Preparation of polycyclic systems by sequential 5-exo-digonal radical cyclization, 1,5-hydrogen transfer from silicon, and 5-endo-trigonal cyclization

1966

J . Org. Chem. 2001, 66, 1966-1983

P r ep a r a tion of P olycyclic System s by Sequ en tia l 5-Exo-Digon a l

Ra d ica l Cycliza tion , 1,5-Hyd r ogen Tr a n sfer fr om Silicon , a n d

5-En d o-Tr igon a l Cycliza tion

Derrick L. J . Clive,* Wen Yang, Aaron C. MacDonald, Zhongren Wang, and Michel Cantin

Chemistry Department, University of Alberta, Edmonton, Alberta, Canada T6G 2G2

derrick.clive@ualberta.ca

Received J uly 24, 2000

Radicals of type 1 undergo 5-exo diagonal cyclization, and the resulting vinyl radical abstracts

hydrogen from silicon to afford a silicon-centered radical. This radical closes in a 5-endo trigonal

manner to generate radicals of type 4, which are reduced (4 f 5) by stannane, except when the

starting acetylene carries a terminal trimethylstannyl group. In this case, radicals 4 expel

trimethylstannyl radical to afford vinyl silanes 6. The stereochemical outcome of the radical cascade

1 f 5 is controlled by the stereochemistry of the oxygen-bearing carbon in 1 (see starred atom).

The sequence can be initiated by carbon-, R-substituted carbon-, oxyacyl-, and carbamoyl radicals

and generates a silicon-containing ring fused onto a carbocycle or heterocycle. Numerous examples

are described, as well as a number of transformations of the final cyclization products, especially

their response to n-Bu₄NF and to BF₃‚OEt₂, reagents that cleave the newly formed carbon-silicon

bond.

Sch em e 1

The sequence of radical reactions outlined in Scheme

1 provides a route to unusual bicyclic or polycyclic

compounds. Earlier publications¹from this laboratory

illustrated the method for a variety of examples that

followed the pathway 1 f 5 and in which the radical

appendageswhich is shown in Scheme 1 for a particular

caseswas varied in length, carried substituents, was part

of an aromatic system, or included heteroatoms; here, full

details and additional examples are described, as well

as some simple transformations of the products, and a

method for diverting the intermediates of type 4 to

vinylsilanes such as 6.

The first step of the sequence (see 1 f 2) involves 5-exo-

digonal cyclization, but the notable features of the

process are, of course, the intramolecular transfer of

hydrogen from silicon to carbon (2 f 3) and the 5-endo

nature of the subsequent trigonal closure (3 f 4). While

many intramolecular 1,5-hydrogen transfers are known,

we were not aware of any prior examples of transfer from

silicon when our work began,¹although a number have

now been reported.^2,3The penultimate carbon radical in

our cascade (see 4) can be intercepted (Scheme 2) to

produce 8, by iodine atom transfer, when the starting

radical 1 is generated (Bu₃SnSnBu₃, light) from an iodide

(e.g., 7) instead of a selenide.^2d,e

Sch em e 2

5-Endo-trigonal cyclizations are encountered much less

frequently than their 5-exo counterpartssin accordance

(1) (a) Clive, D. L. J .; Cantin, M. J . Chem. Soc., Chem. Commun.

1995, 319-320. (b) Clive, D. L. J .; Yang, W. J . Chem. Soc., Chem.

Commun. 1996, 1605-1606. (c) Sannigrahi, M.; Mayhew, D. L.; Clive,

D. L. J . J . Org. Chem. 1999, 64, 2776-2788.

with the Baldwin rules⁴and Beckwith guidelines.⁵In the

present case,⁶the increased length of the bonds to silicon,

as compared to bonds between first-row elements, lowers

the stereoelectronic barrier that normally hinders such

(2) (a) Curran, D. P.; Xu, J . J . Chem. Soc., Perkin Trans. 1 1995,

3061-3063. (b) Curran, D. P.; Xu, J .; Lazzarini, E. J . Am. Chem. Soc.

1995, 117, 6603-6604. (c) Curran, D. P.; Xu, J .; Lazzarini, E. J . Chem.

Soc., Perkin Trans. 1 1995, 3049-3059. (d) Martinez-Grau, A.; Curran,

D. P. J . Org. Chem. 1995, 60, 8332-8333. (e) Martinez-Grau, A.;

Curran, D. P. Tetrahedron 1997, 53, 5679-5698.

(4) Baldwin, J . E. J . Chem. Soc., Chem. Commun. 1976, 734-736.

(5) Beckwith, A. L. J .; Easton, C. J .; Serelis, A. K. J . Chem. Soc.,

Chem. Commun. 1980, 482-483.

(3) Review on silicon radicals: Chatgilialoglu, C. Chem. Rev. 1995,

95, 1229-1251.

Published on Web 02/28/2001

Preparation of Polycyclic Systems

J . Org. Chem., Vol. 66, No. 6, 2001 1967

Ta ble 1

endo cyclizations. However, in first-row element chem-

istry, there is a growing number of 5-endo trigonal

closures. Enamides are particularly prone to follow this

pathway,⁷and a number of other specialized systems

have also been found to undergo efficient 5-endo trigonal

cyclization.⁸

P r ep a r a tion of Sta r tin g Ma ter ia ls. Radicals of type

1, and related species, were generated by stannane-

induced homolysis of carbon-bromine or carbon-sele-

nium bonds, and most of the radical precursors we used

are shown in Table 1 (compounds 9c-21c) and Table 2,

(compounds 29c-34c).

This subdivision is made according to whether the

homolyzable group is connected to the acetylene by an

all-carbon chain (Table 1) or by a chain containing a

heteroatom (Table 2). Table 3 shows several steps in the

preparation of those starting materials (compounds 35d -

39d ) used for the pathway 1 f 6 of Scheme 1.

Most of the sequences summarized in the tables begin

with readily available aldehydes, and of these, com-

pounds 9a ,⁹14a ,¹⁰16a ,¹¹18a ,¹²and 20a ^13,14(all shown

(6) Cf. (a) Cai, Y.; Roberts, B. P. J . Chem. Soc., Perkin Trans. 1 1998,

467-475. (b) Barton, T. J .; Revis, A. J . Am. Chem. Soc. 1984, 106,

3802-3805. (c) Chatgilaloglu, C.; Woynar, H.; Ingold, K. U.; Davies,

A. G. J . Chem. Soc., Perkin Trans. 2 1983, 555-561. (d) Sarasa, J . P.;

Igual, J .; Poblett, J . M. J . Chem. Soc., Perkin Trans. 2 1986, 861-

865. (e) For an example of 5-endo trigonal cyclization involving sulfur,

see: J ournet, M.; Rouillard, A.; Cai, D.; Larsen, R. D. J . Org. Chem.

1997, 62, 8630-8632.

(7) E.g. (a) Clark, A. J .; Dell, C. P.; Ellard, J . M.; Hunt, N. A.;

McDonagh, J . P. Tetrahedron Lett. 1999, 40, 8619-8623. (b) Ishibashi,

H.; Nakamura, N.; Sato, T.; Takeuchi, M. Tetrahedron Lett. 1991, 32,

1725-1728. (c) Sato, T.; Machigashira, N.; Ishibashi, H.; Ikeda, M.

Heterocycles 1992, 33, 139-142. (d) Sato, T.; Nakamura, N.; Ikeda,

K.; Okada, M.; Ishibashi, H.; Ikeda, M. J . Chem. Soc., Perkin Trans.

1 1992, 2399-2407. (e) Sato, T.; Chona, N.; Ishibashi, H.; Ikeda, M. J .

Chem. Soc., Perkin Trans. 1 1995, 1115-1120. (f) Ishibashi, H.;

Kameoka, C.; Kodama, K.; Ikeda, M. Tetrahedron Lett. 1996, 52, 489-

502. (g) Ikeda, M.; Ohtani, S.; Yamamoto, T.; Sato, T.; Ishibashi, H. J .

Chem. Soc., Perkin Trans. 1 1998, 1763-1768. (h) Ishibashi, H.;

Higuchi, M.; Ohba, M.; Ikeda, M. Tetrahedron Lett. 1998, 39, 75-78.

(i) Ikeda, M.; Hamada, M.; Yamashita, T.; Matsui, K.; Sato, T.;

Ishibashi, H. J . Chem. Soc., Perkin Trans. 1 1999, 1949-1956. (j)

Goodall, K.; Parsons, A. F. J . Chem. Soc., Perkin Trans. 1 1994, 3257-

3259. (k) Goodall, K.; Parsons, A. F. Tetrahedron Lett. 1997, 38, 491-

494. (l) Baker, S. R.; Parsons, A. F.; Pons, J .-F.; Wilson, M. Tetrahedron

Lett. 1998, 39, 7197-7200. (m) Baker, S. R.; Parsons, A. F.; Wilson,

M. Tetrahedron Lett. 1998, 39, 2815-2818. (n) Baker, S. R.; Burton,

K. I.; Parsons, A. F.; Pons, J .-F.; Wilson, M. J . Chem. Soc., Perkin

Trans. 1 1999, 427-436. (o) Davies, D. T.; Kapur, N.; Parsons, A. F.

Tetrahedron Lett. 1999, 40, 8615-8618. (p) Cassayre, J .; Quiclet-Sire,

B.; Saunier, J .-B.; Zard, S. Z. Tetrahedron Lett. 1998, 39, 8955-8998.

(q) Cassayre, J .; Dauge, D.; Zard, S. Z. Synlett 2000, 471-474.

(8) E.g. (a) Bogen, S.; Gulea, M.; Fensterbank, L.; Malacria, M.

J . Org. Chem. 1999, 64, 4920-4925. (b) Gimisis, T.; Chatgilialoglu, C.

J . Org. Chem. 1996, 61, 1908-1909. (c) Chatgilialoglu, C.; Gimisis,

T.; Spada, G. P. Chem. Eur. J . 1999, 5, 2866-2876. (d) Kittaka, A.;

Asakura, T.; Kuze, T.; Tanaka, H.; Yamada, N.; Nakamura, K. T.;

Miyasaka, T. J . Org. Chem. 1999, 64, 7081-7093. (e) Rao, A. V.

R.; Singh, A. K.; Rao, B. V.; Reddy, K. M. Tetrahedron Lett. 1993,

34, 2665-2668. (f) Schmalz, H.-G.; Siegel, S.; Bats, J . W. Angew.

Chem., Int. Ed. Engl. 1995, 34, 2383-2385. (g) Mendenhall, G. D.;

Protasiewicz, J . D.; Brown, C. E.; Ingold, K. U.; Lusztyk, J . J . Am.

Chem. Soc. 1994, 116, 1718-1724. (h) Yamamoto, Y.; Ohno, M.; Eguchi,

S. J . Am. Chem. Soc. 1995, 117, 9653-9661. (i) Nonami, Y.; Baran, J .;

Sosnicki, J .; Mayr, H.; Masuyama, A.; Nojima, M. J . Org. Chem. 1999,

64, 4060-4063.

(9) Clive, D. L. J .; Bergstra, R. J . J . Org. Chem. 1990, 55, 1786-

1792.

(10) Bowman, W. R.; Stephenson, P. T.; Terrett, N. K.; Young, A.

R. Tetrahedron 1995, 51, 7959-7980.

(11) Hartman, G. D.; Phillips, B. T.; Halczenko, W. J . Org. Chem.

1985, 50, 2423-2427.

(12) (a) Bailey, R. J .; Card, P. J .; Schechter, H. J . Am. Chem.

Soc. 1983, 105, 6096-6103. (b) Luckenbach, R.; J ensen, A. Zeit.

Naturforsch. B. 1977, 32b, 912-933.

(13) (a) Corresponding acid: Gilman, H.; Gorsich, R. D. J . Am.

Chem. Soc. 1956, 78, 2217-2222. (b) Esterification (EtOH, HCl, 74%)

and DIBAL-H reduction (1 equiv., CH₂Cl₂, -78 °C, 1 h, 86%) gave the

aldehyde (see ref 14).

in Table 1) were known and easily prepared by the

literature methods. Aldehydes 19a and 21a of Table 1

(14) Shuttleworth, R. G.; Rapson, W. S.; Stewart, E. T. J . Chem.

Soc. 1944, 71-73.

1968 J . Org. Chem., Vol. 66, No. 6, 2001

Clive et al.

Ta ble 2

Ta ble 3

Sch em e 3

are new; they were prepared by the conventional methods

summarized in Schemes 3 and 4, respectively.

The aldehydes shown in Table 2 were also readily

prepared, as were the two silylated starting materials

31a and 34a also listed in Table 2. For the preparation

of 29a , advantage was taken of the ability of the PhSeNa

to open γ-lactone-like structures,¹⁵and in the present

case (Scheme 5), the dioxolanone 29bb, made by treat-

ment of glycolic acid with formaldehyde, smoothly gave

the desired ring-opened selenide acid 29cc. This was

esterified (29cc f 29d d ), and DIBAL-H reduction then

afforded aldehyde 29a . The dimethyl analogue 30a was

made in exactly the same way (Scheme 6).

Sch em e 4^a

Silane 31a [as an ca. 3.6:1 (¹H NMR on 31bb) mixture

of C(3) epimers that were separated at a later stage] was

made (Scheme 7) from (S)-2-(triethylsilyloxy)propanal

(31a a )¹⁶by acetylide addition (31a a f 31bb) and silyla-

tion (31bb f 31a ). Although we used optically pure

a

Key: (i) Et₂NH, PhSeCl, hexane; (ii) NaBH₄, MeOH, 49% from

21a a ; (iii) MeOC(O)Cl, pyridine, CH₂Cl₂, 84%; (iv) n-Bu₄NF,

AcOH, THF, 95%; (v) Swern oxidation, 67%.

(15) (a) Liotta, D.; Sunay, U.; Santiesteban, H.; Markiewicz, W. J .

Org. Chem. 1981, 46, 2605-2610. (b) Zima, G.; Liotta, D. Synth.

Commun. 1979, 9, 697-703. (c) Scarborough, R. M., J r.; Smith, A. B.,

III. Tetrahedron Lett. 1977, 4361-4364. (d) Dowd, P.; Kennedy, P.

Synth. Commun. 1981, 11, 935-941. (e) Pedersen, M. L.; Berkowitz,

D. B. Tetrahedron Lett. 1992, 33, 7315-7318.

(16) (a) Ishibashi, T.; Nagisa, O.; Miwako, M. Tetrahedron Lett.

1996, 37, 6165-6168. (b) Cainelli, G.; Panunzio, M.; Bandini, E.;

Martelli, G.; Spunta, G. Tetrahedron 1996, 52, 1685-1698.

starting material we did not monitor the optical integrity

of the derived products, but have no reason¹⁷to suspect

any loss of stereochemical integrity.

(17) Cf. Hirama, M.; Shigemoto, T.; Itoˆ, S. J . Org. Chem. 1987, 52,

3342-3346.

Preparation of Polycyclic Systems

J . Org. Chem., Vol. 66, No. 6, 2001 1969

Sch em e 5^a

Sch em e 9^a

a

Key: (i) (CH₂O)_n, TsOH‚H₂O, PhH, reflux, Dean-Stark ap-

paratus, 14%; (ii) PhSeNa, THF-HMPA, reflux; (iii) MeOH, concd

H₂SO₄, 80% from 29bb; (iv) DIBAL-H, CH₂Cl₂, 80%.

a

Key: (i) PhCdCH, n-BuLi, THF, -78 °C, then add 34a a ,

chromatographic separation of isomer 34bb, 41%; (ii) TFA, CH₂Cl₂;

(iii) t-Bu₂SiHCl, imidazole, CH₂Cl₂, 60% from 34bb.

Sch em e 6^a

X-ray analysisswas treated with TFA to remove the

nitrogen protecting group and then the hydroxyl was

silylated (34bb f 34a ).

The aldehydes listed in Tables 1 and 2 were each

treated with the lithium acetylide derived from one of

the acetylenes 22-28.

a

Key: (i) s-trioxane, TsOH‚H₂O, PhH, reflux, Dean-Stark

apparatus, 82%; (ii) PhSeNa, THF-HMPA, reflux; (iii) MeOH,

concd H₂SO₄, 70% from 30bb; (iv) DIBAL-H, CH₂Cl₂, 90%.

Sch em e 7^a

Of these, 22, 26, and 28 were commercially available,

and the others were made by the literature method of

O-alkylation (23,²¹24,²¹27²²) or, in the case of 25,²³by

silylation with Et₃SiCl. Both alcohol 20b (Table 1) and

the derived silane 20c displayed atropisomerism, re-

vealed by a doubling of many signals in the NMR spectra.

As expected, the acetylenic alcohol 21b (Table 1) was

obtained as a mixture of diastereoisomers (ca. 1:1). The

acetylenic alcohols 36a , 37a , 38a , and 39a (Table 3) were

made in the same general way from the appropriate

aldehydes, except that in the preparation of 36a the

cerium salt of the acetylene was arbitrarily used.

The acetylenic alcohols shown in Tables 1 and 2 were

silylated using t-Bu₂SiHCl in the presence of a base,

usually imidazole, but sometimes Et₃N and a catalytic

amount of DMAP. Reactions were generally complete

after a few hours at the reflux temperature of THF or

benzene, with yields usually well above 80%. The

t-Bu₂Si group of 31a (Table 2) was stable enough to

hydrolytic conditions (H₂O-AcOH-THF) to allow selec-

tive removal of the Et₃Si group also present (31a f 31b).

Compound 31a is an isomer mixture but, after the

hydrolysis, the stereoisomer 31b, having the indicated

absolute configuration, could be isolated in 54% yield; the

isomeric alcohol was discarded. Treatment with COCl₂

and PhSeNa then served to afford the required seleno-

carbonate 31c, as shown in Table 2.

a

Key: (i) BnOCH₂CtCH, n-BuLi, THF, -78 °C, then add 31a a ;

(ii) t-Bu₂SiHCl, Et₃N, CH₂Cl₂, DMAP (for overall yield from 31a a ,

see preparation of 31b).

Sch em e 8^a

a

Key: (i) (CH₂O)_n, TsOH‚H₂O, PhH, reflux, Dean-Stark ap-

paratus, 61%; (ii) PhSeNa, THF-HMPA, reflux; (iii) CH₂N₂, Et₂O,

80% from 33a a ; (iv) DIBAL-H, Et₂O, 83%.

Aldehyde 32a (see Table 2) was formed (22%) by

alkylation of salicylaldehyde with PhSeCH₂I,¹⁸as sum-

marized in eq 1, and aldehyde 33a (see Table 2) was

prepared (see Scheme 8) in a manner similar to that of

29a , once again using PhSeNa to open a type of γ-lactone

ring (33bb f 33cc).

Silane 34a (see Table 2) was derived from S-proline,

as shown in Scheme 9, by way of the known aldehyde

34a a ,¹⁹which was treated with lithium phenylacetylide

(34a a f 34bb) to afford a 1:1 mixture²⁰of two separable

isomers; that having the stereochemistry shown as

34bbsan assignment established at a later stage by

The amine 34a (Table 2) was treated with COCl₂, and

the resulting carbamoyl chloride (34b), which was stable

to chromatography, reacted with PhSeNa to give the

radical precursor 34c (84% overall from 34a ).

The acetylenic trimethylsilyl groups (see Table 3) of

13b, 36a , 37a , 38a , and 39a were removed efficiently by

(18) (a) Beckwith, A. L. J .; Pigou, P. E. Aust. J . Chem. 1986, 39,

77-87. (b) Nakanishi, W. Chem. Lett. 1993, 2121-2122.

(19) Reed, P. E.; Katzenellenbogen, J . A. J . Org. Chem. 1991, 56,

2624-2634.

(20) Cf. Reference 19 and Koskinen, A. M. P.; Paul, J . M. Tetra-

hedron Lett. 1992, 33, 6853-6856.

(21) (a) Montevecchi, P. C.; Navacchia, M. L. J . Org. Chem. 1998,

63, 537-542. (b) We used refluxing THF-DMF, instead of heating the

mixture in a sealed tube.

(22) Kobayashi, Y.; Mizojiri, R.; Ikeda, E. J . Org. Chem. 1996, 61,

5391-5399.

(23) Cf. Lorenz, C.; Schubert, U. Chem. Ber. 1995, 128, 1267-1269.

1970 J . Org. Chem., Vol. 66, No. 6, 2001

Clive et al.

Ta ble 4

Sch em e 10

ing greater opportunities for competing pathwayss

possibly, intramolecular transfer of a propargylic hydro-

gen (see 40). 6-Exo-digonal closures that have been

reported cover a wide range of yields.²⁵Those that

proceed poorly often afford extensive amounts of material

in which simple reduction has occurred (replacement of

the homolyzed group by hydrogen), butsat least in the

research familiar to ussno control experiments have been

done that would establish whether these formal reduction

products arise by way of intramolecular hydrogen trans-

fer, followed by reduction of the resulting propargylic

radical.²⁶

The biphenyl derivative 20c of Table 1 gave a complex

mixture (see Table 4), and appeared to afford little, if any,

of the desired product. This is the only case where the

radical cascade failed.

Selenide 15c also gave a yield at the lower end of the

range (see Table 4), possibly because of the intervention

of the hydrogen abstraction pathway (via a six-membered

transition state) shown in Scheme 10 (41 f 42 f 15e).

Although we did isolate a byproduct with the anticipated

accurate mass corresponding to 15e, it was not further

characterized.²⁷The high yield of 16d (Table 4) estab-

lishes that this type of intramolecular hydrogen transfer

from the side chain does not intervene if the hydrogens

are unactivated. Cyclization product 21d (Table 4) was

obtained as an ca. 1:2 mixture of two isomers, this ratio

being lower than we have subsequently observed^1cin a

related cyclization, where a value of 7:1 was found. We

assume, on the basis of related work,^1cthat the major

isomer has the carbonate appendage syn to the adjacent

ring fusion hydrogen.

the action of n-Bu₄NF in THF at 0 °C, and the resulting

alcohols were silylated on oxygen with t-Bu₂SiHCl, under

our standard conditions. The resulting O-silylated ter-

minal acetylenes 35c-39c (Table 3) were deprotonated

by treatment with n-BuLi and then stannylated by

reaction with Bu₃SnCl. The acetylenic stannanes formed

by this sequence were unstable to chromatography, and

so they were used directly for radical cyclization.

F or m a tion of Ra d ica l Cycliza tion P r od u cts. The

radical cyclizations (cf. Scheme 1) were conducted by slow

addition of separate solutions of Ph₃SnH (or Bu₃SnH) and

AIBN, each in dry PhH, to a refluxing solution of the

substrate in the same solvent, and our results with the

radical precursors of Table 1 are shown in Table 4. For

those reactions involving an initial 5-exo digonal cy-

clization, yields varied between 57% and 91%. The

cyclization of 14c afforded 14d in poor yield (24%). This

reaction involves initial 6-exo digonal cyclization, which

might, like the corresponding trigonal reaction,²⁴be

inherently slower than 5-exo digonal closures, so afford-

(25) E.g. (a) Go´mez, A. M.; Danelo´n, G. O.; Moreno, E.; Valverde,

S.; Lo´pez, J . C. Chem. Commun. 1999, 175-176. (b) Crich, D.; Chen,

C.; Hwang, J .-T.; Yuan, H.; Papadatos, A.; Walter, R. I. J . Am. Chem.

Soc. 1994, 116, 8937-8951. (c) Schinzer, D.; J ones, P. G.; Obierey, K.

Tetrahedron Lett. 1994, 35, 5853-5856. (d) Audin, C.; Lancelin, J .-

M.; Beau, J .-M. Tetrahedron Lett. 1988, 29, 3691-3694. (e) Honda,

T.; Satoh, M.; Kobayashi, Y. J . Chem. Soc., Perkin Trans. 1 1992,

1557-1558. (f) Parsons, P. J .; Penkett, C. S.; Cramp, M. C.; West, R.

I.; Warrington, J .; Saraiva, M. C. Synlett 1995, 507-509. (g) Sha, C.-

K.; J ean, T.-S.; Wang, D.-C. Tetrahedron Lett. 1990, 30, 3745-3748.

(h) Sha, C.-K.; Shen, C.-Y.; J ean, T.-S.; Chiu, R.-T.; Tseng, W.-H.

Tetrahedron Lett. 1993, 34, 7641-7644. (i) Pike, K. G.; Destabil, C.;

Anson, M.; Kilburn, J . D. Tetrahedron Lett. 1998, 39, 5877-5880. (j)

Maudru, E.; Singh, G.; Wightman, R. H. Chem. Commun. 1998, 1505-

1506. (k) Zhou, S.-Z.; Anne´, S.; Vandewalle, M. Tetrahedron Lett. 1996,

37, 7637-7640. (l) Cossy, J .; Cases, M.; Pardo, D. G. Bull. Soc. Chim.

Fr. 1997, 134, 141-144.

(26) Cf. For radical reduction of a propargylic alcohol without

formation of an allene, see: Clive, D. L. J .; Yeh, V. S. C. Tetrahedron

Lett. 1998, 39, 4789-4792.

(24) Beckwith, A. L. J .; Schiesser, C. H. Tetrahedron 1985, 41, 3925-

3941.

(27) Cf. Reference 2e.

Preparation of Polycyclic Systems

J . Org. Chem., Vol. 66, No. 6, 2001 1971

Ta ble 5

Ster eoch em istr y of Ra d ica l Ca sca d e P r od u cts.

The stereochemistry of the radical cascade products

follows from the mechanistic pathway summarized in

Scheme 1. However, X-ray analyses were obtained for

34d (see Table 5) and for 9f (see Table 8, which is

discussed later). The structures found confirm the mecha-

nistic prediction that the product stereochemistry is

determined by the stereochemistry of the starting alcohol

and, in the case of 34d (Table 5), served to identify which

isomer from the original acetylide addition (see Scheme

9) had been selected.

Some comment is also necessary about the stereo-

chemistry of 31d (Table 5). The precursor alcohol 31b

(see Table 2) was separated from an isomer mixture, and

the stereochemistry shown was established by examining

the ¹H NMR spectrum of the final radical cyclization

product 31d (Table 5). The CH₃C(6)H- signal is a quartet

(δ 4.65), and there is no coupling to the adjacent C(6a)H.

Dreiding models show the two hydrogens at C(6) and

C(6a) must be anti, because a syn relationship would

result in a large coupling.

It is noteworthy that, in the formation of 32d (see Table

5), intramolecular hydrogen abstraction (see 43) does not

occur to any appreciable extent, if at all, even though the

hydrogen that would be removed is both benzylic and

propargylic. However, the factors responsible for the

Ta ble 6

small, or nonexistent, extent of hydrogen abstraction

have not been identified. The facility of such hydrogen

transfers would depend not only on the accessible geom-

etries³¹of the system and the strength of the C-H_abond

(see 43) but also on certain characteristics of the radical

‚

(here ArOCH₂), such as resonance stabilization and

polarity.³²The relative importance of these factors is

unknown, but we note that efficient 6-exo-trigonal clo-

sures of alkoxymethyl radicals have also been observed

in systems that lack the additional activating features

of the propargylic hydrogen in 43,³³and the absence of

intramolecular transfer during these reactions or in the

6-exo-digonal closure described here^1a,2dmay be a general

and synthetically useful characteristic of alkoxymethyl

radicals. Hydrogen transfer is also insignificant or absent

in the cyclization of acyl³⁴or 1,1-difluoroalkyl³⁵radicals.

Compound 32d (Table 5) was converted into the known

alcohol 32e (see Table 9 ), a result that again supports

the stereochemical assignment to 32d .

The cyclizations shown in Table 5 represent those cases

in which the radical source is connected to the acetylenic

unit by a chain incorporating a heteroatom. As can be

seen, the sequence is very efficient in these examples.

Cyclization of 34c²⁸proceeds via a carbamoyl radical, a

species that has been investigated in greater detail by

others.²⁹Evidently, closure of these radicals is faster than

decarbonylation, as is the case with alkoxycarbonyl

radicals.³⁰

The cyclization results collected in Table 6 correspond

to the pathway 4 f 6 of Scheme 1, and the yields shown

refer to two stepssstannylation of the acetylene (see

Table 3) as well as the radical cascade. In all these cases,

the final carbon radical (cf. 4) expels a stannyl radical,

so as to generate a vinylsilane.

Use of Differ en t Silicon Su bstitu en ts. We exam-

ined briefly the use of i-Pr, Ph, and Me substituents on

(31) Cf. Stork, G.; Mook, J r., R.; Biller, S. A.; Rychnovsky, S. D. J .

Am. Chem. Soc. 1983, 105, 3741-3742.

(32) (a) Beckwith, A. L. J .; Glover, S. A. Aust. J . Chem. 1987, 40,

157-173. (b) Roberts, B. P. Chem. Soc. Rev. 1999, 28, 25-35.

(33) (a) Rawal, V. H.; Singh, S. P.; Dufour, C.; Michoud, C. J . Org.

Chem. 1991, 56, 5245-5247. (b) Burke, S. D.; Rancourt, J . J . Am.

Chem. Soc. 1991, 113, 2335-2336. (c) Bachi, M. D.; Frolow, F.;

Hoornaert, C. J . Org. Chem. 1983, 48, 1841-1849.

(28) Yang, W. Ph.D. Thesis, University of Alberta, Edmonton,

Canada, J anuary, 1998.

(29) (a) Rigby, J . H.; Danca, D. M.; Horner, J . H. Tetrahedron Lett.

1998, 39, 8413-8416. (b) Keck, G. E.; Grier, M. C. Abtracts of Papers.

214th National Meeting of the American Chemical Society, Las Vegas,

NV, Sep 1997; American Chemical Society: Washington, DC, 1997;

ORGN 337.

(34) (a) Chen, C.; Crich, D.; Papadatos, A. J . Am. Chem. Soc. 1992,

114, 8313-8314. (b) Bachi, M. D.; Denenmark, D. Heterocycles 1989,

28, 583-588.

(35) Arnone, A.; Bravo, P.; Frigerio, M.; Viani, F.; Cavicchio, G.;

Crucianelli, M. J . Org. Chem. 1994, 59, 3459-3466.

(30) Cf. Forbes, J . E.; Zard, S. Z. J . Am. Chem. Soc. 1990, 112, 2034-

2036 and references therein.

1972 J . Org. Chem., Vol. 66, No. 6, 2001

Clive et al.

Ta ble 7

Ta ble 8

silicon, and our results for the radical cascades are

summarized in Table 7.

The diisopropyl silane 44a gave a poor yield in the

cyclization, possibly due to undesired hydrogen transfer^2c

from the isopropyl groups. The diphenyl- and dimethyl-

silyl compounds decomposed on silica gel and on alumina;

the cyclization products were difficult to purify and

appeared to be formed in poor yield. For the dimethylsilyl

series, the intramolecular hydrogen transfer step (cf. 2

f 3 of Scheme 1) is not as efficient as with the di-tert-

butyl series, since an appreciable amount of olefinic

product was formed. Surprisingly, the diphenylsilane 45a

also gave a poor yield, but it was not clear if this reflected

the difficulty of handling the compound.

Mod ifica tion s of th e Ra d ica l Cycliza tion P r od -

u cts. As shown in Table 8, the crude products 45b and

46b from radical cyclization experiments were treated

with fluoride ion under conditions of the Tamao oxida-

tion³⁶(30% H₂O₂, KHCO₃, KF‚2H₂O in 1:1 MeOH-THF

at 60 °C) to yield diols. Diol 45c was isolated in the first

case (14%) and both 46c () 45c) (27%) and 46d (29%) in

the second. The olefinic alcohol 46d most probably arises

from an O-silyl precursor of type 47 in the crude radical

cyclization product, suggesting, as mentioned above, that

hydrogen transfer from silicon is not particularly efficient

in the dimethylsilyl case.

Using several cyclization products of the di-tert-butyl

series, a number of experiments (Table 8) were done to

modify the structures and, especially, to break the newly

formed carbon-silicon bond. Treatment of 9d with BF₃‚

OEt₂(Table 8, entry 3) produced a hydroxyfluorosilane

(9d f 9e). The hydroxyl group could be protected and

the fluorine replaced by OH (9e f 9f f 9g, entry 4).

When an O-benzyl side chain is present (10d , entry 5),

hydrogenolysis releases the free hydroxyl group (10d f

10e), and treatment with BF₃‚OEt₂gives an olefinic

fluorosilane (10e f 10f). The same compound (10f) is

obtained directly from the O-benzyl precursor by the

action of BF₃‚OEt₂(10d f 10f). Alcohol 10e was oxidized

(Swern) to the corresponding aldehyde (10g, see entry

6) and converted by treatment with t-BuOK into the

olefinic hydroxysilane 10h . Compound 11d (entry 7) was

treated with DDQ, and the expected alcohol (11e) () 10e)

was released. Hydrolysis of carbonate 21d (entry 8) gave

a

As indicated in the text, 46d probably arises from 47 present

in crude 46b.

mainly the desired alcohol 21f, but a small amount of

the silicon O f O migration product 21g was isolated.

Several of the radical cyclization products shown in

Table 5 were also modified, as summarized in Table 9.

Treatment of 29d with n-Bu₄NF in DMF³⁷gave 29e

(Table 9), and 32d gave the known compound 32e³⁸under

1

the same conditions. Comparison of the H NMR spec-

trum of our material with the data published for 32e³⁸

served to confirm the stereochemistry of 32d . Lactone

31d was transformed into the olefinic fluorosilane 31e

on treatment with BF₃‚OEt₂(Table 9).

(37) Koreeda, M.; Wu, J . Synlett 1995, 850-852, and references

therein.

(38) Gomis, M.; Kirkiacharian, B. S.; Likforman, J .; Mahuteau, J .

Bull. Soc. Chim. Fr. 1988, 585-590.

(36) J ones, G. R.; Landais, Y. Tetrahedron 1996, 52, 7599-7662

Preparation of Polycyclic Systems

J . Org. Chem., Vol. 66, No. 6, 2001 1973

Ta ble 9

Gen er a l P r oced u r e for Silyla tion of Alcoh ols. The

alcohol and imidazole were placed in a round-bottomed flask

equipped with

a Teflon-coated stirring bar and a reflux

condenser that was sealed with a septum. The system was

flushed with Ar for 2-5 min, and dry THF or dry PhH was

injected. A solution of the dialkylchlorosilane in dry THF or

PhH was injected. A white precipitate formed rapidly, and the

reaction mixture was refluxed, usually for several hours, and

then cooled and processed as described for the individual

experiments.

Gen er a l P r oced u r e for Ra d ica l Cycliza tion . The sub-

strate was placed in a round-bottomed flask equipped with a

Teflon-coated stirring bar and a reflux condenser that was

sealed with a septum. The system was flushed with Ar for

5-10 min, and dry PhH was injected. The solution was

refluxed, and separate solutions of Ph₃SnH (or Bu₃SnH) and

AIBN, each in dry PhH, were injected simultaneously by

syringe pump over several h. Refluxing was continued for an

arbitrary time after the addition was complete. The reaction

mixture was cooled, and the solvent was evaporated to give a

residue that was processed as described for the individual

experiments.

1-P h en yl-6-(p h en ylselen o)-1-h exyn -3-ol (9b). The gen-

eral procedure for addition of an acetylide to an aldehyde was

followed, using 22 (2.96 mg, 2.90 mmol) in THF (15 mL),

n-BuLi (1.6 M in hexanes, 1.64 mL, 2.62 mmol), an initial

reaction time of 15 min, and 9a ⁹(379.5 mg, 1.750 mmol) in

THF (1.5 mL plus 1 mL as a rinse). Stirring at -78 °C was

continued for 45 min, water (50 mL) was added, and the

mixture was allowed to attain room temperature and was

extracted with CH₂Cl₂. The combined organic extracts were

dried (Na₂SO₄) and evaporated. Flash chromatography of the

residue over silica gel (1.8 × 20 cm), using 1:9 EtOAc-hexane,

gave 9b (454.7 mg, 79%) as a colorless oil: FTIR (CDCl₃cast)

Finally, some comment is appropriate about the chemi-

cal properties of the vinyl silanes shown above in Table

6. A proper study of their reaction with electrophiles

was not undertaken, as a cursory examination, using

dimethyldioxirane or AcCl/AlCl₃gave rather complex

mixtures.

Con clu sion

3362, 2936, 1578, 1489, 1477, 1437, 757, 735, 690 cm^-^{1 1}H

;

The radical cascade summarized in Scheme 1, and

illustrated by the examples collected in the Tables,

represents a method for making unusual heterocycles

containing silicon. The new asymmetric centers that are

generated have a predictable stereochemistry relative to

the initial stereogenic center (the hydroxyl-bearing car-

bon). The carbon-silicon bond in the products can be

cleaved and, in previous work from this laboratory,^1cthe

sequence of Scheme 1 has been used in formal syntheses

of Corey lactones and methyl epi-jasmonate. The cycliza-

tion of selenocarbamate 34c (see Table 5), together with

other more extensive published work,²⁹illustrates the

utility of carbamoyl radicals.

NMR (CDCl₃, 300 MHz) δ 1.86-2.01 (m, 4 H), 2.08 (br s, 1 H),

2.89-3.03 (m, 2 H), 4.60 (br s, 1 H), 7.17-7.33 (m, 6 H), 7.33-

7.42 (m, 2 H), 7.45-7.60 (m, 2 H); ¹³C NMR (CDCl₃, 75.5 MHz)

δ 25.8 (t′), 27.5 (t′), 37.7 (t′), 62.4 (d′), 85.2 (s′), 89.7 (s′), 122.5

(s′), 126.8 (d′), 128.3 (d′), 128.5 (d′), 129.1 (d′), 130.2 (s′), 131.7

(d′), 132.7 (d′); exact mass m/z calcd for C₁₈H₁₈O⁸⁰Se 330.0522,

found 330.0527. Anal. Calcd for C₁₈H₁₈OSe: C, 65.65; H, 5.51.

Found: C, 65.48; H, 5.53.

Bis(1,1-d im eth yleth yl)[[3-p h en yl-1-[3-(p h en ylselen o)-

p r op yl]-2-p r op yn yl]oxy]sila n e (9c). The general procedure

for silylation of alcohols was followed, using 9b (239.3 mg, 1.00

mmol) in THF (8 mL), imidazole (136.2 mg, 2.00 mmol), t-Bu₂-

SiHCl (223.5 mg, 1.25 mmol) in THF (1 mL plus 1 mL as a

rinse), and a reflux time of 2.5 h.⁴⁰The mixture was cooled,

diluted with water (50 mL), and extracted with Et₂O. The

combined organic extracts were dried (Na₂SO₄) and evapo-

rated. Flash chromatography of the residue over silica gel (2

× 15 cm), using 3:47 CH₂Cl₂-hexane, gave 9c (427.8 mg, 91%)

as a colorless oil: FTIR (CHCl₃cast) 2929, 2856, 2096, 1470,

Exp er im en ta l Section

Gen er a l P r oced u r es. Unless stated to the contrary, the

general procedures used previously³⁹were followed. The

symbols s′, d′, t′, and q′ used for ¹³C NMR signals indicate 0,

1, 2, or 3 attached hydrogens, respectively, the assignments

being made from APT spectra.

1

1084, 826 cm^-1; H NMR (CDCl₃, 400 MHz) δ 1.00 (s, 9 H),

1.05 (s, 9 H), 1.88-2.04 (m, 4 H), 2.99 (t, J ) 7.0 Hz, 2 H),

4.14 (s, 1 H), 4.70 (t, J ) 5.5 Hz, 1 H), 7.20-7.25 (m, 3 H),

7.26-7.34 (m, 3 H), 7.35-7.41 (m, 2 H), 7.48-7.54 (m, 2 H);

¹³C NMR (CDCl₃, 75.5 MHz) δ 19.8 (s′), 20.2 (s′), 25.7 (t′), 27.38

(q′), 27.43 (q′), 27.8 (t′), 38.4 (t′), 66.3 (d′), 85.2 (s′), 99.0 (s′),

123.0 (s′), 126.8 (d′), 128.2 (d′), 128.3 (d′), 129.0 (d′), 130.4 (s′),

130.6 (d′), 132.8 (d′); exact mass m/z calcd for C₂₆H₃₆O⁸⁰SeSi

472.1701, found 472.1696. Anal. Calcd for C₂₆H₃₆OSeSi: C,

66.22; H, 7.69. Found: C, 66.08; H, 7.82.

Gen er a l P r oced u r e for Ad d ition of a n Acetylid e to a n

Ald eh yd e. The acetylene was placed in a round-bottomed

flask sealed with a septum and equipped with a Teflon-coated

stirring bar. The system was flushed with Ar for 2-5 min,

and dry THF was injected. The solution was lowered into a

cooling bath (-78 °C) and stirred for 5 min. A solution of

n-BuLi (1.6 M in hexanes) was injected dropwise, the mixture

was stirred at -78 °C for 5-15 min, and a solution of the

aldehyde in dry THF was then injected at a rapid dropwise

rate. Stirring at -78 °C was continued for 15-60 min, and

the mixture was then quenched, usually with saturated

aqueous NH₄Cl. The cooling bath was removed, and the

mixture was allowed to reach room temperature, and then

processed as described for the individual experiments.

(3r,3a â,6a â)-2,2-Bis(1,1-d im et h ylet h yl)h exa h yd r o-3-

p h en yl-2H-cyclop en t[d ]-1,2-oxa silole (9d ). The general

procedure for radical cyclization was followed, using 9c (141.5

mg, 0.30 mmol) in PhH (45 mL), Ph₃SnH (210.6 mg, 0.60

mmol) in PhH (7.5 mL), AIBN (24.6 mg, 0.5 mmol) in PhH

(7.5 mL), and an addition time of 6 h. Refluxing was continued

for 0.5 h after the stannane addition. Evaporation of the

solvent and flash chromatography of the residue over silica

(39) Clive, D. L. J .; Wickens, P. L.; Sgarbi, P. W. M. J . Org. Chem.

1996, 61, 7426-7437.

(40) McCombie, S. W.; Ortiz, C.; Cox, B.; Ganguly, A. K. Synlett

1993, 541-547.

1974 J . Org. Chem., Vol. 66, No. 6, 2001

Clive et al.

gel (1.8 × 14 cm), using increasing amounts of CH₂Cl₂in

hexane (from 5% to 7%), gave an oil that was purified by

filtration through a pad (1 × 6 cm) of neutral alumina (Grade

I), using 1:199 Et₂O-hexane, to give 9d (68.5 mg, 72%) as a

white solid: mp 49-51 °C; FTIR (CDCl₃cast) 2960, 2938, 2859,

2H₂O (4.1 mg, 0.043 mmol), K₂CO₃(6.0 mg, 0.043 mmol), and

9f (16.5 mg, 0.043 mmol) in 1:1 MeOH-THF (2 mL). The

mixture was heated at 65 °C overnight, cooled, diluted with

water (20 mL), and extracted with CH₂Cl₂. The combined

organic extracts were dried (Na₂SO₄) and evaporated. Flash

chromatography of the residue over silica gel (0.5 × 5 cm),

using 1:19 EtOAc-hexane, gave 9g (14.3 mg, 87%) as a

yellowish solid: mp 106-111 °C; FTIR (CH₂Cl₂cast) 3649,

3501, 2937, 2858, 1474, 1044, 821 cm^-1; ¹H NMR (CDCl₃, 400

MHz) δ 1.00 (s, 9 H), 1.11 (s, 9 H), 1.56-1.93 (m, 6 H), 2.01-

2.11 (m, 1 H), 2.44-2.55 (m, 1 H), 2.87 (d, J ) 11.5 Hz, 1 H),

3.11 (s, 3 H), 3.58-3.62 (m, 1 H), 3.78 (d, J ) 6.5 Hz, 1 H),

4.30 (d, J ) 6.5 Hz, 1 H), 7.03-7.11 (m, 1 H), 7.17-7.27 (m, 4

H); ¹³C NMR (CDCl₃, 75.5 MHz) δ 22.1 (s′), 22.6 (t′), 23.0 (s′),

29.1 (q′), 29.2 (q′), 31.0 (t′), 31.1 (t′), 35.8 (d′), 47.5 (d′), 55.3

(q′), 81.0 (d′), 96.9 (t′), 124.9 (d′), 128.2 (d′), 129.5 (d′), 144.2

1

1475, 820 cm^-1; H NMR (CDCl₃, 300 MHz) δ 1.04 (s, 9 H),

1.15 (s, 9 H), 1.54-2.03 (m, 6 H), 2.89-3.01 (m, 1 H), 3.40 (d,

J ) 7.5 Hz, 1 H), 4.48-4.53 (m, 1 H), 7.10-7.15 (m, 1 H), 7.23-

7.33 (m, 4 H); ¹³C NMR (CDCl₃, 75.5 MHz) δ 21.1 (s′), 22.6

(s′), 24.1 (t′), 28.0 (t′), 28.5 (q′), 28.8 (q′), 35.1 (t′), 36.6 (d′),

47.5 (d′), 83.7 (d′), 124.7 (d′), 128.1 (d′), 129.5 (d′), 142.2 (s′);

exact mass m/z calcd for C₂₀H₃₂OSi 316.2222, found 316.2220.

Anal. Calcd for C₂₀H₃₂OSi: C, 75.88; H, 10.19. Found: C, 75.53;

H, 10.25.

[1r,2r(R*)]-2-[[Bis(1,1-d im eth yleth yl)flu or osilyl]p h en -

ylm eth yl]cyclop en ta n ol (9e). BF₃‚Et₂O (0.10 mL, 0.81

mmol) was added dropwise to a stirred and cooled (0 °C)

solution of 9d (72.4 mg, 0.229 mmol) in dry CH₂Cl₂(2.3 mL),

and the mixture was stirred at 0 °C for 7 h. Saturated aqueous

NaHCO₃(1 mL) was added, and stirring was continued for 10

min. The cooling bath was removed, and the mixture was

extracted with CH₂Cl₂. The combined organic extracts were

dried (Na₂SO₄) and evaporated. Flash chromatography of the

residue over silica gel (1 × 10 cm), using increasing amounts

of EtOAc in hexane (5% to 10%), gave 9e (61.7 mg, 80%) as a

white, crystalline solid: mp 115-118 °C; FTIR (CH₂Cl₂cast)

(s′); exact mass m/z calcd for

333.2250, found 333.2246; mass (CI) m/z calcd for C₂₂H₃₉O₃Si

(M + H) 379, found 379.

C₂₀H₃₃O₂Si (M - C₂H₅O)

(3r,3a â,6a â)-2,2-Bis(1,1-d im eth yleth yl)h exa h yd r o-2H-

cyclop en t[d ]-1,2-oxa silole-3-m eth a n ol (10e). A solution of

10d (40.7 mg, 0.113 mmol) in 98% EtOH (1.1 mL) was shaken

with Pd/C (5-10%, 40.7 mg) under H₂(50 psi) in a Parr shaker

for 3 h. The mixture was evaporated, and flash chromatogra-

phy of the residue over silica gel (1 × 10 cm), using 1:9 EtOAc-

hexane, gave 10e (28.9 mg, 95%) as a white solid: mp 64.5-

66 °C; FTIR (CDCl₃cast) 3388, 2960, 2934, 2859, 1474, 1030,

3459, 2939, 2861, 1474, 823, 809, 703, 579 cm^-1

;

¹H NMR

1

(CDCl₃, 300 MHz) δ 0.97 (d, J ) 0.5 Hz, 9 H), 1.11 (d, J _H,F

)

1004, 822 cm^-1; H NMR (CDCl₃, 400 MHz) δ 1.04 (s, 9 H),

1.0 Hz, 10 H), 1.50-1.79 (m, 4 H), 1.80-1.96 (m, 1 H), 1.96-

2.10 (m, 1 H), 2.38-2.52 (m, 1 H), 2.88 (d, J _H,F) 12.0 Hz, 1

H), 3.81-3.89 (m, 1 H), 7.11-7.18 (m, 1 H), 7.24-7.36 (m, 4

H); ¹³C NMR (CDCl₃, 75.5 MHz) δ 22.1 (s′, J _CF) 12.2 Hz),

22.7 (t′), 22.8 (s′, J _CF) 12.6 Hz), 28.4 (q′), 28.8 (q′), 29.4 (t′, J

) 5.8 Hz), 32.7 (t′), 35.4 (d′, J _CF) 12.6 Hz), 48.4 (d′), 73.6 (d′),

125.6 (d′), 128.6 (d′), 129.6 (d′), 141.8 (s′, J ) 5.5 Hz); exact

mass m/z calcd for C₁₆H₂₄FOSi (M - C₄H₉) 279.1581, found

279.1579. Anal. Calcd for C₁₆H₂₄FOSi: C, 71.37; H, 9.88.

Found: C, 71.37; H, 9.88.

1.05 (s, 9 H), 1.39-1.65 (m, 3 H), 1.65-1.78 (m, 2 H), 1.78-

1.89 (m, 1 H), 2.01-2.11 (m, 2 H), 2.50-2.60 (m, 1 H), 3.97 (s,

1 H), 3.97-4.02 (m, 1 H), 4.49 (ddd, J ) 6.0, 6.0, 2.5 Hz, 1 H);

¹³C NMR (CDCl₃, 75.5 MHz) δ 20.6 (s′), 22.0 (s′), 25.1 (t′), 26.2

(t′), 27.9 (q′), 28.6 (q′), 31.9 (d′), 35.6 (t′), 46.0 (d′), 62.3 (t′),

83.8 (d′); exact mass m/z calcd for C₁₁H₂₁O₂Si (M - C₄H₉)

213.1311, found 213.1307. Anal. Calcd for C₁₅H₃₀O₂Si: C,

66.61; H, 11.18. Found: C, 66.85; H, 11.27.

cis-Bis(1,1-d im eth yleth yl)[(2-eth en ylcyclop en tyl)oxy]-

flu or osila n e (10f) fr om 10e. BF₃‚Et₂O (0.10 mL, 0.8 mmol)

was added to a stirred and cooled (0 °C) solution of 10e (27.4

mg, 0.100 mmol) in dry CH₂Cl₂(2.5 mL).⁴¹Stirring at 0 °C

was continued for 1 h, saturated aqueous NaHCO₃(1 mL) was

added, and the cooling bath was removed. The organic layer

was separated, and the aqueous layer was extracted with CH₂-

Cl₂. The combined organic extracts were dried (Na₂SO₄) and

evaporated. Flash chromatography of the residue over silica

gel (0.5 × 5 cm), using hexane, gave 10f (19.9 mg, 77%) as a

colorless oil: FTIR (CDCl₃cast) 2966, 2935, 2862, 1473, 1137,

Crystallographic data for 9e:

C₂₀H₃₃FOSi, MW 336.55,

crystal size 0.59 × 0.58 × 0.58 mm, tetragonal space group

P4₂/n (No. 86), a ) 21.1751(15) Å, c ) 8.8012(8) Å, V )

3946.3(5) Å³, Z ) 8, D_calc) 1.133 g cm^-3, µ ) 0.131 mm^-1, T )

223(1) K, λ ) 0.710 73 Å (Mo KR), 2θ_max) 55.86°, absorption

correction by Gaussian integration (indexing of crystal faces),

range of transmission factors 0.9352-0.9243, R₁(F) ) 0.0473

(for 3038 data with F_og 2σ(F_o²)) and wR₂(F²) ) 0.1341 (for

2

all 4738 independent data), goodness-of-fit (S) ) 1.105, largest

1

difference peak and hole 0.227 and -0.262 e Å^-3

.

1066, 842, 830 cm^-1; H NMR (CDCl₃, 300 MHz) δ 1.02 (d, J

) 0.5 Hz, 9 H), 1.04 (d, J ) 0.5 Hz, 9 H), 1.55-1.92 (m, 6 H),

2.37 (dddd, J ) 9.0, 9.0, 9.0, 4.0 Hz, 1 H), 4.48-4.53 (m, 1 H),

(3r,3a â,6a â)-2,2-Bis(1,1-d im et h ylet h yl)h exa h yd r o-3-

p h en yl-2H-cyclop en t[d ]-1,2-oxa silole (9d ). Anhydrous K₂-

CO₃(19.7 mg, 0.140 mmol) was added to a stirred solution of

9e (47.8 mg, 0.142 mmol) in MeOH (1.4 mL). Stirring was

continued for 45 min, and the mixture was evaporated. Flash

chromatography of the residue over silica gel (1 × 10 cm), using

1:99 EtOAc-hexane, gave 9d (42.2 mg, 94%) as a white solid,

identical [¹H NMR (400 MHz)] to that obtained from radical

cyclization.

4.99-5.09 (m, 2 H), 5.99 (ddd, J ) 17.5, 10.0, 8.0 Hz, 1 H); ¹³

C

NMR (CDCl₃, 75.5 MHz) δ 20.1 (s′, J _CF) 14.5 Hz), 20.7 (s′,

J _CF) 16.0 Hz), 21.8 (t′), 27.0 (s′), 27.2 (s′), 28.9 (t′), 35.3 (t′),

50.6 (d′), 78.6 (d′), 114.8 (s′), 139.3 (d′); exact mass m/z calcd

for C₁₁H₂₀FOSi (M - C₄H₉) 215.1267, found 215.1267.

cis-Bis(1,1-d im eth yleth yl)[(2-eth en ylcyclop en tyl)oxy]-

flu or osila n e (10f) fr om 10d . BF₃‚Et₂O (0.10 mL, 0.8 mmol)

was added to a stirred and cooled (0 °C) solution of 10d (23.8

mg, 0.066 mmol) in dry CH₂Cl₂(2.5 mL).⁴¹Stirring at 0 °C

was continued for 1 h, saturated aqueous NaHCO₃(1 mL) was

added, and the cooling bath was removed. The mixture was

stirred for 15 min, the organic layer was separated, and the

aqueous layer was extracted with CH₂Cl₂. The combined

organic layers were dried (Na₂SO₄) and evaporated. Flash

chromatography of the residue over silica gel (0.5 × 5 cm),

using hexane, gave 10f (11.6 mg, 69%) as a colorless oil, whose

¹H NMR spectrum was identical to that obtained with material

derived from 10e.

[1r(1R*),2r]]-Bis(1,1-d im et h ylet h yl)flu or o[[2-(m et h -

oxym eth oxy)cyclop en tyl]p h en ylm eth yl]sila n e (9f). A so-

lution of MeOCH₂Cl (23.8 mg, 0.295 mmol) in CH₂Cl₂(0.5 mL)

was added at a fast dropwise rate to a stirred solution of 9e

(24.8 mg, 0.074 mmol) and i-Pr₂NEt (47.6 mg, 0.370 mmol) in

CH₂Cl₂(3 mL). Stirring was continued for 24 h, at which point

the reaction was half complete (TLC control, 1:9 silica, EtOAc-

hexane). More MeOCH₂Cl (23.8 mg, 0.295 mmol), i-Pr₂NEt

(47.6 mg, 0.370 mmol), and CH₂Cl₂(3.6 mL) were added, and

stirring was continued for 24 h. Water (10 mL) was added,

and the mixture was extracted with CH₂Cl₂. The combined

organic extracts were dried (Na₂SO₄) and evaporated. Flash

chromatography of the residue over silica gel (1 × 10 cm), using

1:99 EtOAc-hexane, gave 9f (16.7 mg, 60%) as a colorless oil,

which was used directly for conversion into 9g.

cis-Bis(1,1-d im eth yleth yl)[(2-eth en ylcyclop en tyl)oxy]-

sila n ol (10h ). Alcohol 10e (13.5 mg, 0.050 mmol) was added

to a stirred slurry of t-BuOK (8.8 mg, 0.075 mmol) in dry THF

(1 mL). Stirring at room temperature was continued for 10

min, saturated aqueous NH₄Cl (ca. 5 drops) and water (2 mL)

[1r(R*),2r]-Bis(1,1-dim eth ylethyl)[[2-(m eth oxym ethoxy)-

cyclop en tyl]p h en ylm eth yl]sila n ol (9g). H₂O₂(30% in H₂O,

0.18 mL, 1.6 mmol) was added to a stirred mixture of KF‚

(41) Tamao, K.; Ishida, N. Tetrahedron Lett. 1984, 25, 4245-4248.

Preparation of Polycyclic Systems

J . Org. Chem., Vol. 66, No. 6, 2001 1975

were added sequentially, and the mixture was extracted with

CH₂Cl₂. The combined organic extracts were dried (Na₂SO₄)

and evaporated to give 10h (11.2 mg, 83%) as a colorless oil:

FTIR (CHCl₃cast) 3492, 2965, 2934, 2859, 1473, 1136, 1056,

mg, 83%) as an oil: FTIR (CHCl₃cast) 3362, 1474, 1034, 822

1

cm^-1; H NMR (CDCl₃, 200 MHz) δ 1.24 (s, 18 H), 1.38-1.91

(m, 6 H), 1.98-2.11 (m, 2 H), 2.47-2.60 (m, 1 H), 3.97 (d, J )

8.5 Hz, 2 H), 4.47 (td, J ) 6.0, 2.6 Hz, 1 H); ¹³C NMR (CDCl₃,

50.3 MHz) δ 20.5 (s′), 21.9 (s′), 25.0 (t′), 26.2 (t′), 27.9 (q′), 28.6

(q′), 31.8 (d′), 35.5 (t′), 45.9 (d′), 62.2 (t′), 83.7 (d′); exact mass

1

911, 828 cm^-1; H NMR (CDCl₃, 400 MHz) δ 1.00 (s, 18 H),

1.53-1.91 (m, 7 H), 2.36 (dddd, J ) 9.0, 9.0, 9.0, 4.0 Hz, 1 H),

4.41-4.46 (m, 1 H), 5.00-5.09 (m, 2 H), 6.01 (ddd, J ) 17.5,

10.0, 8.0 Hz, 1 H); ¹³C NMR (CDCl₃, 75.5 MHz) δ 20.5 (s′),

20.8 (s′), 21.9 (t′), 27.7 (q′), 27.8 (q′), 28.9 (t′), 35.5 (t′), 50.7

(d′), 77.8 (d′), 114.8 (t′), 140.2 (d′); exact mass m/z calcd for

m/z calcd for

213.13068.

C₁₁H₂₁O₂Si (M - C₄H₉) 213.13109, found

Tr ieth yl(2-p r op yn yloxy)sila n e (25). Compound 25 was

prepared by a method different from that given in the

literature.²³Propargyl alcohol (987.1 mg, 17.64 mmol) and

imidazole (2.396 g, 35.23 mmol) were dissolved in THF (25

mL). Neat Et₃SiCl (332.4 mg, 22.03 mmol) was added dropwise

over 15 min to produce a white slurry, which was refluxed for

12 h. The mixture was cooled, poured into water (100 mL),

extracted with EtOAc, and dried (MgSO₄). Evaporation of the

solvent and flash chromatography of the residue over silica

gel (4 × 25 cm), using hexane, gave 25²³as an oil, characterized

by spectroscopic comparison with published data.

C

₁₅H₃₀O₂Si (M - C₄H₉) 303.1780, found 303.1782.

(3r,3a â,6a â)-[2,2-Bis(1,1-d im eth yleth yl)h exa h yd r o-2H-

cyclop en t[d ]-1,2-oxa silol-3-yl]ca r boxa ld eh yd e (10g). Dry

DMSO (0.17 mL, 2.2 mmol) was added dropwise to a stirred

and cooled (-78 °C) solution of (COCl)₂(0.10 mL, 1.1 mmol)

in CH₂Cl₂(3.5 mL).⁴²Stirring was continued for 15 min, and

a portion of this solution (ca. 0.3 mL) was quickly withdrawn

into a syringe and transferred to a stirred and cooled (-78

°C) solution of 10e (18.5 mg, 0.068 mmol) in CH₂Cl₂(1 mL).

Stirring at -78 °C was continued for 15 min, and dry Et₃N

(0.1 mL) was added. Stirring was continued for 5 min, the

cooling bath was removed, and the mixture was allowed to

reach room temperature. Water (1 mL) was added, the organic

layer was separated, and the aqueous layer was extracted with

CH₂Cl₂. The combined organic extracts were dried (Na₂SO₄)

and evaporated. Flash chromatography of the residue over

silica gel (1 × 5 cm), using 1:9 EtOAc-hexane, gave 10g (12.4

mg, 67%) as a slightly impure [¹H NMR (300 MHz)], colorless

Eth yl 3-[(P h en ylselen o)m eth yl]-4-p yr id in eca r boxyla te

(19bb). PhSeSePh (188.2 mg, 0.60 mg) and NaH (80% disper-

sion in mineral oil, 32.2 mg, 1.07 mmol) and a Teflon-coated

stirring bar were placed in a round-bottomed flask carrying a

condenser sealed with a septum. The system was flushed with

Ar for 10 min, and THF (2 mL) was injected. The solution was

stirred and heated at 60 °C for 1 h to give a bright yellow

suspension, which was then allowed to cool. A solution of

HMPA (0.1 mL) and 19a a ⁴⁴(100.3 mg, 0.83 mmol) in THF (2

mL) was added with stirring, to produce a bright orange

mixture, which was stirred and heated at 60 °C for 22 h, and

then cooled. MeOH (1 mL) was added to quench the reaction,

and the solvents were evaporated. Water (30 mL) was added

to the residue, and the mixture was extracted with Et₂O. The

aqueous phase was evaporated to dryness, and the residue was

dissolved in EtOH that had been saturated with HCl (50 mL).

The resulting solution was refluxed for 5 h, cooled, and

evaporated. Saturated aqueous NaHCO₃(20 mL) and water

(25 mL) were added to the residue, and the mixture was

extracted with EtOAc. Evaporation of the solvent and flash

chromatography of the residue over silica gel (2.5 × 25 cm),

using 1:1 EtOAc-hexane, gave 19bb (180.2 mg, 68%) as an

oil: FTIR (CHCl₃cast) 2979, 1723 cm^-1; ¹H NMR (CDCl₃, 300

MHz) δ 1.29 (t, J ) 7.1 Hz, 3 H), 4.26 (q, J ) 7.2 Hz, 2 H),

4.30 (s, 2 H), 7.05-7.22 (m, 3 H), 7.25-7.30 (m, 2 H), 7.58 (d,

J ) 5.0 Hz, 1 H), 8.12 (s, 1 H), 8.44 (d, J ) 5.0 Hz, 1 H); ¹³C

NMR (CDCl₃, 50.3 MHz) δ 13.9 (q′), 27.5 (t′), 61.5 (t′), 123.4

(d′), 127.8 (d′), 128.8 (d′), 134.7 (d′), 135.2 (s′), 135.4 (s′), 148.5

(d′), 151.5 (d′), 165.4 (s′); exact mass m/z calcd for C₁₅H₁₅NO₂-

Se 321.02679, found 321.026118.

3-[(P h en ylselen o)m et h yl]-4-p yr id in eca r b oxa ld eh yd e

(19a ). Ester 19bb (126.1 mg, 0.39 mmol) and a Teflon-coated

stirring bar were placed in a round-bottomed flask sealed with

a septum. The system was flushed with Ar for 10 min, and

CH₂Cl₂(4 mL) was injected. The solution was cooled to -78

°C, and after 10 min, DIBAL-H (1.0 M in CH₂Cl₂, 0.43 mL,

0.43 mmol) was injected over 2 min with stirring. Stirring was

continued for an additional 25 min, the cooling bath was

removed, and stirring was continued for 10 min. The solution

was then filtered through a pad (1.5 × 4 cm) of Celite, using

CH₂Cl₂. Evaporation of the solvent and flash chromatography

of the residue over silica gel (2 × 25 cm), using 2:3 EtOAc-

hexane, gave 19a (44.6 mg, 41%, 89% corrected for recovered

19bb) as an oil: FTIR (CHCl₃cast) 2794, 1704 cm^-1; ¹H NMR

(CDCl₃, 300 MHz) δ 4.35 (s, 2 H), 7.16-7.40 (m, 5 H), 7.57 (d,

J ) 4.9 Hz, 1 H), 8.29 (s, 1 H), 8.68 (d, J ) 4.9 Hz, 1 H), 10.16

(s, 1 H); ¹³C NMR (CDCl₃, 50.3 MHz) δ 25.6 (t′), 123.8 (d′),

128.2 (s′), 128.6 (d′), 129.3 (d′), 134.8 (s′), 135.5 (d′), 138.1 (s′),

oil: FTIR (CDCl₃cast) 2936, 2860, 1692, 1474, 1069, 823 cm^-1

;

¹H NMR (CDCl₃, 300 MHz) δ 1.03 (s, 9 H), 1.09 (s, 9 H), 1.29-

2.13 (m, 6 H), 3.03 (dd, J ) 8.0, 3.5 Hz, 1 H), 4.53 (ddd, J )

6.0, 6.0, 2.5 Hz, 1 H), 9.92 (d, J ) 3.5 Hz, 1 H); ¹³C NMR

(CDCl₃, 75.5 MHz) δ 20.8 (s′), 22.5 (s′), 25.7 (t′), 27.7 (q′), 27.8

(t′), 28.3 (q′), 34.7 (t′), 45.5 (d′), 47.2 (d′), 84.4 (d′), 203.6 (d′);

exact mass m/z calcd for C₁₅H₂₈O₂Si 268.1859, found 268.1854.

1-Meth oxy-4-[(2-pr opyn yloxy)m eth yl]ben zen e (24). The

following procedure differs from that given in the literature.²¹

NaH (80% dispersion in mineral oil, 1.602 g, 53.51 mmol)

was suspended in a mixture of THF (20 mL) and DMF (2.5

mL), and the mixture was stirred at 0 °C for 10 min. Propargyl

alcohol (1.504 g, 26.76 mmol) was added dropwise over 10 min,

to give a light brown slurry, which was stirred for 2 h.

p-Methoxybenzyl chloride (4.193 g, 26.76 mmol) was added

over 15 min, after which time the ice bath was removed and

stirring was continued overnight. The mixture was poured into

water (150 mL) and extracted with Et₂O. The combined organic

extracts were washed with brine and dried (MgSO₄). Evapora-

tion of the solvent and flash chromatography of the residue

over silica gel (5 × 25 cm), using hexane (750 mL), followed

by 1:19 EtOAc-hexane (1500 mL), gave 24²¹(3.254 g, 69%)

as an oil: FTIR (CH₂Cl₂cast) 3289, 3001, 2937, 2115, 1442,

1

819 cm^-1; H NMR (CDCl₃, 400 MHz) δ 2.53 (t, J ) 2.3 Hz, 1

H), 3.78 (s, 3 H), 4.17 (d, J ) 2.5 Hz, 2 H), 4.55 (s, 2 H), 6.84

(d, J ) 8.7 Hz, 2 H), 7.36 (d, J ) 8.7 Hz, 2 H); ¹³C NMR (CDCl₃,

50.3 MHz) δ 55.18 (q′), 56.96 (t′), 71.10 (t′), 74.7 (d′), 79.93

(s′), 113.86 (d′), 129.40 (s′), 129.81 (d′), 159.45 (s′); exact mass

m/z calcd for C₁₁H₁₂O₂176.08372, found 176.08372.

(3r,3a â,6a â)-2,2-Bis(1,1-d im eth yleth yl)h exa h yd r o-2H-

cyclop en t[d ]-1,2-oxa silole-3-m eth a n ol (11e ) 10e) fr om

11d . Compound 11d (214.4 mg, 0.55 mmol) and a Teflon-

coated stirring bar were placed in a round-bottomed flask that

was sealed with a septum. The system was flushed with Ar

for 20 min, and CH₂Cl₂(7.5 mL) and water (0.35 mL) were

injected. DDQ⁴³(187.2 mg, 0.82 mmol) was added to produce

a dark green mixture, which quickly changed to a light beige

color. Stirring was continued for 1 h. The mixture was poured

into saturated aqueous NaHCO₃(10 mL) and water (30 mL)

and extracted with CH₂Cl₂. The combined organic extracts

were washed with brine and dried (MgSO₄). Evaporation of

the solvent and flash chromatography of the residue over silica

gel (2 × 25 cm), using 3:17 EtOAc-hexane, gave 11e (122.8

149.6 (d′), 152.3 (d′), 191.2 (d′); exact mass m/z calcd for C₁₃H₁₁

-

NO⁸⁰Se 277.00058, found 277.00039.

5-[(1,1-Dim eth yleth yl)d ip h en ylsilyl)oxy]-2-(p h en ylse-

len o)p en ta n a l (21bb). Dry Et₂NH (1.80 mL, 1.27 g, 1.7 mmol)

was added to a stirred and cooled (0 °C) solution of PhSeCl

(42) Mancuso, A. J .; Swern, D. Synthesis 1981, 165-185.

(43) Cf. Horita, K.; Yoshioka, T.; Tanaka, T.; Oikawa, Y.; Yonemitsu,

O. Tetrahedron, 1986, 42, 3021-3028.

(44) Epsztajn, J .; J ozwiak, A.; Szczesniak, A. K. Synth. Commun.

1994, 24, 1789-1798.

1976 J . Org. Chem., Vol. 66, No. 6, 2001

Clive et al.

(1.64 g, 8.56 mmol) in dry hexane (40 mL).⁴⁵The red solution

turned yellow, and a precipitate formed. Stirring at 0 °C was

continued for 15 min, the cooling bath was removed, and the

mixture was allowed to stand for 15 min so that the precipitate

settled. The supernatant layer was transferred by syringe to

a stirred and cooled (-78 °C) solution of 21a a ⁴⁶(2.62 g, 7.70

mmol) in dry CH₂Cl₂(40 mL). The residual salts were washed

with dry hexane (20 mL), and the rinsings were transferred,

again by syringe, into the reaction mixture. Stirring at -78

°C was continued for 30 min, and brine (100 mL) was added.

The cooling bath was removed, and the mixture was allowed

to reach room temperature. The organic layer was separated,

and the aqueous layer was extracted with CH₂Cl₂. The

combined organic layers were dried (Na₂SO₄) and evaporated.

Flash chromatography of the residue over silica gel (2 × 15

cm), using first 2:49 EtOAc-hexane, and then 1:9 EtOAc-

hexane, gave 21bb as an impure [¹H NMR (300 MHz)] oil,

suitable for the next step (formation of 21cc).

3 H), 1.83-1.97 (m, 2 H), 3.30-3.49 (m, 1 H), 3.66 (t, J ) 6.0

Hz, 2 H), 3.75 (s, 3 H), 4.22 (dd, J ) 11.0, 8.5 Hz, 1 H), 4.36

(dd, J ) 11.0, 5.0 Hz, 1 H), 7.24-7.34 (m, 3 H), 7.56-7.62 (m,

2 H); ¹³C NMR (CDCl₃, 75.5 MHz) δ 28.1 (t′), 30.7 (t′), 42.9

(d′), 54.8 (q′), 62.4 (t′), 70.6 (t′), 127.7 (s′), 128.0 (d′), 128.1 (d′),

135.1 (d′), 155.5 (s′); exact mass m/z calcd for C₁₃H₁₈O₄⁸⁰Se

318.0370, found 318.0369. Anal. Calcd for C₁₃H₁₈O₄Se: C,

49.22; H, 5.72. Found: C, 49.10; H, 5.71.

5-Oxo-2-(p h en ylselen o)p en tyl Meth yl Ca r bon a te (21a ).

Dry DMSO (0.49 mL, 6.88 mmol) was added dropwise to a

stirred and cooled (-63 °C) solution of (COCl)₂(0.30 mL, 3.44

mmol) in dry CH₂Cl₂(10 mL). Stirring was continued for 10

min, and a solution of 21ee (876.7 mg, 2.76 mmol) in CH₂Cl₂

(2.5 mL plus 2.5 mL as a rinse) was added over 5 min. Stirring

was continued for 15 min, and dry Et₃N (2.07 mL, 14.9 mmol)

was added. Stirring was continued for 5 min, the cooling bath

was removed, and the mixture was allowed to reach room

temperature. Water (50 mL) was added, and the mixture was

extracted with CH₂Cl₂. The combined organic extracts were

dried (Na₂SO₄) and evaporated. Flash chromatography of the

residue over silica gel (2.8 × 18 cm), using 1:4 EtOAc-hexane,

gave 21a (585.7 mg, 67%) as a slightly yellow oil: FTIR (CHCl₃

cast) 1749, 1723, 1439, 1264 cm^-1; ¹H NMR (CDCl₃, 400 MHz)

δ 1.73-1.86 (m, 1 H), 2.13-2.25 (m, 1 H), 2.65-2.76 (m, 1 H),

2.77-2.87 (m, 1 H), 3.30-3.37 (m, 1 H), 3.76 (s, 3 H), 4.09

(dd, J ) 11.0, 8.5 Hz, 1 H), 4.40 (dd, J ) 11.0, 5.0 Hz, 1 H),

7.25-7.36 (m, 3 H), 7.54-7.60 (m, 2 H), 9.79 (t, J ) 1.0 Hz, 1

H); ¹³C NMR (CDCl₃, 75.5 MHz) δ 24.1 (t′), 42.0 (t′), 42.4 (d′),

54.9 (t′), 70.4 (t′), 127.2 (s′), 128.3 (d′), 129.3 (d′), 135.2 (d′),

155.5 (s′), 201.0 (d′); exact mass m/z calcd for C₁₃H₁₆O₄⁸⁰Se

316.0214, found 316.0212. Anal. Calcd for C₁₃H₁₆O₄Se: C,

49.53; H, 5.12. Found: C, 49.74; H, 5.22.

5-[(1,1-Dim eth yleth yl)d ip h en ylsilyl)oxy]-2-(p h en ylse-

len o)-1-p en ta n ol (21cc). NaBH₄(1.17 g, 3.1 mmol) was added

in 10 portions (over ca. 10 min) to a stirred and cooled (0 °C)

solution of 21bb and 21a a in MeOH (75 mL). Stirring at 0 °C

was continued for 1 h. Water (100 mL) was then added, the

cooling bath was removed, and the mixture was acidified to

ca. pH 6, using AcOH (ca. 1 mL). The mixture was extracted

with Et₂O and the combined organic extracts were dried

(Na₂SO₄) and evaporated. Flash chromatography of the residue

over silica gel (2.8 × 30 cm), using 1:9 EtOAc-hexane, gave

21cc (1.890 g, 49%) as a slightly yellow oil: FTIR (CDCl₃cast)

3432, 3070, 2931, 2857, 1111, 702 cm^-1; ¹H NMR (CDCl₃, 300

MHz) δ 1.00 (s, 9 H), 1.58-1.94 (m, 4 H), 2.25 (br s, 1 H), 3.15-

3.26 (m, 1 H), 3.50 (dd, J ) 11.5, 6.5 Hz, 1 H), 3.60 (dd, J )

11.5, 5.0 Hz, 1 H), 3.64-3.72 (m, 2 H), 7.19-7.45 (m, 9 H),

7.49-7.56 (m, 2 H), 7.62-7.70 (m, 4 H); ¹³C NMR (CDCl₃, 75.5

MHz) δ 19.2 (s′), 26.9 (q′), 28.1 (t′), 30.7 (t′), 50.2 (d′), 63.4 (t′),

64.4 (t′), 127.3 (s′), 127.7 (d′), 128.0 (d′), 129.1 (d′), 129.6 (d′),

133.9 (s′), 135.5 (d′), 135.6 (d′); exact mass m/z calcd for

5-Hydr oxy-7-ph en yl-2-(ph en ylselen o)-6-h eptyn yl Meth -

yl Ca r bon a te (21b). The general procedure for addition of

an acetylide to an aldehyde was followed, using 22 (210 mg,

2.06 mmol) in THF (12 mL), n-BuLi (1.6 M in hexanes, 1.18

mL, 1.89 mmol), an initial reaction time of 15 min, and 21a

(540.9 mg, 1.72 mmol) in THF (2.5 mL plus 2.5 mL as a rinse).

Stirring at -78 °C was continued for 45 min, 10% aqueous

KHSO₄(5 mL) and water (50 mL) were added, and the mixture

was allowed to attain room temperature and extracted with

CH₂Cl₂. The combined organic extracts were dried (Na₂SO₄)

and evaporated. Flash chromatography of the residue over

silica gel (2.8 × 20 cm), using increasing amounts of EtOAc in

hexane (from 15% to 25%), gave 21b (493.5 mg, 69%) as an

inseparable (TLC, silica, 1:9 EtOAc-hexane) 1:1 mixture of

isomers [¹H NMR (400 MHz)]: FTIR (CHCl₃cast) 3440, 3056,

C

₂₇H₃₄O₂⁸⁰SeSi 498.1493, found 498.1493. Anal. Calcd for

₂₇H₃₄O₂SeSi: C, 65.17; H, 6.89. Found: C, 65.34; H, 6.96.

5-[(1,1-Dim eth yleth yl)d ip h en ylsilyl)oxy]-2-(p h en ylse-

len o)p en tyl Meth yl Ca r bon a te (21d d ). MeOCOCl (0.55 mL,

7.1 mmol) was added dropwise to a stirred and cooled (0 °C)

solution of alcohol 21cc (1.798 g, 3.61 mmol) and dry pyridine

(0.58 mL, 7.2 mmol) in dry CH₂Cl₂(36 mL). Stirring at 0 °C

was continued for 1 h, and the cooling the bath was then

removed. CH₂Cl₂(100 mL) was added, and the mixture was

washed with 10% aqueous KHSO₄. The organic layer was dried

(Na₂SO₄) and evaporated. Flash chromatography of the residue

over silica gel (2.8 × 25 cm), using 1:19 EtOAc-hexane, gave

21d d (1.755 g, 84%) as a slightly yellow oil: FTIR (CDCl₃cast)

2931, 1750, 1263, 1111, 702 cm^-1; ¹H NMR (CDCl₃, 400 MHz)

δ 1.05 (s, 9 H), 1.54-1.77 (m, 2 H), 1.85-1.98 (m, 2 H), 3.28-

3.37 (m, 1 H), 3.64-3.70 (m, 2 H), 3.74 (s, 3 H), 4.19 (dd, J )

11.5, 8.5 Hz, 1 H), 4.33 (dd, J ) 11.5, 5.5 Hz, 1 H), 7.23-7.32

(m, 3 H), 7.35-7.46 (m, 6 H), 7.53-7.58 (m, 2 H), 7.64-7.69

(m, 4 H); ¹³C NMR (CDCl₃, 75.5 MHz) δ 19.3 (s′), 26.0 (q′),

28.1 (t′), 30.5 (t′), 43.0 (q′), 54.8 (d′), 63.4 (t′), 70.6 (t′), 127.7

(d′), 127.8 (s′), 128.0 (d′), 129.2 (d′), 129.6 (d′), 133.9 (s′), 135.2

(d′), 135.6 (d′), 155.6 (s′); exact mass m/z calcd for C₂₉H₃₆O₄⁸⁰SeSi

556.1548, found 556.1553. Anal. Calcd for C₂₉H₃₆O₄SeSi: C,

62.69; H, 6.53. Found: C, 62.68; H, 6.50.

5-Hyd r oxy-2-(p h en ylselen o)p en tyl Meth yl Ca r bon a te

(21ee). n-Bu₄NF (3.88 mL, 1.0 M in THF, 3.88 mmol) was

added to a stirred solution of 21d d (1.707 g, 3.07 mmol) and

glacial AcOH (0.22 mL, 3.84 mmol) in dry THF (28 mL).

Stirring was continued for 22 h, and the mixture was evapo-

rated. Flash chromatography of the residue over silica gel (2.8

× 19 cm), using 2:3 EtOAc-hexane, gave 21ee (928.8 mg, 95%)

as a slightly yellow oil: FTIR (CHCl₃cast) 3382, 2953, 1748,

1439, 1265 cm^-1; ¹H NMR (CDCl₃, 400 MHz) δ 1.54-1.78 (m,

1748, 1441, 1266, 692 cm^-^{1 1}H NMR (CDCl₃, 400 MHz) δ

;

1.68-1.85 (m, 1 H), 1.91-2.23 (m, 3 H), 2.30 (br s, 1 H), 3.32-

3.43 (m, 1 H), 3.72 (two s, 3 H), 4.21 and 4.22 (two dd, J )

11.0, 6.5 Hz, 1 H), 4.36 and 4.37 (two dd, J ) 11.0, 5.0 Hz, 1

H), 4.60-4.68 (m, 1 H), 7.19-7.35 (m, 6 H), 7.38-7.46 (m, 2

H), 7.57-7.63 (m, 2 H); ¹³C NMR (CDCl₃, 75.5 MHz) δ 27.1

(t′), 27.3 (t′), 35.6 (t′), 35.7 (t′), 42.6 (d′), 42.7 (d′), 54.8 (q′),

62.3 (d′), 62.5 (d′), 70.5 (t′), 85.2 (s′), 85.3 (s′), 89.6, 89.6 (two

s′), 122.4 (s′), 127.4 (s′), 127.5 (s′), 128.0 (d′), 128.3 (d′), 128.4

(d′), 129.1 (d′), 132.0 (d′), 135.2 (d′), 135.3 (d′), 155.5 (s′); exact

mass m/z calcd for C₂₁H₂₂O₄⁸⁰Se 418.0683, found 418.0667.

Anal. Calcd for C₂₁H₂₂O₄Se: C, 60.43; H, 5.31. Found: C, 60.29;

H, 5.28.

5-[[Bis(1,1-dim eth yleth yl)silyl]oxy]-7-ph en yl-2-(ph en yl-

selen o)-6-h ep tyn yl Meth yl Ca r bon a te (21c). The general

procedure for silylation of alcohols was followed, using 21b

(443.5 mg, 1.06 mmol) in THF (9 mL), imidazole (144.7 mg,

2.13 mmol), t-Bu₂SiHCl (228.0 mg, 1.28 mmol) in THF (1 mL

plus 1 mL as a rinse), and a reflux time of 1.75 h. The mixture

was cooled, diluted with water (50 mL), and extracted with

CH₂Cl₂. The combined organic extracts were dried (Na₂SO₄)

and evaporated. Flash chromatography of the residue over

silica gel (2 × 15 cm), using 3:97 EtOAc-hexane, gave 21c

(522.3 mg, 88%) as a mixture of isomers [¹H NMR (400 MHz)]:

FTIR (CHCl₃cast) 2957, 2930, 2856, 2096, 1751, 1263, 826

cm^-1; ¹H NMR (CDCl₃, 300 MHz) δ 1.01 and 1.02 (two s, 9 H),

1.06 (two s, 9 H), 1.73-1.86 (m, 1 H), 1.90-2.00 (m, 1 H), 2.05-

2.23 (m, 2 H), 3.34-3.43 (m, 1 H), 3.72 and 3.73 (two s, 3 H),

(45) J efson, M.; Meinwald, J . Tetrahedron Lett. 1981, 22, 3561-

3564.

(46) Barrett, A. G. M.; Flygare, J . A. J . Org. Chem. 1991, 56, 638-

642.

Preparation of Polycyclic Systems

J . Org. Chem., Vol. 66, No. 6, 2001 1977

4.14 (two s, 1 H), 4.22 and 4.24 (two dd, J ) 11.0, 3.0 Hz, 1

H), 4.38 (dd, J ) 11.0, 5.5 Hz, 1 H), 4.70-4.76 (m, 1 H), 7.20-

7.33 (m, 6 H), 7.38-7.44 (m, 2 H), 7.57-7.63 (m, 2 H); ¹³C NMR

(CDCl₃, 75.5 MHz) δ 19.9 (s′), 20.2 (s′), 27.0 (t′), 27.2 (t′), 27.37

(q′), 27.40 (q′), 36.3 (t′), 36.4 (t′), 42.8 (d′), 42.9 (d′), 54.8 (q′),

66.3 (d′), 66.3 (d′), 70.3 (t′), 85.4 (s′), 89.9 (s′), 123.0 (s′), 127.6

(s′), 128.1 (d′), 128.3 (d′), 129.2 (d′), 131.7 (d′), 135.35 (d′),

135.38 (d′), 155.6 (s′); exact mass m/z calcd for C₂₉H₄₀O₄⁸⁰SeSi

560.1861, found 560.1856. Anal. Calcd for C₂₉H₄₀O₄SeSi: C,

62.24; H, 7.20. Found: C, 62.27; H, 7.37.

suspension was stirred and refluxed for 1 h and then cooled

to room temperature. HMPA (0.30 mL, 1.7 mmol) was added,

followed by a solution of 29bb⁴⁷(280.0 mg, 2.64 mmol) in THF

(1 mL plus 1 mL as a rinse). The resulting mixture was

refluxed for 6 h. Water (2 mL) and 6 N HCl (2 mL) were added,

and the mixture was extracted with CH₂Cl₂. The organic layer

was washed with brine, dried (MgSO₄), and evaporated. The

residue (crude 29cc) was redissolved in MeOH (40 mL),

concentrated H₂SO₄(five drops) was added, and the solution

was refluxed overnight. The solvent was evaporated, and the

residue was dissolved in EtOAc (40 mL), washed with satu-

rated aqueous NaHCO₃and brine, and dried (Na₂SO₄). Evapo-

ration of the solvent and flash chromatography of the residue

over silica gel (2 × 20 cm), using 1:10 EtOAc-hexane, gave

29d d (547.0 mg, 80%) as a colorless oil: FTIR (CHCl₃, cast)

[2,2-Bis(1,1-dim eth yl)h exah ydr o-3-ph en yl-2H-cyclopen t-

[d ]-1,2-oxa silol-4-yl]m eth yl Meth yl Ca r bon a te (21d ). The

general procedure for radical cyclization was followed, using

21c (167.9 mg, 0.30 mmol) in PhH (45 mL), Ph₃SnH (210.6

mg, 0.60 mmol) in PhH (7.5 mL), AIBN (24.6 mg, 0.15 mmol)

in PhH (7.5 mL), and an addition time of 6 h. Refluxing was

continued for 30 min after the stannane addition. Evaporation

of the solvent, and flash chromatography of the residue over

silica gel (1.8 × 17 cm), using increasing amounts of CH₂Cl₂

in hexane (from 1% to 5%, 1% increments), gave 21d (82.1 mg,

67%) as a mixture of two isomers [¹H NMR (400 MHz)]: FTIR

1

2951, 1754 cm^-1; H NMR (CDCl₃, 200 MHz) δ 3.78 (s, 3 H),

4.29 (s, 2 H), 5.4 (t, J ) 9.7 Hz, 2 H), 7.22-7.35 (m, 3 H), 7.53-

7.70 (m, 2 H); ¹³C NMR (CDCl₃, 50.3 MHz) δ 52.0 (q′), 65.5

(t′), 72.5 (t′), 127.4 (d′), 129.2 (d′), 130.0 (s′), 132.9 (d′), 169.9

(s′); exact mass m/z calcd for C₁₀H₁₂O₃⁸⁰Se 259.99518, found

259.99503.

1

(CHCl₃cast) 2956, 2859, 1749, 1269 cm^-1; H NMR (CDCl₃,

[(P h en ylselen o)m eth oxy]a ceta ld eh yd e (29a ). DIBAL-H

(0.80 mL, 1.0 M in CH₂Cl₂, 0.80 mmol) was added dropwise to

a stirred and cooled (-78 °C) solution of 29d d (130.0 mg, 0.5

mmol) in CH₂Cl₂(20 mL). The solution was stirred at -78 °C

for 1.5 h after the addition. Water (1 mL) was added, and the

cold bath was removed. Stirring was continued for 1 h, the

solvent was evaporated, and the residue was dissolved in Et₂O

(30 mL), washed with 3 N HCl (3 × 20 mL), and saturated

aqueous Na₂CO₃, and dried (Na₂SO₄). Evaporation of the

solvent and flash chromatography of the residue over silica

gel (2 × 20 cm), using 1:4 EtOAc-hexane, gave 29a (91.0 mg,

80%) as a colorless oil: FTIR (CH₂Cl₂, cast) 3051, 2987, 2814,

1736 cm^-1; ¹H NMR (CDCl₃, 300 MHz) δ 4.21 (s, 2 H), 5.35 (s,

2 H), 7.25-7.35 (m, 3 H), 7.55-7.65 (m, 2 H), 9.71 (s, 1 H);

¹³C NMR (CDCl₃, 75.5 MHz) δ 72.9 (t′), 74.2 (t′), 127.6 (d′),

129.2 (d′), 129.7 (s′), 132.9 (d′), 203.9 (s′); exact mass m/z calcd

for C₉H₁₀O₂⁸⁰Se 229.98460, found 229.98376.

300 MHz) δ 1.03 (s, 1.5 H), 1.07 (s, 6.5 H), 1.08 (s, 2.5 H), 1.13

(s, 6.5 H), 1.47-2.68 (m, 6 H), 3.16-3.33 (m, 1 H), 3.61-3.81

(m, 5 H), 4.52-4.58 (m, 0.72 H), 4.66-4.70 (m, 0.28 H), 7.12-

7.20 (m, 1 H), 7.21-7.33 (m, 4 H); ¹³C NMR (CDCl₃, 75.5 MHz)

(signals associated with the minor isomer are marked by an

asterisk) δ 21.2 (s′), 21.6* (s′), 22.5* (s′), 22.7 (s′), 28.25* (q′),

28.30 (t′), 28.4 (q′), 28.7 (q′), 29.3* (q′), 33.4* (t′), 33.7 (t′), 34.3*

(d′), 37.1 (d′), 39.2 (d′), 41.0* (t′), 48.6* (d′), 51.3 (d′), 54.5* (d′),

54.6 (d′), 68.9* (t′), 71.8 (t′), 83.6* (d′), 84.2 (d′), 125.4* (d′),

125.5 (d′), 128.3* (d′), 128.4 (d′), 129.9* (d′), 130.4 (d′), 140.4

(s′), 141.0* (s′), 155.5* (s′), 155.8 (s′); exact mass m/z calcd for

C₂₃H₃₆O₄Si 404.2383, found 404.2388. Anal. Calcd for C₂₃H₃₆O₄-

Si: C, 68.27; H, 8.97. Found: C, 68.18; H, 9.01.

(3r,3a â,4â,6a â)-2,2-Bis(1,1-d im eth yleth yl)h exa h yd r o-3-

ph en yl-2H-cyclopen t[d]-1,2-oxasilole-4-m eth an ol (21f) an d

(4r,4a r,5â,7a r)-3,3-Bis(1,1-d im et h ylet h yl)oct a h yd r o-5-

h yd r oxy-4-p h en ylcyclop en t[d ][1,2]oxa silin (21g). Anhy-

drous K₂CO₃(24.5 mg, 0.18 mmol) was added to a stirred

solution of 21d (71.7 mg, 0.18 mmol) in MeOH (18 mL).

Stirring at room temperature was continued for 3 days, and

the mixture was evaporated. Flash chromatography of the

residue over silica gel (1 × 10 cm), using increasing amounts

of EtOAc in hexane (from 5% to 20%), gave 21g (16.7 mg, 27%)

and 21f (41.3 mg, 67%).

4-P h en yl-1-[(ph en ylselen o)m eth oxy]-3-bu tyn -2-ol (29b).

The general procedure for addition of an acetylide to an

aldehyde was followed, using 22 (40.0 mg, 0.38 mmol) in THF

(15 mL), n-BuLi (1.6 M solution in hexanes, 0.20 mL, 0.32

mmol), an initial reaction time of 30 min, and 29a (72.5 mg

0.32 mmol) in THF (4 mL plus 1 mL as a rinse). Stirring at

-78 °C was continued for 1 h, saturated aqueous NH₄Cl (10

mL) was added, and the mixture was allowed to attain room

temperature and was extracted with Et₂O. The combined

organic extracts were washed with brine, dried (Na₂SO₄) and

evaporated. Flash chromatography of the residue over silica

gel (2 cm × 20 cm), using 1:4 EtOAc-hexane, gave 29b (92.0

mg, 87%) as a colorless oil: FTIR (CHCl₃, cast) 3422, 3055,

Alcohol 21g: mp 120-121.5 °C; FTIR (CHCl₃cast) 3447,

2950, 2933, 2858, 1472, 1076, 1065, 821, 760, 701 cm^-^{1 1}H

;

NMR (CDCl₃, 400 MHz) δ 1.04 (s, 1 H), 1.07 (s, 1 H), 1.24-

1.55 (m, 3 H), 1.68-1.77 (m, 1 H), 1.77-1.86 (m, 1 H), 2.43-

2.57 (m, 1 H), 2.65 (ddd, J ) 13.0, 11.5, 4.0 Hz, 1 H), 3.19 (d,

J ) 13.0 Hz, 1 H), 3.63 (dd, J ) 11.5, 11.5 Hz, 1 H), 4.87-4.95

(m, 2 H), 7.09-7.16 (m, 1 H), 7.22-7.30 (m, 2 H), 7.36-7.43

(m, 2 H); ¹³C NMR (CDCl₃, 75.5 MHz) δ 22.4 (s′), 23.1 (s′), 26.1

(t′), 26.7 (d′), 28.7 (q′), 28.8 (q′), 33.7 (t′), 40.4 (d′), 47.8 (d′),

67.5 (t′), 73.9 (d′), 125.1 (d′), 128.4 (d′), 129.2 (d′), 143.2 (s′);

exact mass m/z calcd for C₂₁H₃₄O₂Si 346.2328, found 346.2332.

The stereochemistry assignment to alcohol 21f was made

by analogy to results with related cyclization products.^1c

Alcohol 21f had: FTIR (CHCl₃cast) 3418, 2936, 2859, 1475,

1

2232 cm^-1; H NMR (CDCl₃, 300 MHz) δ 2.46 (d, J ) 5.4 Hz,

1 H), 3.81 (dd, J ) 9.8, 6.9 Hz, 1 H), 3.89 (dd, J ) 9.8, 3.6 Hz,

1 H), 4.81-4.89 (m, 1 H), 5.39 (dd, J ) 11.3, 10.0 Hz, 2 H),

7.19-7.70 (m, 10 H); ¹³C NMR (CDCl₃, 75.5 MHz) δ 6l.9 (d′),

72.87 (t′), 72.91 (t′), 85.9 (s′), 86.5 (s′), 122.2 (s′), 127.4 (d′),

127.8 (d′), 128.3 (d′), 128.6 (d′), 129.2 (d′), 130.0 (s′), 131.8 (d′),

133.3 (d′); exact mass m/z calcd for C₁₇H₁₆O₂⁸⁰Se 332.03156,

found 332.03159.

Bis(1,1-d im et h ylet h yl)[[3-p h en yl-1-[[(p h en ylselen o)-

m eth oxy]m eth yl]-2-p r op yn yl]oxy]sila n e (29c). t-Bu₂SiHCl

(16.0 mg, 0.089 mmol) was added in one portion to a stirred

solution of 29b (20.4 mg, 0.06 mmol) and Et₃N (0.10 mL, 0.09

mmol) in CH₂Cl₂(1.5 mL), followed by a small crystal of

DMAP. The mixture was refluxed for 2 h, cooled, and evapo-

rated. Flash chromatography of the residue over silica gel (1

× 10 cm), using 1:10 EtOAc-hexane, gave 29c (28.5 mg, 95%)

1

1036, 990, 820, 701 cm^-1; H NMR (CDCl₃, 400 MHz) δ 1.08

(s, 9 H), 1.12 (s, 9 H), 1.21 (br s, 1 H), 1.47-1.57 (m, 1 H),

1.77-1.88 (m, 1 H), 1.88-1.97 (m, 1 H), 2.02-2.15 (m, 1 H),

2.21-2.32 (m, 1 H), 2.45-2.53 (m, 1 H), 3.09 (dd, J ) 10.5,

8.0 Hz, 1 H), 3.26 (dd, J ) 10.5, 5.5 Hz, 1 H), 3.29 (d, J ) 8.0

Hz, 1 H), 4.54 (ddd, J ) 5.0, 5.0, 2.5 Hz, 1 H), 7.13-7.18 (m,

1 H), 7.23-7.36 (m, 4 H); ¹³C NMR (CDCl₃, 75.5 MHz) δ 21.3

(s′), 22.7 (s′), 27.9 (t′), 28.4 (q′), 28.7 (q′), 33.7 (t′), 37.3 (d′),

42.4 (d′), 67.1 (t′), 84.4 (d′), 125.4 (t′), 128.3 (t′), 130.5 (t′), 141.0

(s′); exact mass m/z calcd for C₂₁H₃₄O₂Si 346.2328, found

346.2336.

as a colorless oil: FTIR (CHCl₃, cast) 2104 cm^-^{1 1}H NMR

;

(CDCl₃, 300 MHz) δ 1.05 (s, 9 H), 1.10 (s, 9 H), 3.79-3.92 (m,

2 H), 4.20 (s, 1 H), 4.90 (dd, J ) 6.5, 4.9 Hz, 1 H), 5.20 (d, J )

9.9 Hz, 1 H), 5.31 (d, J ) 9.9 Hz, 1 H), 7.20-7.34 (m, 6 H),

7.40-7.45 (m, 2 H), 7.60-7.70 (m, 2 H); ¹³C NMR (CDCl₃, 75.5

Meth yl [(P h en ylselen o)m eth oxy]a ceta te (29d d ). NaH

(80% dispersion in mineral oil, 142.0 mg, 3.56 mmol) was

added in one portion to a stirred solution of PhSeSePh (623.0

mg, 1.98 mmol) in THF (10 mL) (Ar atmosphere). The

(47) (a) Salomaa, P.; Laiho, S. Acta Chem. Scand. 1963, 17, 103-

110. (b) Farines, M.; Soulier, J . Bull Soc. Chim. Fr. 1970, 332-340.

1978 J . Org. Chem., Vol. 66, No. 6, 2001

Clive et al.

MHz) δ 19.8 (s′), 20.2 (s′), 27.3 (q′), 65.9 (d′), 73.1 (t′), 73.5 (t′),

85.8 (s′), 87.7 (s′), 127.1 (d′), 128.2 (d′), 128.3 (d′), 129.0 (d′),

131.7 (d′), 133.1 (d′). We did not obtain a mass spectrum for

29c.

7.35 (m, 3 H), 7.58-7.70 (m, 2 H), 9.65 (s, 1 H); ¹³C NMR

(CDCl₃, 50.3 MHz) δ 21.0 (q′), 65.6 (s′), 81.9 (t′), 127.5 (d′),

129.3 (d′), 130.2 (s′), 132.7 (d′), 203.4 (d′); exact mass m/z calcd

for C₁₁H₁₄O₂⁸⁰Se 258.01590, found 258.01589.

(3r,3a â,6a â)-2,2-Bis(1,1-d im et h ylet h yl)h exa h yd r o-3-

p h en ylfu r o[3,4-d ]-1,2-oxa silole (29d ). The general proce-

dure for radical cyclization was followed, using 29c (64.3 mg,

0.135 mmol) in PhH (25 mL), Ph₃SnH (90.9 mg, 0.25 mmol)

in PhH (4 mL), AIBN (5.0 mg, 0.03 mmol) in PhH (4 mL), and

an addition time of 6 h. Refluxing was continued for 1 h after

the stannane addition. Evaporation of the solvent, and flash

chromatography of the residue over silica gel (2 × 20 cm), using

1:3 EtOAc-hexane, gave 29d (36.0 mg, 85%) as a white solid:

(2S,3R)- a n d (2S,3S)-6-(P h en ylm eth oxy)-2-[(tr ieth yl-

silyl)oxy]-4-h exyn -3-ol (31bb). n-BuLi (1.6 M solution in

hexanes, 10.0 mL, 16.0 mmol) was added slowly to a stirred

and cooled (-78 °C) solution of 23²¹(2.45 g, 16.78 mmol) in

THF (30 mL). The cold bath was removed and, when the

mixture had reached -30 °C (ca. 30 min), the solution was

cooled to -78 °C. A solution of 31a a ¹⁶(2.743 g, 14.5 mmol) in

THF (3 mL plus 1 mL as a rinse) was added dropwise to the

acetylide solution, and the mixture was stirred for 3 h at -78

°C. Saturated aqueous NH₄Cl (2 mL) was then added, most of

the solvent was evaporated and the residue was mixed with

EtOAc (60 mL). The organic phase was washed with brine and

dried (MgSO₄). Evaporation of the solvent and flash chroma-

tography of the residue over silica gel (2 × 20 cm), using 1:3

EtOAc-hexane, gave 31bb (3.88 g, 80%) as a mixture of two

isomers which were used directly for the next step (formation

of 31a ).

(5R,6S)-3-(1,1-Dim eth yleth yl)-8,8-dieth yl-2,2,6-tr im eth yl-

5-[3-(p h en ylm eth oxy)-1-p r op yn yl]-4,7-d ioxa -3,8-d isila d e-

ca n e (31a ). t-Bu₂SiHCl (1.65 g, 9.22 mmol) was added in one

portion to a stirred solution of 31bb (2.60 g, 7.77 mmol) in

CH₂Cl₂(5 mL). Et₃N (2.50 mL, 10 mmol) was then added,

followed by DMAP (ca. 120 mg), and the solution was refluxed

for 2 h (TLC control, silica, 1:10 EtOAc-hexane). Evaporation

of the solvent and flash chromatography of the residue over

silica gel (3 × 30 cm), using increasing amounts of EtOAc in

hexane (100% hexane to 1:10 EtOAc-hexane), gave crude 31a

(3.32 g,), which was used directly for the next step (formation

of 31b).

mp 106-108 °C; FTIR (CHCl₃, cast) 2965, 2931, 1600 cm^-1

;

¹H NMR (CDCl₃, 300 MHz) δ 1.05 (s, 9 H), 1.14 (s, 9 H), 3.30-

3.37 (m, 1 H), 3.47 (d, J ) 7.9 Hz, 1 H), 3.85 (dd, J ) 9.8, 3.2

Hz, 1 H), 3.92 (dd, J ) 9.2, 7.5 Hz, 1 H), 4.05 (t, J ) 9.3 Hz,

2 H), 4.62-4.68 (m, 1 H), 7.10-7.30 (m, 5 H); ¹³C NMR (CDCl₃,

100.6 MHz) 21.2 (s′), 22.3 (s′), 28.2 (q′), 28.4 (q′), 35.1 (d′), 46.8

(d′), 70.2 (t′), 75.6 (t′), 81.9 (d′), 125.2 (d′), 128.4 (d′), 128.8 (d′),

140.9 (s′); exact mass m/z calcd for C₁₉H₃₀O₂Si 318.20151,

found 318.20106.

cis-3-Hyd r oxy-4-(p h en ylm eth yl)tetr a h yd r ofu r a n (29e).

n-Bu₄NF (1.0 M in THF, 0.75 mL, 0.75 mmol) was added to a

stirred solution of 29d (20.0 mg, 0.063 mmol) in DMF (1 mL),

and stirring was continued for 2 h. Evaporation of the solvent

and flash chromatography of the residue over silica gel (2 ×

10 cm), using EtOAc, gave 29e (8.0 mg, 71%) as a colorless

oil: FTIR (CHCl₃, cast) 3387, 3083 cm^-1; ¹H NMR (CDCl₃, 360

MHz) δ 1.59 (d, J ) 1.9 Hz, 1 H), 2.45-2.57 (m, 1 H), 2.75

(dd, J ) 13.9, 7.27 Hz, 1 H), 2.95 (dd, J ) 13.9, 8.3 Hz, 1 H),

3.65 (dd, J ) 10.3, 8.1 Hz, 1 H), 3.82 (dd, J ) 10.0, 0.9 Hz, 1

H), 3.90-4.00 (m, 2 H), 4.24 (dd, J ) 8.6, 4.1 Hz, 1 H), 7.18-

7.36 (m, 5 H); ¹³C NMR (CDCl₃, 50.3 MHz) 31.8 (t′), 46.6 (d′),

71.2 (t′), 72.6 (d′), 76.3 (t′), 126.3 (d′), 128.6 (two d′), 140.4 (s′);

exact mass m/z calcd for C₁₁H₁₄O₂178.09938, found 178.09902.

Meth yl 2-Meth yl-2-[(ph en ylselen o)m eth oxy]pr opan oate

(30d d ). NaH (80% dispersion in mineral oil, 1.00 g, 33.3 mmol)

was added in portions to a stirred solution of PhSeSePh (5.800

g, 18.55 mmol) in THF (100 mL) (Ar atmosphere). The mixture

was refluxed for 1 h and then cooled to room temperature.

HMPA (2.5 mL, 14.38 mmol) was added, followed by a solution

of 30bb⁴⁷(2.8728 g, 24.74 mmol) in THF (3 mL plus 3 mL as

a rinse). Refluxing was resumed and continued overnight. The

solution was cooled to room temperature, and MeOH (2 mL)

was added. The solvent was evaporated, and the residue was

partitioned between water (50 mL) and Et₂O (50 mL). The

aqueous layer was acidified (3 N HCl) and extracted with Et₂O.

The combined organic extracts were washed with brine and

dried (MgSO₄). The solvent was evaporated and the residue

(crude 30cc) was redissolved in MeOH (50 mL). Concentrated

H₂SO₄(five drops) was added and the mixture was refluxed

overnight. Most of the solvent was evaporated and the residue

was dissolved in Et₂O (50 mL). The solution was washed with

saturated aqueous NaHCO₃, and brine, and dried (Na₂SO₄).

Evaporation of the solvent and flash chromatography of the

residue over silica gel (3 × 30 cm), using 1:5 EtOAc-hexane,

gave 30d d (5.0 g, 70%) as a colorless oil: FTIR (CHCl₃, cast)

(2S,3R)-3-[[Bis(1,1-d im eth yleth yl)silyl]oxy]-6-(p h en yl-

m eth oxy)-4-h exyn -2-ol (31b). Water (0.5 mL) and glacial

AcOH (4 mL) were added to a stirred solution of 31a (100.0

mg, 0.21 mmol) in THF (4 mL). Stirring at room temperature

was continued for ca. 7 h (TLC control, silica, 1:3 EtOAc-

hexane). Water (10 mL) was added, and the mixture was

extracted with CH₂Cl₂. The combined organic extracts were

washed with saturated aqueous Na₂CO₃and dried (MgSO₄).

Evaporation of the solvent and flash chromatography of the

residue over silica gel (2 cm × 20 cm), using 1:5 EtOAc-

hexane, gave two isomers (85.0 mg, 72%, assuming crude 31a

was pure). The major (less polar) isomer (31b) (41.2 mg, 54%)

was fully characterized and used in the next step (formation

1

of 31c): FTIR (CHCl₃, cast) 3431, 3032, 2100 cm^-1; H NMR

(CDCl₃, 300 MHz) δ 1.02 (s, 9 H), 1.04 (s, 9 H), 1.29 (d, J )

6.3 Hz, 3 H), 2.32 (d, J ) 4.7, 1 H), 3.84-3.90 (m, 1 H), 4.20

(s, 1 H), 4.25 (d, J ) 1.6 Hz, 1 H), 4.40-4.50 (m, 1 H), 4.62 (s,

2 H), 7.30-7.42 (m, 5 H); ¹³C NMR (CDCl₃, 75.5 MHz) δ 17.8

(q′), 19.8 (s′), 20.2 (s′), 27.2 (q′), 27.3 (q′), 57.3 (t′), 70.6 (d′),

71.1 (d′), 71.4 (t′), 82.9 (s′), 84.0 (s′), 127.9 (d′), 128.1 (d′), 128.4

(d′), 137.5 (s′); exact mass m/z calcd for C₂₀H₃₀O₃Si (M - C₄H₉)

330.20151, found 330.20129. The polar isomer had: ¹H NMR

(CDCl₃, 300 MHz) δ 1.02 (s, 18 H), 1.33 (d, J ) 6.4 Hz, 3 H),

2.50 (d, J ) 4.7, 1 H), 4.05-4.15 (m, 2 H), 4.25 (s, 2 H), 4.40-

4.45 (m, 1 H), 4.60 (s, 2 H), 7.30-7.42 (m, 5 H).

Se-P h en yl (1S,2R)-O-[2-[[Bis(1,1-d im eth yleth yl)silyl]-

oxy]-1-m eth yl-5-(p h en ylm eth oxy)-3-p en tyn yl]ca r bon ose-

len oa te (31c). A solution of COCl₂in PhMe (ca. 1:1 v/v) was

added by pipet in small portions to a stirred solution of 31b

(300.0 mg, 0.82 mmol) in THF (5 mL) until all the starting

material had reacted (several min) (TLC control, silica, 1:10

EtOAc-hexane). The solution was then concentrated to half

its original volume, using a rotary evaporator in which the

receiving flask contained aqueous NaHCO₃solution. A freshly

prepared solution of PhSeNa [from PhSeSePh (256.0 mg, 0.82

mmol) and NaBH₄(65.0 mg, 1.72 mmol) in EtOH (10 mL)]

was added, and stirring was continued for 4 h (TLC control,

silica, 1:10 EtOAc-hexane). The mixture was then diluted

with Et₂O (30 mL) and washed with water and brine. The

organic extract was dried (Na₂SO₄) and evaporated. Flash

chromatography of the residue over silica gel (2 cm × 20 cm),

using 1:10 EtOAc-hexane, gave 31c (358.0 mg, 80%) as a

1

1738, 1478 cm^-1; H NMR (CDCl₃, 300 MHz) δ 1.45 (s, 6 H),

3.68 (s, 3 H), 5.20 (s, 2 H), 7.23-7.32 (m, 3 H), 7.55-7.65 (m,

2 H); ¹³C NMR (CDCl₃, 50.3 MHz) δ 24.6 (q′), 52.2 (q′), 65.6

(s′), 79.0 (t′), 127.2 (d′), 129.0 (d′), 130.9 (s′), 132.8 (d′), 174.5

(s′); exact mass m/z calcd for C₁₂H₁₆O₃⁸⁰Se 288.02646, found

288.02598.

2-Met h yl-2-[(p h en ylselen o)m et h oxy]p r op a n a l (30a ).

DIBAL-H (1.0 M in CH₂Cl₂, 12.0 mL, 0.012 mmol) was added

dropwise to a stirred and cooled (-78 °C) solution of 30d d (3.45

g, 11.9 mmol) in CH₂Cl₂(100 mL). The solution was stirred at

-78 °C for 4 h, and 2 N HCl (20 mL) was then added. The

aqueous phase was extracted with CH₂Cl₂, and the combined

organic extracts were dried (Na₂SO₄) and evaporated. Flash

chromatography of the residue over silica gel (3 × 30 cm), using

1:3 EtOAc-hexane, gave 30a (2.78 g, 90%) as a colorless oil:

FTIR (CHCl₃, cast) 3071, 3057, 2983, 2804, 1735 cm^-1

;

¹H

NMR (CDCl₃, 200 MHz) δ 1.30 (s, 6 H), 5.29 (s, 2 H), 7.25-

Preparation of Polycyclic Systems

J . Org. Chem., Vol. 66, No. 6, 2001 1979

slightly yellowish oil: FTIR (CHCl₃, cast) 2963, 2097 (Si-H),

1728 cm^-1; ¹H NMR (CDCl₃, 200 MHz) δ 1.06-1.11 (two close

s, 18 H), 1.45 (d, J ) 6.4 Hz, 3 H), 4.18 (s, 1 H), 4.24 (d, J )

1.6 Hz, 2 H), 4.61 (s, 2 H), 4.72-4.78 (m, 1 H), 5.09-5.21 (m,

1 H), 7.25-7.45 (m, 8 H), 7.59-7.72 (m, 2 H); ¹³C NMR (CDCl₃,

50.3 MHz) δ 14.5 (q′), 20.0 (s′), 20.3 (s′), 27.2 (q′), 27.4 (q′),

57.2 (t′), 68.0 (d′), 71.4 (t′), 77.4 (d′), 82.6 (s′), 83.7 (s′), 126.1

(s′), 127.9 (d′), 128.2 (d′), 128.5 (d′), 129.1 (d′), 129.3 (d′), 135.8

(d′), 137.4 (s′), 166.6 (s′); exact mass m/z calcd for C₂₄H₂₉O₄⁸⁰SeSi

(M - C₄H₉) 489.10004, found 489.09938. Anal. Calcd for

C₂₈H₃₈O₄⁸⁰SeSi: C 61.63, H 7.02. Found: C 61.56, H 6.76.

(3r,3a â,6â,6a â)-2,2-Bis(1,1-d im et h ylet h yl)t et r a h yd r o-

6-m eth yl-3-[(p h en ylm eth oxy)m eth yl]fu r o[3,4-d ]-1,2-oxa -

silol-4(2H)-on e (31d ). The general procedure for radical

cyclization was followed, using 31c (268.0 mg, 0.49 mmol) in

PhH (60 mL), Ph₃SnH (256.0 mg, 0.73 mmol) in PhH (8 mL),

AIBN (10.0 mg, 0.06 mmol) in PhH (8 mL), and an addition

time of 6 h. Refluxing was continued for 1 h after the stannane

addition. Evaporation of the solvent and flash chromatography

of the residue over silica gel (2 × 20 cm), using 1:9 EtOAc-

hexane, gave 31d (169.0 mg, 85%) as an oil: FTIR (CHCl₃,

cast) 3087, 1769 cm^-1; ¹H NMR (CDCl₃, 300 MHz) δ 1.05 (two

close s, 18 H), 1.30 (d, J ) 6.9 Hz, 3 H), 2.20-2.28 (m, 1 H),

3.38 (dd, J ) 9.9, 5.3 Hz, 1 H), 3.95 (dd, J ) 9.1, 6.4 Hz, 1 H),

4.29 (d, J ) 5.3 Hz, 1 H), 4.40 (dd, J ) 10.2, 9.1 Hz, 1 H), 4.54

(d, J ) 11.5 Hz, 1 H), 4.61 (AB q, ∆ν_AB) 35.1 Hz, J ) 11.5

Hz, 2 H)), 7.19-7.42 (m, 5 H); ¹³C NMR (CDCl₃, 75.5 MHz)

18.9 (q′), 20.4 (s′), 21.4 (s′), 25.2 (d′), 26.9 (q′), 27.7 (q′), 43.7

(d′), 66.7 (t′), 73.2 (t′), 82.1 (d′), 82.6 (d′), 127.5 (d′), 128.0 (d′),

128.3 (d′), 138.9 (s′), 175.7 (s′); exact mass m/z calcd for

(d′), 129.0 (s′), 129.7 (d′), 133.8 (d′), 135.9 (d′), 159.6 (s′), 189.5

(d′); exact mass m/z calcd for C₁₄H₁₂O₂⁸⁰Se 292.00024, found

292.00048. Anal. Calcd for C₁₄H₁₂O₂⁸⁰Se: C 57.96, H 3.92. Found:

C 57.74, H 4.15.

(3r,3a â,9bâ)-2,2-Bis(1,1-d im eth yleth yl)-2,3,3a ,9b-tetr a -

h ydr o-3-ph en yl-4H-1,2-oxasilolo[4,5-c][1]ben zopyr an (32d).

The general procedure for radical cyclization was followed,

using 32c (110.0 mg, 0.252 mmol) in PhH (40 mL), Ph₃SnH

(116.0 mg, 0.328 mmol) in PhH (5 mL), AIBN (5.0 mg, 0.03

mmol) in PhH (5 mL), and an addition time of 4.5 h. Refluxing

was continued for 1 h after the stannane addition. Evaporation

of the solvent, and flash chromatography of the residue over

silica gel (2 × 20 cm), using 1:10 CH₂Cl₂-hexane, gave 32d

(60.0 mg, 85%) as a white solid: mp 128.0-131.0 °C; FTIR

(CHCl₃, cast) 3035, 1610, 1586 cm^-^{1 1}H NMR (CDCl₃, 300

;

MHz) δ 1.10 (s, 9 H), 1.20 (s, 9 H), 2.90-3.09 (m, 1 H), 3.49 (d,

J ) 7.4 Hz, 1 H), 3.95 (dd, J ) 12.4, 11.0 Hz, 1 H), 4.25 (dd,

J ) 10.7, 3.2 Hz, 1 H), 4.85 (d, J ) 4.1 Hz, 1 H), 6.88 (d, J )

8.2 Hz, 1 H), 6.99 (dd, J ) 7.5, 1.0 Hz, 1 H), 7.16-7.40 (m, 6

H), 7.47 (dd, J ) 7.6, 1.5 Hz, 1 H); ¹³C NMR (CDCl₃, 75.5 MHz)

23.0 (s′), 28.7 (q′), 29.1 (q′), 35.3 (d′), 42.1 (d′), 64.7 (t′), 71.6

(d′), 116.7 (d′), 120.7 (d′), 123.7 (s′), 125.6 (d′), 128.5 (d′), 129.1

(d′), 130.2 (d′), 131.7 (d′), 138.8 (s′), 154.9 (s′); exact mass m/z

calcd for C₂₄H₃₂O₂Si 380.21716, found 380.21579.

cis-3,4-Dih yd r o-3-(p h en ylm eth yl)-2H-1-ben zop yr a n -4-

ol (32e). n-Bu₄NF (1.0 M in THF, 1.0 mL, 1.0 mmol) was

injected in one portion into a stirred solution of 32d (40.0 mg,

0.10 mmol) in DMF (3 mL). The color of the solution quickly

changed to brownish red. Stirring was continued for 30 min,

and then Et₂O (20 mL) and water (10 mL) were added. The

organic phase was separated, and the aqueous layer was

extracted with Et₂O. The combined organic extracts were

washed with water and brine, dried (MgSO₄), and evaporated.

Flash chromatography of the residue over silica gel (2 × 20

cm), using 1:3 EtOAc-hexane, gave 32e³⁸(21.5 mg, 90%) as a

white solid: mp 103.0-105.0 °C; FTIR (CHCl₃cast) 3439,

3061, 3026, 772 cm^-1; ¹H NMR (CDCl₃, 400 MHz) δ 1.70 (s, 1

H), 2.29-2.41 (m, 1 H), 2.68 (dd, J ) 13.7, 7.3, 1 H), 2.90 (dd,

J ) 13.7, 8.4, 1 H), 4.05-4.15 (m, 2 H), 4.52 (d, J ) 2.0, 1 H),

6.82-6.94 (m, 2 H), 7.17-7.41 (m, 7 H); ¹³C NMR (CDCl₃, 100.6

MHz) 32.9 (t′), 40.0 (d′), 64.97 (d′), 65.00 (t′), 117.0 (d′), 120.6

(d′), 124.2 (s′), 126.4 (d′), 128.6 (d′), 129.1 (d′), 130.0 (d′), 130.2

(d′), 139.2 (s′), 154.4 (s′); exact mass m/z calcd for C₁₆H₁₆O₂

240.11504, found 240.11534.

C

₂₂H₃₄O₄Si 390.22263, found 390.22092.

(3S,4R,5S)-4-[[Bis(1,1-d im et h ylet h yl)flu or osilyl]oxy]-

3-eth en yld ih yd r o-5-m eth yl-2(3H)-fu r a n on e (31e). BF₃‚

OEt₂(0.34 mL, 2.73 mmol) was added to a stirred solution of

31d (88.0 mg, 0.225 mmol) in CH₂Cl₂(10 mL). The mixture

was stirred for 8 h, transferred to a separatory funnel, washed

with brine, and dried (Na₂SO₄). Evaporation of the solvent and

flash chromatography of the residue over silica gel (2 × 10

cm), using 1:3 EtOAc-hexane, gave 31e (51.0 mg, 75%) as a

colorless oil: FTIR (CHCl₃, cast) 3066, 1765 cm^-^{1 1}H NMR

;

(CDCl₃, 400 MHz) δ 1.05 (s, 18 H), 1.40 (d, J ) 6.8 Hz, 3 H),

3.40 (dd, J ) 7.9, 5.7 Hz, 1 H), 4.50 (dd, J ) 5.6, 2.0 Hz, 1 H),

4.56 (d of q, J ) 6.7, 1.9 Hz, 1 H), 5.34-5.45 (m, 2 H), 5.70-

5.86 (m, 1 H); ¹³C NMR (CDCl₃, 50.3 MHz) 17.8 (q′), 19.6, 19.9

(two s′, J _C-F) 12.8 Hz), 20.5, 20.9 (two s′, J _C-F) 15.9 Hz),

26.7 (q′), 26.9 (q′), 48.9 (d′), 77.2 (d′), 82.3 (d′), 121.9 (t′), 128.3

(d′), 175.0 (s′); exact mass m/z calcd for C₁₁H₁₈FO₃Si (M - C₄H₉)

245.10092, found 245.10098.

2-[(P h en ylselen o)m et h oxy]b en za ld eh yd e (32a ). Dry

acetone (20 mL) was added to PhSeCH₂Cl^18a(3.16 g, 15.4

mmol) and NaI (11.52 g, 76.9 mmol), and the mixture was

stirred and refluxed for 3 h, cooled to room temperature, and

evaporated. Et₂O (20 mL) was added and the solid was filtered

off, and washed with Et₂O. The combined washings were

evaporated to give crude PhSeCH₂I,^18bwhich was used directly

for the next step.

Salicylaldehyde (32a a ) (1.22 g, 10.0 mmol) in THF (2 mL)

was added by cannula over ca. 1 min to a stirred and cooled

(0 °C) suspension of NaH (60% dispersion in mineral oil, 0.45

g, 12 mmol) in THF (40 mL). The mixture was stirred at 0 °C

for 20 min, and then a solution of crude PhSeCH₂I in THF (5

mL) was added by cannula over ca. 1 min. The mixture was

refluxed for 4 h, and then cooled to room temperature. Water

(10 mL) was added, and the mixture was extracted with CH₂-

Cl₂. The combined organic extracts were dried (Na₂SO₄) and

evaporated. Flash chromatography of the residue over silica

gel (3 × 25 cm), using increasing amounts of EtOAc in hexane

(from 5% to 15%), gave 32a (650.0 mg, 22%) as a colorless oil:

1,1-Dim et h ylet h yl

5-Oxo-3-oxa zolid in eca r b oxyla t e

(33bb). N-Boc-glycine (33aa) (4.38 g, 25.0 mmol) and paraform-

aldehyde (1.0 g, 28 mmol) were dissolved in PhH (120 mL).

p-TsOH‚H₂O (250 mg, 1.5 mmol) was added, and the mixture

was refluxed for 1 h, using a Dean-Stark apparatus, and then

cooled to room temperature. Evaporation of the solvent and

flash chromatography of the residue over silica gel (2 × 20

cm), using 1:3 EtOAc-hexane, gave 33bb⁴⁸(2.85 g, 61%) as a

colorless oil, which solidified on standing: mp 39-40 °C; FTIR

1

(CHCl₃, cast) 2979, 1809, 1759, 1712 cm^-1; H NMR (CDCl₃,

400 MHz) δ 1.36 (s, 9 H), 3.88 (s, 2 H), 5.24 (s, 2 H); ¹³C NMR

(CDCl₃, 50.3 MHz) 28.4 (q′), 44.0 (t′), 78.7 (s′), 82.2 (t′), 151.9

(s′), 170.1 (s′); exact mass m/z calcd for C₈H₁₃NO₄187.08446,

found 187.08414.

Meth yl N-[(1,1-Dim eth yleth oxy)car bon yl]-N-[(ph en ylse-

len o)m eth yl]glycin a te (33d d ). NaH (80% dispersion in

mineral oil, 190.0 mg, 6.3 mmol) was added in small portions

to a stirred solution of PhSeSePh (1.10 g, 3.50 mmol) in THF

(10 mL) (Ar atmosphere). The suspension was refluxed for 2

h and then cooled to room temperature. HMPA (0.56 mL, 3.22

mmol) was added in one portion, followed by a solution of 33bb

(871.4 mg, 4.65 mmol) in THF (2 mL plus 1 mL as a rinse).

The solution was refluxed for 5 h (TLC control, silica, 1:3

EtOAc-hexane), cooled to room temperature, and diluted with

water (1 mL). The THF was evaporated under water pump

vacuum, and the residue was partitioned between water (20

mL) and Et₂O (20 mL). The organic extract was washed with

FTIR (CH₂Cl₂cast) 3072, 3057, 2859, 2759, 1689, 1598 cm^-1

;

¹H NMR (CDCl₃, 400 MHz) δ 5.80 (t, J _C-Se) 8.7 Hz, 2 H),

7.02 (d, J ) 8.4 Hz, 1 H), 7.11 (t, J ) 7.5 Hz, 1 H), 7.21-7.40

(m, 3 H), 7.49-7.64 (m, 3 H), 7.86 (dd, J ) 7.7, 1.8 Hz, 1 H),

10.38 (d, J ) 0.5 Hz, 1 H); ¹³C NMR (CD₂Cl₂, 75.5 MHz)

68.6 (t′), 114.8 (d′), 122.4 (d′), 126.7 (s′), 128.3 (d′), 128.7

(48) Cf. Walter, M. W.; Adlington, R. M.; Baldwin, J . E.; Chuhan,

J .; Schofield, C. J . Tetrahedron Lett. 1995, 36, 7761-7764.

1980 J . Org. Chem., Vol. 66, No. 6, 2001

Clive et al.

water, and the combined aqueous extracts were acidified with

3 N HCl to ca. pH 2. The acidic solution was extracted with

EtOAc, and the combined organic extracts were washed with

water and brine, and filtered through a column [4 (diameter)

x 7 cm] of anhydrous MgSO₄. The filtrate was evaporated and

the residue (crude 33cc) was redissolved in Et₂O (10 mL),

and cooled to 0 °C in an ice-water bath. Ethereal CH₂N₂was

added dropwise with stirring until all the acid had been

esterified (TLC control, silica, 1:3 EtOAc-hexane). Evapora-

tion of the solvent and flash chromatography of the residue

over silica gel (3 × 30 cm), using 1:3 EtOAc-hexane, gave

33d d (1.33 g, 80%) as a colorless oil: FTIR (CHCl₃, cast), 1753,

1703 cm^-1; ¹H NMR (CDCl₃, 200 MHz) δ 1.3 (two s, 9 H), 3.69

(two s, 3 H), 3.99 (two s, 2 H), 4.90 (two s, 2 H), 7.20-7.32 (m,

3 H), 7.53-7.65 (m, 2 H); ¹³C NMR (CDCl₃, 50.3 MHz) δ 28.1

(three q′ from rotamers), 47.7 (four t′ from rotamers), 52.1 (d′),

81.2 (t′), 127.9 (two d′ from rotamers), 128.4 (two s′ from

rotamers), 129.1 (d′), 135.0 (two d′ from rotamers), 154.1 (two

(s′), 131.6 (d′), 135.0 (d′), 135.8 (d′), 154.4 (s′); exact mass m/z

calcd for C₂₀H₂₉NO₃Si (M - PhSe - C₄H₉) 360.19949, found

360.19932.

1,1-Dim et h ylet h yl (3r,3a â,6a â)-2,2-Bis(1,1-d im et h yl-

eth yl)h exa h ydr o-3-ph en yl-5H-1,2-oxa silolo[4,5-c]p yr r ole-

5-ca r boxyla te (33d ). The general procedure for radical

cyclization was followed, using 33c (150.0 mg, 0.262 mmol) in

PhH (40 mL), Ph₃SnH (140.0 mg, 0.40 mmol) in PhH (8 mL),

AIBN (5.0 mg, 0.03 mmol) in PhH (8 mL), and an addition

time of 8 h. Refluxing was continued for 1 h after the stannane

addition. Evaporation of the solvent and flash chromatography

of the residue over silica gel (3 × 30 cm), using 1:3 EtOAc-

hexane, gave 33d (105.0 mg, 95%) as a white solid, which was

a mixture of rotamers in solution (NMR): mp 126.0-128.0 °C;

1

FTIR (CHCl₃, cast) 2971, 2895, 1697 cm^-1; H NMR (CDCl_3,

200 MHz, 55 °C) δ 1.05 (s, 9 H), 1.16 (s, 9 H), 1.43 (s, 9 H),

3.15-3.32 (m, 1 H), 3.39 (d, J ) 7.3 Hz, 1 H), 3.51 (dd, J )

7.5, 4.3 Hz, 2 H), 3.59-3.90 (m, 2 H), 4.55 (t, 4.2 Hz, 1 H),

7.05-7.40 (m, 5 H); ¹³C NMR (CDCl₃, 50.3 MHz) 21.0 (s′), 22.5

(s′), 23.4 (q′), 25.2 (q′), 28.4 (q′), 28.5 (q′), 28.7 (q′), 35.9 (d′),

36.1 (d′), 45.0 (d′), 45.8 (d′), 48.3 (t′), 53.7 (s′), 54.0 (s′), 79.2

(t′), 79.9 (d′), 80.8 (d′), 125.3 (d′), 128.4 (d′), 128.8 (d′), 140.3

(s′), 140.5 (s′), 154.5 (s′); exact mass m/z calcd for C₂₄H₃₉NO₃-

Si 417.26993, found 417.26881.

s′ from rotamers), 169.8 (s′); exact mass m/z calcd for C₁₅H₂₁

-

NO₄⁸⁰Se 359.06357, found 359.06256.

N-[(1,1-Dim eth yleth oxy)ca r bon yl]-N-[(p h en ylselen o)-

m eth yl]glycin a l (33a ). DIBAL-H (1.0 M solution in CH₂Cl₂,

3.0 mL, 3.0 mmol) was added dropwise to a stirred and cooled

(-78 °C) solution of 33d d (510.0 mg, 1.42 mmol) in dry Et₂O

(20 mL). After 30 min, little starting material remained (TLC

control, silica, 1:5 EtOAc-hexane). More DIBAL-H (1.0 M

solution in CH₂Cl₂, 1.5 mL, 1.5 mmol) was added, and stirring

was continued for 15 min. MeOH (1 mL) was then added, and

the solution was poured into saturated aqueous potassium

sodium tartrate (30 mL). The mixture was extracted with Et₂O,

and the combined organic extracts were washed with water

and brine and dried (MgSO₄₎. Evaporation of the solvent and

flash chromatography of the residue over silica gel (3 × 20

cm), using 1:5 EtOAc-hexane, gave 33a (279.0 mg, 83%) as a

colorless oil: FTIR (CH₂Cl₂cast) 3071, 3057, 2977, 2931, 2872,

2819, 2720, 1735, 1698, 1579 cm^-1; ¹H NMR (CD₂Cl₂, 400 MHz)

δ 1.30 (two close s, 9 H), 3.92 (two close s, 2 H), 4.92 (two close

s, 2 H), 7.21-7.39 (m, 3 H), 7.55-7.65 (m, 2 H), 9.45-9.50

(two close s, 1 H); ¹³C NMR (CD₂Cl₂, 100.6 MHz) δ 28.0 (q′),

28.1 (q′), 47.9 (t′), 48.5 (t′), 56.6 (t′), 57.2 (t′), 81.6 (s′), 81.8

(s′), 128.1 (d′), 128.5 (d′), 128.6 (s′), 128.7 (s′), 129.5 (d′), 129.6

(d′), 134.9 (d′), 135.8 (d′), 154.2 (s′), 154.7 (s′), 198.5 (d′), 198.5

(d′); exact mass (HR electrospray) m/z calcd for C₁₄H₂₀NO₃⁸⁰Se

(M + H) 330.060839, found 330.059420.

1,1-Dim et h ylet h yl (2-H yd r oxy-4-p h en yl-3-b u t yn yl)-

[(p h en ylselen o)m eth yl]ca r ba m a te (33b). The general pro-

cedure for addition of an acetylide to an aldehyde was followed,

using 22 (224.0 mg, 2.19 mmol) in THF (10 mL), n-BuLi (1.6

M in hexanes, 1.30 mL, 2.08 mmol), an initial reaction time

of 10 min, and 33a in THF (2 mL plus 1 mL as a rinse), added

in two equal portions. Stirring at -78 °C was continued for 3

h, several drops of saturated aqueous NH₄Cl were then added,

and the mixture was allowed to attain room temperature. The

THF was evaporated, and the residue was dissolved in CH₂-

Cl₂and dried (MgSO₄). Evaporation of the solvent gave crude

33b, which was used directly in the next step (formation of

33c).

1,1-Dim eth yleth yl [2R*(S*)]-2-(1-Hyd r oxy-3-p h en yl-2-

p r op yn yl)-1-p yr r olid in eca r boxyla te (34bb). The general

procedure for addition of an acetylide to an aldehyde was

followed, using 22 (320.0 mg, 3.13 mmol) in THF (10 mL),

n-BuLi (1.6 M in hexane, 1.90 mL, 3.04 mmol), an initial

reaction time of 15 min, and freshly prepared 34a a ¹⁹(292.9

mg, 1.56 mmol) in THF (4 mL plus 1 mL as a rinse). Stirring

at -78 °C was continued for 2 h, water (five drops) was added,

and the mixture was allowed to attain room temperature.

Evaporation of the solvent and flash chromatography of the

residue over silica gel (2 × 20 cm), using 1:3 EtOAc-hexane,

gave equal amounts of two isomers (¹H NMR, 300 MHz). The

less polar diastereomer 34bb (192.0 mg, 41%) was carried on

to the next step (formation of 34a ). The compound had: FTIR

1

(CHCl₃, cast) 3380, 2976, 1737, 1693 cm^-1; H NMR (CDCl₃,

200 MHz) δ 1.50 (s, 9 H), 1.70-2.20 (m, 4 H), 3.30-3.60 (m, 2

H), 4.10 (dd, J ) 12.6 Hz, 6.0 Hz, 1 H), 4.62 (d, J ) 5.9 Hz, 1

H), 7.21-7.33 (m, 3 H), 7.34-7.50 (m, 2 H); ¹³C NMR (CDCl₃,

50.3 MHz) δ 23.9 (t′), 28.5 (q′), 28.7 (t′), 47.7 (t′), 62.8 (d′), 67.4

(d′), 80.7 (s′), 85.1 (s′), 88.7 (s′), 122.8 (s′), 128.2 (d′), 128.3 (d′),

131.7 (d′), 157.5 (s′); exact mass m/z calcd for C₁₄H₁₅NO₃(M -

C₄H₉) 245.10519, found 245.10452.

The more polar isomer had: ¹H NMR (CDCl₃, 300 MHz) δ

1.49 (s, 9 H), 1.70-2.19 (m, 4 H), 3.29-3.60 (m, 2 H), 4.01-

4.19 (br t, J ) 6.81 Hz, 1 H), 4.54-4.70 (br s, 1 H), 7.21-7.31

(m, 3 H), 7.32-7.47 (m, 2 H).

[2R*(S*)]-2-[1-[[Bis(1,1-dim eth yleth yl)silyl]oxy]-3-ph en -

yl-2-p r op yn yl]p yr r olid in e (34a ). TFA (3.0 mL) was added

to a stirred solution of 34bb (181.0 mg, 0.60 mmol) in CH₂Cl₂

(5 mL). Stirring was continued for 1 h, and the mixture was

diluted with CH₂Cl₂(30 mL), washed with saturated aqueous

NaHCO₃, and dried (Na₂SO₄). The solvent was evaporated, and

the residue was redissolved in dry THF (5 mL). Imidazole (43.0

mg, 0.63 mmol) was added, followed by t-Bu₂SiHCl (112.8 mg,

0.63 mmol), and the solution was refluxed overnight. The

mixture was cooled and evaporated, and flash chromatography

of the residue over silica gel (2 × 20 cm), using 1:4 EtOAc-

hexane, gave 34a (122.0 mg, 60%) as a slightly yellowish oil:

1,1-Dim eth yleth yl [2-[[Bis(1,1-dim eth yleth yl)silyl]oxy]-

4-p h en yl-3-b u t yn yl][(p h en ylselen o)m et h yl]ca r b a m a t e

(33c). Imidazole (118.0 mg, 1.70 mmol) and t-Bu₂SiHCl (193.5

mg, 1.10 mmol) were added successively to a stirred solution

of crude 33b in THF (10 mL), and stirring was continued for

3 h. Evaporation of the solvent and flash chromatography of

the residue over silica gel (3 × 30 cm), using increasing

amounts of EtOAc in hexane (from 10% to 25%), gave 33c

(503.0 mg, 82%) as an oil: FTIR (CHCl₃, cast), 2101, 1703

cm^-1; ¹H NMR (CDCl₃, 300 MHz) δ 0.99 (s, 9 H), 1.03 (s, 9 H),

1.29 (s, 4.6 H), 1.39 (s, 4.4 H), 3.48-3.70 (m, 2 H), 4.10-4.20

(m, 1 H), 4.80-5.23 (m, 3 H), 7.18-7.36 (m, 6 H), 7.37-7.42

(m, 2 H), 7.55-7.70 (m, 2 H); ¹³C NMR (CDCl₃, 50.3 MHz)

(mixture of rotamers) 19.6 (s′), 20.3 (s′), 27.3 (q′), 28.1 (q′), 28.3

(q′), 48.1 (t′), 49.9 (t′), 52.5 (s′), 65.2 (d′), 65.4 (d′), 80.6 (t′),

80.8 (t′), 86.4 (s′), 88.2 (s′), 127.7 (d′), 128.0 (d′), 128.3 (d′), 128.8

FTIR (CHCl₃, cast) 3336, 3179, 3081, 2103 cm^-^{1 1}H NMR

;

(CDCl₃, 200 MHz) δ 1.02 (s, 4.5 H), 1.05 (s, 4.5 H), 1.70-2.09

(m, 4 H), 2.60 (br s, 1 H), 2.85-3.21 (m, 2 H), 3.40 (dd, J )

12.0 Hz, 6.0 Hz, 2 H), 4.22 (s, 1 H), 4.64 (d, J ) 6.1 Hz, 1 H),

7.25-7.36 (m, 3 H), 7.37-7.50 (m, 2 H); ¹³C NMR (CDCl₃, 50.3

MHz) 19.8 (s′), 20.3 (s′), 25.3 (t′), 27.4 (t′), 27.5 (q′), 46.5 (t′),

64.0 (d′), 69.9 (d′), 85.9 (s′), 88.6 (s′), 123.0 (s′), 128.3 (d′), 131.6

(d′); exact mass m/z calcd for C₁₇H₂₄NOSi (M - C₄H₉) 286.16268,

found 286.16249.

Se-P h en yl [2R*(S*)]-2-[1-[[Bis(1,1-d im eth yleth yl)silyl]-

oxy]-3-p h en yl-2-p r op yn yl]-1-p yr r olid in eselen oca r boxyl-

a te (34c). A solution of COCl₂in PhMe (ca. 1:1 v/v) was added

dropwise to a stirred solution of 34a (120.0 mg, 0.35 mmol) in

Preparation of Polycyclic Systems

J . Org. Chem., Vol. 66, No. 6, 2001 1981

THF (4 mL). Acylation was complete in 10 min (TLC control,

silica, 1:10 EtOAc-hexane). Evaporation of the solvent, using

a rotary evaporator in which the receiving flask contained

aqueous NaHCO₃, and flash chromatography of the residue

over silica gel (2 × 20 cm), using 1:20 EtOAc-hexane, gave

34b. This was dissolved in dry THF (2 mL plus 1 mL as a

rinse) and added by syringe to a stirred solution of freshly

prepared PhSeNa [from PhSeSePh (244.0 mg, 0.78 mmol) and

NaBH₄(59.0 mg, 1.56 mmol) in EtOH (10 mL)]. Stirring at

room temperature was continued for 6 h. The mixture was

diluted with EtOAc (30 mL), washed with brine, and dried

(Na₂SO₄). Evaporation of the solvent and flash chromatogra-

phy of the residue over silica gel (2 × 20 cm), using 1:10

EtOAc-hexane, gave 34c (154.4 mg, 84%) as a slightly

yellowish solid: mp 94.5-95.5 °C; FTIR (CHCl₃, cast) 3059,

(d′), 129.0 (d′), 130.1 (s′), 132.7 (d′); exact mass m/z calcd for

C₁₂H₁₄O⁸⁰Se 254.02089, found 254.02117.

Bis(1,1-d im eth yleth yl)[[1-[3-(p h en ylselen o)p r op yl]-2-

p r op yn yl]oxy]sila n e (35c). The general procedure for silyl-

ation of alcohols was followed, using 35b (1.040 g, 4.1 mmol)

in THF (30 mL), imidazole (559.0 mg, 8.2 mmol), neat t-Bu₂-

SiHCl (1.24 mL, 6.15 mmol), and a reflux time of 2 h. The

mixture was cooled, diluted with water (10 mL), and extracted

with Et₂O. The combined organic extracts were dried (Na₂-

SO₄) and evaporated. Flash chromatography of the residue

over silica gel (4.5 × 30 cm), using 1:49 EtOAc-hexane, gave

35c (1.452 g, 90%) as a colorless oil: FTIR (CH₂Cl₂cast) 3309,

1

2962, 2929, 2890, 2856, 2094, 1580, 1471, 826, 735 cm^-1; H

NMR (CD₂Cl₂, 300 MHz) δ 0.98 (s, 9 H), 1.02 (s, 9 H), 1.75-

1.93 (m, 4 H), 2.46 (d, J ) 2.0 Hz, 1 H), 2.96 (t, J ) 6.9 Hz, 2

H), 4.06 (s, 1 H), 4.5 (ddd, J ) 5.7, 5.7, 2.0, Hz, 1 H), 7.21-

7.30 (m, 3 H), 7.46-7.53 (m, 2 H); ¹³C NMR (CDCl₃, 50.3 MHz)

δ 19.7 (s′), 20.0 (s′), 25.4 (t′), 27.2 (q′), 27.6 (t′), 38.1 (t′), 65.5

(d′), 73.0 (d′), 84.3 (s′), 126.8 (d′), 129.0 (d′), 130.3 (s′), 132.7

(d′) (two peaks overlap in this spectrum); exact mass m/z calcd

for C₂₀H₃₂O⁸⁰SeSi 396.13876, found 396.13842.

Bis(1,1-d im eth yleth yl)[[1-[3-(p h en ylselen o)p r op yl]-3-

tr ibu tylsta n n yl-2-p r op yn yl]oxy]sila n e (35d ). n-BuLi (1.6

M in hexanes, 0.33 mL, 0.53 mmol) was injected dropwise over

ca. 20 s to a stirred and cooled (-78 °C) solution of 35c (197.8

mg, 0.50 mmol) in THF (1 mL). The mixture was stirred at

-78 °C for 15 min, and a solution of Bu₃SnCl (0.15 mL, 0.53

mmol) in THF (0.5 mL plus 0.5 mL as a rinse) was then added

by cannula at a rapid dropwise rate. Stirring at -78 °C was

continued for 20 min after the addition, and the mixture was

then quenched with water (1 mL). The cooling bath was

removed, stirring was continued while the mixture reached

room temperature (ca. 30 min), and the mixture was then

extracted with Et₂O. The combined organic extracts were dried

(Na₂SO₄) and evaporated, to give crude 35d (350 mg, ca. 0.51

mmol) as a colorless oil, which was used in the next step

(formation of 35e) without further purification. The compound

was not stable to silica chromatography.

1

2961, 2098, 1732 cm^-1; H NMR (CDCl₃, 400 MHz) δ 1.01 (s,

7.5 H), 1.09 (s, 7.5 H), 1.14 (two close s, 3 H), 1.88-2.02 (m, 1

H), 2.05-2.21 (m, 1 H), 2.26-2.51 (m, 2 H), 3.52-3.70 (m, 2

H), 4.15 (s, 1 H), 4.29-4.39 (m, 1 H), 5.20 (d, J ) 5.4 Hz, 1 H),

5.40 (d, J ) 4.9 Hz, 1 H), 7.30-7.49 (m, 8 H), 7.60-7.70 (m, 2

H); ¹³C NMR (CDCl₃, 50.3 MHz) 19.9 (s′), 20.0 (s′), 24.0 (t′),

26.2 (t′), 27.3 (q′), 48.0 (t′), 63.0 (d′), 66.0 (d′), 85.8 (s′), 88.1

(s′), 122.9 (s′), 126.7 (s′), 128.4 (d′), 128.8 (d′), 129.2 (d′), 131.5

(d′), 136.5 (d′), 162.9 (s′); exact mass m/z calcd for C₂₈H₃₇

-

NO₂⁸⁰SeSi 527.17590, found 527.17611.

(3r,3a â,8a r,8bâ)-Octa h yd r o-3-p h en yl-1,2-oxa silolo[4,5-

a ]p yr r olizin -4(4H)-on e (34d ). The general procedure for

radical cyclization was followed, using 34c (43.0 mg, 0.082

mmol) in PhH (30 mL), Ph₃SnH (60.0 mg, 0.17 mmol) in PhH

(5 mL), AIBN (5.0 mg, 0.03 mmol) in PhH (5 mL), and an

addition time of 6 h. Refluxing was continued for 1 h after the

stannane addition. Evaporation of the solvent and flash

chromatography of the residue over silica gel (2 × 20 cm), using

1:1 EtOAc-hexane, gave 34d (22.8 mg, 75%) as a white solid:

FTIR (CH₂Cl₂, cast) 3056, 2933, 1692, 1495 cm^-^{1 1}H NMR

;

(CDCl₃, 400 MHz) δ 0.81 (s, 9 H), 1.06 (s, 9 H), 2.05-2.09 (m,

2 H), 2.30-2.41 (m, 1 H), 3.06-3.15 (m, 1 H), 3.20 (d, J )

12.0 Hz, 1 H), 3.50-3.65 (m, 1 H), 3.75 (dd, J ) 12.1, 9.3 Hz,

1 H), 3.89-4.01 (m, 1 H), 4.67 (dd, J ) 9.3, 4.2 Hz, 1 H), 7.02-

7.31 (m, 5 H); ¹³C NMR (CDCl₃, 50.3 MHz) 21.3 (s′), 21.9 (s′),

26.2 (t′), 27.8 (q′), 28.6 (q′), 30.5 (t′), 31.8 (d′), 41.6 (t′), 55.1

(d′), 69.6 (d′), 81.6 (d′), 125.2 (d′), 128.0 (d′), 129.1 (d′), 139.4

(s′), 173.0 (s′); exact mass m/z calcd for C₂₂H₃₃NO₂Si 371.22806,

found 371.22862.

2,2-Bis(1,1-d im et h ylet h yl)-4,5,6,6a -t et r a h yd r o-2H -cy-

clop en t[d ]-1,2-oxa silole (35e). The general procedure for

radical cyclization was followed, using crude stannane 35d

(350 mg) in PhH (50 mL), Bu₃SnH (0.14 mL, 0.50 mmol) in

PhH (7 mL), AIBN (82.1 mg, 0.50 mmol) in PhH (7 mL), and

an addition time of 2 h. Refluxing was continued for 3 h after

the stannane addition. Evaporation of the solvent and flash

chromatography of the residue over silica gel (1 × 20 cm), using

3:7 CH₂Cl₂-hexane, gave 35e (92.0 mg, 77%) as a colorless

oil: FTIR (CH₂Cl₂cast) 2960, 2931, 2890, 2857, 1612, 1108,

Crystallographic data for compound 34d : C₂₂H₃₃NO₂Si, MW

371.58, crystal size 0.81 × 0.66 × 0.09 mm, triclinic space

group P1 (No. 1), a ) 8.907(3) Å, b ) 8.906(2) Å, c ) 27.566(8)

Å, R ) 90.182(5)°, â ) 81.585(5)°, γ ) 83.519(5)°, V )

2149.0(11) Å³, Z ) 4, D_calc) 1.148 g cm^-3, µ ) 0.124 mm^-1

,

1076, 824 cm^-1; H NMR (CDCl₃, 300 MHz) δ 0.99 (s, 9 H),

1

T ) 193(1) K, λ ) 0.71073 Å (Mo KR), 2θ_max) 53.14°,

absorption correction by Gaussian integration (indexing of

crystal faces), range of transmission factors 0.9887-0.9175,

1.02 (s, 9 H), 1.19-1.35 (m, 1 H), 1.75-1.92 (m, 2 H), 2.00-

2.12 (m, 1 H), 2.20-2.45 (m, 2 H), 4.72-4.82 (m, 1 H), 5.50-

5.56 (m, 1 H); ¹³C NMR (CDCl₃, 75.5 MHz) δ 19.9 (s′), 21.6

(s′), 21.7 (t′), 25.5 (t′), 27.3 (q′), 27.7 (q′), 31.8 (t′), 87.5 (d′),

113.8 (d′), 170.1 (s′); exact mass m/z calcd for C₁₄H₂₆OSi

238.17529, found 238.17610. Anal. Calcd for C₁₄H₂₆OSi: C,

70.52; H, 10.99. Found: C, 70.72; H, 10.99.

2

R₁(F) ) 0.1401 (for 14300 data with F_og 2σ(F_o²)) and

wR₂(F²) ) 0.3816 (for all 17271 independent data), goodness-

of-fit (S) ) 1.595, largest difference peak and hole 2.334 and

-0.837 e Å^-3. Because of the poor quality of the final model

this structure should not be used for determination of precise

geometrical parameters (e.g., bond lengths, bond angles,

conformational angles); however, the results do allow the

relative stereochemistry of the product to be assigned satis-

factorily.

6-(P h en ylselen o)-1-h exyn -3-ol (35b). n-Bu₄NF (1.0 M in

THF, 7.5 mL, 7.5 mmol) was injected over 3 min to a stirred

and cooled (0 °C) solution of crude 13b (1.627 g, 6.40 mmol)

in dry THF (10 mL). Stirring at 0 °C was continued for 2 h.

Water (5 mL) was added, and the mixture was extracted with

CH₂Cl₂. The combined organic extracts were dried (MgSO₄)

and evaporated. Flash chromatography of the residue over

silica gel (4.5 × 30 cm), using 1:99 Et₂O-CH₂Cl₂, gave 35b

(1.047 g, 83%) as a colorless oil: FTIR (CH₂Cl₂cast) 3385,

3289, 3071, 3056, 2940, 2860, 2114, 1578, 1478, 737 cm^-1; ¹H

NMR (CDCl₃, 300 MHz) δ 1.78-1.95 (m, 5 H), 2.46 (d, J ) 2.0

Hz, 1 H), 2.91-2.98 (m, 2 H), 4.35-4.43 (m, 1 H), 7.19-7.32

(m, 3 H), 7.45-7.55 (m, 2 H); ¹³C NMR (CDCl₃, 75.5 MHz) δ

25.6 (t′), 27.4 (t′), 37.4 (t′), 61.8 (d′), 73.3 (d′), 84.5 (s′), 126.8

2,2-Bis(d im eth yleth yl)-8,8a -d ih yd r o-2H-in d en o[1,2-d ]-

1,2-oxa silole (36e). The general procedure for radical cycliza-

tion was followed, using crude 36d (221 mg, ca. 0.34 mmol) in

PhH (40 mL), Bu₃SnH (99.0 mg, 0.33 mmol) in PhH (5 mL),

AIBN (54.2 mg, 0.33 mmol) in PhH (5 mL), and an addition

time of 2 h. Refluxing was continued for 1 h after the stannane

addition. Evaporation of the solvent, and flash chromatography

of the residue over silica gel (1 × 20 cm), using 1:19 EtOAc-

hexane, and rechromatography over silica gel (0.6 × 15 cm),

using 3:97 EtOAc-hexane, gave 36e (55.0 mg, 58%) as a

colorless oil: FTIR (CH₂Cl₂cast) 2957, 2930, 2890, 2856, 1612,

1

1601, 832, 824 748 cm^-1; H NMR (CDCl₃, 300 MHz) δ 1.00

(s, 9 H), 1.09 (s, 9 H), 2.67 (dd, J ) 14.4, 8.2 Hz, 1 H), 3.20

(dd, J ) 14.4, 7.7 Hz, 1 H), 5.28 (ddd, J ) 8.2, 7.7, 2.6 Hz, 1

H), 6.02 (d, J ) 2.6 Hz, 1 H), 7.20-7.30 (m, 3 H), 7.45-7.52

(m, 1 H); ¹³C NMR (CD₂Cl₂, 75.5 MHz) δ 20.3 (s′), 22.3 (s′),

27.6 (q′), 28.0 (q′), 38.6 (t′), 88.7 (d′), 113.3 (d′), 122.6 (d′), 126.6

(d′), 127.6 (d′), 129.6 (d′), 136.8 (s′), 145.1 (s′), 167.7 (s′); exact

mass m/z calcd for C₁₈H₂₆OSi 286.17529, found 286.17561.

1982 J . Org. Chem., Vol. 66, No. 6, 2001

Clive et al.

2,2-Bis(1,1-d im et h ylet h yl)-2,4,6,6b -t et r a h yd r o-6,6-d i-

m eth ylfu r o[3,4-d ]-1,2-oxa silole (37e). The general proce-

dure for radical cyclization was followed, using crude 37d (370

mg, ca. 0.56 mmol) in PhH (50 mL), Bu₃SnH (0.14 mL, 0.5

mmol) in PhH (7 mL), AIBN (82.1 mg, 0.5 mmol) in PhH (7

mL), and an addition time of 2 h. Refluxing was continued for

2 h after the addition. Evaporation of the solvent, and flash

chromatography of the residue over silica gel (1 × 20 cm), using

7:95 EtOAc-hexane, and rechromatography over silica gel (0.6

× 15 cm), using 1:31 EtOAc-hexane, gave 37e (108 mg, 81%)

as a colorless oil: FTIR (CH₂Cl₂cast) 3032, 2971, 2932, 2894,

2858, 1620, 1474, 1092, 824 cm^-1; ¹H NMR (CD₂Cl₂, 400 MHz)

δ 0.97 (s, 3 H), 1.03 (s, 9 H), 1.04 (s, 9 H), 1.33 (s, 3 H), 4.18-

4.25 (m, 1 H), 4.35-4.45 (m, 1 H), 4.58-4.62 (m, 1 H), 5.80-

5.83 (m, 1 H); ¹³C NMR (CD₂Cl₂, 100.6 MHz) δ 20.2 (q′), 21.1

(s′), 22.7 (s′), 26.8 (q′), 27.4 (q′), 28.2 (q′), 64.8 (t′), 79.6 (s′),

92.4 (d′), 115.6 (d′), 167.3 (s′); exact mass m/z calcd for

7.33 (m, 3 H), 7.33-7.42 (m, 2 H), 7.46-7.55 (m, 2 H); ¹³C NMR

(CDCl₃, 75.5 MHz) δ 12.5 (d′), 12.6 (d′), 17.4 (q′), 17.5 (q′), 17.6

(q′), 25.9 (t′), 27.7 (t′), 37.4 (t′), 65.1 (d′), 85.1 (s′), 89.9 (s′), 122.9

(s′), 126.8 (d′), 128.3 (d′), 129.0 (d′), 130.3 (s′), 131.6 (d′), 132.8

(d′); exact mass m/z calcd for C₂₄H₃₂O⁸⁰SeSi 444.1389, found

444.1404. Anal. Calcd for C₂₄H₃₂OSeSi: C, 64.99; H, 7.27.

Found: C, 65.18; H, 7.17.

(3r,3a â,6a â)-2,2-Bis(1-m eth yleth yl)h exa h yd r o-3-p h en -

yl-2H-cyclop en t[d ]-1,2-oxa silole (44b). The general proce-

dure for radical cyclization was followed, using 44a (158.9 mg,

0.30 mmol) in PhH (45 mL), Ph₃SnH (210.6 mg, 0.60 mmol)

in PhH (7.5 mL), AIBN (24.6 mg, 0.15 mmol) in PhH (7.5 mL),

and an addition time of 6 h. Refluxing was continued for 0.5

h after the stannane addition. Evaporation of the solvent, and

flash chromatography of the residue over silica gel (1.8 × 19

cm), using increasing amounts of CH₂Cl₂in hexane (from 10%

to 40%), gave an oil that was purified by filtration through a

pad of neutral alumina (grade I) (0.5 × 2.5 cm), using hexane

(ca. 5 mL), to give 44b (30.1 mg, 35%) as a colorless oil: FTIR

C

₁₄H₂₅O₂Si (M - CH₃) 253.16238, found 253.16268. Anal.

Calcd for C₁₅H₂₈O₂Si: C, 67.11; H, 10.51. Found: C, 67.09; H,

10.62.

(CDCl₃cast) 2959, 2942, 2866, 1495, 1465, 1027, 757 cm^-1

;

¹H NMR (CDCl₃, 400 MHz) δ 0.94 (d, J ) 7.0 Hz, 3 H), 1.06

(d, J ) 7.0 Hz, 3 H), 1.07 (d, J ) 7.0 Hz, 3 H), 1.10 (d, J ) 7.0

Hz, 3 H), 1.13-1.28 (m, 2 H) 1.48-1.68 (m, 2 H), 1.69-1.80

(m, 1 H), 1.81-1.98 (m, 2 H), 1.65-1.75 (m, 1 H), 3.07 (d, J )

7.0 Hz, 1 H), 4.46 (td, J ) 4.5, 1.5 Hz, 1 H), 7.11-7.17 (m, 1

H), 7.21-7.30 (m, 1 H); ¹³C NMR (CDCl₃, 75.5 MHz) δ 13.0

(d′), 14.5 (d′), 17.7 (q′), 17.8 (q′), 17.9 (q′), 18.0 (q′), 24.6 (t′),

28.6 (t′), 34.7 (t′), 35.5 (d′), 49.6 (d′), 83.9 (d′), 124.9 (d′), 128.2

(d′), 129.3 (d′), 141.8 (s′); exact mass m/z calcd for C₁₈H₂₈OSi

288.1910, found 288.1908.

2,2-Bis(1,1-dim eth yleth yl)-2,9b-dih ydr o-4H-1,2-oxasilolo-

[4,5-c][1]ben zop yr a n (38e). The general procedure for radi-

cal cyclization was followed, using crude 38d (310 mg, ca. 0.41

mmol) in PhH (40 mL), Bu₃SnH (0.11 mL, 0.40 mmol) in PhH

(6 mL), AIBN (65.7 mg, 0.40 mmol) in PhH (6 mL), and an

addition time of 2 h. Refluxing was continued for 7 h after the

stannane addition. Evaporation of the solvent, and flash

chromatography of the residue over silica gel (2 × 25 cm), using

3:97 EtOAc-hexane, and rechromatography over silica gel

(1 × 20 cm), using 3:7 CH₂Cl₂-hexane, gave 38e (85.0 mg,

70%) as a white solid: mp 80.5-81.5 °C; FTIR (CH₂Cl₂cast)

3074, 3037, 1610, 1582, 1055, 824 cm^-1; ¹H NMR (CD₂Cl₂, 300

MHz) δ 0.88 (s, 9 H), 1.08 (s, 9 H), 4.78-4.94 (m, 2 H), 5.60-

5.66 (m, 1 H), 5.90-5.96 (m, 1 H), 6.79 (dd, J ) 8.1, 1.2 Hz, 1

H), 6.95 (ddd, J ) 7.4, 7.4, 1.2 Hz, 1 H), 7.10-7.18 (m, 1 H),

7.42-7.50 (m, 1 H); ¹³C NMR (CD₂Cl₂, 75.5 MHz) δ 20.2 (s′),

21.6 (s′), 27.5 (q′), 27.7 (q′), 68.6 (t′), 78.5 (d′), 116.4 (d′), 118.9

(d′), 121.2 (d′), 126.4 (d′), 128.3 (s′), 128.6 (d′), 153.5 (s′), 156.5

(s′); exact mass m/z calcd for C₁₈H₂₆O₂Si 302.17020, found

302.16948.

Dip h en yl[[3-p h en yl-1-[3-(p h en ylselen o)p r op yl]-2-p r o-

p yn yl]oxy]sila n e (45a ). The general procedure for silylation

of alcohols was followed, using 9b (98.8 mg, 0.30 mmol) in PhH

(2 mL), imidazole (24.5 mg, 0.36 mmol), Ph₂SiHCl (72.2 mg,

0.33 mmol) in PhH (0.5 mL plus 0.5 mL as a rinse), and a

reflux time of 2 h. The white solid was removed by filtration

of the cooled mixture through glass wool. The clear filtrate

containing 45a was used directly for the next step (formation

1

of 45b). The H NMR spectrum of the product from a similar

experiment, using C₆D₆as solvent, indicated that reaction was

complete.

1,1-Dim eth yleth yl 2,2-Bis(1,1-d im eth yleth yl)-2,4,6,6a -

tetr a h yd r o-5H-1,2-oxa silolo[4,5-c]p yr r ole-5-ca r boxyla te

(39e). The general procedure for radical cyclization was

followed, using crude 39d (151 mg, ca. 0.21 mmol) in PhH (20

mL), Bu₃SnH (60.0 mg, 0.20 mmol) in PhH (3 mL), AIBN (32.8

mg, 0.20 mmol) in PhH (3 mL), and an addition time of 2 h.

Refluxing was continued for 1 h after the stannane addition.

Evaporation of the solvent, and flash chromatography of the

residue over silica gel (1 × 20 cm), using 1:9 EtOAc-hexane,

and rechromatography over silica gel (0.6 × 15 cm), using 1:19

EtOAc-hexane, gave 39e (48.0 mg, 71%) as a colorless oil:

FTIR (CH₂Cl₂cast) 2960, 2931, 2858, 1704, 1629, 1473, 1158,

(3ar,3aâ,6aâ)-Hexa h ydr o-2,2,3-tr iph en yl-2H-cyclop en t-

[d ]-1,2-oxa silole (45b). The general procedure for radical

cyclization was followed, using crude 45a in PhH (45 mL), Ph₃-

SnH (210.6 mg, 0.60 mmol) in PhH (7.5 mL), AIBN (24.6 mg,

0.5 mmol) in PhH, and an addition time of 6 h. Refluxing was

continued for 2 h after the stannane addition. The crude

product was used directly for the next step (formation of 45c),

because of the difficulty of obtaining it free of stannane

residues.

[1r,2r(R*)]-2-[Hyd r oxy(p h en yl)m eth yl]cyclop en ta n ol

(45c). H₂O₂(30% solution in H₂O, 0.70 mL, 6.2 mmol) was

added to a stirred mixture of crude 45b, KHCO₃(60 mg, 0.6

mmol) and KF‚2H₂O (56.4 mg, 0.6 mmol) in 1:1 MeOH-THF

(12 mL) at room temperature. The mixture was heated at 60

°C overnight, cooled to room temperature, diluted with water

(5 mL), and extracted with CH₂Cl₂. The combined organic

extracts were dried (Na₂SO₄) and evaporated. Flash chroma-

tography of the residue over silica gel (1.8 × 9 cm), using

increasing amounts of EtOAc in hexane (from 15% to 25%),

gave 45c (11.0 mg, 14%) as a colorless oil (R_f0.30, silica, 3:7

EtOAc-hexane): FTIR (CDCl₃cast) 3345, 2960, 1451, 1031,

1

1103, 823 cm^-1; H NMR (CD₂Cl₂, 400 MHz) δ 0.99 (s, 9 H),

1.02 (s, 9 H), 1.42 (s, 9 H), 2.70-2.80 (m, 1 H), 3.85-4.03 (m,

3 H), 4.92-4.98 (m, 1 H), 5.86 (s, 1 H); ¹³C NMR (CD₂Cl₂, 50.3

MHz) δ 20.2 (s′), 21.8 (s′), 27.0 (q′), 27.3 (q′), 27.7 (q′), 28.5

(q′), 46.8 (t′), 47.3 (t′), 50.5 (t′), 51.3 (t′), 79.6 (s′), 83.0 (d′), 83.4

(d′), 116.9 (d′), 117.1 (d′), 154.6 (s′), 154.8 (s′), 162.5 (s′), 163.0

(s′) (several peaks overlap in this spectrum); exact mass

(HRES) m/z calcd for C₁₈H₃₄NO₃Si (M + H) 340.230798, found

340.231100.

Bis(1-m eth yleth yl)[[3-p h en yl-1-[3-(p h en ylselen o)p r o-

p yl]-2-p r op yn yl]oxy]sila n e (44a ). The general procedure for

silylation of alcohols was followed, using 9b (329.3 mg, 1.00

mmol) in THF (8 mL), imidazole (136.2 mg, 2.00 mmol), i-Pr₂-

SiHCl (188.1 mg, 1.25 mmol) in THF (1 mL plus 1 mL as a

rinse), and a reflux time of 2.5 h. The mixture was cooled,

diluted with water (50 mL), and extracted with Et₂O. The

combined organic extracts were dried (Na₂SO₄) and evapo-

rated. Flash chromatography of the residue over silica gel (1.8

× 20 cm), using 1:9, and then 3:17 CH₂Cl₂-hexane, gave 44a

(397.1 mg, 90%) as a colorless oil: FTIR (CHCl₃cast) 2942,

1

999 cm^-1; H NMR (CDCl₃, 300 MHz) δ 1.43-1.72 (m, 3 H),

1.73-2.10 (m, 4 H), 2.51 (br s, 1 H), 3.48 (br s, 1 H), 4.33 (td,

J ) 4.5, 2.0 Hz, 1 H), 5.17 (d, J ) 3.5 Hz, 1 H), 7.21-7.29 (m,

1 H), 7.30-7.41 (m, 4 H); ¹³C NMR (CDCl₃, 75.5 MHz) δ 21.8

(t′), 22.0 (t′), 36.0 (t′), 51.7 (d′), 73.9 (d′), 76.6 (d′), 125.8 (d′),

127.1 (d′), 128.3 (d′), 144.2 (s′); exact mass m/z calcd for

C

₁₂H₁₄O (M - H₂O) 174.1045, found 174.1043; mass (CI) m/z

calcd for C₁₂H₁₆O₂(M + NH₄) 210, found 210.

Dim eth yl[[3-p h en yl-1-[3-(p h en ylselen o)p r op yl]-2-p r o-

p yn yl]oxy]sila n e (46a ). Solid NH₄Cl (ca. 1 mg) was added

to a homogeneous mixture of (Me₂SiH)₂NH (60 mg, 0.45 mmol)

and 9b (98.8 mg, 0.30 mmol) in a round-bottomed flask

2863, 2101, 1089, 836 cm^-^{1 1}H NMR (CDCl₃, 300 MHz) δ

;

0.98-1.13 (m, 14 H), 1.88-2.02 (m, 4 H), 2.94-3.03 (m, 2 H),

4.26 (s, 1 H), 4.60-4.68 (m, 1 H), 7.17-7.27 (m, 3 H), 7.27-

Preparation of Polycyclic Systems

septum.⁴⁹The mixture was swirled to

J . Org. Chem., Vol. 66, No. 6, 2001 1983

equipped with

a

dried (Na₂SO₄) and evaporated. Flash chromatography of the

residue over silica gel (1.8 × 10 cm), using increasing amounts

of EtOAc in hexane (from 15% to 25%), gave 46d ^2e(15.1 mg,

29%) as a colorless solid, and 45c (15.4 mg, 27%) as a colorless

oil. Alcohol 46d , had: R_f0.45, silica, 3:7 EtOAc-hexane; mp

115-118 °C; FTIR (CDCl₃cast) 3346, 2958, 1491, 1447, 1384,

distribute the material uniformly over the walls of the flask,

and the flask was allowed to stand at room-temperature

overnight. The mixture was placed under oil-pump vacuum

for 1 h [in order to remove the excess of (Me₂SiH)₂NH], and

the residual crude 46a was used directly for the next step

(formation of 46b). A sample from a similar experiment [NH₄-

Cl (ca. 1 mg), (Me₂SiH)₂NH (20.1 mg, 0.15 mmol), 9b (32.9

mg, 0.10 mmol)] was dissolved in C₆D₆and filtered through

glass wool, to give 46a as a colorless oil: FTIR (C₆D₆cast)

2946, 2123, 1489, 1252, 1086, 1073, 900 cm^-1; ¹H NMR (C₆D₆,

400 MHz) δ 0.19 (d, J ) 2.8 Hz, 3 H), 0.24 (d, J ) 2.8 Hz, 3

H), 1.88-1.93 (m, 4 H), 2.63-2.72 (m, 2 H), 4.51-4.58 (m, 1

H), 4.97-5.04 (m, 1 H), 6.89-7.00 (m, 6 H), 7.34-7.47 (m, 4

H); ¹³C NMR (C₆D₆, 100 MHz) δ -1.0 (q′), -0.8 (q′), 26.1 (t′),

27.5 (t′), 38.6 (t′), 64.4 (d′), 85.7 (s′), 90.4 (s′), 123.3 (s′), 126.8

(d′), 128.4 (d′), 128.5 (d′), 129.2 (d′), 131.0 (s′), 131.9 (d′), 133.0

(d′); exact mass m/z calcd for C₂₀H₂₄O⁸⁰SeSi 388.0762, found

388.0762.

(3r,3a â,6a â)-2,2-Dim et h ylh exa h yd r o-3-p h en yl-2H -cy-

clop en t[d ]-1,2-oxa silole (46b). The general procedure for

radical cyclization was followed, using crude 46a in PhH (45

mL), Ph₃SnH (210.6 mg, 0.60 mmol) in PhH (7.5 mL), AIBN

(24.6 mg, 0.5 mmol) in PhH (7.5 mL), and an addition time of

6 h. Refluxing was continued for 2 h after the stannane

addition. The crude product (46b) was used directly for the

next step (formation of 46d and 45c).

1

1200, 1093, 1076, 1029, 753, 694, 517 cm^-1; H NMR (CDCl₃,

300 MHz) δ 1.59-1.78 (m, 3 H), 1.89-2.05 (m, 2 H), 2.51-

2.62 (m, 1 H), 2.68-2.79 (m, 1 H), 4.55-4.62 (m, 1 H), 6.56-

6.61 (m, 1 H), 7.07-7.25 (m, 4 H); ¹³C NMR (CDCl₃, 75.5 MHz)

δ 22.6 (t′), 29.4 (t′), 34.9 (t′), 77.4 (d′), 123.7 (d′), 126.6 (d′),

128.3 (d′), 128.4 (d′), 137.8 (s′), 147.9 (s′); exact mass m/z calcd

for C₁₂H₁₄O 174.1045, found 174.1042.

Diol 45c was spectroscopically identical to the diol obtained

from oxidation of 45b.

The same three reactions were repeated, but using a

nonaqueous workup in the last step. This procedure improved

the yields. After the oxidation, the mixture was cooled to 0

°C, and well-crushed Na₂S₂O₄‚5 H₂O (ca. 1 g) was added. The

mixture was diluted with Et₂O (20 mL), and filtered through

a pad of Celite (3 × 2 cm). The pad was washed with Et₂O (2

× 20 mL), and the filtrate was evaporated. Flash chromatog-

raphy of the residue over silica gel (1.8 × 8 cm), using

increasing amounts of EtOAc in hexane (from 10% to 30%),

gave 46d (23.3 mg, 45%) and 45c (19.0 mg, 33%).

Ack n ow led gm en t. We thank the Natural Sciences

and Engineering Research Council of Canada for finan-

cial support. A.M. held an NSERC Graduate Fellowship

and M.C. held an FCAR Graduate Fellowship and a

Killam Award.

(E)-2-(P h en ylm eth ylen e)cyclopen tan ol (46d) an d [1r,2r-

(R*)]-2-[Hydr oxy(ph en yl)m eth yl]cyclopen tan ol (45c). H₂O₂

(30% solution in H₂O, 0.70 mL, 6.2 mmol) was added to a

stirred mixture of crude 46b, KHCO₃(60 mg, 0.6 mmol) and

KF‚2H₂O (56.4 mg, 0.6 mmol) in 1:1 MeOH-THF (12 mL) at

room temperature. The mixture was heated at 60 °C overnight,

cooled to room temperature, and diluted with aqueous 5%

KHSO₄(10 mL). Water (10 mL) was added, and the mixture

was extracted with EtOAc. The combined organic extracts were

Su p p or tin g In for m a tion Ava ila ble: All experimental

procedures not given above, NMR spectra of compounds for

which combustion analytical values were not obtained, and

X-ray data for 9f. This material is available free of charge via

the Internet at http://pubs.acs.org.

(49) Tamao, K.; Nakagawa, Y.; Arai, H.; Higuchi, N.; Ito, Y. J . Am.

Chem. Soc. 1988, 110, 3712-3714.

J O001124X

Article Doi

Preparation of polycyclic systems by sequential 5-exo-digonal radical cyclization, 1,5-hydrogen transfer from silicon, and 5-endo-trigonal cyclization

DOI: 10.1021/jo001124x

Source and publish data:

Authors:

Article abstract of DOI:10.1021/jo001124x

Full text of DOI:10.1021/jo001124x

Products guided by the article

R&D Labs maybe for 335164-81-3

Relevant to this article

Hot Product