv) was added in one portion. The reaction mixture

was stirred for 2 h at 0 °C. Sat. aq NaHCO₃(10 mL) and EtOAc (30 mL)

were added and the layers were separated. The organic layer was

washed with brine (10 mL), dried (Na₂SO₄), filtered, and the solvent

was removed in vacuo. The crude product was purified by flash chro-

matography (SiO₂, 2 × 7 cm, P–EtOAc, 1:1) to give the lactone 22a as a

colorless solid; yield: 30.3 mg (75.5 μmol, 97%); mp 181 °C; R_f= 0.20

(P–EtOAc, 4:1) [UV/CAM].

A solution of cyclobutanone 19a (32.6 mg, 84.6 μmol) in anhydrous

MeOH (16 mL) was purged with argon in an ultrasound bath for 15

min. After irradiation (λ = 300 nm) at r.t. for 4 h, the solvent was re-

moved in vacuo. The crude product was purified by flash chromatog-

raphy (SiO₂, 2 × 14 cm, P–EtOAc, 3:1) to provide the methyl ester 24

and acetal 25 as colorless resins.

Methyl Ester 24

IR (ATR): 2949 (vs), 2930 (s), 2857 (m), 1773 (vs), 1664 (vs), 1095 (w),

836 cm^–1(w).

Yield: 18.1 mg (43.3 μmol, 52%); R_f= 0.46 (EtOAc) [UV/CAM].

¹H NMR (500 MHz, CDCl₃): δ = 8.18 (dd, ³J = 7.8 Hz, ⁴J = 1.5 Hz, 1 H,

C9-H), 7.59 (virt. td, ³J ≅ 7.7 Hz, ⁴J = 1.5 Hz, 1 H, C11-H), 7.42 (virt. td,

³J ≅ 7.8 Hz, ⁴J = 1.1 Hz, 1 H, C10-H), 7.32 (dd, ³J = 7.7 Hz, ⁴J = 1.1 Hz, 1

H, C12-H), 5.96 (s, 1 H, C6a-H), 3.85 (dd, ³J = 11.1 Hz, ³J = 4.8 Hz, 1 H,

C1-H), 3.31 (s, 3 H, NCH₃), 3.17–3.11 (m, 1 H, C4a-H), 2.34–2.16 (m, 1

H, C4-HH), 2.09–1.91 (m, 2 H, C2-HH, C3-HH), 1.69–1.48 (m, 3 H, C2-

IR (ATR): 2950 (s), 2928 (s), 2855 (m), 1737 (s), 1653 (vs), 1631 (s),

1604 (m), 1253 (m), 1094 (m), 1074 (m), 835 (s), 773 (s), 700 cm^–1

(m).

¹H NMR (500 MHz, CDCl₃): δ = 8.48 (dd, ³J = 8.0 Hz, ⁴J = 1.5 Hz, 1 H,

C8-H), 7.77 (d, ³J = 8.3 Hz, 1 H, C5-H), 7.64 (ddd, ³J = 8.3 Hz, ³J = 7.0 Hz,

⁴J = 1.5 Hz, 1 H, C6-H), 7.48 (ddd, ³J = 8.0 Hz, ³J = 7.0 Hz, ⁴J = 1.1 Hz, 1

H, C7-H), 7.10 (s, 1 H, C3-H), 4.89 (t, ³J = 6.1 Hz, 1 H, C1′-H), 3.63 (s, 3

HH, C3-HH, C4-HH), 0.68 [s,

9 H, SiC(CH₃)₃], –0.24 [s, 3 H,

Si(CH₃)(CH₃)], –0.75 [s, 3 H, Si(CH₃)(CH₃)].

3

H, CO₂CH₃), 3.60 (s, 3 H, NCH₃), 2.29 (t, J = 7.4 Hz, 2 H, C5′-H₂), 1.80

(virt. td, ³J₁≅ 8.1 Hz, ³J₂= 6.1 Hz, 2 H, C2′-H₂), 1.70–1.55 (m, 2 H, C4′-

H₂), 1.48–1.34 (m, 2 H, C3′-H₂), 0.89 [s, 9 H, SiC(CH₃)₃], 0.07 [s, 3 H,

Si(CH₃)(CH₃)], –0.11 [s, 3 H, Si(CH₃)(CH₃)].

2882

K.-H. Rimböck et al.

Paper

Synthesis

¹³C NMR (126 MHz, CDCl₃): δ = 174.4 (s, C5), 162.7 (s, C8), 139.8 (s,

C12a), 133.2 (d, C11), 129.1 (s, C8a), 128.5 (d, C9), 128.3 (d, C10),

125.9 (d, C12), 91.5 (d, C6a), 77.3 (d, C1), 50.2 (d, C4a), 50.0 (s, C12b),

35.4 (q, NCH₃), 31.8 (t, C2), 26.0 (t, C4), 25.6 [q, SiC(CH₃)₃], 22.8 (t, C3),

17.6 [s, SiC(CH₃)₃], –5.3 [q, Si(CH₃)(CH₃)], –6.0 [q, Si(CH₃)(CH₃)].

1-[(tert-Butyldimethylsilyl)oxy]-6-methyl-2,3,4,4a,5a,6-hexahy-

dro-1H-benzo[2,3]cyclobuta[1,2-c][1,3]dioxolo[4,5-g]isoquino-

line-5,7-dione (19b) and 1-[(tert-Butyldimethylsilyl)oxy]-7-

methyl-2,3,4,4a,6a,7-hexahydro-8H-[1,3]dioxolo[4,5-g]isobenzo-

furo[1,7a-c]isoquinoline-5,8(1H)-dione (22b)

MS (ESI): m/z = 402 [(M + H)⁺].

A solution of the N-alkylated isoquinolone 19a (43.0 mg, 101 μmol,

1.00 equiv) in CH₂Cl₂(2 mL) was treated with NMO monohydrate

(40.7 mg, 301 mmol, 2.98 equiv) and aq 4% OsO₄(32 μL, 1.29 mg, 5.07

μmol, 0.05 equiv). The reaction mixture was stirred for 20 h at r.t. The

reaction was quenched by the addition of sat. aq Na₂S₂O₃(1 mL) and

the resulting mixture was stirred for 1 h. The solvents were removed

in vacuo and the remaining residue was washed with CH₂Cl₂(50 mL)

and the CH₂Cl₂solution was dried (Na₂SO₄). Filtration and removal of

the solvent in vacuo furnished the respective crude diol. The crude

diol was dissolved in acetone (6 mL) and treated with aq NaIO₄(210

mM, 67.3 mg, 315 μmol, 3.12 equiv). The reaction mixture was stirred

for 45 min at r.t. and then filtered over a short pad of Celite. The sol-

vent was removed in vacuo and the residue was partitioned between

EtOAc (30 mL) and brine (20 mL). The layers were separated and the

organic layer was washed with brine (20 mL), dried (Na₂SO₄), and the

solvent was removed in vacuo. The crude product was purified by

flash chromatography (SiO₂, 2 × 15 cm, P–EtOAc, 4:1) to give the cy-

clobutanone 19b and the lactone 22b as colorless resins.

HRMS (ESI): m/z [(M

+

H)⁺] calcd for C₂₂H₃₂NO₄Si: 402.2100;

found: 402.2097.

X-ray Crystal Data³¹

Formula: C₂₂H₃₁NO₄Si; M_r= 401.57; crystal color and shape: yellow

fragment, crystal dimensions = 0.43 × 0.59 × 0.70 mm; crystal system:

monoclinic; space group P 2₁/n (no. 14); a = 11.3546(5), b =

15.6564(6), c = 12.5518(5) Å, β = 99.562(2)°; V = 2200.36(16) Å³;

μ(Mo_Kα) = 0.133 mm^–1; ρ_calcd=1.212 g cm^–3; θ-range = 2.10–25.40°;

data collected: 46842; independent data [I_o>2σ(I_o)/all data/R_int]:

3576/4038/0.0311; data/restraints/parameters: 4038/0/259; R1

[I_o>2σ(I_o)/all data]: 0.0402/0.0474; wR2 [I_o>2σ(I_o)/all data]:

0.1005/0.1060; GOF = 1.049; Δρ_max/min: 0.72/–0.22 e Å^–3

.

1-[(tert-Butyldimethylsilyl)oxy]-6-methyl-5-methylene-

1,2,3,4,4a,5,5a,6-octahydro-7H-benzo[2,3]cyclobuta[1,2-c][1,3]di-

oxolo[4,5-g]isoquinolin-7-one (18b)

NaH (60% dispersion in mineral oil, 11.6 mg, 290 μmol, 1.20 equiv)

was added to a solution of [2+2] photocycloaddition product 7b ((100

mg, 242 μmol, 1.00 equiv) in DMF (9 mL) and the resulting suspension

was stirred for 45 min. MeI (53.7 μL, 122 mg, 208.12 μmol,

3.60 equiv) was added and the reaction mixture was stirred at r.t. for

19 h. Sat. aq NH₄Cl (10 mL), H₂O (5 mL) and Et₂O (20 mL) were added

and the layers were separated. The aqueous layer was extracted with

diethyl ether (3 × 20 mL). The combined organic layers were washed

with brine (30 mL), dried (Na₂SO₄), filtered, and the solvent was re-

moved in vacuo. The crude product was purified by flash chromatog-

raphy (SiO₂, 3.5 × 12 cm, P–EtOAc, 5:1) to give the N-alkylated iso-

quinolone 18b as a colorless resin; yield: 43.0 mg (101 μmol, 42%);

R_f= 0.39 (P–EtOAc, 5:1) [UV/CAM].

Cyclobutanone 19b

Yield: 20.4 mg (52.2 μmol, 52%); R_f= 0.84 (CH₂Cl₂–MeOH, 95:5)

[UV/CAM].

IR (ATR): 2929 (s), 2857 (s), 1786 (vs), 1650 (vs), 1474 (vs), 1268 (s),

1249 (m), 1088 (m), 1038 (m), 839 (m), 775 cm^–1(w).

¹H NMR (500 MHz, CDCl₃): δ = 7.57 (s, 1 H, C8-H), 6.66 (s, 1 H, C12-H),

6.02 (d, ²J = 1.3 Hz, 1 H, OCHHO), 5.99 (d, ²J = 1.3 Hz, 1 H, OCHHO),

4.92 (d, ⁴J = 2.3 Hz, 1 H, C5a-H), 4.04 (dd, ³J = 10.8 Hz, ³J = 5.8 Hz, 1 H,

C1-H), 3.18 (s, 3 H, NCH₃), 3.07 (virt. td, ³J ≅ 10.1 Hz, ⁴J = 2.3 Hz, 1 H,

C4a-H), 2.12–2.05 (m, 1 H, C4-HH), 2.05–1.99 (m, 1 H, C2-HH), 1.94–

1.88 (m, 1 H, C3-HH), 1.58–1.48 (m, 1 H, C2-HH), 1.45–1.38 (m, 2 H,

C3-HH, C4-HH), 0.71 [s, 9 H, SiC(CH₃)₃], –0.15 [s, 3 H, Si(CH₃)(CH₃)],

–0.53 [s, 3 H, Si(CH₃)(CH₃)].

¹³C NMR (126 MHz, CDCl₃): δ = 205.0 (s, C5), 161.8 (s, C7), 151.4 (s,

C11a), 147.6 (s, C8a), 137.7 (s, 12a), 124.5 (s, C7a), 107.8 (d, C8), 106.1

(d, C12), 101.9 (t, OCH₂O), 75.4 (d, C1), 70.4 (d, C5a), 65.0 (d, C4a),

41.8 (s, 12b), 35.3 (q, NCH₃), 31.4 (t, C2), 25.6 [q, SiC(CH₃)₃], 23.4 (t,

C4), 22.8 (t, C3), 17.7 [s, SiC(CH₃)₃], –4.9 [q, Si(CH₃)(CH₃)], –5.6 [q,

Si(CH₃)(CH₃)].

IR (ATR): 2929 (vs), 2856 (s), 1648 (vs), 1473 (vs), 1268 (m), 1247 (m),

836 cm^–1(w).

¹H NMR (500 MHz, CDCl₃): δ = 7.57 (s, 1 H, C8-H), 6.62 (s, 1 H, C12-H),

6.01 (d, ²J = 1.5 Hz, 1 H, OCHHO), 5.98 (d, ²J = 1.5 Hz, 1 H, OCHHO),

4.88–4.83 (m, 1 H, C5-CHH), 4.70 (dd, ²J = 1.2 Hz, ⁴J = 2.4 Hz, 1 H, C5-

4

3

CHH), 4.56 (d, J = 2.4 Hz, 1 H, C5a-H), 3.73 (dd, J = 10.9 Hz, J = 5.9

Hz, 1 H, C1-H), 3.20 (s, 3 H, NCH₃), 2.82–2.69 (m, 1 H, C4a-H), 2.15–

2.06 (m, 1 H, C4-HH), 1.97–1.88 (m, 1 H, C2-HH), 1.82–1.74 (m, 1 H,

C3-HH), 1.52–1.40 (m, 1 H, C2-HH), 1.37–1.20 (m, 2 H, C3-HH, C4-

HH), 0.69 [s, 9 H, SiC(CH₃)₃], –0.20 [s, 3 H, Si(CH₃)(CH₃)], –0.60 [s, 3 H,

Si(CH₃)(CH₃)].

MS (ESI): m/z = 430 [(M + H)⁺].

HRMS (ESI): m/z [(M

found: 430.2048.

+

H)⁺] calcd for C₂₃H₃₂NO₅Si: 430.2050;

¹³C NMR (126 MHz, CDCl₃): δ = 162.4 (s, C7), 152.7 (s, C11a), 150.8 (s,

C5), 146.8 (s, C8a), 140.2 (s, C12a), 124.6 (s, C7a), 107.4 (d, C8), 106.3

(d, C12), 104.1 (t, C5=CH₂), 101.6 (t, OCH₂O), 75.8 (d, C1), 59.5 (d, C5a),

50.9 (d, C4a), 46.5 (s, C12b), 35.4 (q, NCH₃), 32.0 (t, C2), 28.9 (t, C4),

25.6 [q, SiC(CH₃)₃], 22.4 (t, C3), 17.7 [s, SiC(CH₃)₃], –4.9 [q,

Si(CH₃)(CH₃)], –5.6 [q, Si(CH₃)(CH₃)].

Lactone 22b

Yield: 13.3 mg (29.8 μmol, 30%); R_f= 0.77 (CH₂Cl₂–MeOH, 95:5)

[UV/CAM].

IR (ATR): 2929 (s), 2857 (s), 1774 (s), 1660 (s), 1479 (vs), 1286 (m),

1256 (s), 1088 (m), 1038 (m), 837 (m), 776 cm^–1(w).

¹H NMR (500 MHz, CDCl₃): δ = 7.59 (s, 1 H, C9-H), 6.70 (s, 1 H, C13-H),

6.04 (d, ²J = 1.3 Hz, 1 H, OCHHO), 6.02 (d, J = 1.3 Hz, 1 H, OCHHO), 5.91

(s, 1 H, C6a-H), 3.80 (dd, ³J = 11.1 Hz, ³J = 4.8 Hz, 1 H, C1-H), 3.27 (s, 3

H, NCH₃), 3.02 (dd, ³J = 11.6 Hz, ³J = 6.9 Hz, 1 H, C4a-H), 2.27–2.17 (m,

1 H, C4-HH), 2.03–1.92 (m, 1 H, C2-HH), 1.64–1.59 (m, 1 H, C3-HH),

1.55–1.45 (m, 1 H, C2-HH), 1.38–1.17 (m, 2 H, C3-HH, C4-HH), 0.70 [s,

MS (ESI): m/z = 428 [(M + H)⁺].

HRMS (ESI): m/z [(M

+

H)⁺] calcd for C₂₄H₃₄NO₄Si: 428.2257;

found: 428.2257.

9

H, SiC(CH₃)₃], –0.19 [s,

3 H, Si(CH₃)(CH₃)], –0.61 [s, 3 H,

Si(CH₃)(CH₃)].

2883

K.-H. Rimböck et al.

Paper

Synthesis

¹³C NMR (126 MHz, CDCl₃): δ = 174.4 (s, C5), 162.2 (s, C8), 151.9 (s,

C12a), 147.9 (s, C9a), 135.0 (s, C13a), 124.0 (s, C8a), 107.9 (d, C9),

105.3 (d, C13), 102.1 (t, OCH₂O), 91.7 (d, C6a), 76.7 (d, C1), 50.5 (s,

C13b), 50.2 (d, C4a), 35.3 (q, NCH₃), 31.8 (t, C2), 26.1 (t, C4), 25.6 [q,

SiC(CH₃)₃], 22.7 (t, C3), 17.6 [s, SiC(CH₃)₃], –5.2 [q, Si(CH₃)(CH₃)], –5.7

[q, Si(CH₃)(CH₃)].

(Na₂SO₄), filtered, and the solvent was removed in vacuo. The crude

product was purified by flash chromatography (SiO₂, 2 × 10 cm,

EtOAc) to give the N-alkylated γ-lactam 21b as a colorless resin; yield:

8.0 mg (17.4 μmol, 62%); R_f= 0.37 (P–EtOAc, 1:1) [UV/CAM].

IR (ATR): 2929 (s), 2857 (s), 1698 (s), 1651 (vs), 1479 (vs), 1286 (m),

1252 (s), 1088 (m), 1038 (m), 836 (m), 776 cm^–1(w).

MS (ESI): m/z = 446 [(M + H)⁺].

¹H NMR (500 MHz, CDCl₃): δ = 7.54 (s, 1 H, C9-H), 6.74 (s, 1 H, C13-H),

6.02 (d, ²J = 1.4 Hz, 1 H, OCHHO), 5.98 (d, ²J = 1.4 Hz, 1 H, OCHHO),

5.17 (s, 1 H, C6a-H), 3.78 (dd, ³J = 11.2 Hz, ³J = 4.8 Hz, 1 H, C1-H), 3.30

(s, 3 H, N7-CH₃), 2.81 (dd, ³J = 12.2 Hz, ³J = 6.4 Hz, 1 H, C4a-H), 2.75 (s,

3 H, N6-CH₃), 2.23–2.13 (m, 1 H, C4-HH), 2.00–1.87 (m, 2 H, C2-HH,

C3-HH), 1.69–1.52 (m, 1 H, C2-HH), 1.52–1.40 (m, 1 H, C3-HH), 1.33–

1.12 (m, 2 H, C4-HH), 0.72 [s, 9 H, SiC(CH₃)₃], –0.22 [s, 3 H,

Si(CH₃)(CH₃)], –0.57 [s, 3 H, Si(CH₃)(CH₃)].

HRMS (ESI): m/z [(M

+

H)⁺] calcd for C₂₃H₃₂NO₆Si: 446.1999;

found: 446.1996.

1-[(tert-Butyldimethylsilyl)oxy]-7-methyl-2,3,4,4a,6a,7-hexahy-

dro-[1,3]dioxolo[4,5-g]isoindolo[1,7a-c]isoquinoline-5,8(1H,6H)-

dione (20b)

A solution of cyclobutanone 19b (16.7 mg, 38.9 μmol, 1.00 equiv) in

CH₂Cl₂(1 mL) was treated with a solution of MSH¹⁷(13.4 mg, 62.2

μmol, 1.60 equiv) in CH₂Cl₂(1 mL) at 0 °C (CAUTION! For precautions

when working with MSH, see the general remarks section and the lit-

erature^17b). The resulting mixture was stirred for 1 h at 0 °C whereup-

on the solvent was removed in vacuo at r.t. (!). The residue was redis-

solved in a mixture of benzene (750 μL) and MeOH (0.25 μL) and add-

ed to a suspension of activated basic Al₂O₃(activity I, 500 mg) in

MeOH (1 mL). The suspension was stirred for 20 h and then filtered

through a pad of Celite. After removal of the solvents in vacuo, the

crude product was purified by flash chromatography (SiO₂, 2 × 7 cm,

P–EtOAc, 1:1) to give the γ-lactam 20b as a colorless resin; yield: 13.4

mg (30.1 μmol, 77%); R_f= 0.12 [P–EtOAc, 1:1 (1% Et₃N)] [UV/CAM].

¹³C NMR (126 MHz, CDCl₃): δ = 173.3 (s, C5), 162.8 (s, C8), 151.6 (s,

C12a), 147.4 (s, C9a), 137.2 (s, C13a), 124.4 (s, C8a), 107.8 (d, C9),

105.6 (d, C12), 101.9 (t, OCH₂O), 77.2 (d, C1), 75.7 (d, C6a), 50.8 (d,

C4a), 49.6 (C13b), 36.9 (q, N7-CH₃), 32.3 (t, C2), 26.7 (t, C4), 26.4 (q,

N6-CH₃), 25.8 [q, SiC(CH₃)₃], 22.7 (t, C2), 17.8 [s, SiC(CH₃)₃], –5.4 [q,

Si(CH₃)(CH₃)], –5.5 [q, Si(CH₃)(CH₃)].

MS (ESI): m/z = 459 [(M + H)⁺].

HRMS (ESI): m/z [(M + H)⁺] calcd for C₂₃H₃₅N₂O₅Si: 459.2315;

found: 459.2310.

Acknowledgment

IR (ATR): 3226 (w), 2927 (vs), 2856 (s), 1708 (s), 1651 (s), 1479 (s),

1251 (m), 1089 (w), 1038 (w), 836 (w), 776 cm^–1(w).

We thank Olaf Ackermann for technical assistance. Maximilian Koch

(research group of Prof. Sieber) and Tobias Kapp (research group of

Prof. Kessler) are acknowledged for performing most of the MS analy-

ses.

¹H NMR (500 MHz, CDCl₃): δ = 7.57 (s, 1 H, C9-H), 6.73 (s, 1 H, C13-H),

6.03 (d, ²J = 1.3 Hz, 1 H, OCHHO), 6.00 (d, ²J = 1.3 Hz, 1 H, OCHHO),

5.32 (s, 1 H, C6a-H), 3.76 (dd, ³J = 11.3 Hz, ³J = 4.8 Hz, 1 H, C1-H), 3.19

(s, 3 H, N7-CH₃), 2.77 (dd, ³J = 11.9 Hz, ³J = 6.5 Hz, 1 H, C4a-H), 2.24–

2.17 (m, 1 H, C4-HH), 1.95–1.88 (m, 2 H, C2-HH, C3-HH), 1.62–1.53

(m, 1 H, C2-HH), 1.49–1.42 (m, 1 H, C3-HH), 1.38–1.22 (m, 1 H, C4-

HH), 0.70 [s, 9 H, SiC(CH₃)₃], –0.21 [s, 3 H, Si(CH₃)(CH₃)], –0.60 [s, 3 H,

Si(CH₃)(CH₃)].

¹³C NMR (126 MHz, CDCl₃): δ = 176.6 (s, C5), 162.2 (s, C8), 151.6 (s,

C12a), 147.5 (s, C9a), 136.8 (s, C13a), 124.2 (s, C8a), 107.7 (d, C9),

105.7 (d, C12), 102.0 (t, OCH₂O), 77.4 (d, C1), 71.2 (d, C6a), 51.4 (d,

C4a), 50.9 (s, C13b), 35.2 (q, N7-CH₃), 32.1 (t, C2), 27.2 (t, C4), 25.7 [q,

SiC(CH₃)₃], 22.6 (t, C3), 17.7 [s, SiC(CH₃)₃], –5.3 [q, Si(CH₃)(CH₃)], –5.6

[q, Si(CH₃)(CH₃)].

Supporting Information

Supporting information for this article is available online at

http://dx.doi.org/10.1055/s-0034-1380756. Included are additional

procedures and crystallographic data, emission spectrum of 350 nm

light source, and NMR spectra.

S

u

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Primary Data

MS (ESI): m/z = 445 [(M + H)⁺].

HRMS (ESI): m/z [(M + H)⁺] calcd for C₂₃H₃₃N₂O₅Si: 445.2159;

Primary data for this article are available online at http://www.thieme-

connect.com/products/ejournals/journal/10.1055/s-00000084 and can

be cited using the following DOI: 10.4125/pd0067th.

P

m

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P

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2

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found: 445.2155.

1-[(tert-Butyldimethylsilyl)oxy]-6,7-dimethyl-2,3,4,4a,6a,7-hexa-

hydro[1,3]dioxolo[4,5-g]isoindolo[1,7a-c]isoquinoline-5,8(1H,6H)-

dione (21b)

References

(1) Ünver, N.; Gözler, T.; Walch, N.; Gözler, B.; Hesse, M. Phyto-

chemistry 1999, 50, 1255.

NaH (60% dispersion in mineral oil, 3.2 mg, 80.0 μmol, 2.85 equiv)

was added to a solution of γ-lactam 20b (12.5 mg, 28.1 μmol, 1.00

equiv) in DMF (1.5 mL) and the resulting suspension was stirred for

45 min. MeI (10.0 μL, 22.7 mg, 160 μmol, 5.69 equiv) was added and

the reaction mixture was stirred at r.t. for 21 h. Sat. aq NH₄Cl (5 mL),

H₂O (10 mL), and Et₂O (20 mL) were added and the layers were sepa-

rated. The aqueous layer was extracted with Et₂O (3 × 20 mL). The

combined organic layers were washed with brine (40 mL), dried

(2) For structurally related plicamine-type alkaloids, see: (a) Ünver,

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Article Doi

Photocycloaddition and Rearrangement Reactions in a Putative Route to the Skeleton of Plicamine-Type Alkaloids

DOI: 10.1055/s-0034-1380756

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Article abstract of DOI:10.1055/s-0034-1380756

Full text of DOI:10.1055/s-0034-1380756

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