Anoth er ch ir al r educing agent der iv ed fr om a- pinene, lith ium

B-3- pinanyl-9-borabicyclo[3 . 3 . 1] nonane h ydride (Alpine­

Table 7

Hydride® ), also proved ineffectiv e in tr ansferring ch irality to th e

Proposed Cyclic Boat-Like Transition State

product alcoh ols 3 3 (Sch eme 27 ).

for Reductions with R-Alpine-Borane

In 1 97 8 , M idland and co-wor ker s dis cov er ed th at

B- is opinocamph eyl- 9-borabicyclo[3 .3 . 1] nonane (R-Alpine­
Borane® ) r educed deuteroaldeh ydes and acetylenic ketones to
alcohols of ex ceptionally h igh optical purity3 4 (Sch eme 28).
Unfortunately, Alpine-Bor ane prov ed to be uns atis factory for
favored disfavored
the r eduction of aliph atic or ar alkyl ketones under th e conditions
or iginally dev eloped by M idland. As was diagnosed much later ,
the poor optical induction ach ieved in th e r eduction of less r eac­
tiv e ketones by Alpine-Bor ane is due to a s ide r eaction caus ed Scheme 29
by an ach ir al r eduction of th e s ubs tr ate by 9-BBN
formed via a slow unimolecular diss ociation of Alpine-Bor ane. 3 5 *OH
Me
I

i'
With r eactive carbonyl compounds such as aldeh ydes and
a ,/3-acetylenic ketones , Alpine-Borane r eacts directly presumably
(i)#O slow
o
via a s ix- member ed cyclic tr ansition s tate (Table 7 ), to giv e the
•

chiral alcoh ol products . With less r eactiv e ketones s uch as 10% ee

acetoph enone, th e diss ociativ e s ide r eaction predominates
(Scheme 29).
..
However, Br own and Pai discovered that conducting th e r eac­
tions under neat conditions not only increased the rate of th e reac­
(i). Q)
tion but improved th e optical pur ity of th e alcoh ols cons ider ably sfowj ot Me
by s uppr es s ing th e deh ydr obor ation3 6 (Sch eme 30). I

Scheme 27
*

��
I

o
Me

active inactive

Alpine-Hydride

'I 'I �
0 0 0 0
Scheme 30

o
�

i- i '"
Ph.)!..___
HO H
, ,,/\\
0
'\,)J
H OH
neat ..,
H OH H OH
-
25 °C, 7 days

�
Ph x__ (S) -(-) -
78% ee
� �
29% ee 36% ee 37% ee 17% ee
HO ,,,H
,
C
'
'\.
Scheme 28 /
Et02C Me

A Q) -cv
A. . (J) Ph
AD H OH
(S)-(-)-
76% ee

'
ll) + HB
Q)
'-,,, B
HO H
PhA D
Alpine-Borane 1 00 °/� ,ee neat
...
......
/c ,
n- C6H 13 Me
25 °C, 7 days

Ph H (S)-( + )-
44% ee

1 00% ee
Utilizing th es e new neat conditions , var iou s clas s es of ketones
OH wer e r educed using Alpine-Bor ane. Th e r eagent h as proven par­
ticularly efficient for th e ch ir al r eduction of acetylenic ketones
•I
Me2CH CC : CH
(Sch eme 3 1 ), a-keto es ter s (Sch eme 3 2) and h alo-ketones"
I
99% ee (Sch eme 3 3 ).

14 A ldrichimica A cta, Vol. 20, No. I, 1987