A systematic investigation of the direction and degreeof stereose
lectivity in a
ldo
l addition reactions ispresented invo
lving achira
l unsubstituted meta
l eno
late and eno
lsi
lanenuc
leophi
les and chira
l a
ldehydes. TheBF
3·OEt
2mediated Mukaiyama a
ldo
l reaction with
![](/images/gifchars/a<font color=)
lpha.gif" BORDER=0>-unsubstituted,
![](/images/gifchars/beta2.gif)
le">-a
lkoxya
ldehydes afforded good
leve
ls of 1,3-
antiinductionin the absence of interna
l a
ldehyde che
lation. The
leve
l of1,3-induction was found to be primari
ly dependent onthe e
lectrostatic nature of the a
ldehyde
![](/images/gifchars/beta2.gif)
le">-substituent. Arevised mode
l for 1,3-asymmetric induction is presented toaccount for these resu
lts based primari
ly on minimization of interna
le
lectrostatic and steric repu
lsion between thea
ldehyde carbony
l moiety and the
![](/images/gifchars/beta2.gif)
le">-substituents. A fu
llconformationa
l ana
lysis, corroborated by semiempirica
l(AM1) ca
lcu
lations, is presented to support the proposed mode
l.The merged impact of
![](/images/gifchars/a<font color=)
lpha.gif" BORDER=0> and
![](/images/gifchars/beta2.gif)
le"> a
ldehydesubstituentswas a
lso systematica
lly investigated, and an integrated 1,2- and1,3-asymmetric induction mode
l is proposed thatincorporates the sa
lient features of the Fe
lkin-Anh and revised1,3-mode
l. In accordance with this integrated mode
l,uniform
ly high
leve
ls of Fe
lkin, 1,3-
anti diastereofacia
lse
lectivity are observed in Mukaiyama a
ldo
l reactions with
anti substituted
![](/images/gifchars/a<font color=)
lpha.gif" BORDER=0>-methy
l-
![](/images/gifchars/beta2.gif)
le">-a
lkoxy a
ldehydes, whichcontain stereocontro
l e
lements that are in astereoreinforcingre
lationship. In contrast, variab
le
leve
ls of a
ldehyde facia
linduction were observed in the corresponding reactionswith
syn substituted a
ldehyde substrates, which containstereocontro
l e
lements in a non-reinforcing re
lationship.The direction of a
ldehyde facia
l induction in Mukaiyama a
ldo
ladditions to the
syn substituted a
ldehydes wasfoundto be primari
ly dependent on the size of the eno
lsi
lane, with the firstknown examp
les of anti-Fe
lkin se
lectiveMukaiyama a
ldo
l reactions observed under conditions known to prec
ludeche
lation for the addition of the eno
lsi
laneof acetone. We conc
lude that dominant 1,2-stereoinduction wi
ll befound in those reactions proceeding with thereactants in an
antiperiplanar re
lationship, favored bysterica
lly encumbered eno
lsi
lane substituents, whi
ledominant1,3-stereoinduction wi
ll be manifest from a
synclinaltransition state, preferred for
less bu
lky eno
lsi
lanesubstituents.By inspection, the
synclinal transition state may bedestabi
lized by an increase in the steric bu
lk of the Lewisacid,and in accordance with this prediction the trity
l perch
lorate mediatedeno
lsi
lane addition resu
lted in a dramaticreversa
l of facia
l se
lectivity re
lative to theBF
3·OEt
2 mediated reaction. Thesetrends were a
lso documented in themechanistica
lly re
lated addition of a
lly
lstannanes to
antiand
syn disubstituted chira
l a
ldehydes.