On the relative migratory aptitudes of carbon and heteroatoms in borate complexes. A surprising α-thia effect

Article abstract of DOI:10.1039/b311292f

Dimethylsulfoxonium methylide reacts with dicyclohexyl(α- thiophenylmethyl)methylborane via 1,2-alkyl migration and alkyldithiaborolane via 1,2-sulfur migration.

Full text of DOI:10.1039/b311292f

On the relative migratory aptitudes of carbon and heteroatoms in borate
complexes. A surprising a-thia effect
Jonathan M. Stoddard and Kenneth J. Shea*
Department of Chemistry, University of California, Irvine, CA 92697-2025, USA. E-mail: kjshea@uci.edu;
Fax: +1 949 824 2210
Received (in Corvallis, OR, USA) 15th September 2003, Accepted 11th February 2004
First published as an Advance Article on the web 27th February 2004
Dimethylsulfoxonium methylide reacts with dicyclohexyl(a-
thiophenylmethyl)methylborane via 1,2-alkyl migration and
alkyldithiaborolane via 1,2-sulfur migration.
To test this hexyldithiaborolane (3),14 dicyclohexylpentanethia-
borane (4) and dicyclohexylethanethiaborane (5) were synthesized
(Scheme 2).
Thiaborane 4 was reacted with ylide 1 (1 equiv.) in Et2O at 0 °C
for 1 h (Scheme 3) and oxidized with trimethylamine-N-oxide
dihydrate (TAO·2H2O). The crude reaction mixture was analyzed
by GCMS and found to contain cyclohexanol (6) and methyl pentyl
sulfide (7). Cyclohexylmethanol, which would arise from 1,2-mi-
gration of the cyclohexyl group, was not observed. Methyl pentyl
sulfide (7) arises from S-1,2-migration followed by hydrolysis with
water14 introduced by the oxidizing reagent. This result indicates
that sulfur migrates in preference to carbon (2°) in the intermediate
“ate” complex. This result is consistent with previous findings.15
This finding was further supported by the following observation.
Hexyldithiaborolane (3) was reacted with ylide 1 (1 equiv.) and
oxidized with TAO·2H2O (3 equiv.). The crude reaction was
analyzed by GCMS and the relative, uncorrected areas for the
products were monohomologated 10 (5.5%), bishomologated 11
(2.9%), hexanol (12) (77%), and hexylboroxine (13) (9.4%)
(Scheme 4). Products 10 and 11 are derived from the hydrolysis of
intermediate organoboranes 8 and 9, which arise from one and two
S-1,2-migrations. Hexylboroxine (13) arises from the condensation
of hexylboronic acid, an unoxidized borane that is derived from
hydrolysis of unreacted starting material or 8 or 9. Heptanol, the
product from 1,2-hexyl migration, was not detected. The exclusive
Organoborane chemistry has played an important role in the
construction of carbon–carbon bonds.1,2 Many of these reactions
involve formation of a tetrahedral “ate” complex followed by
transfer of a carbon nucleophile to an acceptor. The transfer can be
intermolecular, such as in the Suzuki reaction,3,4 or intra-
molecular.5,6 Examples of the latter include reactions of trialk-
ylboranes with nucleophilic reagents such as ethyl bromoacetate,7
a-chloroacetonitrile,8 a-bromo ketones,9 dihalomethyl lithium,10
dimethylsulfoxonium methylide,11 and various diazo com-
pounds.12 These reactions result in formation of new carbon–
carbon bonds and several have achieved considerable synthetic
importance. The atom-economy of these reactions may be in-
creased by utilizing ligands on boron that allow the transfer of only
a single carbon nucleophile. For example, B-alkyl 9-BBN,
alkylboronate esters, and thexyldialkylboranes have been used to
allow selective transfer of the alkyl substituent.3
Recently, trialkylboranes have been found to react with dime-
thylsulfoxonium methylide (1)13 resulting in multiple insertions of
methylene into the carbon–boron bond. Attempts at using oxygen
ligands as blocking groups for homologation of alkyl boronic esters
with ylide 1 were unsuccessful. For example, phenyl catechol
boronate ester (2) was reacted with 1 equiv. of ylide 1 in toluene at
23 °C (Scheme 1) to form a borate complex (11B NMR 9.6 ppm,
toluene). Heating this complex in THF at 40 °C for 30 min followed
by oxidation with H2O2 and NaOH produced only phenol. Benzyl
alcohol, a product that would arise from homologation, was not
observed. One possible explanation for the failure to observe
phenyl migration is that the electron-deficient oxygen atoms
remove electron density from the phenyl–boron s bond, rendering
it non-nucleophilic toward 1,2-migration. Sulfur has an electro-
negativity very similar to carbon and we surmised that ylide 1
complexes of alkyldithiaborolanes would allow sufficient electron
density to reside at the remaining alkyl group to promote
1,2-migration (Fig. 1).
Scheme 2 Reagents and conditions: i, Br2BH·SMe2, CH2Cl2, 0–24 °C, 2 h;
ii, LiSCH2CH2SLi, 0–24 °C, 18 h; iii, BrBH2·SMe2, THF, 0–23 °C, 2 h; iv,
PenSH, 0–23 °C, 12 h; v, BH3·SMe2, THF, 0 °C, 15 min; vi, EtSH, 23 °C,
17 h.
Scheme 1 Reagents and conditions: i, ylide 1, toluene, 23 °C; ii, 40 °C, 30
min, THF; iii, H2O2, NaOH, 23 °C, 2 h.
Scheme 3 Reagents and conditions: i, ylide 1 (1 equiv.), Et2O, 0–25 °C, 1
h; ii, TAO·2H2O (6 equiv.), 25 °C, 12 h.
Fig. 1
830
C h e m . C o m m u n . , 2 0 0 4 , 8 3 0 – 8 3 1
T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 4

Scheme 4 Reagents and conditions: i, ylide 1 (1 equiv.), toluene, 0–24 °C,
30 min; ii, TAO·2H2O (3 equiv.), 60 °C, 2 h.
formation of products from 1,2-S-migration and the failure to detect
1-heptanol demonstrate that the migratory aptitude of sulfur is
greater than carbon. In neither case were multiple methylene
insertions in the same chain observed.
Fig. 3 B3LYP transition-state structures for Me2BCH2SMe·ylide complex.
Distances are in Å.
The reaction of thiaborane 5 and dithiaborolane 3 with an excess
of ylide 1 was studied in order to determine the relative migratory
aptitudes of alkyl vs. a-thiomethylene ligands. For example,
thiaborane 5 was added to ylide 1 (10 equiv.) at 60 °C, then
oxidized with basic hydrogen peroxide. The products, which were
purified by chromatography and analyzed by GCMS, consisted of
a distribution of cyclohexyl-terminated alcohols with an experi-
mental degree of polymerization, DPexp = 5.1, and polydispersity,
PDI = 1.02 (Fig. 2). Similarly, hexyldithiaborolane 3 was added to
ylide 1 (8.7 equiv.) at 50 °C and oxidized with basic hydrogen
peroxide. Following chromatographic purification, the GCMS
revealed a distribution of straight-chain alcohols (DPexp = 5.2, PDI
= 1.03).
These results establish that upon reaction of ylide 1 with thia- and
dithiaborolanes, S-1,2-migration is preferred over alkyl migration.
Additional equivalents of ylide 1 coordinate and react by C-
1,2-migration to afford cyclohexyl- and n-hexyl-terminated alco-
hols. Thus the a-thio ligand serves as a blocking group for
1,2-migration (Fig. 3).
structures were found for methyl 1,2-migration (Ea = 15.6 kcal
mol21) and CH2SMe 1,2-migration (Ea = 18.8 kcal mol21). The
lower activation energy for 1,2-methyl migration is in agreement
with the experimental results for preferential cyclohexyl and n-
alkyl 1,2-migration of thiaboranes 3 and 5 compared with CH2SEt
1,2-migration.
Oxygen has been used as a ligand on boron to affect the selective
transfer of alkyl or aryl groups in carbon–carbon bond forming
reactions. Sulfur ligands have not enjoyed the same benefit, perhaps
due to their preferential migration over alkyl groups, as demon-
strated by this work. The discovery that a-thia methylene ligands
can serve as blocking groups in the reaction of boranes with ylides
is novel. It is envisioned that a-thia methylene ligands may be
utilized for a broad range of other boron-mediated carbon–carbon
bond forming reactions.
This research was supported by a grant from the National
Sciences Foundation (CHE-9617475).
Notes and references
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B3LYP calculations for the Me2BCH2SMe·ylide complex (Fig.
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Fig. 2 GC of a-cyclohexyl-w-hydroxypolymethylene formed from thiabor-
ane 5 and ylide 1 (10 equiv.) at 60 °C in toluene.
C h e m . C o m m u n . , 2 0 0 4 , 8 3 0 – 8 3 1
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