(Alkynyl)dicobalt hexacarbonyl-mediated radical cyclizations

TETRAHEDRON

Pergamon

Tetrahedron 56 (2000) 2211±2224

(Alkynyl)dicobalt Hexacarbonyl-Mediated Radical Cyclizations

*

Karen L. Salazar and Kenneth M. Nicholas

Department of Chemistry and Biochemistry, University of Oklahoma, Norman, OK 73019, USA

This article is dedicated to Myron Rosenblum and (the late) Roland Pettit, my mentors and pioneers in the use of organometallics in organic synthesis

Accepted 7 December 1999

AbstractÐRadicals ¯anked by the ±(alkynyl)Co₂(CO)₆unit add intramolecularly to carbon±carbon double bonds with unusual stereo- and

regioselectivity. Cationic complex 13a (RCO₂Me) reacts with Zn to produce exclusively the trans-5-exo product 14a. Labile propargyl

bromide complexes 16a±d, prepared from the alcohols 7a±d, undergo cyclization with Et₃B/O₂/Ph₂SiH₂or upon irradiation. Under the latter

conditions atom transfer products (17a±c, 18c,d) were obtained exclusively, whose regio- and stereochemistry were dependant on the

ole®nic acceptor. Thus, irradiation of the ester trans-16a or the phenyl derivative 16b (E/Z mixture) gives the trans-cyclopentyl derivatives

17a and 17b; the bromide 16c (RMe) affords a mixture of the trans-cyclopentyl compound 17c and a comparable amount of the cyclohexyl

derivative 18c; and the parent bromide 16d (RH) is converted exclusively to the cyclohexyl derivative 18d. Heptenyl derivative 20d (RH)

cyclizes exclusively to the 7-endo cycloheptyl derivative 21d. Limited mechanistic experiments suggest the operation of a radical chain,

atom transfer mechanism with a product-like transition state. A tandem cyclization/allylation reaction has been demonstrated in the reaction

Introduction

We recently initiated a program to systematically investi-

gate the chemistry of carbon-centered organotransition

metal radicals. In particular we seek to determine whether

sterically and electronically in¯uential organometallic units

can induce extraordinary radical reactivity. Our initial

efforts demonstrated that the readily accessible and syntheti-

cally useful propargyl cation complexes 1^2b,cundergo

ef®cient reductive coupling, presumably via the correspond-

ing radicals 2, to form 1,5-diyne complexes with extraor-

The modi®ed reactivity of species coordinated to transition

metals is a central paradigm of organometallic chemistry

and this concept provides the basis for the myriad of

stoichiometric and catalytic applications of organometallic

chemistry in organic synthesis. Virtually all the examples of

this concept have involved the coordination of even electron

organic species, both neutral and charged. Indeed, the

ability of transition metal fragments to dramatically alter

the reactivity of species such as carbenes¹and carbocations²

has been widely explored fundamentally and applied

synthetically.

dinary

diastereoselectivities

when

compared

to

dimerizations of typical organic radicals.^6,7

In sharp contrast there is little known of the potential for

transition metal coordination to modify the stability and

reactivity of odd electron species, e.g. carbon-centered

free radicals. There have been scattered reports of the

reductive coupling of cationic metal-pi complexes, e.g.

ferrocenylmethyl¹,^3a±c(benzyl)Cr(CO)¹₃,^3c,d(propargyl)-

Mo₂Cp₂(CO)₄¹,^3eand (pentadienyl)Fe(CO)¹₃,^3f±hwhich are

presumed to proceed via the intermediacy of the corre-

sponding radicals. More recently, (benzyl)Cr(CO)₃radicals

have been implicated as intermediates in radical additions to

double bonds ¯anked by the (arene)Cr(CO)₃unit⁴and the

structure/stability of these radicals have been examined

theoretically.⁵

The discovery of ef®cient, radical-based carbon±carbon

bond-forming reactions has provided a powerful new

array of tools for organic synthesis. Especially valuable

are intramolecular radical additions to carbon±carbon

double bonds as typi®ed by the 5-hexenyl radical cycliza-

tion (Scheme 1).⁸A distinctive and useful feature of this

reaction is the kinetically-controlled, highly regioselective

formation of ®ve-membered rings. The levels of stereo-

selectivity for such reactions, however, are less useful,

e.g. 1-substituted 5-hexenyl radicals undergo cyclization

generally with only a modest preference for cis-1,2-

disubstituted cyclopentanes.⁹

Keywords: radical cyclization; (propargyl)Co₂(CO₆); regio- and stereo-

selectivity.

* Corresponding author. Tel.: 11-405-325-3696; fax: 11-405-325-6111;

e-mail: knicholas@ou.edu

PII: S0040-4020(99)01104-7

2212

K. L. Salazar, K. M. Nicholas / Tetrahedron 56 (2000) 2211±2224

Scheme 1.

In order to further assess the reactivity and synthetic poten-

tial of (propargyl)Co₂(CO)₆radicals (2) we have sought to

engage these radicals in addition reactions to unsaturated

carbon±carbon bonds. We envisioned that the regio- and

stereoselectivity features of such cyclizations could provide

insight into the reactivity, stability, and electronic character,

e.g. nucleophilic or electrophilic, of the intermediate metal-

complexed radicals. In our preliminary investigation we

found that cyclizations of 1-(alkynyl)Co₂(CO)₆-5-hexenyl

radicals (3) not only proceed with exceptionally high

trans-1,2-stereoselectivity in the 5-exo mode, but also

exhibit novel regioselectivity that is remarkably sensitive

to the 6-position substituent.¹⁰In this report we provide a

complete account of the initial study as well as investiga-

tions of the corresponding heptenyl radical cyclization,

some mechanistic probes of these cyclization reactions,

and an initial effort to expand their synthetic utility by

trapping the intermediate cyclized radicals.

high yield upon reaction with Co₂(CO)₈. Compounds

7a±c were produced as E/Z isomeric mixtures; the stereo-

isomers of 7a could be separated chromatographically.

Preparation of the corresponding nonen-yn-ols 10a±d and

their cobalt complexes 12a±d was accomplished either: (a)

by acetylide addition to the monoacetal of adipaldehyde (7)

followed by acetal hydrolysis and Wittig ole®nation or (b)

by initial Wittig reaction of 8 and subsequent hydrolysis and

acetylide addition (Scheme 3). Moderate yields of 10a±d

and 12a±d were obtained and characterized spectro-

scopically.

Reductive cyclizations via the cationic complexes 13

Initially, we investigated the generation of the radicals 3 by

one electron reduction of the cobalt-stabilized cations 13

(Scheme 4). This unconventional approach to radical

generation was initially established in our studies of reduc-

tive dimerization of the remarkably stable (and isolable)

propargyl cation complexes 2.^2b,cThus, treatment of alcohol

complex 7a with excess HBF₄´Et₂O at 2308C in propionic

anhydride followed by ether addition precipitated salt 13a

which was treated with Zn powder in CH₂Cl₂to produce a

single cyclized product 14a (38%). NMR analysis of 14a

indicated the presence of only one isomer, established as the

trans cyclopentane by X-ray diffraction. The yield of 14a

was primarily limited by the appreciable solubility of inter-

mediate salt 13a in ether, resulting in substantial losses

during its isolation.

Results and Discussion

Synthesis of cyclization precursors

Substrates for the cyclization studies were prepared using

conventional reactions as outlined in Schemes 2 and 3. The

octen-yn-ols 6a±d were ef®ciently produced by phenyl-

acetylide addition to glutaraldehyde followed by Wittig

reactions of the intermediate acetylenic hemiacetal 5. The

corresponding cobalt complexes 7a±d were obtained in

Scheme 2. (a) PhCuCLi; (b) Ph₃PCHR; (c) Co₂(CO)₈.

Scheme 3. (a) i. PhCuCLi, ii. HCl/H₂O; (b) Ph₃PCHR; (c) i. Ph₃PCHR, ii. HCl/H₂O; (d) PhCuCLi; (e) Co₂(CO)₈.

K. L. Salazar, K. M. Nicholas / Tetrahedron 56 (2000) 2211±2224

2213

Scheme 4. (a) HBF₄, (EtCO)₂O; (b) Zn/CH₂Cl₂, RCO₂Me.

The successful reductive cyclization of the ester 7a is

signi®cant in three respects: (1) the cationic complex

(13a) itself does not cyclize under these conditions; (2)

the 5-exo cyclization product (14a) is produced regio-

selectively; and (3) its stereochemistry is exclusively

trans. Together, these features are consistent with a reaction

occurring via a radical (i.e. 3a) which cyclizes with typical

regioselectivity but atypical stereoselectivity. That the

cyclization of 13a occurs only upon reaction with zinc

supports a pathway via the radical rather than the cation

and is noteworthy because the propargyl cation complexes

are known to add to electron rich carbon±carbon double

bonds.¹¹Moreover, if cyclization of 13a were to occur via

the cation, the 6-exo product should be preferred, avoiding

development of positive charge a to the electrophilic ester

group. The exclusive trans stereoselectivity observed in the

cyclization stands in contrast to that usually observed for

1-substituted-5-hexenyl radical cyclizations, which is

moderately in favor of the cis product.⁸While bulky (e.g.

t-butyl) groups at C-1 can tip the balance modestly towards

the trans product,⁹the exclusive trans stereoselectivity

found with 13a is extraordinary.

cationic complexes 1 generally proved inef®cient, we

considered more conventional radical precursors which

would be more generally useful and functional group

tolerant. Among the most obvious choices, (propargyl

halide)Co₂(CO)₆, were little known species. Although a

few examples of poorly characterized propargyl chloride

complexes have been reported,^12areactions of cobalt car-

bonyl with propargyl halides were known to produce

complex mixtures, including coupling products.^12bGreen

and coworkers have recently generated metastable

complexes of propargyl chlorides bearing g-electron with-

drawing groups.¹³We found a convenient route to the

desired propargyl bromide derivatives 16 by treatment of

the alcohol complexes 7a±d (CH₂Cl₂, 08C) with

2Br₂´(Ph₂PCH₂CH₂PPh₂)¹⁴(Scheme 5). The alcohol to

bromide conversion was typically accompanied by substan-

1

tial shifts of the H and ¹³C methine NMR absorptions.

Generally these labile complexes decompose during

chromatography or upon standing at room temperature so

they were best stored below 08C or used soon after

preparation.

Because of the thermal instability of the bromide complexes

16, our initial cyclization attempts utilized room tempera-

ture Et₃B/O₂initiation,¹⁵together with Bu₃SnH or Ph₂SiH₂

as prospective H-atom donors. When a benzene solution of

16a (RCO₂Me) was treated with Et₃B and Ph₂SiH₂at

208C, a 1.0:1.8 separable mixture (70% yield from 7a) of

trans 14a and a second compound was obtained. The latter

proved to be the cyclized bromo derivative trans-17a

(epimeric at C-1⁰) based on NMR and MS analysis. This

unexpected result was con®rmed by X-ray crystallographic

determination of one epimer of 17a. The bromo compound

17a is the apparent result of a bromine atom-transfer

cyclization.¹⁶

When the phenyl-substituted alcohol complex 7b was

analogously protonated, addition of pentane:ether produced

a homogeneous solution (rather than precipitating the inter-

mediate salt 13b). Chromatography afforded the epimeric

trans cyclopentyl propionates 15b in good yield (Scheme 4).

This product probably arises from cationic cyclization of the

intermediate complex 13b, facilitated by the more nucleo-

philic styryl double bond. The observed regio- and stereo-

selectivity is consistent with a late transition state favoring

development of positive charge adjacent to the stabilizing

phenyl group.

Atom-transfer cyclizations

Subsequently, it was serendipitously discovered that neat

samples (or benzene solutions) of the propargyl bromide

Since generation of the organometallic radicals 2 from the

Scheme 5. (a) 2Br₂´Ph₂CH₂CH₂PPh₂; (b) Et₃B/O₂/Ph₂SiH₂.

2214

K. L. Salazar, K. M. Nicholas / Tetrahedron 56 (2000) 2211±2224

Scheme 6.

complexes 16, when left in direct sunlight or brie¯y

irradiated with a 300 W sunlamp, were converted exclu-

sively to atom transfer products (Scheme 6) in good yields.

Thus, irradiation of the bromoester trans-16a caused its

smooth conversion to trans-17a (56% from 7a) as the

only characterizable product (epimeric mixture). The

phenyl derivative 16b (E/Z mixture) was likewise converted

to trans-17b (76% from 7b; Scheme 6). The trans stereo-

chemical assignment for 17b was supported by NMR

comparison with the prior cyclization products and also

was con®rmed cystallographically.

The regiochemical course of these reactions was found to

depend dramatically on the C-6 substituent. Thus, the

bromide 16c (RMe) afforded a mixture of isomeric

products (60% from 7c), comprised of the trans cyclopentyl

compound 16c (2:1 stereoisomeric at C-6) and a comparable

amount of the cyclohexyl derivative 18c (isomeric mixture),

the product of 6-endo cyclization. The latter assignment was

supported by 1-D proton decoupling experiments and by

X-ray diffraction analysis of the major isomer, cis, cis

18c. The 6-endo-trig pathway became the exclusive one

when the parent complexed bromide 16d was irradiated;

Scheme 7.

K. L. Salazar, K. M. Nicholas / Tetrahedron 56 (2000) 2211±2224

2215

Scheme 8.

the cyclohexyl derivative 18d was the sole regioisomer

(73% from 7d), isolated as a 2:1 mixture of stereoisomers.

These assignments were based on NMR (DEPT, COSY)

techniques and also con®rmed by X-ray diffraction of one

of the isomers.

lacking a radical stabilizing group, affords the 6-endo

product exclusively. Substrates which previously have

exhibited appreciable 6-endo selectivity either have been

5-substituted¹⁸(sterically blocking the 5-exo mode), confor-

mationally biased¹⁸(e.g. a-halo carbonyl compounds), or

those which produce radicals which cyclize reversibly, i.e.

are under thermodynamic control.¹⁹

The facile cyclizations of bromo complexes 16a±d should

be contrasted with the unreactivity of the free bromo

ene-yne PhCuCCHBrCH₂CH₂CH₂CHvCH₂(19d) under

similar conditions. Thus, 19d was recovered unchanged

after irradiating a neat sample or a benzene solution

containing 10 mol% of Bu₆Sn₂for 3 h.

The distinctive regio- and stereoselectivity of the reactions

of propargylic bromide complexes 16 can be explained in

terms of an atom transfer mechanism having a late, product-

like, transition state for cyclization (Scheme 7). This process

is presumably initiated by cobalt-assisted photoinduced

homolysis of the C±Br bond to generate radical 3 which

is stabilized by metal coordination. As such, the transition

states for the cyclization of 3 (A vs. B) would involve

signi®cant C±C bond making (and breaking) as well as

the development of radical character at the original ole®nic

carbons. With a strongly radical-stabilizing group at C-6

(e.g. Ph or CO₂R) the 5-exo transition state A is favored

because it allows delocalization of the developing radical

at C-6. The 6-endo transition state B may be preferred for

RH since it develops secondary radical character at C-5

(vs. primary C-6 radical character as in A). For RMe, the

partitioning (A vs. B) is between two incipient (and simi-

larly energetic) secondary radicals, producing signi®cant

amounts of both regioisomers.

The high reactivity of the propargyl bromide complexes 16

presumably re¯ects a labilization of the C±Br bond by the

adjacent (alkynyl)dicobalt hexacarbonyl unit which, in

turn, suggests the generation of a relatively stable radical.

Cyclizations of the complexes 16 are arguably the most

facile of the atom transfer reactions reported to date,^17,18

which typically involve organic iodides with one or two

activating groups as substrates; organic bromides generally

display low reactivity. Aside from their extraordinary

facility, the most unusual feature of their reactivity is the

regiochemical dependence (5-exo vs. 6-endo) of cyclization

on the ole®nic substituent. The effect most likely is

electronic in nature. The substrates possessing strongly

radical stabilizing groups, 16a,b (RCO₂Me, Ph) react

exclusively in the 5-exo mode; that bearing a weakly

stabilizing Me group (16c) gives a mixture of 5-exo and

6-endo products; and the parent complex 16d (RH),

Steric interactions between the bulky (alkyne)Co₂(CO)₆

unit and the ±CHR group would be ampli®ed in this later

Scheme 9.

2216

K. L. Salazar, K. M. Nicholas / Tetrahedron 56 (2000) 2211±2224

Scheme 10.

transition state, which could account for the high trans

stereoselectivity observed in the formation of the 5-exo

products. The typically modest cis stereoselectivity of

most 1-substituted hexenyl radical cyclizations is thought

to re¯ect the composition of alternative early chair- and

boat-like transition states with a long C1±C5-developing

bond, the chair-equatorial conformation (C) being the

most important (Scheme 8). The predominance of the

trans-product for substrates bearing a bulky substituent at

C1 (e.g. for R^tBu, trans/cis85:15²⁰), has been noted but

is not quantitatively accounted for in the framework of the

Houk²¹or Beckwith²²force ®eld calculational methods. Of

the four likely transition states (C±F), the exclusive

trans stereoselectivity found in the cyclizations of the

1-(alkynyl)Co₂(CO)₆-5-hexenyl substrates may be accom-

modated by having the very sterically demanding

organocobalt group occupy a pseudoequatorial position in

the `boat-equatorial' transition state (F).

Lower rates and yields in heptenyl cyclizations are not

unusual,⁸although the dropoff was more drastic than

expected. The regioselectivity found in the case of 20d,

providing only the 7-endo product, is also exceptional

among heptenyl radical cyclizations which, for typical

organic radicals, provide a preponderance of the kinetically

favored 6-exo products. The extraordinary regioselectivity,

however, can also be rationalized by our mechanistic

hypothesis involving a later cyclization transition state

having signi®cant product radical character (Scheme 10).

Thus, the observed 7-endo pathway leading to 20d allows

development of radical character on a secondary carbon (G)

whereas the 6-exo mode leads to a developing primary

radical (H).

Mechanistic probes

Several lines of circumstantial evidence point to the

involvement of a radical process for both the reductive

and bromine transfer cyclizations including: (1) the reac-

tions occur ef®ciently regardless of the electronic character

of the ole®nic acceptor; (2) the atom transfer reactions

proceed in the absence of solvent or in non-polar benzene;

(3) cyclization of the ester-substituted complex 16a occurs

in the 5-exo mode (rather than the 6-endo mode expected for

a cationic pathway); (4) the reactions can be induced and

terminated by established radical initiation methods, e.g.

Et₃B/O₂and R₃SnH/R₃SiH; and (5) dimers are produced,

both in the Zn reduction of simple cation complexes

(1)^6b,cand in the photoreactions of the heptenyl substrates

20.

The 1-heptenyl cyclizations of the corresponding bromo

complexes 20a±d were also investigated (Scheme 9).

These were conveniently generated from the precursor

alcohol complexes 12, again using diphos´2Br₂. In general,

the photoinduced cyclizations of 20 proved to be much less

ef®cient than for the above hexenyl systems. Irradiation of

neat 20d (RH) required ca. 90 min for its complete

consumption and produced several products which were

separated chromatographically. Among these only one

appeared to be cyclic judging by NMR and its mass

spectrum indicated it to be isomeric with the starting

bromide. Its structure was determined to be the 7-endo

compound 21d (8%) which exhibited a complex multiplet

for 1H at 4.69 ppm for a ±CHBr unit rather than the simple

doublet expected for the ±CH₂Br group of the 6-exo

derivative 22d. This assignment was supported by homo-

nuclear proton/proton decoupling. Photoinduced cyclization

of the other heptenyl substrates 20a±c proved even less

ef®cient. In no instance was an appreciable quantity of

any cyclic bromide detected. However, besides products

resulting from HBr elimination from or hydrolysis of the

starting materials, NMR and MS analysis indicated the

formation of dimeric products, e.g. 23, in low yield. This

result provides additional evidence for the generation of

radicals by C±Br bond homolysis of the propargyl bromide

complexes 16 and 20.

To supplement the evidence for a radical pathway

uncovered during the above reactivity studies the effect of

two classical radical traps on the cyclizations was brie¯y

examined. The photoinduced cycloisomerization of 16a was

found to be little affected by the presence of 1.5 equiv. of

meta-dinitrobenzene; the cyclization product 17a was still

produced in moderate yield. Interestingly, irradiation of a

benzene solution of 15a in the presence of TEMPO

(1 equiv.) produced the acyclic adduct 23, judging by

NMR and MS analysis, rather than cyclized products

(Scheme 11). A control experiment revealed that the latter

reacted with TEMPO to produce 23 even without irradia-

tion. The failure of dinitrobenzene to signi®cantly inhibit

K. L. Salazar, K. M. Nicholas / Tetrahedron 56 (2000) 2211±2224

2217

Scheme 11.

the transfer cyclizations may simply re¯ect a faster rate of

bromine atom transfer step relative to addition of the inter-

mediate radical to DNB. On the other hand, formation of the

TEMPO adduct 24 could be the result of TEMPO trapping

of low concentrations of the radical 3a present in solutions

of 16a at room temperature in laboratory light or could be

derived from a direct reaction of TEMPO with the bromide

16a itself.

derivative, e.g. 18c, detected (the thermodynamic product);

only products resulting from demetalation of the triple bond

were isolated. Taken together, we have found no evidence

for equilibrium (thermodynamic) control of the cyclizations

of the cobalt complexes. We note also that the temperature

at which these cyclizations proceed is far milder than those

which previously have been found to be reversible.¹⁹

Synthetic studies

Another question of interest was whether the novel regio-

and stereoselectivity associated with the hexenyl and

heptenyl cyclizations of the alkynyl-cobalt complexes was

the result of kinetic or thermodynamic control. Some efforts

were made therefore to determine whether these reactions

are reversible. Resolution of this issue is complicated by the

fact that the starting bromides 16, by virtue of the adjacent

activating organocobalt unit, generate radicals under much

milder conditions than the (unactivated) product bromides

17 and 18. When cyclic bromoester 17a (RCO₂Me) was

irradiated in the presence of the acyclic precursor 16a as a

prospective initiator, only the original cyclic product 17a

was recovered. Bromide 17a was also irradiated together

with Bu₆Sn₂and Bu₃SnH. In this experiment a substantial

quantity of the reduction product 14a with an unaltered

carbon skeleton was produced, indicating successful genera-

tion of the exocyclic radical which was trapped by tin

hydride. Apparently, under these conditions ring opening

is slow, i.e. essentially irreversible, relative to trapping of

the cyclized radical by Bu₃SnH. Since the methyl-substi-

tuted complex 16c cyclizes to form both 5-exo and 6-endo

products, the bromocyclopentane derivative 17c (RMe,

the presumed kinetic product) was also subjected to

potentially equilibrating conditions by: (a) irradiation in

the presence of Bu₆Sn₂or (b) heating with Bu₃SnH and

the radical initiators AIBN or AMVN [2,2⁰-azobis(2,4-

dimethylvaleronitrile)]. In no instance was any cyclohexane

An attractive feature of atom transfer cycloadditions is the

transposition of the functional halogen, which allows for

subsequent synthetic elaboration at the new halogenated

site.^8,16The presence of both the bromine and the (alkynyl)-

Co₂(CO)₆functionalities in the cyclization products 17 and

18 offers interesting and potentially useful opportunities for

further synthetic elaboration. Besides providing access to

the synthetically versatile free carbon±carbon triple bond,

the latter can engage directly in various cycloaddition

reactions, including the Pauson±Khand conversion to

cyclopentenones²³and coupling with alkynes or nitriles to

produce substituted arenes or pyridines.²⁴Accordingly, we

investigated

a cyclization/allylation sequence of the

complexes 16 to set up a subsequent Pauson±Khand

cyclopentannulation (Scheme 12) to produce angular

tricyclic 5±6±5 systems.

Several attempts to trap the cyclized radicals with allyl-

tributyl tin²⁵failed to provide allylated products. Thus,

irradiation of either acyclic 16a or cyclic 17a in the presence

of an excess of Bu₃Sn(allyl) (with and without Bu₆Sn₂,

AIBN or vitamin B₁₂/Zn) afforded only the cyclic bromide

17a and varying amounts of decomposition products.

However, a little utilized radical allylating agent, CpFe-

(CO)₂(h¹-allyl),²⁶ultimately proved successful. When the

acyclic bromide 16a (RCO₂Me) was stirred in benzene

Scheme 12.

2218

K. L. Salazar, K. M. Nicholas / Tetrahedron 56 (2000) 2211±2224

with 5 equiv. of the latter at room temperature in normal lab

light, the cyclic allylated product trans-24a (RCO₂Me)

was isolated in moderate yield as a mixture of C1⁰epimers,

accompanied by CpFe(CO)₂Br. The successful allylation of

16a by CpFe(CO)₂(h¹-allyl), suggests that this compound

could ®nd more general use for mild allyl transfer reactions.

Glutaraldehyde was purchased as a 50% aqueous solution

and the water was removed by freeze-drying. For all reac-

tions the glassware was oven dried at 1258C. Acetal 7²⁸and

CpFe(CO)₂(h¹-allyl)²⁹were prepared by literature methods.

¹H NMR spectra were recorded at 300 or 400 MHz using

CDCl₃as solvent unless noted otherwise using residual

chloroform-H (d 7.24) as internal reference; all J values

are in Hz. ¹³C NMR spectra were recorded at 75 or

100 MHz and were referenced to the d 77.0 resonance of

CDCl₃. FT-IR spectral frequencies are given in cm²¹. Mass

spectra were obtained either by electron impact (EI) or fast

atom bombardment (FAB) methods, the latter using 3-nitro-

benzyl alcohol (3-NBA) as the matrix. Elemental analyses

were performed by Midwest Microlabs, Indianapolis, IN.

Without further optimization of the cyclization/allylation

reaction, Pauson±Khand cyclization of 24a was investi-

gated. Three established protocols were tested: (1) treatment

with N-methylmorpholine N-oxide,²⁷(2) thermal oxidation

on silica gel,²⁷and (3) heating with aqueous ammonia.²⁷

Unfortunately, the former two reactions afforded the

demetallated alkyne 25a as the only characterizable

product, while the latter produced a complex mixture of

organic products. The reason for this failure is not apparent

to us, but could be the result of poor proximity of the trans-

(alkyne)cobalt carbonyl unit and the pendant alkenyl

side chain or may re¯ect ring strain in the prerequisite

intermediate metallacyle.

Preparation of hemiacetal 5

In a round bottom ¯ask under nitrogen a solution of

0.05 mol of phenylacetylene in 70 mL of THF was cooled

to 2788C, then treated dropwise with 0.05 mol of BuLi

(1.6 M in hexanes) and the mixture was then stirred for

15 min. In a second round bottom ¯ask under nitrogen,

0.050 mol of glutaraldehyde was dissolved in 50 mL of

THF and then cooled to 2788C. To this solution the lithium

phenylacetylide solution was transferred via cannula. The

reaction was monitored by TLC (1:1 PE:EE) for the dis-

appearance of glutaraldehyde (ca. 5 h). The reaction was

quenched with 100 mL of 1 M HCl, extracted three times

with 100 mL of Et₂O, the combined ether extracts dried over

MgSO₄, ®ltered through Celite, and then concentrated.

Puri®cation by ¯ash chromatography (1:1 PE/EE) afforded

5 as a light yellow oil (0.090 g, 0.44 mmol, 47%). R_f0.43;

¹H NMR d 7.44±7.41 (m, 4H), 7.29±7.26 (m, 6H), 5.35 (dd,

J6.9, 3.7 Hz, 1H), 5.02±4.99 (m, 1H), 4.79 (dd, J6.3,

2.0 Hz, 1H), 4.46 (dd, J12.0, 2.5 Hz, 1H), 2.86 (d,

J6.0 Hz, 1H), 2.55 (dd, J3.0, 0.9 Hz, 1H), 1.98±1.24

(m, 12 H); ¹³C NMR d 131.8, 131.7, 128.4, 128.3, 128.2,

122.6, 122.5, 96.4, 92.3, 87.9, 87.5, 85.1, 84.5, 66.8, 62.0,

32.1, 31.5, 31.3, 30.3, 21.5, 17.7; IR (CH₂Cl₂) 3587 (m),

2952 (m), 1490 (m), 1192 (m), 1127 (m), 1071 (m), 1026

(s), 973 (s) cm²¹; HRMS m/e calcd for C₁₃H₁₅O₂203.1072,

found 203.1063; 203 ([M1H]¹), 202 ([M]¹).

Conclusions

In summary, we have described facile reductive and atom

transfer cyclizations of 1-[(alkynyl)Co₂(CO)₆]-hexenyl and

-heptenyl systems. The former reactions proceed with

exclusive trans stereoselection in the 5-exo mode. They

also display unusual regioselectivities, favoring either

5-exo- or 6-endo-cyclization depending on the radical stabi-

lizing ability of the alkenyl substituent. One successful

-heptenyl radical cyclization proceeds exclusively in the

7-endo mode.

Taken together, the facility of the atom transfer cyclizations

of the propargyl-cobalt complexes and their unusual regio-

selectivity strongly suggest that the intervening (propargyl)-

Co₂(CO)₆radicals are stabilized relative to typical organic

radicals. Although kinetic data are not yet available, the

ready cyclizations of 16 possessing either electron-rich or

-poor double bonds may indicate that the (propargyl)-

Co₂(CO)₆radicals are ambiphilic. At this time we have no

direct information on the structure of these species nor their

mode of radical stabilization. However, based on studies of

the related stable cations 1,^2b,cwe anticipate that spin

density in the radicals 2 can be highly delocalized onto

the (alkynyl)Co₂(CO)₆fragment. Studies to generate and

characterize persistent derivatives of 2 are planned in

order to address these issues. Our studies to date of the

(propargyl)Co₂(CO)₆radicals suggest that new and unusual

reaction selectivity will be associated with carbon-centered

organometallic radicals. Efforts to further elucidate the

origin of this selectivity and to exploit it in organic synthesis

are underway.

General preparation of ene-yne alcohols 6

In a round bottom ¯ask under nitrogen 2.34 mmol of the

appropriate phosphonium bromide was dissolved in 5 mL of

THF, then 2.34 mmol of BuLi (1.3 M in hexanes) was added

dropwise (in the preparation of ester 6a the commercial ylid

was used directly). The mixture was stirred 15 min before

1.17 mmol of the hemiacetal 5 dissolved in 5 mL of THF

was added dropwise. The reaction was monitored by TLC

(2:1 Et₂O:petroleum ether) for the disappearance of 5. The

reaction was quenched with 10 mL of 1 M HCl, then

extracted three times with 50 mL of Et₂O. The combined

organic extracts were dried over MgSO₄, ®ltered through

Celite, and the concentrate was puri®ed by column chroma-

tography on silica gel (1:1 PE/EE).

Experimental

General methods

6a. (E); light yellow oil; R_f0.2 (10% ethyl acetate/90% PE;

¹H NMR d 7.42±7.36 (m, 2H), 7.31±7.27 (m, 3H), 6.97 (dt,

J15.6, 6.9 Hz, 1H), 5.84, (d, J15.9 Hz, 1H), 4.60 (app t,

J6.0 Hz, 1H), 3.71 (s, 3H), 2.27 (app q, J7.2 Hz, 2H),

Solvents were dried and freshly distilled before use;

PEpetroleum ether, EEdiethyl ether. Organolithium

reagents were standardized by titration before use.

K. L. Salazar, K. M. Nicholas / Tetrahedron 56 (2000) 2211±2224

2219

1.85±1.64 (m, 5H); ¹³C NMR d 167.1, 148.9, 131.6, 128.3,

128.2, 122.5, 121.2, 89.8, 84.9, 62.4, 51.3, 37.0, 31.7, 23.6;

IR (CH₂Cl₂) 3594 (m), 3472 (m), 2950 (m), 2865 (m), 1721

(s), 1658 (s), 1490 (m), 1458 (m), 1438 (m), 1342 (m), 1316

(m), 1200 (m), 1181 (m), 1154 (m), 1100 (m), 1069 (m),

1027 (m) cm²¹; HRMS (FAB, 3NBA) m/e calcd for

C₁₆H₁₈O₃258.1256, found 258.1231; 258 ([M]¹).

mixture stirred for another hour. The solution was then

extracted with ®ve 20 mL portions of diethyl ether, the

combined extracts were washed with 50 mL NaHCO₃,

dried over MgSO₄, ®ltered through Celite, and then concen-

trated. Puri®cation by ¯ash chromatography (1:1 PE/EE/

silica gel) afforded 0.485 g (2.24 mmol, 24%) of 9 (yellow

oil). ¹H NMR d 9.76 (s, 1H), 7.41±7.39 (m, 2H), 7.29±7.24

(m, 3H), 4.59 (t, J6.8 Hz, 1H), 2.46 (t, J6.8 Hz, 2H),

1.91 (s broad, 1H), 1.83±1.73 (m, 2H), 1.72±1.66 (m,

2H), 1.59±1.53 (m, 2H). IR (CH₂Cl₂) 3598 (m), 3054 (m),

6b. (E/Z) light yellow oil; R_f0.5 (3:1 petroleum ether:-

diethyl ether); H NMR major isomer (E) d 7.43±7.16 (m,

1

10H), 6.40 (d, J15.9 Hz, 1H), 6.22 (dt, J15.9, 7.9 Hz,

1H), 4.63±4.58 (m, 1H), 2.29 (app q, J7.2 Hz, 2H), 1.89±

1.79 (m, 5H); minor isomer (Z) d 7.43±7.16 (m, 10H), 6.43

(d, J11.9 Hz, 1H), 5.66 (dt, J11.9, 7.9 Hz, 1H), 4.63±

4.58 (m, 1H), 2.41 (app q, J7.0 Hz, 2H), 1.76±1.66 (m, 5

H); ¹³C NMR (E/Z, CDCl₃,) d 138.0, 137.9. 132.3, 131.8,

130.6, 130.4, 129.6, 128.8, 128.5, 128.4, 128.3, 128.2,

126.9, 126.6, 126.1, 122.9, 90.3, 85.2, 63.0, 62.9, 37.6,

32.6, 28.2, 25.6, 25.1; IR (CH₂Cl₂) 3595 (m), 3082 (w),

3026 (m), 2943 (m), 2862 (m), 1598 (m), 1490 (s), 1379

(m), 1070 (m), 1025 (m), 967 (s) cm²¹; HRMS (FAB,

3NBA) m/e calcd for C₂₀H₂₀O 276.1514, found 276.1492;

276 ([M]¹).

2986 (m), 2946 (m), 2865 (m), 2305 (m), 1723 (s) cm²¹

.

EIMS (12 eV) m/z: [M]¹216.

Preparation of 10a,d

In a side-arm round bottom ¯ask equipped with a stirring bar

under nitrogen 2.93 g (8.82 mmol) of Ph₃PCH(CO₂CH₃)

was dissolved in 20 mL of THF. A solution of 0.950 g

(4.37 mmol) of acetylenic aldehyde 8 in 5 mL of THF was

then added. The ¯ask was equipped with a water-cooled

condenser and the mixture was heated to re¯ux and the

reaction was monitored by TLC for the disappearance of 9

(10% ethyl acetate in petroleum ether, ca. 3 h). The reaction

was quenched with 20 mL of water, then extracted three

times with 10 mL portions of diethyl ether. The extracts

were dried over magnesium sulfate, ®ltered through Celite,

and then concentrated. The resulting crude unsaturated

acetal was then dissolved in 40 mL of acetone, 0.6 mL of

water was added followed by 0.4 g of Amberlyst-15. After

stirring the mixture for 24 h, the solvent was evaporated and

the residue chromatographed (silica gel, 10% ethyl acetate/

PE) affording 10a (0.930 g, 3.42 mmol, 78%) as a yellow

oil. ¹H NMR d 7.49±7.30 (m, 2H), 7.28±7.20 (m, 3H), 6.90

(dt, J15.6, 6.9 Hz, 1H), 5.76 (d, J15.6 Hz, 1H), 4.57±

4.86 (m, 1H), 3.64 (s, 3H), 2.21±2.15 (m, 2H), 1.82 (d,

J4.2 Hz, 1H), 1.78±1.67 (m, 2H), 1.54±1.40 (m, 4H);

¹³C NMR d 166.9, 149.2, 131.4, 128.1, 128.0, 122.4,

120.8, 90.0, 84.6, 62.5, 51.3, 37.4, 32.0, 27.6, 24.7; IR

(CH₂Cl₂) 3594 (m), 3320 (m), 2940 (m), 2862 (m), 1721

(s), 1712 (s), 1657 (m) cm²¹; MS (FAB, 3NBA) m/z: 273

[M1H]¹.

6c. (E/Z); light yellow oil; R_f0.8 (1:1 PE/EE); ¹H NMR d

7.41±7.19 (m, 10H), 5.49±5.36 (m, 4H), 4.61±4.57 (m,

2H), 2.13±2.02 (m, 4H), 1.84±1.73 (m, 4H), 1.63±1.54

(m, 12H); ¹³C NMR major isomer d 131.6, 130.1, 128.3,

128.2, 124.3, 122.6, 90.1, 84.8, 62.8, 37.3, 26.4, 25.1, 12.8;

minor isomer d 131.6, 130.8, 128.3, 128.2, 125.3, 122.6,

90.1, 84.8, 62.8, 37.3, 32.1, 25.1, 17.9; IR (CH₂Cl₂) 3593

(s), 3452 (m), 3014 (m), 2938 (s), 2862 (s), 1654 (w), 1598

(m), 1490 (s), 1457 (m), 1443 (m), 1378 (s), 1069 (s), 1026

(s), 971 (s) cm²¹; HRMS (FAB, 3NBA) m/e calcd for

C₁₅H₁₉O 215.1436, found 215.1426; 215 ([M1H]¹), 214

([M]¹).

1

6d. (light yellow oil); R_f0.9 (3:1 PE/EE); H NMR d

7.45±7.41 (m, 2H), 7.32±7.26 (m, 3H), 5.83 (ddt, J17.1,

10.2, 6.6 Hz, 1H), 5.04 (dd, J17.1, 1.6 Hz, 1H), 4.98 (ddt,

J10.2, 1.6, 1.0 Hz, 1H), 4.61 (dd, J12.0, 6.6 Hz, 1H),

2.14 (app q, J7.2 Hz, 2H), 1.94 (d, J5.4 Hz, 1H),

1.86±1.78 (m, 2H), 1.68±1.58 (m, 2H); ¹³C NMR d

138.4, 131.6, 128.3, 128.2, 122.5, 114.8, 90.0, 84.8, 62.7,

37.2, 33.2, 24.4; IR (CH₂Cl₂) 3594 (s), 3447 (m), 3080 (m),

2930 (s), 2863 (s), 1640 (m), 1598 (m), 1490 (s), 1379 (m),

1070 (s), 1027 (s), 997 (s), 917 (s) cm²¹; HRMS (FAB,

3NBA) m/e calcd for C₁₄H₁₇O 201.1279, found 201.1265;

201 ([M1H]¹), 200 ([M]¹).

Compound 10d was prepared similarly from 9 and the

corresponding benzyl ylid (52%, light yellow oil). ¹H

NMR d 7.41±7.39 (m, 2H), 7.29±7.28 (m, 3H), 5.48 (ddt,

J17.0, 10.3, 6.8 Hz, 1H), 4.99 (d, J17.0 Hz, 1H), 4.93 (d,

J10.2 Hz, 1H), 4.60±4.55 (m, 1H), 2.10±2.04 (m, 2H),

1.94 (bs, 1H), 1.82±1.76 (m, 2H), 1.56±1.41 (m, 4H); ¹³C

NMR d 138.7, 131.6, 128.3, 128.2, 122.5, 114.4, 90.0, 84.8,

62.9, 37.6, 33.6, 28.5, 24.6; IR (CH₂Cl₂) 3596 (s), 2931 (s),

2360 (m), 2228 (m), 1639 (m), 1599 (m), 1490 (s) cm²¹

;

Preparation of 9

EIMS (12 eV) m/z: [M]¹214.

In a side-arm round bottom ¯ask equipped with a stirring

bar, 1.0 mL (9.4 mmol) of phenylacetylene was dissolved in

25 mL of THF under nitrogen. The solution was cooled to

08C, then 5.9 mL (9.4 mmol, 1.6 M in hexanes) of BuLi was

added dropwise. In a separate 250 mL side-arm round

Preparation of 10b,c

A solution of unsaturated aldehyde 11c (1.23 g, 6.53 mmol)

in 45 mL of THF was added dropwise to a solution of

lithium phenylacetylide prepared by treating 0.72 mL of

phenyl acetylene in 50 mL with 6.5 mL of 1.0 M butyl

lithium (hexane). After stirring for 2 h TLC analysis indi-

cated consumption of the starting aldehyde. The reaction

mixture was added to aqueous ammonium chloride solution

and the mixture extracted with three 50 mL portions of

bottom ¯ask equipped with

a stirring bar, 1.51 g

(9.42 mmol) of 7 was dissolved in 30 mL of THF. This

¯ask was cooled to 08C under nitrogen, then the phenyl-

acetylide solution was added dropwise over 45 min. The

reaction was monitored by TLC for the disappearance of 7

(about 2 h). Then 50 mL of 1 N HCl was added and the

2220

K. L. Salazar, K. M. Nicholas / Tetrahedron 56 (2000) 2211±2224

ether. The combined ether extracts were dried over MgSO₄,

®ltered and concentrated. The residual oil was ¯ash

chromatographed (2:1 PE/EE) over silica gel to provide

1.89 g of 10c (73% yield). Compound 10b was prepared

analogously from 11b in 70% yield.

2091 (s), 2058 (s), 2048 (s), 2028 (s), 1607 (w) cm²¹; Anal.

Calcd for C₂₆H₂₀O₇Co₂: C, 55.54; H, 3.58; found C, 55.33;

H, 3.31.

7c. (E/Z) red oil; ¹H NMR major isomer d 7.53 (dd, J7.8,

1.7 Hz, 2H), 7.39±7.32 (m, 3H), 5.52±5.33 (m, 2H), 5.06±

5.00 (m, 1H), 2.14 (app q, J6.6 Hz, 2H), 1.93 (d,

J5.1 Hz, 1H), 1.89±1.69 (m, 4H), 1.60 (d, J6.3 Hz,

3H); minor isomer d 7.53 (dd, J7.8, 1.7 Hz, 2H), 7.39±

7.32 (m, 3H), 5.52±5.33 (m, 2H), 5.06±5.00 (m, 1H), 2.09±

2.04 (m, 2H), 1.92 (d, J5.1 Hz, 1H), 1.89±1.69 (m, 4H),

1.64 (d, J4.0 Hz, 3H); ¹³C NMR major isomer d 137.6,

129.8, 129.5, 128.9, 127.9, 124.5, 101.9, 90.7, 72.4, 39.2,

26.4, 26.2, 12.7; minor isomer 137.6, 130.6, 129.5, 128.9,

127.9, 125.6, 101.9, 90.7, 72.3, 39.1, 32.1, 26.1, 17.8; IR

(neat) 3596 (m), 3558 (m), 3481 (br), 3078 (m), 3014 (s),

2934 (s), 2860 (s), 2090 (s), 2051 (s), 2020 (s), 1615 (m)

cm²¹; Anal. Calcd for C₂₁H₁₈O₇Co₂: C, 50.42; H, 3.63;

found C, 50.44; H, 3.50.

10c. (E/Z, yellow oil) ¹H NMR d 7.40±7.38 (m, 4H),

7.37±7.32 (m, 6H), 5.42±5.30 (m, 4H), 4.55±4.50 (m,

2H), 2.06±1.93 (m, 6H), 1.77±1.71 (m, 4H), 1.62±1.54

(m, 6H), 1.52±1.43 (m, 4H), 1.41±1.32 (m, 4H); ¹³C

NMR (mixture) d 131.7, 131.2, 130.4, 128.3, 128.2,

124.9, 123.9, 122.8, 90.3, 84.9, 63.0, 37.9, 32.4, 29.2,

26.7, 24.8, 24.7, 17.7, 12.6; IR (CH₂Cl₂) 3595 (m), 3052

(m), 3013 (m), 2937 (s), 2860 (s), 2305 (w), 1599 (m) cm²¹

;

HRMS-FAB (m/z): calcd. for C₁₆H₂₀O 228.1514; found,

228.1552.

10b. (E/Z, yellow oil) ¹H NMR d 7.41±7.11 (m, 10H), 6.38

(d, J11.5 Hz, 1H), 6.36 (d, J16.0 Hz, 1H), 6.18 (dt,

J16.0, 7.0 Hz, 1H), 5.63 (dt, J11.5, 7.0 Hz, 1H),

4.61±4.52 (m, 2H), 2.36±2.31 (m, 2H), 2.34±2.19 (m,

2H), 1.95±1.91 (m, 2H), 1.82±1.76 (m, 4H), 1.57±1.52

(m, 8H); ¹³C NMR d 137.9, 137.8, 132.6, 131.6, 130.6,

130.1, 129.1, 128.7, 128.4, 128.3, 128.2, 128.1, 126.7,

126.4, 125.9, 122.7, 90.2, 84.9, 62.9, 37.7, 32.8, 29.6,

29.0, 28.4, 24.9, 24.7; IR (CH₂Cl₂) 2931 (s), 2862 (s),

1063 (s) cm²¹; HRMS-FAB (m/z): [M1H]¹calcd for

C₂₁H₂₂O 290.1670; found 290.1655.

1

7d. (red oil) H NMR d 7.53 (dd, J6.0, 1.5 Hz, 2H),

7.39±7.32 (m, 3H), 5.81 (ddt, J17.1, 10.2, 6.7 Hz, 1H),

5.07±4.96 (m, 3H), 2.18±2.12 (m, 2H), 1.92 (d, J5.1 Hz,

1H), 1.90±1.61 (m, 4H); ¹³C NMR d 138.1, 137.5, 129.5,

128.9, 127.9, 115.0, 101.8, 90.7, 72.2, 39.1, 33.3, 25.5; IR

(CH₂Cl₂) 2091 (s) 2059 (s), 2048 (s), 2028 (s), 2015 (s)

cm²¹

.

12a. (red oil) ¹H NMR d 7.52±7.48 (m, 2H), 7.39±7.29 (m,

3H), 6.95 (dt, J15.6, 6.9 Hz, 1H), 5.80 (dt, J15.6, 1.5 Hz,

1H), 5.02 (m, 1H), 3.72 (s, 3H), 2.55±2.52 (m, 2H), 1.95 (d,

J5.1 Hz, 1H), 1.88±1.65 (m, 2H), 1.60±1.52 (m, 2H). ¹³C

NMR d 199.3, 167.0, 149.1, 137.4, 129.4, 128.9, 127.9,

121.1, 101.6, 90.7, 72.3, 51.4, 39.4, 32.0, 27.7, 26.0; IR

(CH₂Cl₂) 2904 (m), 2862 (m), 2091 (S) 2026 (s), 1720

(m) cm²¹; MS (FAB, 3NBA) m/z 541 [(M1H)2H₂O]¹,

502 [M22(CO)]¹.

Preparation of complexed alcohols 7a±d and 12a±d

In a well-ventilated hood a side-arm round bottom ¯ask was

charged with 4.12 mmol of Co₂(CO)₈and 75 mL of CH₂Cl₂

under nitrogen. A solution of the alcohol 6 or 10 (4.12 mmol

in 5 mL of CH₂Cl₂) was then added dropwise. The reaction

mixture bubbled as CO was being produced. The reaction

was monitored by TLC (1:1 Et₂O:petroleum ether) for the

disappearance of the starting alcohol (1±3 h). The mixture

was then ®ltered through alumina and the ®ltrate concen-

trated. Puri®cation was done by ¯ash chromatography over

silica gel (1:1 PE/EE).

12b. (red oil) ¹H NMR (E/Z) d 7.49 (dd, J6.0, 2.3 Hz, 4H),

7.37±7.26 (m, 6H), 5.45±5.29 (m, 4H), 5.03±4.97 (m, 2H),

2.03 (q, J6.9 Hz, 2H), 1.91 (d, J5.1 Hz, 1H), 1.89±1.34

(m, 21H); ¹³C NMR (mixture) d 137.6, 131.0, 130.2, 129.5,

128.9, 127.9, 125.0, 124.0, 102.0, 90.8, 72.4, 39.7, 32.4,

29.2, 26.6, 26.0, 25.9, 17.8, 12.6; IR (CH₂Cl₂) 2997 (m),

2937 (s), 2863 (s), 2090 (s), 2049 (s), 2026 (s) cm²¹; MS

(FAB, 3NBA) m/z 497 [(M1H)218]¹, 458 [M22(CO)]¹.

7a. (E); red solid; R_f0.45 (1:1 petroleum ether:diethyl

1

ether); H NMR d 7.50 (dd, J6.0, 1.5 Hz, 2H), 7.39±

7.32 (m, 3H), 6.97 (dt, J15.6, 6.9 Hz, 1H), 5.82 (d,

J15.6 Hz, 1H), 5.05±5.01 (m, 1H), 3.72 (s, 3H), 2.29

(app q, J6.0 Hz, 2H), 2.13 (d, J 5.1 Hz, 1H), 1.88±

1.67 (m, 4H); ¹³C NMR d 167.0, 148.6, 137.4, 129.4,

129.0, 128.0, 121.4, 101.5, 90.7, 72.1, 51.4, 38.9, 31.8,

24.8; IR (CH₂Cl₂) 2091 (s), 2058 (s), 2050 (s), 2028 (s),

12c. (red oil) ¹H NMR (E/Z) d 7.51±7.13 (m, 20H), 6.4 (d,

J11.4 Hz, 1H), 6.34 (d, J15.9 Hz, 1H), 6.17 (dt, J15.9,

6.9 Hz, 1H), 5.62 (dt, J11.4, 7.2 Hz, 1H), 5.04±4.96 (m,

2H), 2.33 (q, J5.7 Hz, 2H), 2.21 (q, J6.3 Hz, 2H), 1.91

(d, J5.4 Hz, 1H), 1.88 (d, J5.1 Hz, 1H), 1.84±1.63 (m,

6H), 1.59±1.51 (m, 6H); ¹³C NMR (mixture) d 137.8, 137.6,

132.5, 130.4, 130.2, 129.4, 129.2, 128.9, 128.7, 128.4,

128.1, 127.9, 126.8, 126.4, 125.9, 101.9, 90.8, 72.4, 39.7,

32.8, 29.6, 29.1, 28.4, 26.1, 26.0; IR (CH₂Cl₂) 2936 (s),

2091 (s), 2052 (s), 2025 (s) cm²¹; MS (FAB, 3NBA) m/z

559 ([M1H]2H₂O]¹, 520 [M22(CO)]¹.

1720 (m), 1716 (m) cm²¹

.

7b. (E/Z); red solid crystallized from diethyl ether; ¹H NMR

major isomer d 7.52±7.48 (m, 2H), 7.35±7.20 (m, 8H), 6.39

(d, J15.9 Hz, 1H), 6.20 (dt, J15.9, 6.9 Hz, 1H), 5.10±

5.05 (m, 1H), 2.32 (app q, J6.9 Hz, 2H), 1.93 (d,

J5.1 Hz, 1H), 1.96±1.69 (m, 4H); minor isomer d 7.52±

7.48 (m, 2H), 7.35±7.20 (m, 8H), 6.46 (d, J11.5 Hz, 1H),

5.65 (dt, J11.5, 7.2 Hz, 1H), 5.03±4.97 (m, 1H), 2.43 (app

q, 6.9 Hz, 2H), 1.90 (d, J5.4 Hz, 1H), 1.96±1.69 (m, 4H);

¹³C NMR d 137.6, 137.5, 132.1, 130.5, 130.0, 129.4, 128.9,

128.7, 128.4, 128.1, 127.9, 126.9, 126.5, 125.9, 101.8, 90.7,

72.5, 72.2, 39.1, 39.0, 32.4, 28.1, 26.7, 25.9; IR (CH₂Cl₂)

12d. (red oil). ¹H NMR d 7.45 (d, J6.8 Hz, 2H), 7.36±7.29

(m, 3H), 5.76 (ddt, J17.1, 10.7, 6.0 Hz, 1H), 5.02±4.90

(m, 3H), 2.04 (q, J6.8 Hz, 2H), 1.90 (d, J4.8 Hz, 1H),

1.85±1.42 (m, 6H); ¹³C NMR d 138.3, 137.6, 129.5, 128.9,

K. L. Salazar, K. M. Nicholas / Tetrahedron 56 (2000) 2211±2224

2221

127.9, 114.6, 101.9, 90.9, 72.5, 39.7, 33.6, 28.6, 25.9; IR

(CH₂Cl₂) 2935 (m), 2089 (s), 2060 (s) cm²¹; MS (FAB,

3NBA) m/z 483 [(M1H)218]¹, 472 [M2CO]¹.

(10% diethyl ether in petroleum ether/silica gel) afforded

14a and 17a (epimers).

General preparation of the complexed bromides 16, 20

General procedure for the reductive cyclization via the

salts 13

Under nitrogen a side-arm round bottom ¯ask containing

0.21 mmol of Ph₂PCH₂CH₂PPh₂dissolved in 14 mL of

CH₂Cl₂was cooled to 08C. Bromine (2.4 mmol) in 3 mL

of CH₂Cl₂was added dropwise and the mixture stirred for

an additional 15 min followed by the addition of 0.21 mmol

of the alcohol complex 7 and 12 in 3 mL of CH₂Cl₂. The

reaction mixture was then stirred for an hour. Addition of

diethyl ether and pentane (1:2:4 CH₂Cl₂:Et₂O:pentane)

produced a white precipitate. The mixture was ®ltered

through Celite under nitrogen and concentrated under

vacuum to provide the complexed bromides 16 and 20 as

thermally sensitive red oils.

In a side-arm round bottom ¯ask containing a stir bar,

1.00 mmol of the complexed alcohol 7a was dissolved in

0.41 mL (3.2 mmol) of propionic acid under nitrogen and

then cooled to 2458C. HBF₄´OEt₂(0.43 mL, 2.9 mmol) was

then added dropwise. After stirring for 45 min the reaction

mixture was triturated with 10 mL portions of cold

anhydrous diethyl ether. When the ether washes were nearly

colorless, the resulting dark red salt 13a was dried under

vacuum. The salt was then dissolved in 20 mL of methylene

chloride and then 0.032 g (0.50 mmol) of zinc was added.

After ca. 1 h TLC analysis (1:1 PE/EE) indicated the dis-

appearance of hydrolyzed starting material. The mixture

was ®ltered through Celite, concentrated, and the residue

subjected to ¯ash chromatography (5:1 PE/EE) to afford

16a. (E isomer; red oil) ¹H NMR d 7.62 (dd, J7.6, 1.7 Hz,

2H), 7.41±7.33 (m, 3H), 6.97 (dt, J15.7, 6.9 Hz, 1H), 5.85

(dt, J15.7, 1.5 Hz, 1H), 5.46 (dd, J9.3, 4.5 Hz, 1H), 3.73

(s, 3H), 2.36±2.26 (m, 2H), 2.23±2.15 (m, 2H), 2.05±1.90

(m, 1H), 1.84±1.69 (m, 1H); ¹³C NMR (CDCl₃, partial) d

148.0, 129.5, 128.8, 128.0, 121.7, 56.2, 51.4, 40.6, 31.1,

26.5.

1

0.090 g (38%) of 14a (red solid). H NMR (C₆D₆) d 7.49

(d, J7.8 Hz, 2H), 7.06±6.93 (m, 3H), 3.24 (s, 3H) 2.49

(app q, J8.0 Hz, 1H), 2.53 (dd, J15.3, 3.9 Hz, 1H),

2.30±2.20 (m, 1H), 2.07 (dd, J15.0, 9.9 Hz, 1H), 2.05±

1.89 (m, 2H), 1.68±1.29 (m, 4H); ¹³C NMR 172.8, 138.2,

129.0, 128.8, 127.7, 103.1 92.4, 51.4, 48.4, 45.5, 39.1, 36.2,

32.8, 23.9; IR (CH₂Cl₂) 2927 (w), 2088 (s), 2051 (s), 2023

1

16b. (mixture of diastereomers; red oil) H NMR (E) d

7.61±7.56 (m, 2H), 7.34±7.18 (m, 8H), 6.39 (d,

J15.7 Hz, 1H), 6.19 (dt, J15.7, 6.7 Hz, 1H), 5.50 (dd,

J9.6, 3.5 Hz, 1H), 2.45±1.69 (m, 6H); (Z) 7.61±7.56 (m,

2H), 7.34±7.18 (m, 8H), 6.45 (d, J13.5 Hz, 1H), 5.68±

5.60 (m, 1H), 5.42 (dd, J9.0, 4.5 Hz, 1H), 2.45±1.69 (m,

6H).

(s), 1731 (m) cm²¹

.

Protonation of 7b as above precipitated a salt which after

stirring at 08C for an hour dissolved upon addition of ether/

pentane. Concentration of this solution followed by ¯ash

chromatography of the residue (1:1 PE/EE) afforded

0.14 g (0.26 mmol) of propionate 15b (red oil). The epimers

of 15b could be separated by preparative TLC (1:1 PE/

16c. (E,Z; red oil) ¹H NMR d 7.64±7.31 (m, 10H),

5.53±5.38 (m, 6H), 2.26±2.24 (m, 8H), 6.94±1.78 (m,

2H), 1.70±1.60 (m, 8H).

1

ether). H NMR (major) d 7.43±7.40 (m, 2H), 7.34±7.18

(m, 8H), 5.95 (d, J4.5 Hz, 1H), 3.49±3.41 (m, 1H), 2.41

(q, J7.8 Hz, 2H), 2.33±2.23 (m, 1H), 1.92±1.84 (m, 1H),

1.77±1.61 (m, 3H), 1.29±1.20 (m, 2H), 1.48 (t, J1.8 Hz,

3H); IR (major) (CH₂Cl₂) 3045 (w), 2965 (w), 2087 (s),

16d. (red oil) ¹H NMR d 7.61 (d, J6.0 Hz, 2H), 7.51±7.17

(m, 3H), 5.79 (ddt, J16.6, 10.2, 6.3 Hz, 1H), 5.46 (dd,

J9.3, 3.3 Hz, 1H), 5.02 (d overlapping, J16.6 Hz, 1H),

4.98 (d overlapping, J10.2 Hz, 1H), 2.28±1.64 (m, 6H).

1

2048 (s), 2023 (s), 1738 (m), 1605 (w) cm²¹; H NMR

(minor) d 7.55±7.52 (m, 2H, 7.36±7.26 (m, 8H), 5.55 (d,

J10.2 Hz, 1H), 3.61±3.56 (m, 1H), 2.70±2.62 (m, 1H),

2.42±2.30 (m, 1H), 2.12 (q, J7.2 Hz, 2H), 1.73±1.63

(m, 5H), 0.95 (t, J7.2 Hz, 3H); IR (minor) (CH₂Cl₂)

2086 (m), 2045 (s), 2020 (s), 1734 (m) cm²¹; EIMS

(12 eV) m/z 562 [M22(CO]¹, 450 (20.6) [M26(CO)]¹.

The bromides 20a±d were prepared as above and subjected

to irradiation without further characterization.

General photochemical preparation of the cyclized

bromides 17, 18, and 21

Irradiation of the complexed bromides 16a±d as a thin ®lm

or in benzene solution was accomplished under a 300 W GE

halogen ¯oodlight (ca. 0.5 m) for 1 h. The products

were puri®ed by column chromatography over silica gel

or deactivated alumina (10±20% Et₂O/petroleum ether);

yields (from 7, 12): 17a (56%), 17b (76%), 17c/18c

(60%), 18d (73%), 21d (8%).

Cyclization of 16a,d using Ph₂SiH₂and Et₃B

The bromide 16a, prepared from 0.2 mmol of alcohol 7a,

was dissolved in 20 mL of benzene in a two-neck round

bottom ¯ask equipped with a stir bar under nitrogen.

Ph₂SiH₂(0.04 mL, 0.20 mmol) and Et₃B (0.04 mL,

0.04 mmol, 1 M in hexanes) were added. The valve to the

¯ask was then closed and 0.9 mL of oxygen injected by

syringe through the septum. With continued stirring the

color of the reaction mixture changed from red to brown

and 16a was consumed after 1±4 h (monitored by TLC 4:1

PE/EE). The reaction mixture was ®ltered through Celite,

then concentrated. Puri®cation by column chromatography

17a. (red oil); ¹H NMR major isomer d 7.53±7.48 (m, 2H),

7.39±7.31 (m, 3H), 4.59 (d, J3.2 Hz, 1H), 3.70 (s, 3H),

3.51 (app q, J8.0 Hz, 1H), 2.38±2.23 (m, 3H), 2.01 (app

q, J6 Hz, 2H), 1.85±1.69 (m, 2H); minor isomer d

7.53±7.48 (m, 2H), 7.39±7.31 (m, 3H), 4.32 (d,

J8.0 Hz, 1H), 3.77 (s, 3H), 3.63 (m, 1H), 2.76±2.68 (m,

2222

K. L. Salazar, K. M. Nicholas / Tetrahedron 56 (2000) 2211±2224

1H), 2.38±2.23 (m, 2H), 2.14±2.06 (m, 2H), 1.85±1.69 (m,

2H); ¹³C NMR major isomer 199.4, 169.3, 137.8, 129.0,

128.9, 127.9, 101.8, 92.8, 53.0, 52.2, 50.9, 46.5, 36.1,

28.9, 24.4; minor isomer 199.4, 169.3, 138.1, 129.1,

128.8, 127.7, 103.9, 94.4, 52.9, 52.2, 48.7, 46.9, 36.4,

30.2, 24.9; IR (CH₂Cl₂) 2089 (s), 2050 (s), 2025 (s), 1745

[M]¹; and cyclization product 21d (red oil) ¹H NMR d 7.52

(d, J6.4 Hz, 2H), 7.35±7.27 (m, 3H), 4.70±4.68 (m, 1H),

3.57 (t, J6.0 Hz, 1H), 2.57 (br d, J12.0 Hz, 1H), 2.68±

2.19 (m, 4H), 1.85±1.71 (m, 2H), 1.62±1.40 (m, 3H); ¹³C

NMR d 199.7, 138.1, 129.3, 128.8, 127.7, 54.6, 46.5, 39.1,

38.5, 37.3, 27.7, 24.4; IR (CH₂Cl₂) 2088 (s), 2050 (s), 2022

(s) cm²¹; MS (FAB, 3NBA) m/z 536 [M1221(CO)]¹.

(m), 1738 (m) cm²¹

;

(FAB, 3NBA) m/z 580

[M1221(CO)]¹.

Preparation of 19

17b. (red oil, E/Z) ¹H NMR major isomer d 7.54 (d,

J6.3 Hz, 2H), 7.41±7.30 (m, 8H), 5.30 (d, J2.7 Hz,

1H), 3.66 (app q, J7.5 Hz, 1H), 2.39±2.15 (m, 3H),

2.02±1.67 (m, 4H); minor isomer d 7.53 (d, J7.6 Hz,

2H), 7.33±7.27 (m, 8H), 4.89 (d, J10.8 Hz, 1H), 3.90±

3.88 (m, 1H), 3.06±3.01 (m, 1H), 2.41±2.35 (m, 1H),

1.83±1.59 (m, 4H), 1.42±1.36 (m, 1H); ¹³C NMR (CDCl₃,

partial) major isomer 199.6, 141.3, 138.1, 103.4, 93.5 61.1,

55.7, 35.7, 29.1, 24.1; minor isomer 199.6, 141.0, 138.3,

105.8, 93.0, 59.7, 55.7, 48.3, 35.4, 30.5, 25.2; IR (CH₂Cl₂)

2088 (s), 2046 (s), 2028 (s), 1605 (w) cm²¹; MS (FAB,

3NBA) m/z 598 [M1221(CO)]¹.

In a 250 mL side-arm round bottom ¯ask containing a stir

bar under nitrogen, Ph₂PCH₂CH₂PPh₂(0.501 g, 1.26 mmol)

was dissolved in 12 mL of CH₂Cl₂. The reaction mixture

was cooled to 08C, then a solution of Br₂(0.013 mL,

2.52 mmol) in 2.5 mL of CH₂Cl₂was added dropwise.

The reaction mixture was allowed to stir for 5 min, then a

solution of 6d (0.211 g, 1.05 mmol) in 2.5 mL of CH₂Cl₂

was added. The mixture was stirred at 08C for an hour, then

allowed to warm to room temperature with stirring for

another 1.5 h. After 6d had been consumed (TLC), 70 mL

of pentane and 35 mL of diethyl ether was added, producing

a white precipitate. The mixture was ®ltered through Celite,

the ®ltrate concentrated, and the residue puri®ed by ¯ash

chromatography (3:1 PE/EE/silica gel) affording 0.273 g

17c. (red oil) ¹H NMR d 7.56±7.54 (m, 2H), 7.39±7.30 (m,

3H), 4.38 (dq, J7.0, 2.4 Hz, 1H), 3.54 (app q, J8.0 Hz,

1H), 2.29±2.21 (m, 1H), 1.97±1.69 (m, 6H), 1.65 (d,

J6.8 Hz, 3 H).

1

(1.04 mmol, 99%) of 19 as a yellow oil. H NMR d 7.43±

7.36 (m, 2H), 7.30±7.25 (m, 3H), 5.81 (ddt, J17.1, 10.0,

6.0 Hz, 1H), 5.04 (d, J17.1 Hz, 1H), 4.98 (d, J10.0 Hz,

1H), 4.76 (t, J6.0 Hz, 1H), 2.15±2.07 (m, 3H), 1.73±1.65

(m, 3H); ¹³C NMR d 137.8, 131.7, 128.7, 128.2, 122.1,

115.1, 87.9, 86.9, 39.1, 37.7, 32.7, 26.5; IR (CH₂Cl₂) 2974

(m), 2933 (m), 2867 (m), 2226 (w), 1640 cm²¹; MS (FAB,

3NBA) m/z 183 [M279]¹.

1

18c/17c⁰(red oil; mixture) H NMR 18c: d 7.46±7.25 (m,

5H), 4.24 (dq, J6.5, 6.4 Hz, 1H), 3.41(app q, J6.0 Hz,

1H), 2.31±2.60 (m, 2H), 2.07±1.52 (m, 5H), 1.68 (d,

J6.8 Hz, 3H); 17c: d 7.46±7.25 (m, 5H), 4.40 (dt,

J11.6, 4.4 Hz, 1H), 3.16 (dt, J11.6, 3.6 Hz, 1H), 2.49±

2.45 (m, 2H), 2.07±1.52 (m, 5H) 1.03 (d, 6.8 Hz, 3H); IR

(CH₂Cl₂) mixture 3059 (w), 2946 (w), 2868 (w), 2088 (s),

2048 (s), 2025 (s), 2016 (s) cm²¹

.

Reaction of 16a with TEMPO

1

cis-18d. (red solid, crystallized from heptane) H NMR d

7.45 (d app, J7.6 Hz, 2H), 7.36±7.27 (m, 3H), 4.14 (app tt,

J11.8, 4.0 Hz, 1H), 3.02 (app tt, J11.8, 3.4 Hz, 1H), 2.66

(app d, J12.4 Hz, 1H), 2.38 (app d, J12.8 Hz, 1H), 2.11

(app d, J12.8 Hz, 1H), 1.95±1.74 (m, 3H), 1.54 (app tq,

1H), 1.37 (app dq, 1H); ¹³C NMR 199.6, 138.0, 129.1,

128.9, 127.5, 102.8, 91.2, 49.7, 46.2, 42.6, 37.7, 33.8,

26.8; IR (CH₂Cl₂) 2089 (s), 2051 (s), 2024 (s) cm²¹; MS

(mixture) (FAB, 3NBA) m/z 565 [M1H]¹; Anal. Calcd for

C₂₀H₁₅O₆BrCo₂C, 43.75; H, 2.75; found C, 44.16; H, 2.75.

The bromide 16a (prepared from 0.081 g, 0.149 mmol of

alcohol 7a) was dissolved in 6 mL of benzene under nitro-

gen in a side-arm round bottom ¯ask which contained a stir

bar followed by 0.056 g of TEMPO (0.24 mmol). Half of

this solution was withdrawn, placed in an 25 mL side-arm

round bottom ¯ask containing a stir bar under nitrogen, and

then irradiated under a 300 W halogen ¯oodlight for 4 h.

The remaining solution was stirred for 4 h without irradia-

tion. Each reaction mixture was concentrated and then

puri®ed using column chromatography (9:1 PE/EE on

activity III alumina). One fraction was isolated from each

puri®cation which was found to be 3 (17±20%, red oil). ¹H

NMR (mixture) d 7.39±7.37 (m, 4H), 7.31±7.25 (m, 6H),

6.98 (dt, J15.7, 6.9 Hz, 1H), 6.75 (dt, J15.7, 6.9 Hz, 1H),

5.84 (d, J15.7 Hz, 1H), 5.51 (d, J15.7 Hz, 1H), 5.18±

5.16 (m, 1H), 4.64 (t, J5.9 Hz, 1H), 3.70 (s, 3H), 3.67 (s,

3H), 2.76±2.70 (m, 1H), 2.26 (q, J6.9 Hz, 2H), 2.15±2.02

(m, 2H), 1.87±1.81 (m, 2H), 1.77±1.66 (m, 2H), 1.55±1.80

(m, 37H), 0.87±0.49 (m, 2H); ¹³C NMR (mixture) d 199.7,

167.1, 166.9, 149.2, 148.6, 138.2. 131.3, 129.0, 128.7,

128.1, 127.8, 127.5, 123.3, 121.0, 120.7, 99.1, 91.3, 90.4,

86.3, 80.6, 75.0, 61.1, 60.4, 59.4, 51.3, 51.2, 40.8, 40.5,

40.0, 36.7, 34.9, 34.6, 34.4, 33.7, 32.0, 31.7, 24.8, 23.7,

20.8, 20.6, 20.4, 20.2, 17.3, 17.1; IR (CH₂Cl₂) 2933 (m),

2871 (m), 2090 (s), 2050 (s), 2026 (s), 1720 (s), 1716 (s),

1658 (m) cm²¹; MS (FAB, 3NBA) m/z 543 [M25(CO)]¹,

527 [M2TEMPO]¹.

trans-18d. (red solid, crystallized from heptane) ¹H NMR d

7.50 (app d, J7.2 Hz, 2H), 7.36±7.27 (m, 3H), 4.80 (s

broad, 1H), 3.60 (tt app, J11.6, 3.0 Hz, 1H), 2.44 (app d,

J14.0 Hz, 1H), 2.15±2.01 (m, 3H), 1.85±1.74 (m, 3H),

1.38 (app dq, 1H); ¹³C NMR d 199.6, 138.1, 129.2, 128.9,

127.7, 104.3, 91.1, 53.6, 43.0, 36.2, 34.7, 34.0, 21.0.

Irrradiation of the bromides 21a±d was carried out similarly

but a longer period was needed to achieve complete

consumption of the starting material. These reactions

produced a number of products including the original

alcohol complexes (20), incompletely characterized elimi-

nation products, dimeric complexes, e.g. 23a (red solid) ¹H

NMR d 7.2±7.4 (bm, 10H), 6.9 (m, 1H), 6.7 (m, 1H), 5.8

(m, 1H), 5.6 (m, 1H), 3.7 (s, 6H), 2.2 (bm, 4H), 2.0 (m, 2H),

1.8 (m, 2H), 0.8±1.6 (m, 6H); MS (FAB, 3NBA) m/z 1082

K. L. Salazar, K. M. Nicholas / Tetrahedron 56 (2000) 2211±2224

2223

Allylation of 16a by CpFe(CO)₂(h¹-allyl)

using monochromated MoKa (l0.71073 A) radiation.

The data were corrected for Lorentz and polarization

effects; no absorption correction was applied since it was

judged to be insigni®cant. The structures were solved by

direct methods (for 14a, 17b and cis,cis-18c) using

Shelxtl 5.0 (Siemens system) or the heavy atom method

(for 18d) and re®ned by full-matrix least-squares on F2

using all re¯ections. Hydrogen atoms were included in the

idealized positions. Details of the crystal data and re®ne-

ment for 14a, 17b, trans-18d, and cis,cis-18c, along with

tables of fractional atomic coordinates, thermal parameters,

bond lengths and angles have been deposited at the

Cambridge Crystallographic Data Center, 12 Union Road,

Cambridge CB2 1EZ.

Ê

The bromide 16a (prepared from 0.411 g, 0.757 mmol of

alcohol 6a) was transferred into a side-arm round bottom

¯ask containing a stir bar under nitrogen and then dissolved

in 10 mL of benzene. A solution of 0.787 g (3.75 mmol) of

CpFe(CO)₂(h¹-allyl) in 10 mL of benzene was then added

via cannula. The mixture was stirred for 3 h without being

irradiated. When 16a had been consumed (TLC), the

mixture was ®ltered through silica gel and then concen-

trated. Puri®cation was performed using ¯ash chromato-

graphy (5:1 PE/EE/silica gel). Six fractions were isolated

and a proton NMR spectrum was taken of each. The ®rst

fraction contained 0.100 g (0.177 mmol, 23%) of 25a as a

dark red oil; the structures of the compounds in the other

fractions were not be determined. ¹H NMR d 7.47±7.43 (m,

4H), 7.34±7.26 (m, 6H), 5.62 (ddt, J17.0, 9.9, 8.0 Hz, 2H),

5.02±4.91 (m, 4H), 3.65 (s, 3H), 3.58 (s, 3H), 3.46 (q,

J6.7 Hz, 1H), 3.36 (q, J6.5 Hz, 1H), 2.80±2.76 (m,

1H), 3.28±2.59 (m, 1H), 2.50±2.42 (m, 2H), 2.33±2.06

(m, 6H), 1.92±1.82 (m, 4H), 1.80±1.56 (m, 6H); ¹³C

NMR d 199.7, 175.0, 174.2, 138.4, 135.6, 135.4, 129.2,

129.1, 128.8, 128.7, 127.5, 116.6, 116.5, 104.9, 104.7,

93.4, 93.2, 51.2, 50.6, 50.1, 47.3, 47.2, 46.3, 46.0, 36.5,

36.1, 31.7, 28.4, 28.1, 24.8; IR (CH₂Cl₂) 2952 (w), 2871

(m), 2087 (s), 2047 (s), 2024 (s), 1730 (m), 1641 (w),

1605 (w) cm²¹; MS (FAB, 3NBA) m/z 512 [M22(CO)]¹.

The methoxy group of 14a (C22A and C22B) was

disordered at two sites with unequal population. The size

of the C22A and C22B atoms in the difference map, and

re®nement of the partial occupancy factor for these atoms,

suggested 65 and 35% occupancy, respectively for these

atoms. Details of the crystal data and re®nement are given

in the Supporting Table. Figures are drawn with 15%

thermal ellipsoids. For the sake of clarity, C22B and all

the hydrogens except H15A and H19A are omitted.

The crystals of 18d appeared to be affected by internal

twinning and, in general, peaks were either split or broad.

Structure solution and re®nement were tried both in P21 and

P21/m. A reasonable re®nement can only be obtained in the

P21 space group. The ®nal re®ned model has superimposed

mirror images of the molecule and re®ned also as racemic

twinned as suggested by the Shelxtl program. Because of

this twinning problem, the re®nement was poor and the

accuracy of the ®nal parameters is limited. However, the

important features of the six-membered ring and the loca-

tion of the bromine atom and (alkynyl)Co₂(CO)₆unit are

unambiguously established.

Attempted Pauson±Khand reaction of 24a

In a side-arm round bottom ¯ask under nitrogen containing

a stir bar 0.042 g (0.075 mmol) of 24a was dissolved in

10 mL of CH₂Cl₂, then 0.053 g (0.045 mmol) of N-methyl

morpholine N-oxide was added and the reaction mixture

was stirred at room temperature. After 2 h TLC indicated

a reaction had occurred, but 24a was still present in the

reaction mixture. The mixture was ®ltered through silica

gel, concentrated, and then puri®ed by PTLC (5:1 PE/EE).

Four fractions were isolated. The ®rst fraction was

recovered 24a. The second fraction contained 0.0070 g

(0.026 mmol, 36%) of decomplexed alkyne 25a (yellow

Acknowledgements

1

oil) H NMR (partial) d 7.37±7.35 (m, 2H), 7.30±7.23

We thank Dr Masood Khan, O.U. Analytical Services, for

X-ray diffracion analysis. Helpful discussions with G.

Melikyan, W. Giering, M. Rosenblum and D. Curran are

also acknowledged. We are grateful for partial ®nancial

support provided by the Petroleum Research Fund of the

American Chemical Society (27375AC) and a Patricia

Roberts-Harris Fellowship to K. L. S.

(m, 3H), 5.83±5.68 (m, 2H), 5.05 (d, J17.4 Hz, 2H),

4.98 (d, J9.9 Hz, 2H), 3.64 (s, 3H), 3.60 (s, 3H); MS

(FAB, 3NBA) m/z 283 [M1H]¹.

For the reaction of 24a with O₂on silica gel a CH₂Cl₂

solution of 24a (0.067 g, 0.118 mmol) was mixed with 4 g

of silica gel and the solvent was removed by rotary evapora-

tion. The ¯ask containing the adsorbed 24a was then heated

to 458C while being rotated on the evaporator for 2 h as

oxygen was admitted to the system. The silica gel (blue)

was then triturated with diethyl ether and the extracts

concentrated to provide a yellow oil. Puri®cation was

performed by PTLC (5:1 PE/EE) providing one fraction

(0.019 g) whose NMR spectrum indicated it to be 25a

(0.068 mmol, 57%).

References

1. Reviews: Doyle, M. P. In Comprehensive Organometallic

Chemistry II; Hegedus, L., Ed.; Pergamon: New York, 1995;

Vol. 12, Chapter 5.1, pp 388±420; Chapter 5.2, pp 422±468;

Wulff, W. D. Chapter 5.3, p 547; Hegedus, L. S. Chapter 6.4,

pp 549±576; Stille, J. R. Chapter 5.5, pp 577±599.

X-Ray crystal structure determinations of 14a, 17b,

trans-18d, and cis, cis-18c

2. Reviews: (a) Watts, W. E. J. Organometal. Chem. Lib. 1979, 7,

399. (b) Nicholas, K. M. Acc. Chem. Res. 1987, 20, 207. (c) Caffyn,

A. J. M.; Nicholas, K. M. In Comprehensive Organometallic

Chemistry II; Hegedus, L., Ed.,; Pergamon: NY, 1995; Vol. 12,

Chapter 7.1, pp 685±739. (d) Pearson, A. J. In Comprehensive

Crystals were obtained by slow crystallization from pentane

or heptane at 2208C. The data were collected at 2708C

2224

K. L. Salazar, K. M. Nicholas / Tetrahedron 56 (2000) 2211±2224

Organometallic Chemistry II; Hegedus, L., Ed.; Pergamon: New

York, 1995; Vol. 12, Chapter 6.3, pp 637±683.

1972, 11, 692; Nozaki, K.; Oshima, K.; Utimoto, K. Tetrahedron

Lett. 1988, 29, 6125.

3. (a) Baker, C.; Horspool, W. H. J. Chem. Soc. Perkin Trans. I,

1979, 1862; 2294; 2298. (b) Forrester, A. R.; Hepburn, S. P.;

Dunlop, R. S.; Mills, H. H. J. Chem. Soc. Chem. Commun. 1969,

698. (c) Creary, X.; Mehrsheikh-Mohammadi, M. E.; McDonald,

S. J. Org. Chem. 1989, 54, 2904. (d) Top, S.; Jaouen, G.

J. Organomet. Chem. 1987, 336, 143. (e) Le Berre-Cosquer, N.;

Kergoat, R.; L'Haridon, P. Organometallics, 1992, 11, 721. (f)

Meyer, A.; McCabe, D. J.; Curtis, M. D. Organometallics, 1987,

6, 1491. (g) Sapienza, R. S.; Riley, P. E.; Davis, R. E.; Pettit, R.

J. Organomet. Chem. 1976, 121, C35. (h) Pearson, A. J.; Chen,

Y.-S.; Daroux, M. L.; Tanaka, A. A.; Zettler, M. J. Chem. Soc.

Chem. Commun. 1987, 155.

16. Tanner, D. D.; Chen, J. J. J. Org. Chem. 1989, 54, 3842.

17. Curran, D. P. Synthesis 1988, 417.

18. (a) Curran, D. P. Synthesis, 1988, 489. (b) Curran, D. P.; Chen,

M.-H.; Kim, D. J. Am. Chem. Soc. 1986, 108, 2489. (c) Giese, B.;

Horler, H.; Leising, M. Chem. Ber. 1986, 119, 444. (d) Curran,

D. P.; Chang, C.-T. Tetrahedron Lett. 1987, 28, 2477. (e) Curran,

D. P.; Chen, M.-H.; Spletzer, E.; Seong, C. M.; Chang, C.-T. J. Am.

Chem. Soc. 1989, 111, 8872. (f) Curran, D. P.; Chang, C.-T. J. Org.

Chem. 1989, 54, 3140.

19. Julia, M. Acc. Chem. Res. 1971, 4, 386; Julia, M.; Maumy, M.

Bull. Soc. Chim. Fr. 1969, 2415; Curran, D. P.; Shu, M. Bull. Soc.

Chim. Fr. 1993, 130, 314.

4. Schmalz, H.-G.; Siegel, S.; Bats, J. W. Angew. Chem. Int. Ed.

Eng. 1995, 34, 2383; Merlic, C. A.; Walsh, J. C. Tetrahedron Lett.

1998, 39, 2083.

20. (a) Beckwith, A. L. J.; Cliff, M. D.; Schiesser, C. H.

Tetrahedron 1992, 48, 4641. (b) Keck, G. E.; Tafesh, A. M. Synlett

1990, 257. (c) Curran, D. P.; Shen W. J. Am. Chem. Soc. 1993, 115,

6051. (d) Ueno, Y.; Khare, R. K.; Okawara, M. J. Chem. Soc.

Perkin Trans. 1, 1983, 2637.

5. Merlic, C. A.; Walsh, J. C.; Tantillo, D. J.; Houk, K. N. J. Am.

Chem. Soc. 1999, 121, 3596.

6. (a) Melikyan, G. G.; Vostrowsky, O.; Bauer, W.; Bestmann,

H. J.; Khan, M. A.; Nicholas, K. M. J. Org. Chem. 1994, 59,

222. (b) Melikyan, G. G.; Combs, R. C.; Lamirand, J.; Khan,

M. A.; Nicholas, K. M. Tetrahedron Lett. 1994, 35, 363. (c)

Melikyan, G. G.; Khan, M. A.; Nicholas, K. M. Organometallics

1995, 14, 2170.

21. Spellmeyer, D. C.; Houk, K. N. J. Org. Chem. 1987, 52, 959.

22. Beckwith, A. L. J.; Easton, C. J.; Lawrence, T.; Serelis, A. K.

Aust. J. Chem. 1983, 36, 545; Beckwith, A. L. J.; Easton, C. J.;

Serelis, A. K. J. Chem. Soc. Chem. Commun. 1980, 482; Beckwith,

A. L. J.; Lawrence, T.; Serelis, A. K. J. Chem. Soc. Chem.

Commun. 1980, 484.

7. Ruchardt, C. Top. Curr. Chem. 1980, 88, 1±32; Porter, N. A.;

Krebs, P. J. Top. Stereochem., 1988, 18, 97±127.

23. Review: Shore, N. E. In Comprehensive Organometallic

Chemistry II; Hegedus, L. S., Ed.; Pergamon: Oxford, 1995, Vol.

12, Chapter 7.2, pp 703±739.

8. (a) Giese, B.; Kopping, B; Gobel, T.; Dickhaut, J.; Thoma, G.;

Kulicke, K. J.; Trach, F. Radical Cyclization Reactions. In Organic

Reactions; Paquette, L., Ed.; Wiley: New York, 1996, pp 301±856.

(b) Curran, D. P. In Comprehensive Organic Synthesis; Trost,

B. M., Ed.; Pergamon: London, 1991, Vol. 4, Chapter 4.2.

9. Curran, D. P.; Porter, N. A.; Geise, B. Stereochemistry of

Radical Reactions, VCH: Weinheim, 1996 (pp 30±76 and

references therein).

24. Review: Grotjahn, D. B. In Comprehensive Organometallic

Chemistry II; Hegedus, L. S., Ed.; Pergamon: Oxford, 1995,

Vol. 12, Chapter 7.3, pp 741±770.

25. Keck, G. E.; Yates, J. B. J. Am. Chem. Soc. 1982, 104, 5829.

Keck, G. E.; Enholm, E. J.; Yates, J. B. Tetrahedron, 1985, 41,

4079.

26. Lee, M. T.; Waterman, P. S.; Magnuson, R. H.; Meirowitz,

R. E.; Prock, A.; Giering, W. P. Organometallics 1988, 7, 2146.

27. (a) Shambayati, S.; Crowe, W. E.; Schreiber, S. L.

Tetrahedron Lett. 1990, 31, 5289. (b) Simonian, S. O.; Smit,

W. A.; Gybin, A. S.; Shahshkov, A. S.; Mikaelian, B. S.; Tarasov,

V. A.; Ibragimov, I. I.; Caple, R.; Froen, D. E. Tetrahedron Lett.

1986, 27, 1245. (c) Sugihara, T.; Yamada, M.; Ban, H.;

Yamaguchi, M.; Kaneko, C. Angew. Chem. Int. Ed. Engl. 1997,

36, 2801.

10. Salazar, K. L.; Khan, M. A.; Nicholas, K. M. J. Am. Chem.

Soc. 1997, 119, 9053.

11. Kraft, M. E.; Cheung, Y. Y.; Wright, C.; Coli, R. J. Org.

Chem. 1996, 61, 3912.

12. (a) Tirpak, M. R.; Hollingsworth, C. A.; Wotiz, J. H. J. Org.

Chem. 1960, 25, 687. (b) Melikyan, G. G.; Mkrtchyan, V. M.;

Atanesyan, K. A.; Asaryan, G. K.; Badanyan, S. O. Bioorg.

Khim. 1990, 16, 1000.

13. Vizniowski, C. S.; Green, J.; Breen, T. L.; Dalacu, A. V. J. Org.

Chem. 1995, 60, 7496.

28. Claus, R. E.; Schreiber, S. L. Org. Syn. 1986, 64, 150.

29. Cutler, A.; Ehntholt, D.; Giering, W. P.; Lennon, P.; Raghu, S.;

Rosan, A.; Rosenblum, M.; Tancrede, J.; Wells, D. J. Am. Chem.

Soc. 1976, 98, 3495.

14. Schmidt, S. P.; Brooks, D. W. Tetrahedron Lett. 1987, 28, 767.

15. Brown, H. C.; Midland, M. M. Angew. Chem. Int. Ed. Engl.

Article Doi

(Alkynyl)dicobalt hexacarbonyl-mediated radical cyclizations

DOI: 10.1016/S0040-4020(99)01104-7

Source and publish data:

Authors:

Article abstract of DOI:10.1016/S0040-4020(99)01104-7

Full text of DOI:10.1016/S0040-4020(99)01104-7

Products guided by the article

R&D Labs maybe for 195518-91-3

Relevant to this article

Hot Product