868 J . Org. Chem., Vol. 62, No. 4, 1997
Dhokte and Brown
as described for 2d . However, under these conditions,
the hydroboration of 1f (1.20 equiv) with 9-BBN (1 equiv)
was complicated by the formation of undesired species
(20-25%) along with the required trialkylborane 2f.
Consequently, an indirect method for the synthesis of
trialkylborane 2f was developed.
apopinenes (1.10-1.20 equiv), hydroboration with 9-BBN
(1.0 equiv) is readily achieved under neat conditions at
65 °C in 14-24 h. Unfortunately, hydroboration of the
more sterically-demanding, 2-isopropylapopinene (1f),
with 9-BBN, did not proceed satisfactorily to furnish the
desired B-(2-Rap)-9-BBN (2-Rap ) 2-isopropylapopinyl
skeleton). Fortunately, an indirect method, the reaction
of (2-isopropylapoisopinocampheyl)borane (i-PraBH2) with
1,5-COD, achieves the synthesis of the desired trialkyl-
borane 2f, following thermal isomerization, in nearly
quantitative yield. Consequently, this indirect approach
provides an independent route to the sterically bulkier
B-2-organylapopinyl-9-BBN compounds, difficult to ob-
tain via direct hydroboration. Thus, the syntheses of
these B-2-organylapopinyl-9-BBN compounds 2c-f pro-
vide easy access to them to study the effect of the
2-organyl group on the selective asymmetric reduction
of acetylenic ketones and R-keto esters. Also, the corre-
sponding optically pure lithium trialkylborohydrides
3c-f should provide sterically bulkier analogues of
lithium B-isopinocampheyl-9-borabicyclo[3.3.1]nonyl hy-
dride (Alpine-Hydride),5 possibly more effective for the
asymmetric reduction of prochiral ketones.
Syn th esis of B-(2-Isop r op yla p oisop in oca m p h eyl)-
9-bor a bicyclo[3.3.1]n on a n e (2f). An alternative syn-
thesis of B-(2-isopropylapoisopinocampheyl)-9-borabicyclo-
[3.3.1]-nonane (2f) was developed. It has been demon-
strated in previous work from this laboratory that the
cyclic hydroboration of 1,5-COD with thexylborane (Thx-
BH2) gives two regioisomeric products, arising from the
1,4- and 1,5-cycloaddition in a 4:1 ratio, respectively.18
It has also been reported that the chiral monoalkylbo-
ranes (R1*BH2) react with 1,5-COD to give a 70:30
mixture of the 1,4- and 1,5-cyclic adducts.19 Apparently,
the hydroboration proceeds in two stages. The first step
is the hydroboration of one of the double bonds. The
second stage is the intramolecular cyclic hydroboration,
which favors formation of the five-membered boracyclane
over the six-membered ring (eq 5). The less stable 1,4-
regioisomer is readily isomerized to the 1,5-isomer at 65
°C.19
Exp er im en ta l Section
All glassware was dried at 140 °C overnight, assembled hot,
and cooled to ambient temperature in a stream of nitrogen.20
All reactions involving air- or moisture-sensitive compounds
were performed under a static pressure of dry nitrogen.20
Reported melting points are uncorrected. 11B NMR spectra
were recorded at 96 MHz and were referenced relative to
BF3‚EE. 1H and 13C NMR spectra were recorded at 200 and
50 MHz, respectively, relative to internal tetramethylsilane
(TMS). Chemical shifts in the 1H and 13C NMR spectra are
reported as parts per million (ppm) downfield from TMS. All
materials for which optical rotation information is provided
were purified by preparative GC on a 6 ft × 0.5 in. column
packed with 20%-SE 30 on Chromosorb W (60-80 mesh).
Optical rotations were measured on a digital polarimeter in a
1-dm cell. GC analyses for chemical purity and rate data were
performed using columns packed either with 10%-SE 30 on
Chromosorb W (100-120 mesh) or 10% Carbowax on Chro-
mosorb W (80-100 mesh). Capillary GC analyses were
performed using the SPB-5 column (30 m).
Ma ter ia ls. Tetrahydrofuran (THF) was distilled from
sodium benzophenone ketyl and used as required. Anhydrous
diethyl ether was used without purification. The 2-R-apo-
pinenes 1b-f were synthesized by the known procedures.7b,8,11,13
The 2-R-apopinenes 1b-d ,f were derived from (+)-R-pinene,
while (+)-phenylapopinene (1e) was synthesized from (+)-â-
pinene.13
Gen er a l P r oced u r e for th e Deter m in a tion of th e Ra te
of t h e H yd r ob or a t ion of 2-R -a p op in en es 1a -f w it h
9-BBN. The reactions were carried out in THF at 24 °C. In
all these experiments, 10-12 mmol of 2-R-apopinenes 1a -f
were used for the reaction with 9-BBN. The concentration of
2-R-apopinenes with 9-BBN was maintained at 0.50 M each.
The progress of the reaction was monitored at appropriate time
intervals by the following analytical techniques: (i) 11B NMR
spectral analysis, for trialkylborane and dialkylborane (9-
BBN),21 of an aliquot taken after definite time intervals; (ii)
GC analysis of either residual 2-R-apopinenes or silyl ether
(5a -f) (silylation was done with bis(trimethylsilyl)acetamide
using a catalytic amount of pyridine in THF)16 of the product
2-organylapoisopinocampheol, resulting from the hydrobora-
Thus, the hydroboration of 1,5-COD with an ethereal
solution of (2-isopropylapoisopinocampheyl)borane (i-
PraBH2) at 0 °C for 1 h achieved the quantitative
formation of the 1:1 mixed trialkylboranes as determined
by 11B NMR (δ 81, 86), and the GC analysis of the
products resulted after alkaline peroxide oxidation.17 The
thermal isomerization of the less stable 1,4-isomer to the
more stable desired trialkylborane 2f (11B NMR: δ 83)
was complete in 24 h in refluxing THF. The reaction was
monitored periodically by 11B NMR of aliquots and also
by GC analysis of the silyl ethers of the alcohols, produced
by alkaline peroxide oxidation of the boron components.
Optical and chemical purity of the trialkylborane 2f,
obtained after the isomerization reaction, was determined
as described previously.
Con clu sion s
This paper describes a detailed study of the behavior
of six representative sterically different 2-organylapo-
pinenes (2-R-apopinenes; R ) Me, Et, Pr, i-Bu, Ph and
i-Pr) in the hydroboration with the bulkier 9-BBN in THF
at 24 °C. We have demonstrated that as the R group in
the 2-R-apopinenes become bulkier, the rate of hydrobo-
ration slows, becoming so slow with the latter three 2-R-
apopinenes as to be impractical. However, for sterically-
demanding terpenes, such as 2-isobutyl- and 2-phenyl-
(20) Brown, H. C.; Kramer, G. W.; Levy, A. B.; Midland, M. M.
Organic Synthesis via Boranes; Wiley-Interscience: New York, 1975.
(21) Borane species mentioned in this paper showed distinct 11B
NMR signals adequate for their approximate percentage determina-
tion. Srebnik, N.; Cole, T. E.; Ramachandran, P. V.; Brown, H. C. J .
Org. Chem. 1989, 54, 6085.
(18) Brown, H. C.; Negishi, E. J . Am. Chem. Soc. 1972, 94, 3567.
(19) Brown, H. C.; J oshi, N. N.; Pyun, C.; Singaram, B. J . Am. Chem.
Soc. 1989, 111, 1754.