On the radical Brook rearrangement. Reactivity of α-silyl alcohols, α- silyl alcohol nitrite esters, and β-haloacylsilanes under radical-forming conditions

Article abstract of DOI:10.1021/jo9912855

Two alkoxyl radical generation methods, lead tetraacetate treatment of alcohols and photolysis of nitrites, were applied to α-silyl alcohols 21 and to the corresponding nitrites 25 with a view to forming α-silyl alkoxyl radicals 23 and studying their possible radical Brook rearrangement to α- silyloxy carbon radicals 24. LTA treatment of 21 led to their quick and efficient conversion into mixed acetyl-silyl acetals 33 under very mild conditions. Photolysis of α-alkylmonosubstituted α-silyl nitrites 25 to the corresponding aldehydes is considered to proceed through α-silyl alkoxyl radical intermediates 23. A concerted process is, however, proposed for the case of the benzyl nitrites analogues. On the basis of these results, it is postulated that resonance stabilization can have a major influence on the evolution of α-silyl alkoxyl radicals: should this stabilization be possible, they quickly evolve by α-silyl fragmentation; otherwise, they tend to undergo radical Brook rearrangement. It was also found that the radical Brook rearrangement of α-silyl cyclopropyloxyl radicals generated from β- bromoacylsilanes under standard tin-radical conditions is too slow to compete with β-fragmentation.

Full text of DOI:10.1021/jo9912855

2292
J . Org. Chem. 2000, 65, 2292-2304
On th e Ra d ica l Br ook Rea r r a n gem en t. Rea ctivity of r-Silyl
Alcoh ols, r-Silyl Alcoh ol Nitr ite Ester s, a n d â-Ha loa cylsila n es
u n d er Ra d ica l-F or m in g Con d ition s
M. D. Paredes and R. Alonso*
Departamento de Quı´mica Orga´nica y Unidad Asociada al CSIC, Universidad de Santiago de
Compostela, 15706 Santiago de Compostela, Spain
Received August 11, 1999
Two alkoxyl radical generation methods, lead tetraacetate treatment of alcohols and photolysis of
nitrites, were applied to R-silyl alcohols 21 and to the corresponding nitrites 25 with a view to
forming R-silyl alkoxyl radicals 23 and studying their possible radical Brook rearrangement to
R-silyloxy carbon radicals 24. LTA treatment of 21 led to their quick and efficient conversion into
mixed acetyl-silyl acetals 33 under very mild conditions. Photolysis of R-alkylmonosubstituted R-silyl
nitrites 25 to the corresponding aldehydes is considered to proceed through R-silyl alkoxyl radical
intermediates 23. A concerted process is, however, proposed for the case of the benzyl nitrites
analogues. On the basis of these results, it is postulated that resonance stabilization can have a
major influence on the evolution of R-silyl alkoxyl radicals: should this stabilization be possible,
they quickly evolve by R-silyl fragmentation; otherwise, they tend to undergo radical Brook
rearrangement. It was also found that the radical Brook rearrangement of R-silyl cyclopropyloxyl
radicals generated from â-bromoacylsilanes under standard tin-radical conditions is too slow to
compete with â-fragmentation.
In tr od u ction
photoreaction of acylsilanes 1 with electron-poor olefins
2 (Table 1, entry 1).3 ESR spectroscopy subsequently
showed the migration of the silyl group to be extraordi-
narily fast, proceeding even at -83 °C for the simple
trimethylsilylmethyloxyl radical 7 (Table 1, entry 2).4 At
the same time it was successfully used as the basis of a
new synthesis of cyclopentanols and cyclohexanols 13
from, respectively, δ- and ꢀ-halogenated acylsilanes 10
(Table 1, entry 3).5a
As a result of the above reports, the radical Brook
rearrangement came to be regarded as the process most
likely to be undergone by R-silyl alkoxyl radicals, pre-
ferred over other processes usually followed by nonsilyl-
substituted alkoxyl radicals. In fact further syntheses
were based on the rearrangement of variously function-
alized analogues of 11 (Table 1, entry 3), obtained from
acylsilanes by 1,5- or 1,6-exo cyclization of carbon
radicals.5b Moreover, an ab initio study of the rearrange-
ment 14 f 16 (Table 1, entry 4) predicted energy barriers
in total agreement with the experimentally observed ease
of silyl migration.6
Starting materials and intermediates featuring silicon-
bearing groups are now common place in organic syn-
theses, regardless of whether the end-product does or
does not contain silicon. Besides being able to protect
sensitive functional groups (where silicon mainly behaves
as an spectator preserving the integrity of the protected
functionality), there are other instances where the pres-
ence of silicon in an organic species greatly affects its
reactivity.1 A notable example in the field of radical
chemistry is the case of R-silyl alkoxyl radicals I, which
because of the geminal silyl group can evolve to carbon
radicals II (eq 1). This type of conversion, known as the
radical Brook rearrangement,2 was initially proposed in
1981 to explain the formation of cyclopropanes 5 by
However, not all the results obtained to date have
conformed to the above pattern. In particular it has been
reported that R-silyl alkoxyl radicals 18, formed from R,â-
unsaturated epoxysilanes 17 (Table 1, entry 5), do not
undergo the expected Brook rearrangement; instead they
eject the trimethylsilyl radical, which subsequently re-
* To whom correspondence should be addressed. Fax 34-981-547085.
e-mail: qoraa@correo.usc.es.
(1) For
a recent review on the use of silyl groups to control
stereochemistry, see: Fleming, I.; Barbero, A.; Walter, D. Chem. Rev.
1997, 97, 2063-2192. For their use as tethers, see: Stork, G.; Suhi,
M. S.; Kim, G. J . Am. Chem. Soc. 1991, 113, 7054-7056. Bols, M.;
Skrydstrup, T. Chem. Rev. 1995, 95, 1253-1277. Fensterbank, L.;
Malacria, M.; Sieburth, S. McN. Synthesis 1997, 813-854. Hutchinson,
J . H.; Daynard, T. S.; Gillard, J . W. Tetrahedron Lett. 1991, 32, 573-
576.
(2) For the radical Brook rearrangement, see refs 3-8. The ionic
rearrangement was known previously: Brook, A. G. J . Am. Chem. Soc.
1958, 80, 1886-1889. A review can be found in Brook, A. G. Acc. Chem.
Res. 1974, 7, 77-84. For a recent use of the ionic Brook rearrangement
as a key step in an efficient [3 + 4] annulation affording seven-
membered carbocycles, see: Takeda, K.; Nakajima, A.; Takeda, M.;
Hoshii, E. Org. Synth. S. F. Martin, Eds. 1998, 76, 199-213.
(3) Dalton, J . C.; Bourque, R. A. J . Am. Chem. Soc. 1981, 103, 699-
700.
(4) Harris, J . M.; MacInnes, I.; Walton, J . C.; Maillard, B. J .
Organomet. Chem. 1991, 403, C25-C28.
(5) (a) Tsai, Y.-M.; Cherng, C.-D. Tetrahedron Lett. 1991, 32, 3515-
3518. (b) Chang, S.-Y.; J iaang, W.-T.; Cherng, C.-D.; Tang, K.-H.;
Huang, C.-H.; Tsai, Y.-M. J . Org. Chem. 1997, 62, 9089-9098 and
references therein.
(6) Schiesser, C.; Styles, M. L. J . Chem. Soc., Perkin Trans. 2 1997,
2335-2340.
10.1021/jo9912855 CCC: $19.00 © 2000 American Chemical Society
Published on Web 03/29/2000

Radical Brook Rearrangement
J . Org. Chem., Vol. 65, No. 8, 2000 2293
Ta ble 1. Selected Stu d ies In volvin g r-silyl Alk oxyl Ra d ica ls
a
b
See refs 3, 4, 5, 6, and 7 for entries 1, 2, 3, 4, and 5, respectively. R-Trimethylsilyl-hydroxymethyl radicals were also formed in
addition to 7. c A translocation barrier of 4.76 kcal mol-1 was predicted at the MP2/DZP + ZPVE level. See ref 6 for details.
Sch em e 1
adds to the R,â-unsaturated system 19 to render the
aldehyde 20.7 This anomalous result suggests that the
fate of R-silyl alkoxyl radicals I may depend on the
radical-generation method and/or the nature of the
substrate. In the work reported herein we found ad-
ditional evidence of this in experiments to determine
whether generation of the R-silyl alkoxyl radicals 23 from
R-silyl alcohols 218 (or from their nitrites 25) leads to
carbon radicals 24 (Scheme 1). We also addressed the
possibility of forming cyclopropanols 29 by radical cy-
clization of â-acylsilane carbon radicals 26 and subse-
quent Brook rearrangement of R-silyl alkoxyl radicals 27
(Scheme 1).9
Resu lts a n d Discu ssion
A. Syn th esis of r-Silyl Alcoh ols 21. The R-silyl
alcohols 21a -e, 21h , and 21k (Chart 1) were prepared
by treatment of the corresponding aldehydes with di-
methylphenylsilyllithium (63-84%, 48% for 21k ),10,11 as
illustrated in eq 2 for 21b.
(9) At present there is no general radical methodology for the
preparation of cyclopropane; see for example Srikrishna, A.; Sharma,
G. V. R. J . Chem. Soc., Perkin Trans. 1 1997, 177-181. J ournet, M.;
Malacria, M. J . Org. Chem. 1994, 59, 718-719. Weng, W.; Luh, T. J .
Org. Chem. 1993, 58, 5574-5575. Zhang, W.; Dowd, P. Tetrahedron
Lett. 1992, 33, 7307-7310 and references therein. See also Curran,
D. P.; Gabarda, A. E. Tetrahedron 1999, 55, 3327-3336.
(10) For the preparation of R-silyl alcohols, see Chenede, A.; Abd.
Rahman, N.; Fleming, I. Tetrahedron Lett. 1997, 38, 2381-2382 and
references therein. (Dimethylphenylsilyl)lithium was prepared from
chlorophenyldimethylsilane as described by: Fleming, I.; Newton, T.
W.; Roessler, F. J . Chem. Soc., Perkin Trans. 1 1981, 2527-2532.
(11) Barrett, A. G. M.; Hill, J . Tetrahedron Lett. 1991, 32, 3285-
3288.
(7) Robertson, J .; Burrows, J . N. Tetrahedron Lett. 1994, 35, 3777-
3780.
(8) Our preliminary results on the reaction of R-hydroxysilanes 21
with lead tetraacetate have recently been published elsewhere: Pare-
des, M. D.; Alonso, R. Tetrahedron Lett. 1999, 40, 3973-3976.

2294 J . Org. Chem., Vol. 65, No. 8, 2000
Paredes and Alonso
radicals 24 from r-silyl alcohols 21 (Scheme 1) consisted
in their treatment with lead tetraacetate (LTA).16 This
choice was based on the well-precedented thermal or
photochemical generation of r-alkoxyl radicals from
alcohols on exposure to LTA in nonpolar solvents.17
B1. r-Alk yl- a n d r-Ar yl-Mon osu bstitu ted r-Silyl
Alcoh ols. Treatment of R-silyl alcohol 21a under stan-
dard LTA oxidation conditions (110 mol % of LTA,
refluxing benzene) gave compound 33a (73%, Table 2,
entry 1). Other monosubstituted alkyl and aryl R-silyl
alcohols 21b-e behaved similarly, giving the correspond-
ing mixed acetals 33b-e (Table 2). During these experi-
ments we realized that it was not necessary to run the
reaction in refluxing benzene; these transformations took
place at room temperature, almost instantaneously, and
in essentially quantitative yield with just 1 equiv of LTA.
It may also be noted that the mixed acyl-silyl acetals 33,18
though rather unusual,19 have been used to protect
aldehyde groups,20 and their reactions with silyl enol
ethers and allyltrimethylsilane in the presence of a Lewis
acid have been described.21 They have also been reduced
by DIBALH22a and efficiently hydrolyzed under both
acidic23 and basic22 conditions to the corresponding al-
dehydes. In this respect, we noted that the aromatic
acetals obtained are particularly prone to hydrolysis; in
fact, acetals 33d and 33e underwent complete conversion
to the carbonyl derivatives on filtration through silica gel
or alumina.
The fully R-substituted silyl alcohol 21f and the R,R-
bis-silyl-substituted alcohol 21g12 (Chart 1, 60% and 90%)
Ch a r t 1
B2. r,r-Disu bstitu ted -r-Silyl Alcoh ols. The reaction
of LTA with the R,R-disubstituted-R-silyl alcohols 21f and
21g proceeded similarly to give the mixed ketals 33f
(88%) and 33g (94%). In the latter case, addition of silica
to the crude reaction mixture resulted in hydrolysis to
34, completing a synthetic pathway from esters to acyl-
silanes (32 f 21g f 33g f 34; Scheme 3).
B3. Tr a p p in g Exp er im en ts. The efficient conversion
of R-silyl alcohols 21 into mixed acetals 33 appeared to
indicate that the two well-precedented processes dis-
cussed above, the LTA-induced formation of alkoxyl
radicals from alcohols (i.e., 21 to 23, Scheme 4) and the
Brook radical rearrangement of R-silyl alkoxyl radicals
(i.e., 23 to 24), could in fact be successfully chained to
afford R-silyloxy carbon radicals 24. To see if these
putative intermediates could undergo other synthetically
useful transformations, e.g., internal trapping, faster
than oxidative transformation to 33, we selected R-silyl
alcohols 21h and 21j as suitable precursors of 24h and
24j. However, attempts to obtain a cyclized product of
type 35 by treatment of 21h with lead tetraacetate led
only to the mixed acetal 33h in 97% yield. When we tried
were prepared analogously starting from cyclohexanone13
and ethyl 3-phenylpropanoate, respectively. Attempts to
apply this transformation to the aldehydes 21n -q re-
sulted in complex mixtures.
The R-methyl-substituted R-silyl alcohols 21i and 21m
were prepared from 21h and 21d , respectively, by oxida-
tion to the acylsilanes14 followed by treatment with
methyllithium,15 as exemplified for 21i in Scheme 2. The
silyl alcohol 21j was prepared from 21i by ozonolysis to
the lactol 31 followed by Horner-Emmons olefination
(Scheme 2).
B. Tr ea tm en t of r-Silyl Alcoh ols w ith Lea d Tet-
r a a ceta te. The first method we tried to generate carbon
Sch em e 2

Radical Brook Rearrangement
J . Org. Chem., Vol. 65, No. 8, 2000 2295
Ta ble 2. Tr ea tm en t of r-Silyl Alcoh ols 21 w ith Lea d
Sch em e 3
Tetr a a ceta te
formation of large quantities of the silyl enol ether that
upon prolonged heating were hydrolyzed to ketone 37j.
Acetate 38j was only observed toward the end of the
reaction as a result of overoxidation of ketone 37j on
addition of more LTA (up to 150 mol %).
B4. Discu ssion of th e Mech a n ism . As already
indicated above, the reaction of R-silyl alcohols 21 with
LTA to give mixed silyl-substituted acetals 33 could be
understood as proceeding through the path 21 f 22a f
23 f 24 f 33 outlined in Scheme 5. The first two steps
of this transformation (the formation of alkoxylead
derivatives 22a and of alkoxyl radicals 23) would be
similar to those accepted for the LTA oxidation of
nonsilyl-substituted alcohols 39.17a The intermediate
alkoxyl radicals 23 would then undergo a radical Brook
rearrangement to 24 which would be finally oxidized to
33. It should be noted that these last two steps are
different to those of their nonsilyl-substituted alkoxyl
radical analogues 40 which preferentially evolve by 1,5-H
abstraction to carbon-radical intermediates 41 in their
way to 42.
In connection with this mechanistic proposal, two
facts: (a) the unexpectedly high speed of the reaction, and
(b) the failure to obtain cyclized products from 21h and
21j, deserve further discussion.
(a) Regarding the speed of the process, it is surprising
that the transformation of R-silyl alcohols 21 to acetals
33 occurs so readily, being essentially instantaneous and
a
Yields after isolation by column chromatography. Reactions
performed with LTA (110 mol %) in refluxing benzene at the 100
mg scale. To a solution of the R-silyl alcohol (0.04-0.05 mmol)
b
in 0.5 mL of C6D6 prepared in an NMR tube were added
1,4-dichlorobenzene (6 mg) and Pb(OAc)4 (100 mol %). The tube
was shaken for about 2 min and immediately subjected to proton
NMR spectroscopy, which showed complete transformation. Yield
was estimated by integration of the well-defined NMR signal of
the acetal proton of the product, using 1,4-dichlorobenzene as the
internal standard. c Standard LTA oxidation conditions, 100 mg
scale. The proton NMR of the crude residue obtained by filtration
of the reaction mixture and concentration under reduced pressure
showed an 87:13 ratio of 33d versus the corresponding aldehyde.
Filtration of this mixture through alumina or silica gel gave the
d
aldehyde in quantitative yield. When the reaction was performed
in refluxing benzene (100 mg scale), chromatography isolated
piperonal and its monoacetoxy derivative at the methylenedioxy
group in 58% and 37% yield, respectively.
(17) (a) Evidence for the formation of alkoxyl radicals from alcohols
on treatment with LTA has been obtained from ESR studies and from
the isolation of epimeric products derived from reversible fragmenta-
tion of these intermediates; a detailed and well-documented mecha-
nistic description of this reaction is given by Mihailovic M. Lj.; Cekovic,
Z.; Lorenc, Lj. In Organic Synthesis by Oxidation with Metal Com-
pounds; Mijs, W. J ., de J onge, C. R. H. I., Eds.; Plenum Press: New
York 1986; Chapter 14, pp 741-816. (b) For another leading review,
see Heusler, K.; Kalvoda, J . Angew. Chem., Int. Ed. Engl. 1964, 3, 525-
538.
the reaction with 21j, which has a better radical acceptor,
we again isolated no cyclized products, but only the silyl
enol ether 36j (9%), the ketone 37j (47%), and the acetate
38j (23%). TLC monitoring clearly showed the initial
(18) This is the first reported method for direct conversion of R-silyl
alcohols to acetals. It complements the known oxidations of these
substrates to aldehydes: (a) Fleming, I.; Ghosh, U. J . Chem. Soc.,
Perkin Trans. 1 1994, 257-262, and to acylsilanes: (b) Ireland, R. E.;
Norbeck, D. W. J . Org. Chem. 1985, 50, 2198-2200.
(19) A search of Chemical Abstracts for acyl-silyl acetal substruc-
tures found just 23 references between 1967 and mid 1997.
(20) Mander, L. N.; Owen, D. J . Tetrahedron 1997, 53, 2137-2162.
(21) Shaw, J . T.; Woerpel, K. A. J . Org. Chem. 1997, 62, 442-443
and 6706-6707.
(22) (a) AÄ lvarez, E.; Rico, M.; Rodr´ıguez, R. M.; Zurita, D.; Mart´ın,
J . D. Tetrahedron Lett. 1992, 33, 3385-3388. (b) Deprotection with
KF has also been reported: Giese, B.; Horler, H. Tetrahedron 1985,
41, 4025-4037.
(23) Duff, J . M.; Brook, A. G. Can. J . Chem. 1973, 51, 2869-2883.
Nakatani, S.; Yoshida, J .; Isoe, S. Tetrahedron 1993, 49, 2011-2024.
(12) This substrate had been prepared before: Fleming, I.; Ghosh,
U. J . Chem. Soc., Perkin Trans. 1 1994, 257-262.
(13) Typical examples of the addition of the dimethylphenylsilyl-
lithium to ketones are described in Koreeda, M.; Koo, S. Tetrahedron
Lett. 1990, 31, 831-834; Bishop, P. M.; Pearson, J . R.; Sutherland, J .
K. J . Chem. Soc., Chem. Commun. 1983, 123-124. Vedejs, E.; Arnost,
M. J .; Eustache, J . M.; Krafft, G. A. J . Org. Chem. 1982, 47, 4384-
4386.
(14) Mancuso, A. J .; Huang, S. L.; Swern, D. J . J . Org. Chem. 1978,
43, 2480-2482.
(15) Nakada, M.; Urano, Y.; Kobayashi, S.; Ohno, M. J . Am. Chem.
Soc. 1988, 110, 4826-4827.
(16) Cekovic, Z.; Mihailovic M. Lj. In Encyclopedia of Reagents for
Organic Synthesis; Paquette, L. A., Ed.; J ohn Wiley and Sons:
Chichester, 1995; Vol. 5; pp 2949-2954 and references therein.

2296 J . Org. Chem., Vol. 65, No. 8, 2000
Paredes and Alonso
Sch em e 4
Sch em e 5
would require that the formation of alkoxyl radicals 23
from the silylated alkoxylead(IV) acetates 22a (RR
)
SiMe2Ph) would be faster as compared to the nonsilylated
analogues 22b (RR ) H, alkyl). This could well be the
case as homolysis of the Pb-O bond in 22a could be
favored by stabilization of the incipient oxygen-radical
being formed by the â-positioned silyl group as compared
to nonsilyl-substituted alcohols.26
(b) On the other hand, the nearly quantitative forma-
tion of 33h from 21h (Scheme 4) could also appear
surprising at first sight: the carbon radical intermediate
24h , because of its 5-hexenyl nature, was expected to
undergo quick 1,5-exo cyclization and hence afford cy-
clized products such as 35. However, preferential oxida-
tion over 1,5-exo cyclization of carbon radicals is not
without precedent under these reaction conditions. In fact
the formation of 33h by oxidation of 24h would parallel
the behavior previously observed by Cekovic27 for the
carbon radical analogue 41a (Scheme 6) which, generated
under similar conditions, preferentially evolved oxida-
tively to the tetrahydrofuran 43 instead of giving a
cyclopentane derivative by 1,5-exo cyclization. Moreover,
in the case of 24h , preference for oxidation would be even
higher than for 41a because of its comparatively higher
nucleophilicity due to R-alkoxy substitution. It is inter-
(25) Tsunoi, S.; Ryu, I.; Okuda, T.; Tanaka, M.; Komatsu, M.;
Sonoda, N. J . Am. Chem. Soc. 1998, 120, 8692-8701.
quantitative even at room temperature and with no
excess of LTA. This behavior contrasts with that of non-
R-silyl alcohols, significant quantities of which are re-
covered even after quite lengthy refluxing with up to a
2-fold excess of LTA.24 Since the reactions of non-R-silyl
alcohols 39 seem to be limited by slow homolysis of the
alkoxylead(IV) acetate intermediates 22b,25 acceptance
of the radical mechanism for the conversion of 21 to 33
(26) A silyl group can stabilize â-carbon radicals through “σ-π
hyperconjugation” and “ p-d homoconjugation”. See Hwu, J . R.; King,
K. Y.; Wu, I.-F.; Hakimelahi, G. H. Tetrahedron Lett. 1998, 39, 3721-
3724. Ibrahim, M. R.; J orgensen, W. L. J . Am. Chem. Soc. 1989, 111,
819-824. Davidson, I. M. T.; Barton, T. J .; Hughes, K. J .; Ijadi-
Maghsoodi, S.; Revis, A.; Paul, G. C. Organometallics 1987, 6, 644-
646. N. Auner, R. Walsh, J . Westrup. J . Chem. Soc., Chem. Commun.
1986, 207-208; J ackson, R. A.; Ingold, K. U.; Griller, D.; Nazran, A.
S. J . Am. Chem. Soc. 1985, 107, 208-211. Kawamura, T. J .; Kochi. K.
J . Am. Chem. Soc. 1972, 94, 648-650.
(27) Cekovic and Ilijev suggested that the hypothesized carbon
radical 41a (Scheme 6) constitutes a tight radical pair with a lead(III)
species such as Pb(OAc)3: Cekovic, Z.; Ilijev, D. Tetrahedron Lett. 1988,
29, 1441-1444.
(24) Partch, R. E. J . Org. Chem. 1965, 30, 2498-2502. Mihailovic,
M. Lj.; Cekovic, Z.; Maksimovic, Z.; J eremic, D.; Lorenc, Lj.; Mamuzic,
R. I. Tetrahedron 1965, 21, 2799-2812.

Radical Brook Rearrangement
Sch em e 6
J . Org. Chem., Vol. 65, No. 8, 2000 2297
Sch em e 7
Sch em e 8
esting to note, however, that under appropriate condi-
tions (CO, 80 atm) carbon radicals generated by treat-
ment of alcohols with LTA can be efficiently trapped
before being oxidatively transformed, as recently dem-
onstrated by Ryu25 which reported the successful syn-
thesis of δ-lactones 45 from primary or secondary alcohols
39 through δ-carbon- and acyl-radical intermediates 41b
and 44, respectively.
Similarly, preferential oxidation over cyclization of 24j
to acetal 33j would had taken place starting from 21j
(Scheme 4). In this case, however, the acetal 33j is
R,R,â,â-tetrasubstituted and would have quickly evolved
by elimination to the silyl enol ether 36j (9%) and hence
to ketone 37j (47%) and acetate 38j (23%).
strong support to the radical mechanism hypothesis. In
the event, however, LTA treatment of 21k gave only the
mixed acetal 33k in 92% yield, affording no conclusive
evidence.
To explain the conversion of R-silyl alcohols 21 into
mixed acetyl-silyl acetals 33, we alternatively considered
nonradical pathways. In a particularly appealing one,
alkoxylead(IV) acetates 22b would evolve to the corre-
sponding carbonyl derivatives 46 by concerted elimina-
tion of Pb(OAc)2 and AcOSiMe2Ph via a seven-membered
transition state (Scheme 7), resembling the evolution of
enolates 48 in the LTA-promoted R-acetoxylation of
carbonyl compounds.28 Formation of the final mixed
acetals 33 would be the result of the direct reaction of
46 with acetoxysilane 47. This last step is a conceivable
process because acetoxysilanes are able to silylate alkox-
ides, alcohols, and amines.29 However, both pivalaldehyde
and piperonal remained unaltered on treatment with
acetoxysilane 47 in benzene, even when Pb(OAc)4 or
HOAc were added in variable amounts to reproduce the
reaction conditions as close as possible.
C. r-Silyla ted Nitr ites. Since alkoxyl radicals formed
by photolysis of nitrites are reported to be unassociated
with the released nitric oxide,30 we hypothesized that
photolysis of R-silylated nitrites 25 (Scheme 1) might give
R-silyl alkoxyl radicals 23 with structures and behaviors
resembling those of radicals formed from δ- and ꢀ-halo-
genated acylsilanes (11; Table 1, entry 3) and which
would therefore evolve by radical Brook rearrangement
to the corresponding R-silyloxy carbon radicals 24. These
latter would presumably be liable to further transforma-
tions paralleling those undergone by carbon radicals
generated by 1,5-H transfer of alkoxyl radicals formed
under these conditions.31
C1. Syn th esis of r-Silyla ted Alip h a tic Nitr ites 25.
The R-silylated nitrites 25 (Table 3) were prepared from
the corresponding R-silyl alcohols 21 by transfer of the
Finally, experiments were carried out with silyl alcohol
21k ; the formation of products such as 49 by opening of
the cyclopropane ring (Scheme 8) would have given
(30) Barton, D. H. R.; Beaton, J . M.; Geller, L E.; Pechet, M. M. J .
Am. Chem. Soc. 1960, 82, 2640-2641. Barton, D. H. R.; Beaton, J . M.;
Geller, L E.; Pechet, M. M. J . Am. Chem. Soc. 1961, 83, 4076-4083.
Barton, D. H. R. Pure Appl. Chem. 1968, 16, 1-15.
(31) Akhtar, M.; Barton, D. H. R.; Sammes, P. G. J . Am. Chem. Soc.
1965, 87, 4601-4607. Akhtar, M.; Barton, D. H. R.; Sammes, P. G. J .
Am. Chem. Soc. 1964, 86, 3394-3395.
(28) Reference 17a, pp 783-787.
(29) Deardorff, D. R.; Shambayati, S.; Linde II, R. G.; Dunn, M. M.
J . Org. Chem. 1988, 53, 189-191. Hudrlik, P. F.; Feasley, R. Tetra-
hedron Lett. 1972, 18, 1781-1784.

2298 J . Org. Chem., Vol. 65, No. 8, 2000
Paredes and Alonso
Ta ble 3. P h otolysis of Alip h a tic r-Silyl Nitr ites 25
Ta ble 4. Tr ea tm en t of Ben zyl r-silyl Alcoh ols w ith
t-Bu ONO
a
The benzyl R-silyl nitrite intermediates, inferred by TLC,
b
evolved directly to the carbonyl compounds. Overall yield for the
one-pot conversion from the R-silyl-benzyl alcohols 21.
Photolysis of the R,R-disubstituted nitrites 25i and 25j,33
for which the Brook rearrangement to tertiary R-alkoxy
carbon radicals was expected to be easier than for 25h ,
gave only complex mixtures.
a
Overall yields for the one-pot conversion from alcohol 21a by
irradiation of a solution of the crude nitrite 25a in acetonitrile or
benzene, respectively. Major product by TLC. c Starting nitrites
b
25i and 25j contained variable amounts of the R-silyl alcohol
precursors 21i and 21j.
C4. r-Silyla ted Ben zyl Nitr ites. Much to our sur-
prise, attempts to make the nitrite of 21d by treatment
with tert-butyl nitrite in chloroform at room temperature,
either under ordinary light conditions or in the dark,
resulted in complete conversion of 21d to 3,4,5-tri-
methoxybenzaldehyde (98%, Table 4). TLC analysis
showed that the aldehyde was not formed directly from
21d , but from an intermediate with an Rf in agreement
with that expected for the corresponding nitrite. An
analogous result was obtained with 21e, although in this
case the reaction was slower.
Since R-silyl-substituted aliphatic nitrites, like the
corresponding nonsilyl-substituted benzyl nitrites, are
stable at room temperature under ordinary light, it was
concluded that the R-silyl substituent and the R-phenyl
ring work together to facilitate the evolution of the R-silyl
benzyl nitrites to the corresponding carbonyl compounds.
The high yields and the mild reaction conditions make
R-silyl benzyl alcohols protected precursors of benzyl
carbonyls.
tert-Butyl nitrite treatment of the R,R-disubstituted
R-silyl alcohol 21m under nitrosyl exchange conditions
gave methyl ketone 52 in 77% yield (Table 4), showing
that equilibrium between the fully R-substituted nitrite
and its R-silyl alcohol precursorsthe main problem in the
formation of the aliphatic analogues 25i and 25jsis
circumvented by in situ conversion to the ketone. The
route 50 f 51 f 21m f 52 from aromatic aldehydes to
methyl,aryl-ketones (eq 3), should in principle be ap-
plicable to the preparation of other alkyl,aryl- or diaryl-
ketones.
nitrosyl group from tert-butyl nitrite as reported by
Doyle.32 This method worked reasonably well for the
R-monosubstituted derivatives 25a (65% yield) and 25b
(62%), and poorly for 25h (20%, one run, unoptimized)
and for the R,R-disubstituted nitrites 25i (20%) and 25j
(20%). These latter could only be obtained as mixtures
with the starting R-silyl alcohols, with which they were
in equilibrium under the reaction conditions and to which
they were partially transformed during attempts at
chromatographic purification.
C2. P h otolysis of Alip h a tic r-Silyla ted Nitr ites.
Irradiation of a solution of nitrite 25b in benzene at 0
°C with a tungsten sun lamp (300 W) or halogen lamp
(300 W) surprisingly gave volatile cyclohexanecarbalde-
hyde as the major product (Table 3). Irradiation at 450
W with a medium-pressure Hanovia Hg lamp, also at 0
°C, gave the same product more quickly, in 30 min
instead of several hours. Under these latter conditions,
nitrite 25a also gave the corresponding aldehyde (deca-
nal), in 68% yield. In fact, treatment of 21a with tert-
butyl nitrite, dilution of the crude reaction mixture with
acetonitrile or benzene, deoxygenation, and irradiation
gave decanal in an overall yield of 70% (in CH3CN) or
74% (in C6H6) without intervening purification of the
nitrite 25a .
C3. Tr a p p in g Exp er im en ts. An aldehyde was also
obtained when nitrite 25h was used in an attempt to trap
any radical intermediate with its internal double bond.
(33) As indicated, nitrites 25i and 25j were obtained as mixtures
with their alcohol precursors, 21i and 21j, respectively. These mixtures
were used in the photolysis experiments.
(32) Doyle, M. P.; Terpstra, J . W.; Pickering, R. A.; LePoire, D. M.
J . Org. Chem. 1983, 48, 3379-3382.

Radical Brook Rearrangement
J . Org. Chem., Vol. 65, No. 8, 2000 2299
Sch em e 9
C5. Discu ssion of th e Mech a n ism . The formation
of carbonyl compounds by photolysis of R-silyl aliphatic
nitrites 25 (R1 ) R2 ) H, alkyl) can be explained by
formation of the alkoxyl radical 23 followed by Brook
rearrangement to R-silyloxy carbon radical 24 and final
collapse to 46 by interaction with nitric oxide (Scheme
9, path C). Alternatively, in analogy with the proposed
evolution of the R-silyl alkoxyl radical 18 (Table 1, entry
5), the carbonyl compound could be formed directly from
the intermediate R-silyl alkoxyl radical 23 by â-fragmen-
tation with (path D) or without (path E) the assistance
of the NO radical. Attempts to differentiate between
these pathways by running the reaction with the nitrite
derived from the R-silyl alcohol 21k (Chart 1) were
unavailing, a complex mixture being obtained on pho-
tolysis.
Sch em e 10
By contrast, the involvement of alkoxyl radical inter-
mediates of type 23 in the conversion of the benzyl nitrite
analogues (25, R1 or R2 ) Ar) into their corresponding
carbonyl compounds 46 seems unlikely because the
process takes place without UV irradiation (even in the
dark), and the presence of the phenyl ring is not expected
to favor the O-NO bond breaking as an isolated event
to any appreciable extent. In this case, the reaction is
better explained by a concerted process through a species
such as 53, where CdO bond formation by simultaneous
O-NO and C-Si bond breaking would be favored by
conjugation with the aromatic ring (path F, Scheme 9).
On the basis of the different behavior of benzyl versus
aliphatic nitrites, it is tempting to suggest that stabiliza-
tion by resonance could similarly be a major factor
affecting the evolution of other R-silyl alkoxyl species. In
particular, π-conjugating substituents in R-silyl alkoxyl
radicals I could facilitate CdO bond formation by C-Si
bond breaking, i.e., they would preferentially evolve to
46 by â-silyl fragmentation of the intermediate 54 rather
than undergoing the radical Brook rearrangement to II
(Scheme 10). This would explain the results obtained to
date on the evolution of R-silyl alkoxyl radicals I; in
particular the evolution of 18 to 19 would be attributable
to the presence of the double bond.
Treatment of a 0.02 M solution of 56 in deoxygenated
benzene by slow addition of n-Bu3SnH (150 mol %) and
AIBN (10%) in the same solvent failed to afford cyclo-
propanol 29a (Scheme 11). This result is in keeping with
the recent report on the attempted cyclization of diphe-
nylmethyl(3-phenylselenopropanoyl)silane 57, which on
treatment with n-Bu3SnH gave only the reduced product
58 (79%).5b In our case, isolation of the rearranged
product 60 (62%) showed that the failure to obtain
cyclopropanols was not due to nonoccurrence of 1,3-exo
radical cyclization (26a f 27a ), which appears to be
efficient, but to the radical Brook rearrangement of 27a
to 28a being slower than reopening of 27a to the tertiary
carbon radical 59, which eventually afforded 60.34
Su m m a r y
This work investigated whether radical Brook rear-
rangement can be reliable induced so as (a) to generate
R-silyloxy carbon radicals 24 from R-silyl alcohols 21 and
(b) to form cyclopropanols 29 through â-acylsilane carbon
radicals 26. For the first goal the formation of R-silyl
alkoxyl radical intermediates 23 was attempted by LTA
treatment of R-silyl alcohols 21 and by photolysis of their
D. â-Ha loa cylsila n es. To evaluate the possibility of
forming cyclopropanols 29 by cyclization of â-acylsilane
carbon radicals 26 to R-silyl alkoxyl radicals 27 and
subsequent Brook rearrangement (Scheme 1), we pre-
pared the â-bromo acylsilane 56 from commercially
available 2,2-dimethyl-3-hydroxypropanal 55 as indicated
in eq 4.
(34) In line with our result on the acylsilane 56, Curran observed a
similar rearrangement of an R-seleno cyclopropyloxy radical obtained
by 1,3-exo cyclization of a â-acylgermane carbon radical analogous to
26a : opening was faster than the alternative â-elimination of selenyl
radicals to the corresponding cyclopropanone: Curran, D. P.; Dieder-
ichsen, U.; Palovich, M. J . Am. Chem. Soc. 1997, 119, 4797-4804.

2300 J . Org. Chem., Vol. 65, No. 8, 2000
Paredes and Alonso
Sch em e 11
PhMe2SiLi (18.4 mL, 6.91 mmol, 180 mol %). 1H NMR (300
MHz, CDCl3) 7.58 (m, 2H), 7.37 (m, 3H), 3.52 (dd, J ) 6.2 Hz,
J ) 7.5 Hz, 1H), 1.54 (m, 2H), 1.50-1.20 (m, 15H), 0.90 (t, J
) 6.7 Hz, 3H), 0.36 (s, 3H), 0.35 (s, 3H); 13C NMR (75 MHz,
CDCl3) 136.8, 134.1, 129.2, 127.8, 65.4 (C1), 33.4, 31.9, 29.58,
29.56, 29.46, 29.3, 26.8, 22.6 (C2-C9), 14.1 (C10), -5.4 (CH3-
Si), -5.7 (CH3Si); IR (neat) 3438 (OH) cm-1; MS m/z (%) 277
[3, (M - Me)+], 165 [10, (PhMe2SiCHOH)+].
Cycloh exyl(dim eth ylph en ylsilyl)m eth an ol (21b). It was
prepared by reaction of PhMe2SiLi (13.1 mL, 4.90 mmol, 110
mol %) with cyclohexanecarbaldehyde (500 mg, 4.45 mmol).
Purification (EtOAc-hexane 6:94) gave 21b (875 mg, 79%) as
a pale yellow oil. 1H NMR (300 MHz, CDCl3) 7.61 (m, 2H),
7.40 (m, 3H), 3.37 (d, J ) 5.8 Hz, 1H), 1.90-1.56 (m, 6H),
1.31-1.01 (m, 6H), 0.40 (s, 6H); 13C NMR (75 MHz, CDCl3)
137.8, 134.0, 129.1, 127.8, 70.9 (C-OH), 42.0, 30.7, 29.5, 26.4,
26.3, 26.2, -3.9, -4.3; IR (neat) 3451 (OH) cm-1; MS m/z (%)
248 [1, M+], 165 [16, (PhMe2SiCHOH)+].
2,2-Dim eth yl-1-(d im eth ylp h en ylsilyl)p r op a n -1-ol (21c).
Treatment of trimethylacetaldehyde (400 mg, 4.64 mmol) with
PhMe2SiLi (24.8 mL, 9.29 mmol, 200 mol %) afforded, after
chromatography (EtOAc-hexane 5:95), 21c as a pale yellow
oil (735 mg, 71%). 1H NMR (300 MHz, CDCl3) 7.63 (m, 2H),
7.38 (m, 3H), 3.21 (s, 1H, H1), 1.44 (br s, 1H, OH), 0.94 (s, 9H,
H3), 0.45 (s, 6H, (CH3)2Si); 13C NMR (75 MHz, CDCl3) 138.6,
134.1, 129.0, 127.8, 75.3 (C1), 36.0 (C2), 27.6 (3C, C3), -2.2
(CH3Si), -3.0 (CH3Si); IR (neat) 3477 (OH) cm-1; MS m/z (%)
223 [1, (M+1)+], 222 [1, M+], 165 [18, (PhMe2SiCHOH)+].
nitrites 25. The second goal was addressed by studying
the cyclization of the â-bromoacylsilane 56 under typical
n-Bu3SnH conditions.
The most striking result of the first study was the
dramatic influence of a geminal silyl group on the
reaction of the hydroxy group with LTA: while nonsilyl-
substituted alcohols with an accessible δ-hydrogen are
converted into cyclic ethers, R-silyl alcohols 21 are
efficiently transformed into mixed acyl-silyl acetals.
Silyl substitution also affected the photolysis of R-silyl
nitrites, which in this case afforded the corresponding
carbonyl compounds. The most surprising observation in
these experiments was the clean, efficient, conversion of
the presumptive benzyl R-silyl nitrite intermediates
(assumed to be formed on treatment of the benzyl R-silyl
alcohols with tert-butyl nitrite) into the corresponding
aromatic aldehydes and ketones without irradiation.
Facilitation of the fragmentation process by the aromatic
ring is tentatively explained in terms of a concerted
process with the resonance-stabilized transition structure
53. π-Delocalization is similarly put forward as a possible
explanation of why some R-silyl alkoxyl radicals I appear
to undergo Brook rearrangement and others â-fragmen-
tation. Finally we found that the radical Brook rear-
rangement of R-silyl cyclopropyloxyl radicals 27 is not
fast enough to compete with their opening by â-fragmen-
tation, which rules out their use for the preparation of
cyclopropanols.
(Dim eth ylp h en ylsilyl)(3,4,5-tr im eth oxyp h en yl)m eth a -
n ol (21d ). It was prepared by reaction of 3,4,5-trimethoxy-
benzaldehyde (500 mg, 2.55 mmol) and PhMe2SiLi (10.2 mL,
3.82 mmol, 150 mol %). Purification (CH2Cl2 100%) gave 21d
1
(711 mg, 84%) as an oil. H NMR (300 MHz, CDCl3) 7.44 (m,
Exp er im en ta l Section
2H), 7.35 (m, 3H), 6.21 (s, 2H), 4.60 (s, 1H), 3.80 (s, 3H), 3.60
(s, 6H), 1.88 (br s, 1H), 0.33 (s, 3H), 0.30 (s, 3H); 13C NMR (75
MHz, CDCl3) 152.7, 139.1, 135.83, 135.77, 134.3, 129.3, 127.6,
102.0, 70.1 (C-OH), 60.8 (CH3O-C4), 55.8 (2C, CH3O-C3),
-5.8, -5.9; IR (neat) 3485 (OH) cm-1; MS m/z (%) 333 [2, (M
+ 1)+], 332 [11, M+], 165 [22, (PhMe2SiCHOH)+]; HRMS calcd
for C18H24O4Si m/z 332.1444, found 332.1442.
Ben zo[1,3]d ioxol-5-yl(d im et h ylp h en ylsilyl)m et h a n ol
(21e). It was obtained as a colorless oil (chromatography: CH2-
Cl2-hexane 75:25, 447 mg, 78%) by reaction of benzaldehyde
(300 mg, 2.00 mmol) and PhMe2SiLi (8 mL, 3.00 mmol, 150
mol %). 1H NMR (300 MHz, CDCl3) 7.52 (m, 2H), 7.39 (m, 3H),
6.72 (d, J ) 8.0 Hz, 1H), 6.63 (d, J ) 1.5 Hz, 1H), 6.54 (dd, J
) 1.5, 8.0 Hz, 1H), 5.92 (s, 2H), 4.61 (s, 1H), 1.79 (br s, 1H),
0.32 (s, 3H), 0.28 (s, 3H); 13C NMR (75 MHz, CDCl3) 147.4,
145.6, 137.6, 136.0, 134.3, 129.4, 127.7, 118.1, 107.8, 106.1,
100.7, 69.8 (C-OH), -5.3, -6.3; IR (neat) 3423 (OH) cm-1; MS
m/z (%) 287 [3, (M + 1)+], 286 [11, M+], 165 [8, (PhMe2-
SiCHOH)+]; HRMS calcd for C16H18O3Si m/z 286.1025, found
286.1030.
1-(Dim eth ylp h en ylsilyl)cycloh exa n -1-ol (21f). Reaction
of cyclohexanone (100 mg, 1.02 mmol) with PhMe2SiLi (4.3 mL,
1.63 mmol, 160 mol %) gave after purification (EtOAc-hexane
5:95), 21f as a colorless oil (145 mg, 60%). 1H NMR (300 MHz,
CDCl3) 7.62 (m, 2H), 7.41 (m, 3H), 1.75-1.64 (m, 5H), 1.51-
1.44 (m, 4H), 1.27-1.19 (m, 2H), 0.40 (s, 6H); 13C NMR (75
MHz, CDCl3) 136.9, 135.0, 129.6, 128.2, 65.8 (C1), 33.5, 26.4,
20.5, -5.9; IR (neat) 3472 (OH) cm-1; MS m/z (%): 234 [0.2,
Gen er a l. All reactions were carried out under argon with
the exclusion of moisture. The reagents were purchased from
Sigma-Aldrich Chemical Co. and Fluka Chemical Co. and were
used without further purification. THF, Et2O, and benzene
were distilled from sodium benzophenone ketyl; CH3CN, CH2-
Cl2, CHCl3, and Et3N from calcium hydride. Anhydrous Na2-
SO4 was used to dry the organic solutions during workups.
Flash column chromatography was performed using 230-400
mesh silica gel (Merck). Analytical thin-layer chromatography
was done on precoated silica gel aluminum plates containing
a fluorescent indicator (GF-254 Merck). 1H NMR spectra were
recorded at 250 or 300 MHz; 13C NMR spectra at 63 or 75 MHz.
CDCl3 or C6D6 were used as solvents. (Dimethylphenylsilyl)-
lithium10 and compounds 21b and 21g were synthesized
according to literature methods.
Gen er a l p r oced u r e for th e P r ep a r a tion of r-Silyl
Alcoh ols. PhMe2SiLi (0.375 M in THF, 110-200 mol %) was
added dropwise to a 0.2 M solution of the corresponding
aldehyde in THF at -78 °C. The reaction mixture was allowed
to warm slowly to 0 °C, while being monitored by TLC and
then quenched with saturated NH4Cl. The aqueous layer was
extracted with Et2O (3×), and the combined organic extracts
were dried, filtered, and concentrated in vacuo. Column
chromatography gave the corresponding R-silyl alcohol.
1-(Dim eth ylp h en ylsilyl)d eca n -1-ol (21a ). It was obtained
(chromatography: EtOAc-hexane 6:94, 714 mg, 63%) as a
colorless oil by treatment of decanal (0.75 mL, 3.83 mmol) with

Radical Brook Rearrangement
J . Org. Chem., Vol. 65, No. 8, 2000 2301
M+], 219 [7, (M - Me)+]; HRMS calcd for C14H22OSi m/z
234.1440, found 234.1439.
acylsilane (0.48 M) in THF at -78 °C. Once the starting
material was completely consumed, saturated NH4Cl (aq) was
added, and the aqueous phase was extracted with Et2O. The
combined organic extracts were washed with saturated NaH-
CO3 and brine, dried, and filtered, and the volatiles were
removed. Column chromatography through silica gel afforded
the desired tertiary R-methyl-R-silyl alcohols.
1,1-Bis(dim eth ylph en ylsilyl)-3-ph en ylpr opan -1-ol(21g).12
1H NMR (300 MHz, CDCl3) 7.65 (m, 4H), 7.42 (m, 6H), 7.40-
7.19 (m, 3H), 6.99 (d, J ) 7.6 Hz, 2H), 2.56 (m, 2H), 2.06 (m,
2H), 0.43 (s, 6H), 0.37 (s, 6H); 13C NMR (75 MHz, CDCl3) 142.6,
137.5, 134.6, 129.2, 128.3, 128.1, 127.7, 125.7, 63.5 (C-OH),
39.6, 31.7, -2.9, -3.3; IR (neat) 3560 (OH) cm-1; EM m/z (%)
405 [0.4, (M + H)+].
3,7-Dim eth yl-2-(dim eth ylph en ylsilyl)oct-6-en -2-ol (21i).
Obtained from MeLi (2.20 mL, 3.30 mmol, 170 mol %) and
acylsilane 30 (535 mg, 1.95 mmol). Purification (EtOAc-
hexane, 6:94) gave 21i (523 mg, 92%) as a 1:1 mixture of two
diastereomers. Higher Rf isomer: 1H NMR (300 MHz, CDCl3)
7.61 (m, 2H, ArH), 7.38 (m, 3H, ArH), 5.09 (m, 1H, H6), 2.05
(m, 1H, H5), 1.88-1.70 (m, 1H, H5), 1.68 (s, 3H, H8), 1.68-
1.58 (m, 2H, H3, H4), 1.58 (s, 3H, H8), 1.15 (s, 3H, H1), 1.05-
0.91 (m, 2H, H4, OH), 0.86 (d, J ) 7.0 Hz, 3H, CH3-C3), 0.41
(s, 6H, (CH3)2Si); 13C NMR (75 MHz, CDCl3) 137.4 (Ar), 134.5
(Ar), 131.3 (C7), 129.1 (Ar), 127.7 (Ar), 124.7 (C6), 69.5 (C2),
40.7 (C3), 30.0 (C5), 26.4 (C4), 25.6 (C8), 20.0 (C1), 17.6 (C8),
15.6 (CH3-C3), -3.9 (CH3Si), -4.3 (CH3Si). Lower Rf isomer:
1H NMR (300 MHz, CDCl3) 7.60 (m, 2H, ArH), 7.37 (m, 3H,
ArH), 5.02 (m, 1H, H6), 2.06-2.00 (m, 1H, H5), 1.88-1.79 (m,
1H, H5), 1.68 (s, 3H, H8), 1.69-1.57 (m, 1H, H3), 1.59 (s, 3H,
H8), 1.46-1.41 (m, 1H, H4), 1.13 (s, 3H, H1), 1.00-0.86 (m,
2H, H4, OH), 0.86 (d, J ) 6.7 Hz, 3H, CH3-C3), 0.40 (s, 6H,
(CH3)2Si); 13C NMR (75 MHz, CDCl3) 137.4 (Ar), 134.6 (Ar),
131.5 (C7), 129.1 (Ar), 127.7 (Ar), 124.4 (C6), 69.3 (C2), 40.3
(C3), 32.9 (C5), 26.2 (C4), 25.7 (C8), 19.9 (C1), 17.6 (C8), 12.2
(CH3-C3), -3.8 (CH3Si), -4.1 (CH3Si); IR (mixture of diaster-
eomers, neat) 3466 (OH) cm-1; MS (mixture of diastereomers)
m/z (%) 290 [1, M+]; HRMS calcd for C18H30OSi m/z 290.2066,
found 290.2055.
1-(Dim et h ylp h en ylsilyl)-1-(3,4,5-t r im et h oxyp h en yl)-
eth a n ol (21m ). Obtained as a yellow oil (EtOAc-hexane 20:
80, 157 mg, 94%) from (dimethylphenylsilyl)-3,4,5-trimethox-
yphenyl)methanone (51) (160 mg, 0.48 mmol) and MeLi (0.48
mL, 0.73 mmol, 150 mol %). 1H NMR (300 MHz, CDCl3) 7.40-
7.34 (m, 5H), 6.29 (s, 2H), 3.82 (s, 3H), 3.69 (s, 6H), 1.60 (s,
3H), 1.41 (s, 1H), 0.32 (s, 3H), 0.30 (s, 3H); 13C NMR (75 MHz,
CDCl3) 152.4, 143.1, 135.8, 135.6, 134.7, 129.4, 127.5, 102.0,
70.0 (C-OH), 60.8 (CH3O-C4), 55.8 (2C, CH3O-C3), 26.1
(CH3COH), -5.9 (CH3Si), -6.2 (CH3Si); IR (neat) 3478 (OH)
cm-1; MS m/z (%) 346 [2, M+]; HRMS calcd for C19H26O4Si m/z
346.1600, found 346.1619.
2,6-Dim ethyl-1-(dim eth ylphen ylsilyl)hept-5-en-1-ol(21h).
It was obtained from 2,6-dimethyl-5-heptenal (5 mL, 24.96
mmol) and PhMe2SiLi (100 mL, 37.4 mmol, 150 mol %) as a
1
mixture of two diastereomers A:B, 1:1 (5.55 g, 82%). H NMR
(250 MHz, CDCl3) 7.57 (m, 4H), 7.40-7.30 (m, 6H), 5.04 (m,
2H), 3.52 (m, 1H), 3.38 (m, 1H), 2.10-1.80 (m, 4H), 1.67 (br s,
6H), 1.58 (br s, 6H), 1.48 (m, 2H), 1.25-1.05 (m, 4H), 1.11 (d,
J ) 5.3 Hz, 1H), 1.06 (d, J ) 5.1 Hz, 1H), 0.90 (d, J ) 6.8 Hz,
6H), 0.38 (s, 6H); 13C NMR (75 MHz, CDCl3) 137.7, 134.04,
134.01, 131.43, 131.38, 129.1, 127.86, 127.85, 124.6, 124.5,
71.0, 69.3, 36.8, 35.9, 34.4, 33.1, 25.7, 25.7, 25.4, 17.68, 17.64,
17.1, 16.0, -3.7, -4.0, -4.2; IR (neat) 3448 (OH) cm-1; MS
m/z (%) 276 [0.2, M+]; HRMS calcd for C17H28OSi m/z 276.1909,
found 276.1899.
(Dim et h ylp h en ylsilyl)(1-p h en ylcyclop r op yl)m et h a -
n ol (21k ). Treatment of 1-phenyl-1-cyclopropanecarbaldehyde
(400 mg, 2.74 mmol) with PhMe2SiLi (10.2 mL, 3.83 mmol,
140 mol %) gave (EtOAc-hexane 10:90) 21k as a pale yellow
1
oil (370 mg, 48%). H NMR (300 MHz, CDCl3) 7.52-7.21 (m,
10H), 3.14 (s, 1H), 1.65 (br s, 1H), 1.02 (m, 1H), 0.90-0.71 (m,
3H), 0.19 (s, 3H), 0.01 (s, 3H); 13C NMR (75 MHz, CDCl3) 142.7,
137.6, 134.0, 130.4, 129.0, 127.9, 127.6, 126.7, 74.4 (C-OH),
30.0 (C-Ph), 12.6 (CH2), 10.9 (CH2), -4.5 (CH3Si), -5.2 (CH3-
Si); IR (neat) 3458 (OH) cm-1; MS m/z (%) 283 [1, (M + 1)+],
282 [4, M+]; HRMS calcd for C18H22OSi m/z 282.1440, found
282.1448.
Typ ica l P r oced u r e for th e Oxid a tion of r Silyl Alco-
h ols to Acylsila n es. DMSO (400 mol %) in dry CH2Cl2 was
added to a solution of oxalyl chloride (200 mol %, 0.45 M) in
the same solvent at -78 °C. The R-silyl alcohol (0.8 M in dry
CH2Cl2) and dry Et3N (500 mol %) were successively added,
and the mixture was allowed to warm. After consumption of
the starting material as monitored by TLC, water was added,
the layers were separated, and the aqueous phase was
extracted with additional CH2Cl2. The combined organic
extracts were dried and concentrated. Purification by flash
chromatography afforded the desired acylsilanes.
5,6-Dim eth yl-6-(dim eth ylph en ylsilyl)tetr ah ydr opyr an -
2-ol (31). Ozone was passed through a solution of 21i (higher
Rf isomer, 700 mg, 2.41 mmol) and dry pyridine (1 mL) in
MeOH (30 mL) kept at -78 °C. When a blue color appeared,
the solution was purged with N2, and (EtO)3P (2 mL) was
added. The reaction was allowed to warm to room temperature,
the solvents were rotary evaporated, and the residue was
partitioned between Et2O and water. The organic layer was
washed with 1% HCl, dried, filtered, and concentrated. Puri-
fication through silica gel (EtOAc-hexane, 15:85 f 20:80)
afforded 31 as a white and volatile oil (565 mg, 89%, 4.7:1
2,6-Dim et h yl-1-(d im et h ylp h en ylsilyl)h ep t -5-en -1-on e
(30). This compound was obtained as a pale yellow oil
(chromatography: EtOAc-hexane 3:97, 980 mg, 71%) by
oxidation of 21h (1380 mg, 4.99 mmol) with oxalyl chloride
(0.87 mL, 9.98 mmol, 200 mol %), DMSO (1.43 mL, 19.96
mmol, 400 mol %), and Et3N (3.48 mL, 24.95 mmol, 500 mol
1
%). H NMR (250 MHz, CDCl3) 7.58-7.55 (m, 2H), 7.43-7.35
(m, 3H), 4.92 (m, 1H), 2.86 (m, 1H), 1.81 (m, 2H), 1.70-1.59
(m, 1H), 1.65 (s, 3H), 1.51 (s, 3H), 1.12 (m, 1H), 0.88 (d, J )
6.9 Hz, 3H), 0.50 (s, 6H); 13C NMR (75 MHz, CDCl3) 248.9 (C1),
134.9, 134.0, 131.9, 129.7, 128.0, 123.8, 50.0 (C2), 30.9 (C4),
25.6 (C7), 25.5 (C3), 17.6 (C7), 14.1 (CH3-C2), -4.2 (CH3Si),
-4.3 (CH3Si); IR (neat) 1639 (CO) cm-1; MS m/z (%) 275 [0.3,
(M + 1)+], 274 [1, M+]; HRMS calcd for C17H26OSi m/z
274.1752, found 274.1764.
1
mixture of isomers A:B). H NMR (250 MHz, CDCl3) 7.63 (m,
4H), 7.37 (m, 6H), 5.25 (m, 1H), 4.90 (m, 1H), 2.49 (m, 1H),
2.44 (m, 1H), 1.91-1.44 (m, 8H), 1.30-1.14 (m, 2H), 1.25 (s,
6H), 0.72 (d, J ) 6.5 Hz, 3H), 0.64 (d, J ) 6.5 Hz, 3H), 0.38 (s,
6H), 0.36 (s, 6H); 13C NMR (75 MHz, CDCl3) 137.5, 134.8,
134.7, 128.94, 128.87, 127.5, 92.0, 89.8, 74.0, 72.0, 34.1, 33.6,
30.7, 27.0, 21.2, 18.6, 18.3, 17.5, 13.3, -4.3, -4.6, -5.0; IR
(neat) 3411 (OH) cm-1; MS m/z (%) 265 [0.3, (M + 1)+], 264
[1, M+]; HRMS calcd for C15H24O2Si m/z 264.1545, found
264.1549.
Eth yl (E)-7-Hyd r oxy-6-m eth yl-7-(d im eth ylp h en ylsilyl)-
oct-2-en oa te (21j). Triethylphosphonoacetate (509 mg, 2.27
mmol, 150 mol %) was added to a suspension of sodium hydride
(91 mg, 2.27 mmol, 150 mol %) in THF (3.8 mL) at 0 °C. After
the evolution of hydrogen stopped, the reaction was cooled to
-78 °C and a solution of the lactol 31 (400 mg, 1.51 mmol) in
THF (0.5 mL) was added. The reaction was allowed to warm
slowly until no starting material was detected by TLC. The
solvent was removed and the residue redisolved in EtOAc. The
organic layer was washed with water, saturated NaHCO3, and
(Dim eth ylp h en ylsilyl)(3,4,5-tr im eth oxyp h en yl)m eth a -
n on e (51). It was obtained as a bright yellow oil (chromatog-
raphy: EtOAc-hexane 15:85, 182 mg, 91%) from 21d (202 mg,
0.61 mmol), oxalyl chloride (109 µL, 1.21 mmol, 200 mol %),
DMSO (174 µL, 2.43 mmol, 400 mol %), and Et3N (0.4 mL,
1
3.04 mmol, 500 mol %). H NMR (300 MHz, CDCl3) 7.63 (m,
2H), 7.41 (m, 3H), 7.00 (s, 2H), 3.85 (s, 3H), 3.66 (s, 6H), 0.61
(s, 6H); 13C NMR (75 MHz, CDCl3) 231.5 (CO), 153.0, 142.0,
136.6, 136.5, 134.0, 129.9, 128.4, 105.3, 60.8 (CH3O-C4), 55.4
(2C, CH3O-C3), -3.2 (2C, (CH3)2Si); IR (neat) 1572 (CO) cm-1
;
MS m/z (%) 331 [7, (M + 1)+], 330 [29, M+]; HRMS calcd for
C
18H22O4Si m/z 330.1287, found 330.1279.
Rea ction of MeLi w ith Acylsila n es. MeLi (1.5 M in Et2O,
150-170 mol %) was added to a solution of the corresponding

2302 J . Org. Chem., Vol. 65, No. 8, 2000
Paredes and Alonso
brine. Purification by chromatography (silica gel, EtOAc-
hexane, 15:85) afforded the R,â-unsaturated ester 21j (403 mg,
80%) as a pale yellow oil. 1H NMR (300 MHz, CDCl3) 7.58 (m,
2H), 7.37 (m, 3H), 6.93 (dt, J ) 15.6 Hz, J ) 6.8 Hz, 1H), 5.78
(dt, J ) 15.6 Hz, J ) 1.5 Hz, 1H), 4.17 (c, J ) 7.1 Hz, 2H),
2.31-2.20 (m, 1H), 2.08-1.99 (m, 1H), 1.90-1.79 (m, 1H),
1.66-1.60 (m, 1H), 1.28 (t, J ) 7.1 Hz, 3H), 1.14 (s, 3H), 1.14-
1.01 (m, 1H), 0.93 (br s, 1H), 0.84 (d, J ) 6.9 Hz, 3H), 0.39 (s,
6H); 13C NMR (75 MHz, CDCl3) 166.7 (CO), 149.4, 137.1, 134.5,
129.2, 127.8, 121.1, 69.3 (C7), 60.0 (OCH2CH3), 40.6 (C6), 30.7,
28.2, 19.8 (C8), 15.5 (OCH2CH3), 14.2 (CH3-C6), -3.9 (CH3-
Si), -4.5 (CH3Si); IR (neat) 3493 (OH), 1712 (CO)cm-1; MS
m/z (%) 334 [0.1, M+]; HRMS calcd for C19H30O3Si m/z
334.1964, found 334.1940.
Acet oxy (d im et h ylp h en ylsilyloxy) (3,4,5 -t r im et h oxy-
p h en yl)m eth a n e (33d ). Meth od A: From R-silyl alcohol 21d
(105 mg, 0.31 mmol) and Pb(OAc)4 (154 mg, 0.35 mmol, 110
1
mol %). After workup, the H NMR of the crude showed 33d
and 3,4,5-trimethoxybenzaldehyde in a ratio 87:13. Attempts
to separate these two compounds by filtration through silica
gel or alumina gave the aldehyde in quantitative yield. 33d :
1H NMR (250 MHz, CDCl3) 7.58 (m, 2H), 7.37 (m, 3H), 6.85
(s, 1H), 6.65 (s, 2H), 3.84 (s, 3H), 3.82 (s, 6H), 1.98 (s, 3H),
0.49 (s, 3H), 0.47 (s, 3H).
2-Acetoxy-[1,3]-ben zod ioxol-5-ca r ba ld eh yd e. Meth od
A: Reaction of R-silyl alcohol 21e (100 mg, 0.35 mmol) with
Pb(OAc)4 (170 mg, 0.38 mmol, 110 mol %) afforded after puri-
fication (CH2Cl2-hexane, 45:55 f 65:35) piperonal (31 mg,
58%) and 2-acetoxy-[1,3]-benzodioxol-5-carbaldehyde (27 mg,
37%): 1H NMR (250 MHz, CDCl3) 9.88 (s, 1H, CHO), 7.78 (s,
1H), 7.57 (dd, J ) 8.0 Hz, J ) 1.4 Hz, 1H), 7.51 (d, J ) 1.4 Hz,
1H), 7.11 (d, J ) 8.0 Hz, 1H), 2.14 (s, 3H); 13C NMR (63 MHz,
CDCl3) 190.1 (CHO), 168.5 (CH3COO), 150.0, 146.0, 132.6,
128.5, 113.4, 109.3, 108.3, 20.9 (CH3COO); IR (neat) 1762
(COO), 1686 (CHO) cm-1; MS m/z (%) 209 [2, (M + 1)+], 208
[12, M+]. HRMS calcd for C10H8O5 m/z 208.0372, found
208.0368.
Tr ea tm en t of r-Silyl a lcoh ols w ith Lea d Tetr a a ceta te.
Meth od A: A mixture of the R-silyl alcohol (0.14 M in
degassed benzene) and Pb(OAc)4 (110 mol %) was refluxed in
a light protected vessel until no starting material was detected
by TLC. The suspension was filtered and the solid washed with
EtOAc. The resulting filtrate was concentrated and purified
by chromatography. Meth od B: To a solution of the R-silyl
alcohol (0.04-0.05 mmol) in 0.5 mL of C6D6 prepared in an
NMR tube were added 1,4-dichlorobenzene (6 mg) and Pb-
(OAc)4 (100 mol %). The tube was shaken for a few minutes
(held vertically with a cloth and moved rapidly to and fro in
this “sheath”, measured internal temperature 35 °C) and
immediately subjected to proton NMR spectroscopy, which
showed complete transformation. Yield was estimated by
integration of the defined signal of the acetal proton of the
product, using dichlorobenzene as the internal standard.
1-Acet oxy-1-(d im et h ylp h en ylsilyloxy)d eca n e (33a ).
Meth od A: Treatment of 21a (150 mg, 0.51 mmol) with Pb-
(OAc)4 (250 mg, 0.56 mmol, 110 mol %) afforded 33a (chro-
matography: EtOAc-hexane 3:97, 130 mg, 73%) as a clear
oil. 1H NMR (300 MHz, CDCl3) 7.59 (m, 2H), 7.38 (m, 3H),
6.01 (t, J ) 5.4 Hz, 1H), 1.90 (s, 3H), 1.65 (m, 2H), 1.26 (m,
Acet oxy(b en zo[1,3]d ioxol-5-yl)(d im et h ylp h en ylsilyl-
oxy)m eth a n e (33e). Meth od B: Treatment of 21e (21 mg,
0.07 mmol) and Pb(OAc)4 (48 mg, 0.11 mmol, 150 mol %)
1
afforded 33e in 92% yield. H NMR (250 MHz, C6D6) 7.63 (m,
2H), 7.23 (m, 3H), 7.14 (s, 1H), 6.93 (dd, J ) 8.0 Hz, J ) 1.7
Hz, 1H), 6.78 (m, 1H), 6.60 (d, J ) 8.0 Hz, 1H), 5.29 (s, 2H),
1.57 (s, 3H), 0.46 (s, 3H), 0.45 (s, 3H); 13C NMR (63 MHz, C6D6)
169.6 (CH3COO), 148.5-128.1 (Ar), 120.3, 108.0, 107.0, 101.1,
91.9, 20.7, -1.2, -1.4.
Acet oxy(d im et h ylp h en ylsilyloxy)cycloh exa n e (33f).
Meth od B: 33f was obtained in 88% yield from R-silyl alcohol
21f (15 mg, 0.06 mmol) and Pb(OAc)4 (50 mg, 0.11 mmol, 170
1
mol %). H NMR (250 MHz, C6D6) 7.72 (m, 2H), 7.28 (m, 3H),
14H), 0.89 (t, J ) 6.7 Hz, 3H), 0.444 (s, 3H), 0.439 (s, 3H); 13
C
2.45 (m, 2H), 1.77 (m, 2H), 1.63 (s, 3H), 1.60-1.37 (m, 4H),
1.25 (m, 2H), 0.49 (m, 6H); 13C NMR (63 MHz, C6D6) 168.5
(CH3COO), 139.3-127.9 (6C), 37.3, 25.2, 23.7, 22.0, 0.7.
1-Acetoxy-1-(d im eth ylp h en ylsilyl)-1-(d im eth ylp h en yl-
silyloxy)-3-p h en ylp r op a n e (33g). Meth od B: It was ob-
tained from 21g (12 mg, 0.03 mmol) and Pb(OAc)4 (13 mg, 0.03,
NMR (75 MHz, CDCl3) 170.0 (CH3COO), 137.1, 133.4, 129.7,
127.7, 92.8 (C1), 36.6, 31.8, 29.4, 29.2, 29.1, 23.9, 22.6, 21.1,
14.1, -1.4, -1.5; IR (neat) 1741 (CO) cm-1; MS m/z (%) 335
[2, (M - Me)+], 291 [4, (M - AcO)+]. Meth od B: 33a was
obtained in 84% yield from 21a (20 mg, 0.07 mmol) and Pb-
(OAc)4 (32 mg, 0.07 mmol, 100 mol %). 1H NMR (250 MHz,
C6D6) 7.68 (m, 2H), 7.26 (m, 3H), 6.30 (t, J ) 5.3 Hz, 1H), 1.76
(m, 2H), 1.64 (s, 3H), 1.39-1.10 (m, 14H), 0.94 (t, J ) 6.5 Hz,
3H), 0.49 (s, 6H).
1
100 mol %) in 94% yield. H NMR (250 MHz, C6D6) 7.75 (m,
2H), 7.67 (m, 2H), 7.61-7.01 (m, 11H), 2.77 (m, 2H), 2.60 (m,
1H, 2.26 (m, 1H), 1.51 (s, 3H), 0.71 (s, 3H), 0.62 (s, 3H), 0.49
(s, 3H), 0.48 (s, 3H); 13C NMR (63 MHz, C6D6) 169.1 (CH3COO),
142.1-126.1 (18C), 108.0 (OCO), 41.9, 30.6, 20.6, 1.11, 1.07,
-2.1, -2.5.
Ace t oxycycloh e xyl(d im e t h ylp h e n ylsilyloxy)m e t h -
a n e (33b). Meth od A: It was obtained as a colorless oil
(chromatography: EtOAc-hexane 4:96, 99 mg, 71%) by treat-
ment of 21b (113 mg, 0.45 mmol) with Pb(OAc)4 (221 mg, 0.5
1-(Dim et h ylp h en ylsilyl)-3-p h en ylp r op a n -1-on e (34).
Treatment of the crude mixture of 33g in the NMR tube with
silica (230-400 mesh) afforded the acylsilane 34 in 72% overall
1
mmol, 110 mol %). H NMR (300 MHz, CDCl3) 7.60 (m, 2H),
1
7.39 (m, 3H), 5.80 (d, J ) 5.6 Hz, 1H), 1.89 (s, 3H), 1.88-1.53
(m, 6H), 1.25-0.98 (m, 5H), 0.43 (s, 6H); 13C NMR (75 MHz,
CDCl3) 170.2 (CH3COO), 137.2, 133.5, 129.6, 127.7, 95.1
(OCHO), 43.4, 27.2, 27.0, 26.2, 25.62, 25.59, 21.0, -1.4, -1.6;
IR (neat) 1738 (CO) cm-1; MS m/z (%) 291 [0.5, (M - Me)+],
247 [16, (M - AcO)+]. Meth od B: Prepared in 93% yield from
21b (12 mg, 0.05 mmol) and Pb(OAc)4 (23 mg, 0.05 mmol, 100
yield from 21. H NMR (250 MHz, C6D6) 7.59-6.96 (m, 10H),
2.86-2.70 (m, 4H), 0.32 (s, 6H); 13C NMR (63 MHz, C6D6) 242.7
(CO), 142.0-126.0 (12C), 50.5, 28.6, -4.9.
1-Acet oxy-2,6-d im et h yl-1-(d im et h ylp h en ylsilyloxy)-
h ep t-5-en e (33h ). Meth od A: Reaction of R-silyl alcohol 21h
(100 mg, 0.36 mmol, 1:1 diastereomeric mixture) and Pb(OAc)4
(160 mg, 0.36 mmol, 100 mol %) gave 33h (chromatography:
EtOAc-hexane 3:97, 1:1 mixture of diastereomers, 70 mg,
58%) as a colorless oil. 1H NMR (300 MHz, CDCl3) 7.59 (m,
4H, ArH), 7.38 (m, 6H, ArH), 5.90 (m, 2H, H1), 5.06 (m, 2H,
H5), 2.06-1.87 (m, 4H, H4), 1.90 (s, 3H, CH3COO isom B),
1.89 (s, 3H, CH3COO isom A), 1.74-1.63 (m, 2H, H2), 1.69 (s,
6H, H7), 1.59 (s, 6H, H7), 1.57-1.44 (m, 2H, H3), 1.21-1.08
(m, 2H, H3), 0.93 (d, J ) 5.3 Hz, 3H, CH3-C2 isom A), 0.91
(d, J ) 5.3 Hz, 3H, CH3-C2 isom B), 0.43 (s, 12H, (CH3)2Si);
13C NMR (isom A, 75 MHz, CDCl3) 170.0 (CO), 137.1 (Ar),
133.5 (Ar), 131.5 (C6), 129.6 (Ar), 127.7 (Ar), 124.4 or 124.3
(C5), 94.7 (C1), 38.4 (C2), 31.0 (C3), 25.7 (C7), 25.3 (C4), 21.1
or 21.0 (CH3COO), 17.6 (C7), 13.6 (CH3-C2), -1.6 (2C, (CH3)2-
Si); 13C NMR (isom B, 75 MHz, CDCl3) 170.0 (CO), 137.1 (Ar),
133.5 (Ar), 131.5 (C6), 129.6 (Ar), 127.7 (Ar), 124.4 or 124.3
(C5), 94.1 (C1), 38.2 (C2), 31.3 (C3), 25.7 (C7), 25.3 (C4), 21.1
or 21.0 (CH3COO), 17.6 (C7), 13.3 (CH3-C2), -1.4 (2C, (CH3)2-
Si); IR (neat) 1730 (CO) cm-1; MS m/z (%) 275 [9, (M - AcO)+],
1
mol %). H NMR (250 MHz, C6D6) 7.69 (m, 2H), 7.26 (m, 3H),
6.07 (d, J ) 5.3 Hz, 1H), 1.94 (m, 1H), 1.67-1.08 (m, 5H), 1.63
(s, 3H), 0.74-0.48 (m, 5H), 0.50 (s, 3H), 0.48 (s, 3H).
1-Acet oxy-2,2-d im et h yl-1-(d im et h ylp h en ylsilyloxy)-
p r op a n e (33c). Meth od A: Reaction of 21c (150 mg, 0.67
mmol) with Pb(OAc)4 (299 mg, 0.67 mmol, 100 mol %) gave
33c as a transparent oil (chromatography: EtOAc-hexane
1
3:97, 148 mg, 78%). H NMR (300 MHz, CDCl3) 7.62 (m, 2H),
7.39 (m, 3H), 5.76 (s, 1H), 1.91 (s, 3H), 0.92 (s, 9H), 0.44 (s,
6H); 13C NMR (75 MHz, CDCl3) 170.4 (CH3COO), 137.3, 133.5,
129.6, 127.7, 96.7 (C1), 36.0 (C2), 24.2 (3C, C3), 21.0 (CH3-
COO), -1.4 (CH3Si), -1.6 (CH3Si); IR (neat) 1742 (CO) cm-1
;
MS m/z (%) 221 [4, (M - OAc)+]. Method B: Obtained in 92%
yield by reaction of 21c (11 mg, 0.05 mmol) and Pb(OAc)4 (23
mg, 0.05 mmol, 100 mol %). 1H NMR (250 MHz, C6D6) 7.69
(m, 2H), 7.26 (m, 3H), 5.97 (s, 1H, H1), 1.58 (s, 3H, CH3COO),
0.97 (s, 9H, H3), 0.48 (s, 3H, CH3Si), 0.47 (s, 3H, CH3Si).

Radical Brook Rearrangement
J . Org. Chem., Vol. 65, No. 8, 2000 2303
223 [5, (PhMe2SiOCHOAc)+], 137 (92), 135 [100, (PhMe2Si)+],
123 (55), 117 (46), 103 (76). Meth od B: Obtained in 97% yield
from 21h (13 mg, 0.05 mmol) and Pb(OAc)4 (22 mg, 0.05 mmol,
NMR (300 MHz, CDCl3): 7.52 (m, 4H), 7.36 (m, 6H), 5.40 (d, J
) 4.2 Hz, 1H), 5.29 (d, J ) 6.2 Hz, 1H), 4.95 (m, 2H), 1.94-
1.82 (m, 6H), 1.64 (s, 6H), 1.56 (s, 3H), 1.55 (s, 3H), 1.28-1.21
(m, 2H), 1.21-1.05 (m, 2H), 0.83 (d, J ) 6.9 Hz, 6H), 0.37 (s,
6H), 0.34 (s, 6H). UV (EtOH) λmax: 226 nm.
P h otolysis of Alip h a tic r-Silyl Alcoh ol Nitr ite Ester s
25. A solution of the corresponding nitrite in degassed benzene
(0.03 M) was irradiated at 0 °C with a 450 W Hanovia mercury
lamp for 30 min. The solvent was concentrated and the residue
chromatographed through silica gel. In this way the known
aldehydes decanal (41 mg, 68%), cyclohexanecarbaldehyde,
and 2,6-dimethyl-5-heptenal (9 mg, 40%) were obtained from
25a (124 mg, 0.38 mmol), 25b, and 25h (50 mg, 0.16 mmol),
respectively.
On e-P ot P r oced u r e for th e F or m a tion a n d P h otolysis
of r-Silyl Nitr ite 25a . To a solution of the R-silyl alcohol 21a
(150 mg, 0.51 mmol) in 2.5 mL of dry benzene was added
t-BuONO (127 µL, 1.02 mmol, 200 mol %). After consumption
of the starting material, additional benzene (14.5 mL) was
added, the solution was degassed with a stream of argon and
irradiated at 0 °C with a Hanovia lamp (450 W) for 30 min.
Removal of the volatiles and purification (EtOAc-hexane 4:96)
gave decanal (59 mg, 74% overall) as a colorless oil.
1
100 mol %). H NMR (250 MHz, C6D6) 7.68 (m, 2H), 7.26 (m,
3H), 6.20 (m, 1H), 5.19 (m, 1H), 2.29-1.92 (m, 2H), 1.88-1.58
(m, 11H), 1.40-1.22 (m, 1H), 1.04 (m, 3H), 0.49 (s, 3H), 0.48
(s, 3H).
Tr ea tm en t of 21j w ith P b(OAc)4. Meth od A: Reaction
of 21j (56 mg, 0.17 mmol) with Pb(OAc)4 (111 mg, 0.24 mmol,
150 mol %) gave, after purification (EtOAc-hexane 10:90 f
20:80), silyl enol ether 36j (5 mg, 9%), ketone 37j (15 mg, 47%)
and R-acetoxyketone 38j (10 mg, 23%). Eth yl (2E)-6-m eth yl-
7-(dim eth ylph en ylsilyloxy)octa-2,6-dien oate (36j). 1H NMR
(300 MHz, CDCl3) 7.59 (m, 2H, ArH), 7.37 (m, 3H, ArH), 6.92
(m, 1H, H3), 5.79 (m, 1H, H2), 4.18 (c, J ) 7.1 Hz, 2H, OCH2-
CH3), 2.26-2.04 (m, 4H, H4, H5), 1.72 (m, 3H, H8), 1.57 (m,
CH3-C6), 1.29 (m, 3H, OCH2CH3), 0.42 (s, 6H, (CH3)2Si); IR
(neat) 1720 (CO) cm-1; MS m/z (%) 332 [2, M+]. Eth yl (E)-6-
m eth yl-7-oxooct-2-en oa te (37j). 1H NMR (250 MHz, CDCl3)
6.91 (dt, J ) 15.5 Hz, J ) 7.0 Hz, 1H), 5.82 (dt, J ) 15.5 Hz,
J ) 1.5 Hz, 1H), 4.18 (c, J ) 7.2 Hz, 2H), 2.53 (m, 1H), 2.26-
2.14 (m, 2H), 2.14 (s, 3H), 1.84 (m, 1H), 1.49 (m, 1H), 1.28 (t,
J ) 7.2 Hz, 3H), 1.11 (d, J ) 7.1 Hz, 3H); 13C NMR (75 MHz,
CDCl3) 211.8 (C7), 166.4 (COO), 147.9, 121.9, 60.1, 46.2, 30.7,
29.6, 28.1, 16.2, 14.2; IR (neat) 1717 (2CO) cm-1; MS m/z (%)
199 [1, (M + 1)+], 198 [5, M+]; HRMS calcd for C11H18O3 m/z
198.1256, found 198.1270. Eth yl (E)-8-a cetoxy-6 m eth yl-7-
Tr ea tm en t of Ben zyl r-Silyl Alcoh ols 21d , 21e, a n d
21m w ith t-Bu ONO. Following the procedure described above
to form nitrite esters from aliphatic R-silyl alcohols, 3,4,5-
trimethoxybenzaldehyde (50) (116 mg, 98%), piperonal (71 mg,
75%), and methyl (3,4,5-trimethoxyphenyl) ketone 52 (chro-
matography: EtOAc-hexane 15:85, white solid, 65 mg, 77%)
were obtained from 21d (200 mg, 0.60 mmol), 21e (180 mg,
0.63 mmol), and 21m (140 mg, 0.40 mmol), respectively, on
treatment with t-BuONO (410 µL, 3.3 mmol, 550 mol % for
21d ; 117 µL, 0.94 mmol, 150 mol % for 21e; and 75 µL, 0.061
mmol, 150 mol % for 21m ). TLC indicated the initial formation
of a less-polar compound, which directly evolved in situ to the
final carbonyl compounds. Methyl (3,4,5-trimethoxyphenyl)
ketone 52: 1H NMR (300 MHz, CDCl3) 7.18 (s, 2H), 3.89 (s,
9H), 2.56 (s, 3H); 13C NMR (75 MHz, CDCl3) 196.9 (CO), 153.0,
1
oxooct-2-en oa te (38j). H NMR (250 MHz, CDCl3) 6.90 (dt,
J ) 15.7 Hz, J ) 7.0 Hz, 1H, H3), 5.83 (br d, J ) 15.7 Hz, 1H,
H2), 4.74 (d, J ) 17.0 Hz, 1H, H8), 4.66 (d, J ) 17.0 Hz, 1H,
H8), 4.18 (c, J ) 7.1 Hz, 2H, OCH2CH3), 2.62 (m, 1H, H6),
2.25-2.16 (m, 2H, H4), 2.17 (s, 3H, CH3COO), 1.89 (m, 1H,
H5), 1.54 (m, 1H, H5), 1.28 (t, J ) 7.1 Hz, 3H, OCH2CH3),
1.14 (d, J ) 6.9 Hz, 3H, CH3-C6); 13C NMR (75 MHz, CDCl3)
206.6 (C7), 170.2, 166.1, 147.6, 122.1, 67.1, 60.3, 41.8, 30.7,
29.4, 20.4, 16.3, 14.2; IR (neat) 1752, 1721 (3CO) cm-1; MS
m/z (%) 211 [9, (M - EtO)+].
Acet oxy(d im et h ylp h en ylsilyloxy)(1-p h en ylcyclop r o-
p yl)m eth a n e (33k ). Meth od B: Obtained by reaction of 21k
(11 mg, 0.04 mmol) and Pb(OAc)4 (19 mg, 0.04 mmol, 100 mol
142.6, 132.4, 105.8, 60.9, 56.3, 26.4); IR (neat) 1680 (CO) cm-1
;
MS m/z (%) 211 [7, (M + 1)+], 210 [57, M+]; HRMS calcd for
1
%) in 92% yield. H NMR (250 MHz, C6D6) 7.60 (m, 2H), 7.41
C
11H14O4 m/z 210.0892, found 210.0886.
(d, J ) 7.1 Hz, 2H), 7.25-7.08 (m, 6H), 6.27 (s, 1H), 1.54 (s,
3H), 1.07 (m, 2H), 0.75 (m, 2H), 0.42 (s, 3H), 0.41 (s, 3H); 13C
NMR (63 MHz, C6D6) 169.6 (CH3COO), 141.3-127.1 (12C),
94.6, 30.7, 20.5, 9.8, 9.2, -1.3, -1.4.
P r ep a r a tion of Alip h a tic r-Silyl Alcoh ol Nitr ite Ester s
25 by Nitr osyl Exch a n ge. Typ ica l P r oced u r e. A solution
of the R-silyl alcohol (0.2 M in dry CHCl3) and excess t-BuONO
(150-300 mol %) was stirred at room temperature in the
darkness until TLC showed total consumption of the starting
material. The volatiles were then rapidly removed, and the
resulting residue was chromatographed.
2,2-Dim eth yl-3-(tetr a h yd r op yr a n -2-yloxy)p r op a n a l. A
mixture of 2,2-dimethyl-3-hydroxy-propanal (55) (500 mg, 4.89
mmol), DHP (617 mg, 7.34 mmol, 150 mol %), and PPTS (123
mg, 10 mol %) in dry CH2Cl2 (34 mL) was stirred at room
temperature overnight. The solution was diluted with Et2O
and washed with brine. The organic layer was dried, filtered,
and concentrated. Purification of the residue (EtOAc-hexane,
25:75) gave the protected aldehyde (733 mg, 80%) as a colorless
oil. 1H NMR (250 MHz, CDCl3) 9.54 (s, 1H, CHO), 4.55 (m,
1H), 3.75 (d, J ) 9.7 Hz, 1H), 3.49 (m, 2H), 3.32 (d, J ) 9.7
Hz, 1H), 1.52 (m, 6H), 1.08 (s, 3H), 1.05 (s, 3H); 13C NMR (63
MHz, CDCl3) 204.5 (C1), 98.3 (OCHO), 71.8, 61.2, 46.2 29.9,
29.8, 25.0, 18.5; IR (neat) 1730 (CO) cm-1; MS m/z (%) 187 [8,
(M + H)+], 186 [0.3 M+].
1-(Dim eth ylp h en ylsilyl)d ecyl Nitr ite (25a ). It was ob-
tained as a yellow oil (chromatography: hexane 100%, 142 mg,
65%) from 21a (200 mg, 0.68 mmol) and t-BuONO (125 mg,
1
1.16 mmol, 170 mol %). H NMR (250 MHz, CDCl3) 7.53 (m,
2,2-Dim eth yl-1-(d im eth ylp h en ylsilyl)-3-(tetr a h yd r op y-
r a n -2-yloxy)p r op a n -1-ol. It was obtained (2076 mg, 60%,
eluent for chromatography: EtOAc-hexane, 12:88) as a
mixture of diastereomers (A:B, 1:1.3) from 2,2-dimethyl-3-
(tetrahydropyran-2-yloxy)propanal (2 g, 10.73 mmol) and
PhMe2SiLi (43 mL, 16.10 mmol, 150 mol %), following the
general procedure indicated above to transform aldehydes into
R-silyl alcohols. 1H NMR (250 MHz, CDCl3): 7.61 (m, 4H), 7.36
(m, 6H), 4.47 (m, 1H), 4.17 (m, 1H), 3.85-3.70 (m, 2H), 3.66
(d, J ) 9.4 Hz, 1H), 3.59 (d, 1H), 3.48-3.43 (m, 4H), 3.21 (d,
1H), 3.19 (d, J ) 9.1 Hz, 1H), 3.10 (d, J ) 9.4 Hz, 1H), 2.92 (d,
J ) 6.7 Hz, 1H), 1.83-1.44 (m, 12H), 1.00 (s, 3H), 0.89 (s, 3H),
0.84 (s, 3H), 0.79 (s, 3H), 0.42 (s, 6H), 0.41 (s, 6H); IR (neat):
2H), 7.39 (m, 3H), 5.36 (dd, J ) 3.3 Hz, J ) 9.5 Hz, 1H), 1.64
(m, 2H), 1.20 (m, 14H), 0.88 (t, J ) 6.0 Hz, 3H), 0.36 (s, 3H),
0.33 (s, 3H); 13C NMR (75 MHz, CDCl3) 135.6, 134.0, 129.6,
127.9, 31.8, 31.2, 29.5, 29.4, 29.3, 29.1, 26.9, 22.6, 14.1, -4.9,
-5.2; IR (neat) 1637 (NO) cm-1; MS m/z (%) 291 [0.5, (M -
NO)+], 275 [1, (M - ONO)+].
1-Cycloh exyl-1-(d im et h ylp h en ylsilyl)m et h yl Nit r it e
(25b). Treatment of 21b (250 mg, 1.01 mmol) with t-BuONO
(0.375 mL, 3.02 mmol, 300 mol %) gave 25b (chromatogra-
phy: hexane 100%, 173 mg, 62%) as a yellow oil. 1H NMR (300
MHz, CDCl3) 7.54 (m, 2H), 7.38 (m, 3H), 5.29 (d, J ) 6.1 Hz,
1H), 1.67-1.52 (m, 6H), 1.29-0.85 (m, 5H), 0.39 (s, 3H), 0.35
(s, 3H); 13C NMR (75 MHz, CDCl3) 136.5, 133.9, 129.4, 127.8,
40.7, 31.0, 29.9, 26.2, 26.1, 26.0, -3.6, -3.9; IR (neat) 1637
(NO) cm-1; MS m/z (%): 247 [1, (M - NO)+].
3478 (OH) cm-1
.
2,2-Dim eth yl-1-(d im eth ylp h en ylsilyl)-3-(tetr a h yd r op y-
r a n -2-yloxy)p r op a n -1-on e. It was obtained as a pale yellow
oil (740 mg, 75%, eluent for chromatography: EtOAc-hexane
10:90) from 2,2-dimethyl-1-(dimethylphenylsilyl)-3-(tetrahy-
dropyran-2-yloxy)propan-1-ol (995 mg, 3.08 mmol), oxalyl
chloride (0.58 mL, 6.17 mmol, 200 mol %), DMSO (0.87 mL,
2,6-Dim et h yl-1-(d im et h ylp h en ylsilyl)h ep t -5-en yl Ni-
tr ite (25h ). It was obtained as a pale yellow oil (chromatog-
raphy: 100% hexane, 58 mg, 20%) from 21h (258 mg, 0.93
mmol) and t-BuONO (0.25 mL, 2.10 mmol, 225 mol %). 1H

2304 J . Org. Chem., Vol. 65, No. 8, 2000
Paredes and Alonso
12.34 mmol, 400 mol %), and Et3N (2.15 mL, 15.42 mmol, 500
mol %), following the general procedure indicated above for
the oxidation of R-silyl alcohols to acylsilanes. H NMR (250
degassed benzene, a solution of n-Bu3SnH (97 µL, 0.36 mmol,
150 mol %) and AIBN (10.5 mg, 0.06 mmol, 25 mol %) in the
same solvent was slowly added (syringe pump, 1h). The
reaction was monitored by TLC (Et2O-hexane, 10:90) until
consumption of the starting material was observed. Removal
of the solvent and chromatographic purification (PTLC, Et2O-
1
MHz, CDCl3) 7.56 (m, 2H), 7.35 (m, 3H), 4.39 (m, 1H), 3.73
(m, 1H), 3.64 (d, J ) 9.6 Hz, 1H), 3.46 (m, 1H), 3.35 (d, J )
9.6 Hz, 1H), 1.52 (m, 6H), 1.06 (s, 3H), 0.97 (s, 3H), 0.53 (s,
3H), 0.51 (s, 3H); 13C NMR (63 MHz, CDCl3) 247.5 (CO), 136.1,
134.1, 129.6, 128.0, 98.7 (OCHO), 73.2, 61.7, 53.3, 30.3, 25.3,
19.0, 20.5, 20.4, -2.5, -2.7; IR (neat) 1633 (CO) cm-1; MS m/z
(%) 320 [0.2, M+].
3-Br om o-2,2-d im eth yl-1-(d im eth ylp h en ylsilyl)p r op a n -
1-on e (56). CBr4 (188 mg, 0.57 mmol, 280 mol %) was added
to a solution of 2,2-dimethyl-1-(dimethylphenylsilyl)-3-(tet-
rahydropyran-2-yloxy)propan-1-one (65 mg, 0.20 mmol) in CH2-
Cl2 (1 mL) at room temperature. After 10 min the mixture was
cooled to 0 °C and Ph3P (298 mg, 1.13 mmol, 560 mol %) was
added, allowing the reaction to warm to room temperature
overnight. The mixture was concentrated to ca. half its volume
and filtered through silica gel. After evaporation of the solvent,
the residue was purified by PTLC (EtOAc-hexane 8:92) af-
fording the â-bromoacylsilane 56 (25 mg, 41%) as a colorless
oil. 1H NMR (250 MHz, CDCl3) 7.61 (m, 2H), 7.40 (m, 3H),
3.36 (s, 2H), 1.10 (s, 6H), 0.56 (s, 6H); 13C NMR (63 MHz,
CDCl3) 245.4 (CO), 135.6, 134.4, 130.2, 128.5, 53.6, 40.7, 22.4,
-2.5; IR (neat) 1634 (CO) cm-1; MS m/z (%) 135 [51,
(PhMe2Si)+].
1
hexane, 10:90) afforded 60 (32 mg, 62%). H NMR (300 MHz,
CDCl3) 7.55 (m, 2H), 7.40 (m, 3H), 2.46 (d, J ) 6.6 Hz, 2H),
2.13 (m, 1H), 0.80 (d, J ) 6.7 Hz, 6H), 0.49 (s, 6H); 13C NMR
(63 MHz, CDCl3) 246.9 (CO), 134.5, 133.9, 129.8, 128.1, 57.7,
22.9, 22.6, -4.8; IR (neat) 1640 (CO) cm-1; MS m/z (%) 221
[0.2, (M + 1)+], 220 [2, M+]; HRMS calcd for C13H20OSi m/z
220.1283, found 220.1277.
Ack n ow led gm en t. We thank the Xunta de Galicia
and the DGES for funding this work under projects
(XUGA 20902B97) and (PB95-0824), respectively. M.D.P.
also thanks the Xunta de Galicia and the Fundacio´n
Bene´fico-Docente Segundo Gil Da´vila for fellowships.
Su p p or t in g In for m a t ion Ava ila b le: 1H NMR and 13C
NMR spectra for 33a -h ,k , 36j, 37j, 38j, 25a ,b,h , 56, and 60.
This material is available free of charge via the Internet at
http://pubs.acs.org.
1-(Dim eth ylp h en ylsilyl)-3-m eth ylbu ta n -1-on e (60). To
a refluxed solution of 56 (72 mg, 0.24 mmol) in 12 mL of
J O9912855