1
A b oad scope syn hesis o es e p ecu so s o non- unc ionalized chi al alcohols based on he
asymme ic hyd ogena ion o ,-dialkyl-, ,-dia yl- and -alkyl--a yl- inyl es e s
Félix León,¶ Ped o J. González-Lis e,§ Se gio E. Ga cía-Ga ido,§ Inmaculada A ibas,¶ Miguel
Rubio,¶,† Vic o io Cadie no§,* and An onio Pizzano¶,*
¶Ins i u o de In es igaciones Químicas (IIQ) and Cen o de Inno ación en Química A anzada
(ORFEO-CINQA), CSIC and Uni e sidad de Se illa, Amé ico Vespucio 49, 41092 Se illa,
Spain.
§Labo a o io de Compues os O ganome álicos y Ca álisis (Unidad Asociada al CSIC), Cen o de
Inno ación en Química A anzada (ORFEO-CINQA), Depa amen o de Química O gánica e
Ino gánica, Ins i u o Uni e si a io de Química O ganome álica “En ique Moles”, Uni e sidad de
O iedo, 33006 O iedo, Spain.
Co esponding Au ho
*E-mail: [email p o ec ed] (A. P.).
*E-mail: [email p o ec ed] (V. C.).
P esen Add esses
† Repsol Technology Cen e , 28935 Mós oles, Mad id, Spain.
2
GRAPHICAL ABSTRACT
3
Abs ac
The ca aly ic asymme ic hyd ogena ion o isubs i u ed enol es e s using Rh ca alys s bea ing
chi al phosphine-phosphi e ligands (P-OP) has been s udied. Subs a es co e ed comp ise ,-
dialkyl, -alkyl--a yl and ,-dia yl inyl es e s, he co esponding hyd ogena ion p oduc s
being sui able p ecu so s o p epa e syn he ically ele an chi al non- unc ionalized alcohols. A
compa ison o eac i i y indica es ha i dec eases in he o de : ,-dialkyl > -alkyl--a yl >
,-dia yl. Based on he highly modula s uc u e o P-OP ligands employed, ca alys sc eening
iden i ied highly enan ioselec i e ca alys s o ,-dialkyl (95-99 % ee) and nea ly all o -
alkyl--a yl subs a es (92-98 % ee), wi h he excep ion o -cyclohexyl--phenyl inyl ace a e
which exhibi ed a low enan ioselec i i y (47 % ee). Finally, ,-dia yl inyl subs a es showed
somewha lowe enan ioselec i i ies (79-92 % ee). In addi ion, some o he ca alys s p o ided a
high enan ioselec i i y in he hyd ogena ion o E/Z mix u es (ca. Z/E = 75:25) o ,-
dialkyl inyl subs a es, while a d ama ic dec ease on enan ioselec i i y was obse ed in he case
o -me hyl--anisyl inyl ace a e (Z/E = 58:42). Complemen a y deu e a ion eac ions a e in
acco d wi h a highly enan ioselec i e hyd ogena ion o bo h ole in isome s in he case o ,-
dialkyl inyl es e s. In con as , deu e a ion shows a complex beha io o -me hyl--
anisyl inyl ace a e de i ed om he pa icipa ion o he E isome in he eac ion.
4
In oduc ion
Ca aly ic asymme ic hyd ogena ion cons i u es one o he mos e icien ools o he
p epa a ion o chi al building blocks wi h high enan ioselec i i y.1,2 As well, due o he inhe en
ad an ages ha usually cha ac e ize his kind o p ocesses (e.g. high ca alys e iciency, pe ec
a om economy, simple wo k-up), hey ha e ex ensi ely been used in indus ial applica ions.3
Among di e se classes o compounds p epa ed using asymme ic hyd ogena ion eac ions, a
pa icula ly ema kable one co esponds o non- unc ionalized chi al alcohols o gene al
s uc u e A (R1, R2 = alkyl, a yl; Figu e 1).
Figu e 1. Hyd ogena ion ou es o alcohols A
A e y con enien and di ec ou e o alcohols A is p o ided by he asymme ic hyd ogena ion
o ke ones B (pa h a). The easibili y o his op ion is, howe e , s ongly dependen on he na u e
o R1 and R2 subs i uen s. Thus, he hyd ogena ion o a yl-alkyl ke ones cons i u es one o he
highes achie emen s in asymme ic ca alysis due o he excep ional le els o ca alys ac i i y
and enan ioselec i i y eached.4 As well, e y e icien ca alys s ha e been desc ibed o he
hyd ogena ion o e -alkyl-alkyl ke ones.5 None heless, he hyd ogena ion o dialkyl ke ones
5
cha ac e ized by less bulky alkyl subs i uen s has a conside able di icul y and high
enan ioselec i i ies ha e only been achie ed in a limi ed numbe o cases.4i,6,7 Likewise, benzyl-
alkyl ke ones cons i u es ano he class o p oblema ic subs a es and no sa is ac o y
hyd ogena ion ca alys s ha e so a been epo ed.8,9 Howe e , chi al alkanols and homobenzylic
alcohols a e e y e sa ile building blocks o syn hesis,10 he e o e he de elopmen o e icien
me hods o ob ain hem in a high enan iome ic pu i y has a conside able in e es . Towa ds his
aim, he asymme ic hyd ogena ion o enol es e s C cons i u es an appealing al e na i e, as es e s
D can i ially be con e ed in o alcohols A h ough deacyla ion (pa h b).11 Al hough he
hyd ogena ion o B and C a e mechanis ically di e en eac ions, he p epa a ion o A wi h high
enan ioselec i i y by ei he pa h a o b ul ima ely depends on an e ec i e disc imina ion o
p ochi al subs a e aces by he co esponding hyd ogena ion ca alys . In his ega d, he
hyd ogena ion o enol es e s is cha ac e ized by subs a e chela ion, which enables a powe ul
ecogni ion o he ole inic subs a e.12 In con as , he di e en ia ion o enan io opic aces o
ke ones bea ing no e y dissimila R1 and CH2R2 subs i uen s is an ex emely di icul ask, as
e idenced by he backg ound men ioned abo e. In his con ex , a meaning ul case is p o ided by
he hyd ogena ion o -alkyl inyl es e s (C, R1 = alkyl, R2 = H), which has enabled a b oad
scope and highly e icien ou e o he syn hesis o chi al 2-alkanols.13
A highly aluable expansion o pa h b ou e co esponds o he hyd ogena ion o isubs i u ed
subs a es C (R1, R2 = alkyl, a yl), as i may p o ide access o a as ange o chi al es e s
conside ing he coun less possible combina ions o R1 and R2. Ne e heless, he inclusion o a
subs i uen in posi ion o he inyl agmen in oduces undamen al eac i i y aspec s o s udy.
Fi s ly, in compa ison wi h widely s udied disubs i u ed subs a es,14 inc ease in ole in
subs i u ion should be accompanied by a educed ca alys ac i i y,15 u he o he ela i ely low

6
eac i i y o enol es e s.16 Secondly, he enan ioselec i i y o he hyd ogena ion may c i ically be
dependen on he ole in con igu a ion,17 which can limi se e ely he use ulness o his app oach
as enol es e s a e o en ob ained as E/Z mix u es and hei sepa a ion is usually cumbe some. On
he o he hand, nea ly all enol es e s examined in asymme ic hyd ogena ion possess an -
elec on-wi hd awing subs i uen (ca boxyla e, phosphona e, i luo ome hyl, cyano o a yl),
which is an impo an elemen in he cou se o he eac ion.18 As a esul o his backg ound,
he e is e y li le in o ma ion in he li e a u e abou he enan ioselec i e hyd ogena ion o
isubs i u ed subs a es bea ing an alkyl subs i uen in  posi ion.19,20 P eceden s a e limi ed o a
s udy on he hyd ogena ion o -alkyl--me hyl inyl es e s, as mix u es o he co esponding E
and Z isome s, desc ibed by Goossen and cowo ke s. Thus, hese au ho s ha e epo ed
enan ioselec i i ies up o 98 % ee in he case o he -me hyl-subs i u ed subs a es, as well as a
dec ease down o 82 and 78 % ee o es e s bea ing -nP and -nBu subs i uen s, espec i ely.19
Finally, we would like o ema k also he e ha no p eceden s o he asymme ic hyd ogena ion
o ,-dia yl inyl es e s ha e been desc ibed so a in he li e a u e.
In a p elimina y con ibu ion we s udied he syn hesis and hyd ogena ion o -alkyl--a yl-
subs i u ed subs a es C2 (Figu e 2),21 using Rh ca alys s based on chi al phosphine-phosphi e
ligands (P-OP).22 He ein we p esen a b oade s udy on he hyd ogena ion o isubs i u ed enol
es e s co e ing in addi ion hose o ypes C1 and C3. Mo eo e , he educ ion o mix u es o
E/Z-isome s, p o iding in o ma ion abou he in luence o subs a e con igu a ion on he
eac ion, has also been s udied in de ail.
7
Figu e 2. Gene al s uc u es o enol es e s C1-C3
Resul s and Discussion
Syn hesis o subs a es. In o de o examine he scope o he asymme ic hyd ogena ion o
isubs i u ed enol es e s o ypes C1-C3, a wide ange o subs a es co e ing he h ee ypes o
s uc u es has been p epa ed (Figu e 3). Thus, ega ding hose o ype C1, compounds 1a and 1b
ha e been p epa ed by a gold ca alyzed addi ion o benzoic acid o 2-bu yne (Scheme 1a),
ollowing he p ocedu e desc ibed by Kim and Cha y.23,24 Also based on he wo k o hese
au ho s, 1c and 1d we e syn hesized by a gold ca alyzed andem addi ion-isome iza ion eac ion
(Scheme 1b). Wo h o no e, 1a and 1b we e ob ained as he pu e Z isome s, while 1c and 1d as
mix u es wi h a Z/E a io o 74:26 and 72:28, espec i ely.
8
Figu e 3. Range o enol es e s 1 co e ed in he p esen s udy
Rega ding subs a es o ype C2, we ha e p e iously p epa ed -me hyl--a yl inyl ace a es
1e-1i, wi h gene ally good yields and selec i i y (Z:E ≥ 95:5) upon he acyla ion o me hyl
benzyl ke ones.21,25 Mo eo e , a ange o 1-alkyl-2-a yl inyl subs a es (1k-1q, 1 -1z) whe e
s e eoselec i ely p epa ed as he Z isome s by a Suzuki coupling o e (Z)--iodoalkenyl
ace a es.21,26 In o de o comple e he se o compounds C2, new subs a e 1j bea ing a 1-e hyl
subs i uen has been p epa ed in good yield (62 %) by he o me me hod. Likewise, compounds
1 and 1s, possessing 2-phenyle hyl and 3-phenylp opyl subs i uen s, ha e been p epa ed by he
9
Suzuki coupling ou e in good yields om he co esponding iodo-alkenes 2 (75 and 79 %,
espec i ely; Scheme 2).
Scheme 1. Syn hesis o enol es e s 1a-1d
To widen he ange o subs a es, se e al examples o ype C3 ha e also been p epa ed.
Ini ially, diphenyl subs a e 1aa was p epa ed in mode a e yield by he eac ion o Scheme 1a.
Mo eo e , se e al examples cha ac e ized by a -Ph and di e se a yl o he e oa yl agmen s in
 posi ion ha e been syn hesized by he Suzuki coupling ou e (1ab-1ae; Scheme 2). Finally,
wi h he in en ion o explo e he in oduc ion o an alkyl subs i uen in posi ion o he C=C
bond, a Negishi ype coupling was s udied using (Z)--benzyl--iodo inyl ace a e.27 This
eac ion p o ided he (Z)-enol es e 1a , albei in a a he low yield (Scheme 3).
16
chi al ligands,33 inally poin ing o ca alys om 4h as he mo e e icien one which could educe
1n unde mild condi ions (4 ba H2, 40 ºC, DCE, S/C = 100-250, 24 h) wi h 98 % ee (en ies 10,
11, Table 2). A ele an ea u e o 1n is a ma kedly lowe eac i i y han ha o 1a owa ds
hyd ogena ion (en ies 1-5, 8 and 9). In con as , he a ainmen o a good enan ioselec i i y is
no as demanding and ela i ely good enan ioselec i i ies, wi h alues be ween 92 and 98 % ee,
we e ob ained wi h ca alys s 4e, 4h and 4i (en ies 5, 8 and 9, espec i ely). As well, a posi i e
e ec on con e sion was obse ed when DCE was used as sol en (en y 10). Since he
inco po a ion o he P-s e eogenic phophine agmen is he mos demanding aspec o he
p epa a ion o he P-OP ligand 3h, we explo ed he beha io o ca alys s based on ligands 3 and
3g, cha ac e ized by a non-s e eogenic ialkylphosphine agmen and by a less elabo a ed
syn hesis, as a possible p ac ical imp o emen . Howe e , co esponding ca alys p ecu so s 4
and 4g p o ided lowe con e sion alues han 4h, poin ing again o he achie emen o a sui able
ca alys ac i i y as a challenging aspec o he p esen ca aly ic sys em. No wi hs anding ha , 4
and 4g showed ela i ely good enan ioselec i i ies, 92 and 94 % ee, espec i ely (en ies 6, 7).
Table 2. Hyd ogena ion o 1n pe o med wi h ca alys p ecu so s 4a
En y
Ca . P ec.
Sol en
Con (%)
% ee (con )
1
4a
DCM
13
n.d.
2
4b
DCM
<5
n.d.
3
4c
DCM
<5
n.d.
4
4d
DCM
<5
n.d.

17
5
4e
DCM
62
96 (S)
6
4
DCM
59
92 (R)
7
4g
DCM
34
94 (S)
8
4h
DCM
79
98 (S)
9
4i
DCM
38
94 (R)
10
4h
DCE
100
98 (S)
11b
4h
DCE
98
98 (S)
aReac ions a 40 ºC, [Rh] = 1 × 10-3 M, S/C = 100, 4 ba H2 ini ial p essu e and 24 h eac ion
ime, unless o he wise s a ed. Con e sion de e mined by 1H NMR and enan iome ic excess by
chi al HPLC. See expe imen al sec ion o de e mina ion o con igu a ion. b[Rh] = 1 × 10-3 M,
S/C = 250.
Rega ding subs a e scope, 4h p o ided high enan ioselec i i ies wi h a wide ange o
subs a es (Table 3). Thus, compounds 1i (en y 5), 1k-1p (en ies 7-12) and 1 -1z (en ies 19-
25) we e hyd ogena ed wi h enan ioselec i i ies be ween 93 and 98 % ee using ou s anda d o
simila eac ion condi ions (see oo no es o Table 3 o de ails). Wo h o no e, 4h p o ided a
somewha lowe enan ioselec i i y in he case o 1e (91 % ee, no shown), ou pe o med by 4e
(97 % ee, en y 1). Upon his esul , 4e was used wi h sa is ac o y esul s in he case o subs a es
1 -1h (en ies 2-4).
Rega ding newly added subs a es, 1j was sa is ac o ily hyd ogena ed wi h 4h (94 % ee, en y
6), while 1 and 1s showed a lowe eac i i y unde s anda d condi ions leading o uncomple ed
eac ions (en ies 15, 17). A simila dec ease was obse ed in he hyd ogena ion o 4-phenyl-1-
bu en-2-yl benzoa e13d and i is p obably ela ed o he o ma ion o low eac i e Rh-6-a ene
species.11a,16b In con as , ull con e sion and good enan ioselec i i ies we e obse ed unde 20
ba H2 o 1 (93 % ee, en y 16) and 1s (88 % ee, en y 18).
18
Finally, a limi a ion o he p esen eac ion was ound wi h he -cyclohexyl-subs i u ed
subs a e 1q. This compound exhibi ed a ma kedly low eac i i y and only a good con e sion
was ob ained wi h 4i unde 20 ba H2 (90 %), while bo h 4h and 4i p o ided a a he low
enan ioselec i i y (40-47 % ee, en ies 13, 14).
Table 3. Hyd ogena ion o -alkyl--a yl inyl es e sa
En y
Subs. (Ak, A )
Ca . P ec.
H2 (ba )
% con .
% ee (con .)
1
1e (Me, 4-MeO-C6H4)
4e
4
100
97 (S)
2
1 (Me, 4-Me-C6H4)
4e
10
100
91 (S)
3
1g (Me, 4-F-C6H4)
4e
4
100
98 (S)
4
1h (Me, 2-MeO-C6H4)
4e
4
100
99 (S)
5
1i [Me, 3,4-(MeO)2-C6H3]
4h
4
100
93 (S)
6
1j (E , Ph)
4h
4
100
94 (S)
7
1k (nP , Ph)
4h
4
100
94 (S)
8
1l (nBu, Ph)
4h
4
100
98 (S)
9
1m (nPen, Ph)
4h
4
100
98 (S)
10
1n (nHex, Ph)
4h
4
100
98 (S)
11
1o [(CH2)2iP , Ph]
4h
4
100
98 (S)
12b
1p (cC3H5, Ph)
4h
4
100
92 (n.d.)
13c
1q (Cy, Ph)
4h
20
50
47 (n.d.)
14c
1q (Cy, Ph)
4i
20
90
40 (n.d.)
15
1 [(CH2)2Ph, Ph]
4h
4
89
96 (S)
19
16
1 [(CH2)2Ph, Ph]
4h
20
100
93 (S)
17
1s [(CH2)3Ph, Ph]
4h
4
84
87 (S)
18
1s [(CH2)3Ph, Ph]
4h
20
100
88 (S)
19
1 (nHex, 4-F-C6H4)
4h
4
100
96 (S)
20d
1u (nHex, 4-MeO-C6H4)
4h
4
100
93 (S)
21
1 (nHex, 4-Me-C6H4)
4h
20
100
93 (S)
22
1w (nHex, 4-Cl-C6H4)
4h
4
100
95 (S)
23
1x (nHex, 4-Ph-C6H4)
4h
4
100
96 (S)
24
1y [nHex, 3,4-(MeO)2-C6H3]
4h
20
100
95 (S)
25
1z [nHex, 3,5-(MeO)2-C6H3]
4h
4
100
96 (S)
aHyd ogena ions pe o med a 40 ºC in DCE, [Rh] = 1 × 10-3 M, S/C = 100, a ini ial p essu e
(ba H2) indica ed, and 24 h eac ion ime unless o he wise s a ed. Con e sion de e mined by 1H
NMR and enan iome ic excess by chi al HPLC. See expe imen al sec ion o de e mina ion o
con igu a ion. bReac ion pe o med a 30 ºC. c48 h eac ion ime. d[Rh] = 2 × 10-3 M, S/C = 100.
Enabled by he a he e sa ile syn he ic p ocedu es o subs a es 1, an appealing applica ion
o he p esen sys em is he hyd ogena ion o 1a , which swi ches he posi ion o he ole in
subs i uen con aining he a yl agmen and should hen p o ide he co esponding
homobenzylic es e 5a wi h opposi e con igu a ion (wi h ega d o ha obse ed in he
hyd ogena ion o 1j-1o wi h 4h; en ies 6-11 in Table 3). G a i yingly, hyd ogena ion o 1a wi h
4h unde ou s anda d eac ion condi ions p o ided (R)-5a wi h excellen con e sion and
enan ioselec i i y (Scheme 5).
Scheme 5. Hyd ogena ion o 1a
20
Hyd ogena ion o ,-dia yl inyl es e s. To comple e his explo a o y analysis we nex
examined he hyd ogena ion o 1aa as an example o s uc u e o ype C3. Reac ions pe o med
in DCM unde ou s anda d condi ions (4 ba H2, 40 ºC and S/C = 100) wi h se e al ca alys
p ecu so s (en ies 1-6, Table 4), a o ded a he low con e sion alues, being only mode a e in
he case o 4h (en y 5). Howe e , ull con e sion and good enan ioselec i i y was obse ed
when DCE was used as sol en (92 % ee, en y 7). Despi e he simili ude be ween DCM and
DCE, i is no ewo hy ha a signi ican inc ease on con e sion wi h he la e is bo h obse ed
wi h ep esen a i e subs a es 1n and 1aa, u he p o iding sa is ac o y esul s o he se ies o
subs a es C2 and C3. In his con ex i is pe inen o men ion ha an enhancemen on
enan ioselec i i y was obse ed by he g oup o Ding in he hyd ogena ion o ela ed enol es e s
when using DCE ins ead o DCM,13b while a signi ican ly be e pe o mance in DCE o e DCM
in he hyd ogena ion o an acyl hyd azone wi h a Rh-diphosphine ca alys has been epo ed by
Haddad and cowo ke s.34 We ha e no ound an explana ion o he sol en e ec obse ed
he ein, bu i should be no ed ha despi e DCE and DCM a e a he simila sol en s,
cha ac e ized by a poo ly coo dina ing cha ac e , he o me has some abili y o ac as a chela ing
ligand.35 As in e media es con aining coo dina ed sol en a e p oposed in he hyd ogena ion
ca aly ic cycle, i is no un easonable o expec a di e en in luence o hese sol en s in he
ca aly ic p ocess.
In addi ion, some ,-dia yl inyl subs a es o ype C3 we e examined o comple e he esul s
ob ained wi h 1aa. By compa ison wi h hese esul s, i appea s ha subs i u ion o a yl ing o
posi ion  is de imen al o con e sion (subs a es 1ab-1ad; en ies 8, 11, 14; Table 4). This is
bo h obse ed wi h elec on-dono and elec on-wi hd awing subs i uen s and may be hen
21
a ibu ed o s e ic e ec s. O e all, subs a es o ype C3 seem less eac i e han hose o ype
C2. Howe e ull con e sion eac ions we e ob ained a highe subs a e concen a ion o unde
20 ba o H2. Thus, enan ioselec i i ies up o 91 % ee (1ab, en y 10), 82 % ee (1ac, en y 12)
and 88 % ee (1ad, en y 16) we e obse ed.36 In addi ion, he hienyl-subs i u ed enol es e 1ae
also p o ided ull con e sion and a ela i ely good enan ioselec i i y (79 % ee, en y 18).
Table 4. Hyd ogena ion o dia yl-subs i u ed subs a es C3 pe o med wi h ca alys p ecu so s 4a
En y
Subs. (A )
Ca . P ec.
Sol en
Con (%)
% ee (con )
1
1aa (Ph)
4a
DCM
6
n.d.
2
1aa (Ph)
4b
DCM
<5
n.d.
3
1aa (Ph)
4c
DCM
7
n.d.
4
1aa (Ph)
4d
DCM
8
n.d.
5
1aa (Ph)
4h
DCM
51
93 (R)
6
1aa (Ph)
4i
DCM
43
91 (S)
7
1aa (Ph)
4h
DCE
100
92 (R)
8
1ab (4-CF3-C6H4)
4h
DCE
67
87 (R)
9b
1ab (4-CF3-C6H4)
4h
DCE
100
90 (R)
10c
1ab (4-CF3-C6H4)
4h
DCE
100
91 (R)
11
1ac (4-MeO-C6H4)
4h
DCE
37
86 (R)
12b
1ac (4-MeO-C6H4)
4h
DCE
100
82 (R)
13c
1ac (4-MeO-C6H4)
4h
DCE
100
77 (R)
14
1ad (4-PhO-C6H4)
4h
DCE
35
69 (R)

22
15b
1ad (4-PhO-C6H4)
4h
DCE
100
71 (R)
16c
1ad (4-PhO-C6H4)
4h
DCE
100
88 (R)
17
1ae (3- hienyl)
4h
DCE
44
71 (R)
18c
1ae (3- hienyl)
4h
DCE
100
79 (R)
aReac ions a 40 ºC, [Rh] = 1 × 10-3 M, S/C = 100, 4 ba H2 ini ial p essu e and 24 h eac ion
ime, unless o he wise s a ed. Con e sion de e mined by 1H NMR and enan iome ic excess by
chi al HPLC. See expe imen al sec ion o de e mina ion o con igu a ion. b[Rh] = 4 × 10-3 M,
S/C = 100. cReac ions pe o med unde 20 ba H2
Mechanis ic conside a ions. The ca alys sc eening pe o med wi h ep esen a i e subs a es
1a, 1n and 1aa indica es ha p oduc con igu a ion is de e mined by he con igu a ion o he
bia yl agmen o he phosphi e. Thus, o ca alys s wi h a con igu a ion S o his agmen , S
enan iome s a e obse ed o p oduc s p oceeding om dialkyl inyl subs a es (1a-1d, Scheme
6). Likewise, S enan iome s a e selec i ely o med om -alkyl--a yl inyl es e s (1e-1z) using
4h o 4e. On he o he hand, R p oduc s a e ob ained in he case o he hyd ogena ion o dia yl
inyl subs a es (1aa-1ae) ca alyzed by 4h. The e o e, he sense o hyd ogen addi ion is
coinciden o he h ee ypes o p oduc s ( he changes in p oduc con igu a ion a e due o he
change o p io i y o de o subs i uen s o he s e eogenic ca bon). I should be inally added ha
his s e eochemical ela ion be ween phosphi e con igu a ion and he sense o hyd ogen addi ion
is analogous o ha obse ed in he hyd ogena ion o s uc u ally ela ed ole ins (enamides and
-acyloxyphosphona es) and discussed in de ail elsewhe e.22a,b
23
Scheme 6. Compa ison o p oduc con igu a ion obse ed in he hyd ogena ion o 1
The high enan ioselec i i y ob ained in he hyd ogena ion o mix u es o ole in isome s o 1c
and 1d wi h 4a is ema kable. This can be a ibu ed o an e icien ans e o chi ali y o
ca alys o bo h isome s o he subs a e o , al e na i ely, o he exis ence o an E-Z ole in
isome iza ion p ocess p io o he hyd ogena ion.37 Following well es ablished cis addi ion o
hyd ogen o he ole in bond,38 he deu e a ion o E and Z isome s will p oduce di e en
dias e eome s (Scheme 7), which could e en ually be dis inguished by NMR. As a equisi e o
his analysis, dias e eo opic p o ons a posi ion  should gene a e sepa a e signals. This was
obse ed o 5c (as well as o 5e, see below) while 5d exhibi ed o e lapped signals. Thus, he
deu e a ion o 1c wi h 4a showed a 72:28 a io o dias e eome s by 1H NMR, labelled a
posi ions  and , namely M-5c-d2 and m-5c-d2 (majo and mino , espec i ely).39 This a io is
a he close o ha o isome s o he s a ing ma e ial (74:26) and is in acco d wi h he absence o
a signi ican isome iza ion be ween he isome s o he s a ing ma e ial. Mo eo e , analysis by
ESI-MS did no show app eciable amoun s o ideu e a ed p oduc s, ypically o med in ole in
isome iza ion eac ions by a e e sible ole in inse ion s ep.37a In his con ex , i is also pe inen
o ecall ha he a ia ion on enan ioselec i i y upon deu e a ion has been aken as an indica ion
24
o compe ing mechanis ic pa hways in asymme ic ole in hyd ogena ion eac ions ca alyzed by
Rh complexes.40 This seems no o occu in he p esen case, as a alue o 96 % ee was obse ed
in he deu e a ion o 1c, sligh ly lowe o ha ob ained in he s anda d hyd ogena ion (99 % ee;
en y 13 in Table 1). O e all, he esul s ob ained a e in good acco d wi h an independen
hyd ogena ion o each isome o 1c by 4a bo h p oducing (R)-5c wi h high enan ioselec i i y.
Scheme 7. S e eoisome s o dideu e a ed 5-d2 esul ing om cis deu e a ion o Z and E isome s
o enol es e s 1
In ou p elimina y communica ion we obse ed only mode a e enan ioselec i i ies in he
hyd ogena ion o a mix u e o isome s o 1e in a Z:E = 58:42 a io,41 in sha p con as wi h
esul s ob ained in he hyd ogena ion o 1c and 1d. This commi ed us o in es iga e in mo e
de ail he hyd ogena ion o 1e. To his aim mix u es wi h Z:E = 95:5 and 58:42 a ios we e es ed
wi h se e al ca alys p ecu so s (Table 5). Rema kably, he hyd ogena ion o he Z:E = 58:42
mix u e p o ided signi ican ly lowe enan ioselec i i ies wi h all ca alys s es ed (ǀ% eeǀ = 15-
47 % ee) han hose pe o med wi h he Z:E = 95:5 mix u e, indica ing ha he hyd ogena ion o
E-1e is app eciably less enan ioselec i e wi h ca alys s 4 han ha o Z-1e. The di e ence is
pa icula ly d ama ic in he case o 4h, o which alues o 44 and 91 % ee, espec i ely, we e
25
obse ed (en y 4). As well, slowe eac ions wi h he 58:42 mix u e we e obse ed. Thus, wi h
he excep ion o he eac ion p epa ed wi h 4h, no comple e con e sions we e obse ed in he
es o he hyd ogena ions (en ies 1-3, 5). Mo eo e , an analysis o he emaining un eac ed
subs a e in hese eac ions showed an en ichmen in isome E, indica ing a slowe eac ion o he
la e compa ed wi h he Z isome . Acco dingly, he dec ease in enan ioselec i i y obse ed in
eac ions pe o med wi h 4d and 4e is a enua ed by uncomple ed eac ions.
Table 5. Hyd ogena ion o 1e (Z:E = 58:42) pe o med wi h ca alys p ecu so s 4a
En y
Ca . P ec.
Con (%)
Z:E (%)b
% ee (con )c
% ee (con )d
1
4a
94
0:100
58 (R)
78 (R)
2
4d
75
0:100
80 (S)
95 (S)
3
4e
76
12:88
81 (S)
97 (S)
4
4h
100
-
44 (S)
91 (S)
5
4i
89
23:77
55 (R)
74 (R)
aReac ions a 40 ºC in DCE, [Rh] = 1 × 10-3 M, S/C = 100, 4 ba H2 ini ial p essu e and 24 h
ea ion ime. Con e sion de e mined by 1H NMR and enan iome ic excess by chi al HPLC.
Con igu a ion was de e mined by compa ison o he op ical o a ion sign wi h li e a u e da a.
bZ/E a io o emaining subs a e. c% ee o 5e ob ained in he hyd ogena ion o Z/E-1e. d% ee o
5e ob ained in he hyd ogena ion o he Z:E = 95:5 a io mix u e.
In addi ion, we ha e s udied he deu e a ion o he isome mix u es o 1e di e ing in he E/Z
a io wi h 4h, as his p ecu so p o ides he only ca alys able o comple e he eac ion in bo h
cases. In con as o he expe imen wi h 1c, he deu e a ion o he Z:E = 58:42 mix u e no only
showed he expec ed M-5e-d2 and m-5e-d2, bu as well a hi d iso opome 5e’-d2 labelled a
posi ions  and ’ (Scheme 8, see SI o NMR spec a), wi h a 59:28:13 espec i e a io. Wo h
o no e, an analysis by MS-ESI did no show an app eciable p esence o i- o monodeu e a ed
32
(0.024 g, 0.05 mmol), AgPF6 (0.013 g, 0.05 mmol) and oluene (3.0 mL) we e in oduced in o a
Te lon-capped sealed ube, and he eac ion mix u e s i ed a 60 (1a-b) o 110 °C (1aa) o 15 h.
A e ha ime, he sol en was emo ed in acuo and he c ude eac ion mix u e pu i ied by
column ch oma og aphy o e silica gel using die hyl e he / hexane (1:10) as eluen , yielding he
co esponding enol es e s as pu e Z isome s.
(Z)-Bu -2-en-2-yl benzoa e (1a):19,24 colo less oil. Yield: 0.118 g (67%).
(Z)-Hex-3-en-3-yl benzoa e (1b):24,46 pale yellow oil. Yield: 0.131 g (64%).
(Z)-1,2-Diphenyl inyl hep anoa e (1aa):24 whi e solid. Yield: 0.163 g (53%).
Gene al p ocedu e o he syn hesis o enol es e s 1c-d: unde an a gon a mosphe e, he
co esponding e minal alkyne (1.2 mmol) and benzoic acid (0.122 g, 1 mmol), [AuCl(PPh3)]
(0.024 g, 0.05 mmol), AgOT (0.016 g, 0.05 mmol) and oluene (5.0 mL) we e s i ed a oom
empe a u e o 15 h. A e ha ime, he sol en was emo ed in acuo and he c ude eac ion
mix u e pu i ied by column ch oma og aphy o e silica gel using die hyl e he / hexane (1:10) as
eluen . The co esponding enol es e s 1c-d we e ob ained as a mix u e o s e eoisome s in 62-
84% yield. Con igu a ion o co esponding isome s was assigned by 2D-NOESY expe imen s.
Oc -2-en-2-yl benzoa e (1c):47 pale yellow oil. Yield: 0.195 g (84%, Z/E = 74:26). Z-1c:
1H NMR (CDCl3, 300 MHz): δ = 8.10 (m, 2H), 7.58 (m, 1H), 7.45 (m, 2H), 5.11 ( , J(H,H) = 6.8
Hz, 1H), 2.00 (s, 3H), 1.97 (m, 2H), 1.31 (m, 6H), 0.86 ( , J(H,H) = 6.9 Hz, 3H) ppm. 13C{1H}
NMR (CDCl3, 75 MHz): δ = 164.5, 145.0, 133.3, 130.0 (3C), 128.5 (2C), 117.5, 31.5, 28.9, 25.5,
22.5, 19.7, 14.0 ppm. E-1c: 1H NMR (CDCl3, 300 MHz): δ = 8.10 (m, 2H), 7.58 (m, 1H), 7.45
(m, 2H), 5.26 ( , J(H,H) = 7.7 Hz, 1H), 2.09 (q, J(H,H) = 7.8 Hz, 2H), 1.97 (s, 3H), 1.31 (m, 6H),

33
0.89 ( , J(H,H) = 7.4 Hz, 3H) ppm. 13C{1H} NMR (CDCl3, 75 MHz): δ = 165.4, 145.5, 133.2,
130.3, 129.9 (2C), 128.4 (2C), 118.0, 31.7, 29.3, 26.7, 22.6, 15.4, 14.1 ppm.
1-Cyclohexylp op-1-en-2-yl benzoa e (1d): pale yellow oil. Yield: 0.151 g (62%, Z/E =
72:28). Z-1d: 1H NMR (CDCl3, 300 MHz): δ = 8.10 (m, 2H), 7.58 (m, 1H), 7.45 (m, 2H), 4.97
(d, J(H,H) = 9.2 Hz, 1H), 2.20 (m, 1H), 1.98 (d, J(H,H) = 0.5 Hz, 3H), 1.68 (m, 5H), 1.20 (m,
5H) ppm. 13C{1H} NMR (CDCl3, 75 MHz): δ = 164.7, 143.6, 133.2, 130.0 (3C), 128.5 (2C),
123.1, 35.0, 32.9 (2C), 26.0, 25.8 (2C), 19.7 ppm. E-1d: 1H NMR (CDCl3, 300 MHz): δ = 8.10
(m, 2H), 7.58 (m, 1H), 7.45 (m, 2H), 5.12 (d, J(H,H) = 9.7 Hz, 1H), 2.20 (m, 1H), 2.0 (d, J(H,H)
= 0.8 Hz, 3H), 1.68 (m, 5H), 1.20 (m, 5H) ppm. 13C{1H} NMR (CDCl3, 75 MHz): δ = 165.3,
143.6, 133.1, 130.6, 129.9 (2C), 128.4 (2C), 123.5, 36.2, 33.3 (2C), 26.0 (2C), 25.9, 15.5 ppm.
HRMS (ESI) m/z: [M+H]+ Calcd o C16H21O2 245.1542; Found 245.1538.
Syn hesis o enol es e 1j: o e a suspension o NaH (0.35 g, 60% in mine al oil, 8.8 mmol),
washed wi h pen ane (3 x 10 mL) in d y 1,2-dime hoxye hane (10 mL), was added d opwise a
solu ion o 1-phenylbu an-2-one (0.78 g, 5.2 mmol) in 1,2-dime hoxye hane (10 mL). The
esul ing mix u e was s i ed o 1 h, gi ing a b igh yellow suspension, which was allowed o
s and o 1 h. The supe na an was added slowly o e dis illed ace ic anhyd ide (1.0 mL, 10
mmol) cooled a 0 ºC. A e all he supe na an enola e solu ion was ans e ed, he esidual
sodium hyd ide was washed wi h addi ional 1,2-dime hoxye hane (5 mL), he mix u e allowed o
s and o 30 min and he esul ing supe na an added o he ace ic anhyd ide solu ion. The
mix u e ob ained was s i ed a oom empe a u e o 0.5 h and pou ed in o a mix u e o n-
hexane (25 mL), wa e (25 mL) and NaHCO3 (2.5 g, 30 mmol). Phases ob ained we e sepa a ed
and he aqueous one was ex ac ed wi h n-hexane (30 mL). The combined n-hexane ac ions
34
we e d ied o e anhyd ous MgSO4 o e nigh , il e ed and sol en e apo a ed. The esul ing oil
was pu i ied by column ch oma og aphy o e silica gel using n-hexane / AcOE (90:10) as
eluen , yielding 1j as he pu e Z isome in 62 % yield.
(Z)-1-Phenylbu -1-en-2-yl ace a e (1j): pale o ange oil. Yield: 0.600 g (62%). 1H NMR
(CDCl3, 400 MHz):

= 7.38 (d, J(H,H) = 7.7 Hz, 2H), 7.31 ( , J(H,H) = 7.9 Hz, 2H), 7.21 ( ,
J(H,H) = 7.5 Hz, 1H), 5.99 (s, 1H), 2.42 (q, J(H,H) = 7.6 Hz, 2H), 2.19 (s, 3H), 1.17 ( , J(H,H) =
7.7 Hz, 3H) ppm. 13C{1H} NMR (CDCl3, 100 MHz):

= 168.7, 151.4, 134.6, 128.4, 128.3 (2C),
127.0 (2C), 114.9, 27.5, 21.2, 11.4 ppm. IR ( ilm): ν = 1757 (s, C=O), 1679 (m, C=C) cm-1.
HRMS (ESI) m/z: [M+Na]+ Calcd o C12H14O2Na 213.0886; Found 213.0882.
Gene al p ocedu e o he syn hesis o enol es e s 1 -s and 1ab-1ae: unde an a gon
a mosphe e, he co esponding (Z)-β-iodoenol ace a e 2 (1.0 mmol), [Pd(PPh3)4] (0.058 g, 0.05
mmol) and oluene (3.0 mL) we e in oduced in o a Te lon-capped sealed ube, and he mix u e
was s i ed a oom empe a u e o 10 min. Then, 0.5 mL o a 4.0 M NaOH aqueous solu ion
(2.0 mmol o NaOH) and he co esponding bo onic acid (1.5 mmol) we e added o he sealed
ube and he eac ion mix u e s i ed a 80 ºC o 12 h. A e ha ime, he sol en was emo ed
in acuo and he c ude eac ion mix u e pu i ied by column ch oma og aphy o e silica gel using
die hyl e he / hexane (1:100) as eluen . The co esponding enol es e s 1 -s and 1aa-1ad we e
ob ained as pu e Z isome s in 42-80% yield.
(Z)-1,4-Diphenylbu -1-en-2-yl ace a e (1 ): o ange oil. Yield: 0.200 g (75%). 1H NMR
(CDCl3, 400 MHz): δ = 7.46 (m, 2H), 7.41 (m, 4H), 7.32 (m, 4H), 6.07 (s, 1H), 2.99 ( , J(H,H) =
7.7 Hz, 2H), 2.83 ( , J(H,H) = 7.7 Hz, 2H), 2.22 (s, 3H) ppm. 13C{1H} NMR (CDCl3, 100 MHz):
δ = 168.5, 149.0, 140.9, 134.3, 128.4 (4C), 128.3 (2C), 128.2 (2C), 127.1, 126.1, 116.4, 36.1,
35
33.3, 20.9 ppm. IR ( ilm): ν = 1757 (s, C=O), 1602 (m, C=C) cm-1. HRMS (ESI) m/z: [M+Na]+
Calcd o C18H18O2Na 289.1204; Found 289.1199.
(Z)-1,5-Diphenylpen -1-en-2-yl ace a e (1s): o ange oil. Yield: 0.221 g (79%). 1H NMR
(CDCl3, 400 MHz): δ = 7.47 (m, 2H), 7.40 (m, 4H), 7.30 (m, 4H), 6.08 (s, 1H), 2.80 ( , J(H,H) =
10.2 Hz, 2H), 2.54 ( , J(H,H) = 10.2 Hz, 2H), 2.26 (s, 3H), 1.99 (m, 2H) ppm. 13C{1H} NMR
(CDCl3, 100 MHz): δ = 168.5, 149.4, 141.8, 134.4, 128.5 (2C), 128.4 (4C), 128.2 (2C), 127.1,
125.9, 116.2, 35.2, 33.9, 28.5, 21.1 ppm. IR ( ilm): ν = 1755 (s, C=O), 1602 (m, C=C) cm-1.
HRMS (ESI) m/z: [M+Na]+ Calcd o C19H20O2Na 303.1361; Found 303.1356.
(Z)-1-Phenyl-2-(4-( i luo ome hyl)phenyl) inyl ace a e (1ab): yellow solid. Mp: 46-49
ºC. Yield: 0.129 g (42%). 1H NMR (CDCl3, 400 MHz): δ = 7.62 (b s, 4H), 7.56 (m, 2H), 7.41
(m, 3H), 6.73 (s, 1H), 2.32 (s, 3H) ppm. 13C{1H} NMR (CDCl3, 100 MHz): δ = 168.4, 148.5,
138.1, 135.2, 129.4 (q, J(C,F) = 32.4 Hz), 129.3, 128.9 (4C), 125.6 (q, 2C, J(C,F) = 3.6 Hz),
125.1 (2C), 124.2 (q, J(C,F) = 270.3 Hz), 115.6, 21.2 ppm. 19F{1H} NMR (CDCl3, 376 MHz): δ
= -62.6 ppm. IR (KB ): ν = 1753 (s, C=O), 1615 (m, C=C) cm-1. HRMS (ESI) m/z: [M+Na]+
Calcd o C17H13F3O2Na 329.0765; Found 329.0761.
(Z)-2-(4-Me hoxyphenyl)-1-phenyl inyl ace a e (1ac):48 yellow solid. Yield: 0.201 g
(75%).
(Z)-2-(4-Phenoxyphenyl)-1-phenyl inyl ace a e (1ad): yellow solid. Mp: 122-124 ºC.
Yield: 0.238 g (72%). 1H NMR (CDCl3, 300 MHz): δ = 7.51 (m, 4H), 7.35 (m, 5H), 7.14 (m,
1H), 7.05 (m, 2H), 6.99 (m, 2H), 6.68 (s, 1H), 2.33 (s, 3H) ppm. 13C{1H} NMR (CDCl3, 75
MHz): δ = 168.7, 157.0, 156.8, 146.0, 135.7, 130.3 (2C), 130.0 (2C), 129.4, 128.8 (2C), 128.7,
124.7 (2C), 123.8, 119.4 (2C), 118.7 (2C), 116.2, 21.3 ppm. IR (KB ): ν = 1761 (s, C=O), 1607
(m, C=C) cm-1. HRMS (ESI) m/z: [M+Na]+ Calcd o C22H18O3Na: 353.1154; Found 353.1149.
36
(Z)-1-Phenyl-2-( hiophen-3-yl) inyl ace a e (1ae): yellow solid. Mp: 103-105 ºC. Yield:
0.195 g (80%). 1H NMR (CDCl3, 300 MHz): δ = 7.55 (m, 2H), 7.37 (m, 6H), 6.80 (s, 1H), 2.38
(s, 3H) ppm. 13C{1H} NMR (CDCl3, 75 MHz): δ = 168.6, 145.7, 135.3, 135.2, 128.7 (2C), 128.6,
127.8, 125.7, 124.6 (2C), 124.4, 111.3, 21.2 ppm. IR (KB ): ν = 1755 (s, C=O), 1595 (m, C=C)
cm-1. HRMS (ESI) m/z: [M+Na]+ Calcd o C14H12O2SNa 267.0456; Found 267.0449.
Syn hesis o (Z)-1-phenyldec-2-en-2-yl ace a e (1a ): unde an a gon a mosphe e, [Pd(PPh3)4]
(0.04 g, 0.034 mmol) and THF (5.0 mL) we e in oduced in o a Te lon-capped sealed ube,
ollowed by TMEDA (0.280 mL; 1.9 mmol) and (Z)-1-iodo-3-phenylp op-1-en-2-yl ace a e (0.5
g, 1.7 mmol). n-Hep ylzinc b omide (0.5 M in THF; 3.8 mL, 1.9 mmol) was hen added
d opwise o he sealed ube and he eac ion mix u e s i ed a oom empe a u e o 12 h. A e
ha ime, he eac ion was quenched wi h sa u a ed NH4Cl solu ion and he p oduc ex ac ed
wi h dichlo ome hane, d ied o e MgSO4 and he sol en emo ed in acuo. The c ude eac ion
mix u e was hen pu i ied by column ch oma og aphy o e silica gel using die hyl e he / hexane
(1:50) as eluen , yielding (Z)-1a in 10% yield.
(Z)-1-Phenyldec-2-en-2-yl ace a e (1a ): yellow oil. Yield: 0.047 g (10%). 1H NMR
(CDCl3, 300 MHz): δ = 7.31 (m, 2H), 7.23 (m, 3H), 5.03 ( , J(H,H) = 7.3 Hz, 1H), 3.51 (s, 2H),
2.09 (s, 3H), 1.93 (q, J(H,H) = 7.1 Hz, 2H), 1.31 (m, 10H), 0.88 ( , J(H,H) = 6.5 Hz, 3H) ppm.
13C{1H} NMR (CDCl3, 75 MHz): δ = 169.0, 147.4, 137.6, 129.2 (2C), 128.5 (2C), 126.7, 118.6,
40.0, 31.9, 29.3, 29.2, 29.1, 25.6, 22.8, 20.8, 14.2 ppm. IR ( ilm): ν = 1760 (s, C=O), 1605 (m,
C=C) cm-1. HRMS (ESI) m/z: [M+Na]+ Calcd o C18H26O2Na: 297.1830; Found 297.1825.
37
Gene al p ocedu e o asymme ic hyd ogena ion: in a glo ebox, a solu ion o 4 (0.5 µmol) and
subs a e 1 (0.05 mmol) in 1,2-dichlo oe hane (0.5 mL) was placed in a HEL CAT-18 o in a
HEL 16 mL eac o . The eac o was pu ged wi h hyd ogen and inally p essu ized a 4 ba .
Deu e a ion eac ions we e p epa ed in he 16 mL eac o , deoxygena ing i wi h a gon and
acuum cycles and inally p essu izing i unde 4 ba D2. The eac ion was hea ed a 40 ºC and
magne ically s i ed o 24 h. Then, he eac o was dep essu ized and he esul ing solu ion
slowly e apo a ed unde acuum. The emaining esidue was analyzed by 1H NMR o de e mine
con e sion and subsequen ly dissol ed in a i-P OH / n-hexane (1:10) mix u e and passed h ough
a sho pad o silica gel o emo e ca alys decomposi ion p oduc s. The solu ion ob ained was
ca e ully e apo a ed and he esidue ob ained was analyzed by chi al ch oma og aphy o
de e mine enan iome ic excess as desc ibed below. Racemic mix u es we e ob ained by
hyd ogena ion o 1 wi h comme cially a ailable [Rh(COD)(DiPFc)]BF4 [DiPFc = 1,1’-
bis(diisop opylphosphino) e ocene] wi h he excep ion o 5p. In he hyd ogena ion o 1p a
complex mix u e was obse ed and ( ac)-5p was al e na i ely p epa ed by acyla ion o 1-
cyclop opyl-2-phenyle han-1-ol.21
sec-Bu yl benzoa e (5a): Chi alcel OB-H, n-hexane, low 1.0 mL/min, 1 = 7.6 min (R), 2
= 8.2 min (S).
Hexan-3-yl benzoa e (5b): Chi alcel AD-H, 99:1 n-hexane:i-P OH, low 0.5 mL/min, 1 =
9.2 min (R), 2 = 9.4 min (S).
Oc an-2-yl benzoa e (5c): Chi alcel AD-H, n-hexane, low 1.0 mL/min, 1 = 20.0 min (R),
2 = 21.8 min (S).
1-Cyclohexylp opan-2-yl benzoa e (5d): Chi alcel OB-H, n-hexane, low 1.0 mL/min, 1
= 5.2 min (R), 2 = 6.3 min (S).

38
1-(4-Me hoxyphenyl)p opan-2-yl ace a e (5e): Chi alcel AD-H, 99:1 n-hexane:i-P OH,
low 1.0 mL/min, 1 = 10.4 min (R), 2 = 11.0 min (S).
1-(4-Me hylphenyl)p opan-2-yl ace a e (5 ): Chi alcel AD-H, 99:1 n-hexane:i-P OH,
low 1.0 mL/min, 1 = 12.4 min (R), 2 = 15.6 min (S).
1-(4-Fluo ophenyl)p opan-2-yl ace a e (5g): Chi alcel AD-H, n-hexane, low 1.0
mL/min, 1 = 22.0 min (R), 2 = 24.7 min (S).
1-(2-Me hoxyphenyl)p opan-2-yl ace a e (5h): Chi alcel OB-H, n-hexane, low 1.0
mL/min, 1 = 29.2 min (S), 2 = 32.8 min (R).
1-(3,4-Dime hoxyphenyl)p opan-2-yl ace a e (5i): Chi alcel AD-H, 98:2 n-hexane:i-
P OH, low 1.0 mL/min, 1 = 22.9 min (R), 2 = 24.9 min (S).
1-Phenylbu an-2-yl ace a e (5j): Chi alcel AD-H, n-hexane, low 1.0 mL/min, 1 = 23.3
min (S), 2 = 25.8 min (R).
1-Phenylpen an-2-yl ace a e (5k): Chi alcel OB-H, n-hexane, low 1.0 mL/min, 1 = 14.8
min (S), 2 = 16.9 min (R).
1-Phenylhexan-2-yl ace a e (5l): Chi alcel OB-H, n-hexane, low 1.0 mL/min, 1 = 16.8
min (R), 2 = 18.1 min (S).
1-Phenylhep an-2-yl ace a e (5m): Chi alcel OB-H, n-hexane, low 1.0 mL/min, 1 = 18.2
min (R), 2 = 22.8 min (S).
1-Phenyloc an-2-yl ace a e (5n): Chi alcel OB-H, n-hexane, low 1.0 mL/min, 1 = 9.7
min (R), 2 = 10.8 min (S).
5-Me hyl-1-phenylhexan-2-yl ace a e (5o): Chi alcel OB-H, n-hexane, low 1.0 mL/min,
1 = 12.8 min (R), 2 = 15.3 min (S).
39
1-Cyclop opyl-2-phenyle hyl ace a e (5p): Chi alcel OB-H, 99:1 n-hexane:i-P OH, low
1.0 mL/min, 1 = 17.5 min (S), 2 = 18.8 min (R).
1-Cyclohexyl-2-phenyle hyl ace a e (5q): Chi alcel OB-H, n-hexane, low 1.0 mL/min, 1
= 7.3 min (R), 2 = 8.1 min (S).
1,4-Diphenylbu an-2-yl ace a e (5 ): Chi alcel AD-H, 99.5:0.5 n-hexane:i-P OH, low
1.0 mL/min, 1 = 10.6 min (R), 2 = 11.7 min (S).
1,5-Diphenylpen an-2-yl ace a e (5s): Chi alcel AD-H, 99.5:0.5 n-hexane:i-P OH, low
1.0 mL/min, 1 = 8.6 min (S), 2 = 12.0 min (R).
1-(4-Fluo ophenyl)oc an-2-yl ace a e (5 ): Chi alcel AD-H, 98:2 n-hexane:i-P OH, low
1.0 mL/min, 1 = 13.9 min (S), 2 = 15.0 min (R).
1-(4-Me hoxyphenyl)oc an-2-yl ace a e (5u): Chi alcel OB-H, 99:1 n-hexane:i-P OH,
low 1.0 mL/min, 1 = 9.9 min (R), 2 = 11.5 min (S).
1-(4-Me hylphenyl)oc an-2-yl ace a e (5 ): Chi alcel OB-H, n-hexane, low 1.0 mL/min,
1 = 14.4 min (R), 2 = 18.2 min (S).
1-(4-Chlo ophenyl)oc an-2-yl ace a e (5w): Chi alcel OB-H, n-hexane, low 1.0 mL/min,
1 = 15.5 min (R), 2 = 20.7 min (S).
1-([1,1'-Biphenyl]-4-yl)oc an-2-yl ace a e (5x): Chi alcel AD-H, 98:2 n-hexane:i-P OH,
low 1.0 mL/min, 1 = 12.5 min (S), 2 = 14.0 min (R).
1-(3,4-Dime hoxyphenyl)oc an-2-yl ace a e (5y): Chi alcel OB-H, 95:5 n-hexane:i-P OH,
low 0.7 mL/min, 1 = 20.0 min (R), 2 = 22.9 min (S).
1-(3,5-Dime hoxyphenyl)oc an-2-yl ace a e (5z): Chi alcel AD-H, 98:2 n-hexane:i-P OH,
low 1.0 mL/min, 1 = 12.9 min (S), 2 = 13.5 min (R).
40
1,2-Diphenyle hyl hep anoa e (5aa): Chi alcel OB-H, n-hexane, low 1.0 mL/min, 1 =
7.7 min (R), 2 = 8.3 min (S).
1-Phenyl-2-(4-( i luo ome hyl)phenyl)e hyl ace a e (5ab): Chi alcel AD-H, 99:1 n-
hexane:i-P OH, low 1.0 mL/min, 1 = 7.2 min (S), 2 = 8.9 min (R).
2-(4-Me hoxyphenyl)-1-phenyle hyl ace a e (5ac): Chi alcel AD-H, 99:1 n-hexane:i-
P OH, low 1.0 mL/min, 1 = 14.0 min (R), 2 = 21.5 min (S).
2-(4-Phenoxyphenyl)-1-phenyle hyl ace a e (5ad): Chi alcel AD-H, 97:3 n-hexane:i-
P OH, low 0.6 mL/min, 1 = 13.3 min (S), 2 = 14.2 min (R).
1-Phenyl-2-( hiophen-3-yl)e hyl ace a e (5ae): Chi alcel OB-H, 97:3 n-hexane:i-P OH,
low 1.0 mL/min, 1 = 10.0 min (R), 2 = 12.3 min (S).
1-Phenyldecan-2-yl ace a e (5a ): Chi alcel AD-H, 99:1 n-hexane:i-P OH, low 1.0
mL/min, 1 = 6.6 min (R), 2 = 7.5 min (S).
De e mina ion o con igu a ion o p oduc s 5: o p oduc s 5a,49 5c,11d 5d,11d 5e,50 5g51 and 5h52
con igu a ion was assigned by compa ison o he sign o op ical o a ion wi h ha desc ibed in
he li e a u e. Fo compounds 5b, 5 , 5i and 5j con igu a ion was assigned by analogy wi h he
p e ious da a. Fo es e 5n con igu a ion was de e mined by deacyla ion and compa ison o he
sign o op ical o a ion o he esul ing alcohol wi h ha desc ibed in he li e a u e.53 Fo
compounds 5k-5m, 5o and 5 -5z con igu a ion was assigned assuming an analogous
s e eochemical cou se o he hyd ogena ion wi h ha o 5n. In addi ion, con igu a ion o 5ac was
assigned upon compa ison o he sign o op ical o a ion wi h ha desc ibed in he li e a u e,54
while con igu a ion o p oduc s 5aa, 5ab, 5ad and 5ae we e assigned by analogy wi h he la e
41
da a. Finally, o 5a , con igu a ion was assigned assuming an analogous s e eochemical cou se
o he hyd ogena ion wi h ha o 5b and 5c.
Cha ac e iza ion o compounds 5: ull cha ac e iza ion o p oduc s 5e-i, 5k-q and 5 -z has been
epo ed in ou p elimina y communica ion.21
(S)-sec-Bu yl benzoa e (5a):49 ob ained acco ding o he gene al p ocedu e (S/C = 100) as
a pale yellow oil using 4d and DCM, ins ead o DCE, as sol en (8.4 mg, 94 % yield, 99 % ee).
Al e na i ely, ob ained using 0.5 mmol 1a and 0.5 µmol 4d in DCE (0.5 mL) unde 20 ba H2 a
40 ºC o 24 h (83.0 mg, 93 % yield, 95 % ee).
(R)-Hexan-3-yl benzoa e (5b):19 ob ained acco ding o he gene al p ocedu e (S/C = 100)
as a pale yellow oil using 4a (9.8 mg, 95 % yield, 99 % ee). [α]D20 = -2.1° (c 1.1, CHCl3, 99 %
ee).
(R)-Oc an-2-yl benzoa e (5c):11d ob ained acco ding o he gene al p ocedu e (S/C = 100)
as a pale yellow oil using 4a (11.7 mg, 94 % yield, 99 % ee).
(R)-2,3-Dideu e o-oc an-2-yl benzoa e (5c-d2): ob ained acco ding o he gene al
p ocedu e (S/C = 100) as a pale yellow oil using 4a unde 4 ba D2 (11.1 mg, 93 % yield, 96 %
ee). 1H NMR (CDCl3, 400 MHz):

= 8.04 (d, J(H,H) = 8.1 Hz, 2H), 7.55 ( , J(H,H) = 7.3 Hz,
1H), 7.44 ( , J(H,H) = 7.7 Hz, 2H), 1.71 (m, 0.7 H, CDH majo dias e eome ), 1.58 (m, 0.3 H,
CDH mino dias e eome ), 1.32 (m, 11H), 0.87 ( , J(H,H) = 6.5 Hz, 3H) ppm. 2H NMR (CHCl3,
61 MHz):

= 5.14 (b s), 1.71 (b s, CDH mino dias e eome ), 1.59 (b s, CDH majo
dias e eome ) ppm. 13C{1H} NMR (CDCl3, 100 MHz):

= 166.3, 132.8, 131.1 (2C), 129.6 (2C),
128.4, 70.1 ( , J(C,D) = 19 Hz), 35.7 ( , J(C,D) = 19 Hz), 31.9, 29.3, 25.6, 22.7, 20.1, 14.2 ppm.
48
3H), 1.62 (s, 9H), 1.59 (d, J(H,P) = 13.6 Hz, 9H), 1.38 (s, 9H), 1.26 (d, J(H,P) = 13.1 Hz, 9H)
ppm. 31P{1H} NMR (CD2Cl2, 162 MHz):

= 121.3 (dd, J(P,Rh) = 250 Hz, J(P,P) = 48 Hz), 23.9
(dd, J(P,Rh) = 134 Hz, J(P,P) = 48 Hz) ppm. 13C{1H} NMR (CD2Cl2, 100 MHz):

= 145.5 (d,
J(C,P) = 8 Hz), 144.9 (d, J(C,P) = 14 Hz), 137.5 (d, J(C,P) = 2 Hz), 137.4 (d, J(C,P) = 4 Hz),
136.7 (d, J(C,P) = 1 Hz), 136.0 (d, J(C,P) = 2 Hz), 134.5 (d, J(C,P) = 2 Hz), 134.4 (d, J(C,P) = 2
Hz), 129.5 (d, J(C,P) = 2 Hz), 129.5 (d, J(C,P) = 2 Hz), 128.9, 128.8, 114.2 (dd, J(C,P) = 11 Hz,
J(C-Rh) = 5Hz), 101.8 (dd, J(C,P) = 14 Hz, J(C,Rh) = 5Hz), 99.3 (dd, J(C,P) = 10 Hz, J(C,Rh) =
4 Hz), 84.0 (dd, J(C,P) = 13 Hz, J(C,Rh) = 7 Hz), 65.2, 39.7 (d, J(C,P) = 14 Hz), 38.9 (d, J(C,P)
= 11 Hz), 35.2, 35.0, 32.8, 32.2, 31.8, 31.6 (d, J(C,P) = 5 Hz), 30.1, 30.1, 29.9 (d, J(C,P) = 4
Hz), 27.8, 20.5, 20.3, 20.2 (dd, J(P,P) = 20 Hz, J(P,P) = 7 Hz), 16.6, 16.3 ppm. Elem Anal Calcd
(%) o C42H66BF4O3P2Rh: C 57.94, H 7.64; Found: C 57.51, H 7.44.
Suppo ing In o ma ion. Selec ed NMR spec a and ch oma og ams. This ma e ial is a ailable
ee o cha ge ia he In e ne a h p://pubs.acs.o g/.
Acknowledgemen s
We g a e ully hank Minis e io de Economia, Indus ia y Compe i i idad o Spain (G an s
CTQ2013-42501-P, CTQ2013-40591-P, CTQ2016-75193-P, CTQ2016-75986-P and CTQ2016-
81797-REDC; AEI/FEDER, UE) and he Regional Go e nmen o As u ias (P ojec GRUPIN14-
006) o inancial suppo .
Re e ences

49
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