N-α-Benzyloxyacetyl derivatives of (S)-4-benzyl-5,5- dimethyloxazolidin-2-one for the asymmetric synthesis of differentially protected α,β-dihydroxyaldehydes

Tetrahedron 60 (2004) 7553–7577

N-a-Benzyloxyacetyl derivatives of (S)-4-benzyl-5,5-

dimethyloxazolidin-2-one for the asymmetric synthesis of

differentially protected a,b-dihydroxyaldehydes

*

Stephen G. Davies, Ian A. Hunter, Rebecca L. Nicholson, Paul. M. Roberts, Edward D. Savory

and Andrew D. Smith

Department of Organic Chemistry, University of Oxford, Chemistry Research Laboratory, Mansﬁeld Road, Oxford OX1 3TA, UK

Received 29 March 2004; revised 19 May 2004; accepted 31 May 2004

Abstract—a-Dibenzylamino- and a-benzyloxy- derivatives of N-acetyl-(S)-4-benzyl-5,5-dimethyloxazolidin-2-one readily undergo highly

stereoselective boron mediated syn-aldol reactions with a range of aromatic and aliphatic aldehydes, generating the syn-aldol products in

good to excellent yields as single diastereoisomers after puriﬁcation. In the a-dibenzylamino series, deprotection of the functionalised aldol

fragments to the corresponding a-amino-b-hydroxy methyl ester or a-amino-b-hydroxyaldehyde proved problematic, with a range of N- and

O-protecting groups giving mixtures of products arising from endocyclic and exocyclic cleavage pathways. However, in the a-benzylox₀y

series, O-silyl protection of the aldol products, and subsequent DIBAL reduction gives stereoselectively the corresponding N-1 -

hydroxyalkyloxazolidin-2-ones, which undergo base promoted fragmentation to the desired highly functionalised and differentially protected

a,b-dihydroxyaldehydes in good yields and without loss of stereochemical integrity.

1. Introduction

Enantiomerically pure aldehydes are versatile synthetic

intermediates that are utilised widely for a range of complex

synthetic transformations. As only limited structural

variations of such species are available indirectly from the

chiral pool, the majority of enantiomerically enriched

aldehydes are synthesised using chiral auxiliary tech-

niques.¹In this area, we have demonstrated previously

that diastereoselective enolate alkylation of (S)-N-acyl-4-

benzyl-5,5-dimethyloxazolidin-2-ones, or conjugate

addition to (S)-N-acryloyl-4-phenyl-5,5-dimethyloxazoli-

din-2-ones and reduction of the resulting a- or b-

substituted-N-acyl-5,5-dimethyloxazolidin-2-ones, respect-

ively, with DIBAL afford non-racemic aldehydes directly

without loss of stereochemical integrity (Fig. 1).²This

approach offers signiﬁcant advantages over the two stage

reduction and selective oxidation protocol typically used³to

generate aldehydes from N-acyl oxazolidinones.⁴

As part of a research programme directed toward the de

novo asymmetric synthesis of carbohydrates and amino

sugars,⁵the extension of this strategy to the synthesis of

polyfunctionalised O- and N-containing aldehydes was

Keywords: Asymmetric aldol; a,b-Dihydroxyaldehydes.

*

Figure 1. Synthetic route to enantiomerically enriched a-alkyl and b-alkyl

aldehydes.

Corresponding author. Tel.: þ44-1865-275695; fax: þ44-1865-275633;

e-mail address: steve.davies@chem.ox.ac.uk

doi:10.1016/j.tet.2004.05.123

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S. G. Davies et al. / Tetrahedron 60 (2004) 7553–7577

investigated. It was predicted that the combination of an

asymmetric aldol reaction of an a-alkoxy or a-amino

oxazolidinone 1, combined with subsequent selective

DIBAL reduction of the resulting aldol product 2, would

allow direct access to differentially protected, highly

functionalised syn-a,b-dihydroxy- and syn-a-amino-b-

hydroxy-aldehydes 3 (Fig. 2). Glycolate enolate aldol and

alkylation reactions have been reported in the literature,⁶

with N-acyl oxazolidinones previously shown to impart high

levels of asymmetric induction in these processes.⁷The

generality of the glycolate aldol protocol has yet to be fully

realised, however, and in particular the direct synthesis of

homochiral differentially protected a,b-dihydroxyalde-

hydes via this procedure has not been previously described.

In the a-amino series, Caddick et al. have recently evaluated

the utility of N-acyl-a-aminoimidazolin-2-one derivatives

to undergo boron mediated diastereoselective syn-aldol

reactions for the synthesis of b-substituted a-phenylserine

derivatives, although the diastereoselectivity of the aldol

protocol was found to be highly sensitive to both the

reaction temperature and nature of the boron reagent used.⁸

We report herein our investigations on N-a-aminoacetyl and

N-a-methylbenzyloxyacetyl derivatives of (S)-4-benzyl-

5,5-dimethyloxazolidin-2-one for the asymmetric synthesis

of differentially protected a-amino-b-hydroxy- and a,b-

dihydroxyaldehydes.

Hu¨nig’s base afforded the corresponding (Z)-boron eno-

lates,⁹while treatment of (S)-5 with titanium tetrachloride

and Hu¨nig’s base furnished the (Z)-titanium enolate.¹⁰

Subsequent reaction with benzaldehyde gave the syn-aldol

adduct (4S,1⁰S,2⁰R)-6 as the major product in .63% yield in

each case, and in .85% d.e. The relative conﬁguration of

the newly formed stereogenic centres within 6 were

1

0

assigned as syn- using H NMR (J_{C(2 )H–C(3 )H}5.3 Hz), on

the basis of the well precedented assumption that the C(3⁰)-

hydroxycarbonyl aldol product 6 exists in solution pre-

dominantly in an intramolecularly hydrogen bonded form,¹¹

with the absolute conﬁguration following from the known

stereodirecting preference of oxazolidinone auxiliaries in

simple glycolate aldol reactions.¹²The boron aldol reaction

using the combination of Et₂BOTf and Hu¨nig’s base proved

optimal in terms of both yield and stereocontrol, affording

the syn-aldol adduct 6 in 96% d.e. and in 77% yield as a

single diastereoisomer after chromatographic puriﬁcation

(Scheme 1).

Scheme 1. Reagents and conditions: (i) n-BuLi, THF, 278 8C then

benzyloxyacetyl chloride; (ii) Et₂BOTf, base, DCM, 0 8C then PhCHO,

278 8C to 0 8C; (iii) 9-BBNOTf, base, DCM, 0 8C then PhCHO, 278 8C to

rt; (iv) TiCl₄, ⁱPr₂NEt, PhCHO, DCM, 278 8C.

Having established an efﬁcient synthetic procedure for the

syn-glycolate aldol reaction of (S)-5 with benzaldehyde, the

aldol reaction using (S)-N,N-dibenzylaminoacetyl-5,5-

dimethyloxazolidin-2-one 7 as a chiral glycine enolate

equivalent with benzaldehyde was investigated. Treatment

of the lithium anion of (S)-benzyl-5,5-dimethyl-oxazolidin-

2-one-4 with bromoacetylbromide gave the corresponding

N-a-bromoacetyloxazolidinone in 73% yield, which upon

displacement with dibenzylamine gave the desired a-

dibenzyloxazolidin-2-one 7 in 76% yield. Treatment of 7

with Et₂BOTf and Hu¨nig’s base and subsequent reaction

with benzaldehyde proceeded to₀only 70% conversion, and

gave the syn-aldol product (4S,1 S,2⁰R)-8 in .95% d.e. and

in 60% yield after chromatographic puriﬁcation, with

starting material (S)-7 being returned in 29% yield.

However, the use of 9-BBNOTf and Hu¨nig’s base and

subsequent reaction with benzaldehyde proceeded to

completion, giving (4S,1⁰S,2⁰R)-8 in .95% d.e. and in

85% yield as a single diastereoisomer after puriﬁcation

(Scheme 2).¹³The syn-relative conﬁguration within

(4S,1⁰S,2⁰R)-8 was proven unambiguously via single crystal

X-ray analysis, with the absolute conﬁguration determined

relative to the known (S)-conﬁguration of the auxiliary (Fig.

Figure 2. Proposed synthetic route to a-amino-b-hydroxy- and a-alkoxy-

b-hydroxyaldehydes.

2. Results and discussion

2.1. The development of asymmetric aldol protocols for

N-a-benzyloxyacetyl and N-a-aminoacetyl derivatives

of (S)-4-benzyl-5,5-dimethyl-oxazolidin-2-one

The development of an efﬁcient glycolate syn-aldol protocol

was chosen as the initial goal, with the asymmetric aldol

reaction of (S)-3-benzyloxyacetyl-4-benzyl-5,5-dimethy-

loxazolidin-2-one-5 with benzaldehyde used as a model

system for reaction optimisation. Glycolate oxazolidinone

(S)-5 was prepared by treatment of the lithium anion of (S)-

4-benzyl-5,5-dimethyl-oxazolidin-2-one-4 with benzylox-

yacetyl chloride, giving the desired product (S)-5 in 89%

yield. Treatment of N-acyl-oxazolidin-2-one (S)-5 with

either Et₂BOTf or 9-BBNOTf, followed by triethylamine or

3). ¹H NMR analysis (J_{C(2 )H–C(3 )H}9.8 Hz) indicated a

larger coupling constant for the syn-conﬁguration within 8

than expected upon the basis of intramolecular hydrogen

bonding between the C(3⁰)-hydroxyl and the b-carbonyl. In

0

S. G. Davies et al. / Tetrahedron 60 (2004) 7553–7577

7555

Scheme 2. Reagents and conditions: (i) n-BuLi (1.5 equiv.), THF, 278 8C

then bromoacetyl bromide (1.2 equiv.), 278 8C to rt; (ii) dibenzylamine

(2.2 equiv.), DCM, rt; (iii) Et₂BOTf, base, DCM, 0 8C then PhCHO,

278 8C to 0 8C; (iv) 9-BBNOTf, DCM, 0 8C; ⁱPr₂NEt, 0 8C; PhCHO,

278 8C to rt; MeOH, H₂O_2(aq)

.

Scheme 3. Reagents and conditions: (i) Et₂BOTf, ⁱPr₂NEt, DCM, 0 8C then

RCHO, 278 8C to 0 8C.

cinnamaldehyde using Hu¨nig’s base and either 9-BBNOTf

or Et₂BBOTf as a Lewis acid gave the syn-aldol products

16-20 in .95% d.e. in each case, giving 16-20 as single

diastereoisomers in generally good isolated yields (up to

81%) upon puriﬁcation. In each case, the reaction with

commercially available 9-BBNOTf proceeded to .90%

completion and proved optimal in terms of isolated yield, as

the reaction with in situ-formed Et₂BBOTf consistently

returned between 20 and 30% starting material. Further-

more, in support of the assigned syn-conﬁguration, ¹H NMR

spectroscopic analysis indicated that the coupling constant

0

J_{C(2 )–C(3 )}was .9.1 and ,9.6 Hz in each case, consistent

with that observed in the benzaldehyde derived aldol 8

(Scheme 4).

Figure 3. Chem 3D representation of the X-ray crystal structure of

(4S,1⁰S,2⁰R)-8 (some H omitted for clarity).

this cas₀e, preferential hy₀drogen bonding in solution between

the C(2 )-amino and C(3 )-hydroxyl funct₀ionalities, as found

in the X-ray crystal structure of (4S,1⁰S,2 R)-8, will result in

an approximately anti-periplanar arrangement of C(2⁰)H

and C(3⁰)H, giving the larger coupling constant.

With asymmetric aldol protocols with benzaldehyde estab-

lished in both the a-benzyloxy- and a-dibenzylamino-N-

acetyloxazolidinone series, the generality of these processes

was tested. Treatment of a-benzyloxy-oxazolidinone (S)-5

with Et₂BOTf and Hu¨nig’s base and subsequent reaction

with pentanal, 2-methyl-propanal, 3-methyl-butanal, cinna-

maldehyde, 4-nitrobenzaldehyde, furfural and pyridine-2-

carboxaldehyde gave the syn-aldol products 9-15 in .92%

d.e. in each case. Chromatographic puriﬁcation gave the a-

benzyloxyaldol products 9-15 as single diastereoisomers

and in good isolated yield (64–83%) (Scheme 3). The syn-

conﬁguration within a-alkoxyaldol products 9-15 was

assigned by analogy to that observed in the benzaldehyde

derived aldol product 6. In support of this conﬁgurational

i

Scheme 4. Reagents and conditions: (i) 9-BBNOTf, DCM, 0 8C; Pr₂NEt,

0 8C; RCHO, 278 8C to rt; MeOH, H₂O_2(aq); (ii) Et₂BOTf, ⁱPr₂NEt, DCM,

0 8C then RCHO, 278 8C to 0 8C.

2.2. Asymmetric synthesis of a-alkoxy-b-hydroxy- and

a-amino-b-hydroxy-carbonyls

With the generality of the asymmetric aldol reaction upon

a-benzyloxy- and a-dibenzylamino-oxazolidinones 5 and 7

demonstrated, the cleavage of the functionalised fragment

from the auxiliary to the corresponding aldehyde via

reduction with DIBAL was investigated, with the benzal-

dehyde aldol products 6 and 8 used as model systems for

reaction optimisation. Attempted direct cleavage of glyco-

late aldol product 6 to the a,b-dihydroxy aldehyde with

DIBAL or Red-Al^w4gave a complex mixture of products,

suggesting that O-protection of the free C(3⁰)-hydroxyl

functionality was required. O-Silyl protection of 6 was

readily achieved by treatment with either TMSCl, TESCl,

1

assignment, H NMR spectroscopic analysis indicated that

0

the coupling constant J_{C(2 )–C(3 )}was ,5.0 Hz in each case.

0

In a similar fashion, further application of the glycine enolate

aldolprotocolwasinvestigated.Boronmediatedaldolreaction

of a-dibenzylamino-oxazolidinone 7 with acetaldehyde,

pentanal, 2-methyl-propanal, 3-methyl-butanal and

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S. G. Davies et al. / Tetrahedron 60 (2004) 7553–7577

TBDMSOTf or TBDMSCl and TIPSOTf, giving a range of

O-silyl ethers 21-24 in excellent yields after chromato-

graphic puriﬁcation (Scheme 5). Treatment of the O-TMS,

O-TES and O-TBDMS protected aldols 21-23 with DIBAL

furnished in each case the corresponding stable N-1⁰-

hydroxyalkyloxazolidin-2-ones 25-27 as single diastereo-

isomers in 99, 81 and 99% yields, respectively.¹⁴Although

the conﬁguration at C(1⁰)-within 25-27 was not established

unambiguously, it was assigned as (S) in each case, by

analogy to that proven by X-ray crystal structure analysis on

an analogous N-1⁰-hydroxy-2⁰-benzyloxy-oxazolidin-2-one

(vide infra). Similar treatment of the O-TIPS protected aldol

24 proceeded to only 80% conversion and gave a mixture of

products, from which the stable N-1⁰-hydroxyalkyloxazoli-

din-2-one 28 was isolated as a single diastereoisomer in

64% yield (Scheme 5).

Scheme 6. Reagents and conditions: (i) K₂CO₃, MeOH, H₂O, rt.

With a synthetic protocol established for the synthesis of

differentially protected a,b-dihydroxy aldehydes, derivati-

sation of a-dibenzylamino-b-hydroxyaldol 8 to its corre-

sponding aldehyde was evaluated. Attempted direct

cleavage of aldol 8 to the corresponding aldehyde with

either DIBAL, LiAlH₄or Red-Al^wgave a complex mixture

of products, while reduction with LiBH₄returned only

starting material. The effect of O-silyl protection upon the

product distribution of these cleavage reactions was next

investigated, with TBDMS or TES protection of aldol 8

giving 33 and 35 in good yields. Subsequent direct reduction

of O-TBDMS protected aldol 33 with LiAlH₄returned

starting material at 278 8C, with reduction at 220 or 0 8C

giving a mixture of products, with only a trace of the desired

1

aldehyde by H NMR spectroscopic analysis. Reduction

with LiBH₄, BH₃, NaBH₄or SuperHydride only returned

starting material, while DIBAL reduction returned 20%

starting material and gave the formate ester product of

endocyclic cleavage 34 in 35% yield as the only other

isolable reaction product. Similarly, DIBAL cleavage of O-

TES protected aldol 35 proceeded to only 40% conversion

under standard conditions, returning starting material in

53% yield and giving formate ester 36 in 30% upon

chromatographic puriﬁcation (Scheme 7).

As an alternative strategy for the release of the functiona-

lised fragment from the auxiliary, the cleavage of a-

aminoaldol products 8, 33 and 35 to the corresponding

carboxylic ester was probed. Direct treatment of unpro-

tected aldol 8 with LiOMe in MeOH gave a 66:34 mixture

of the desired a-amino-b-hydroxyester 40¹⁶and (2R,3S)-3-

phenyl-propionamide 37 (the product of endocyclic clea-

vage) in 44 and 19% isolated yield, respectively. Treatment

of O-TBDMS protected aldol 33 with LiOMe in THF

furnished a 23:77 mixture of methyl ester 41 and amide 38,

isolated in 22% yield and 63% yield, respectively, and in

98% d.e. in each case. Similar treatment of O-TES protected

aldol 35 gave a 17:66:17 mixture of methyl ester 42, O-TES

protected amide 39 and C(3⁰)-hydroxy amide 37 in 8, 46 and

11% yield, respectively, and as single diastereoisomers in

each case (Scheme 8).

Scheme 5. Reagents and conditions: (i) TMSCl, imidazole, DMAP, DMF,

rt; (ii) TESCl, imidazole, DMAP, DMF, rt; (iii) TBDMSCl, imidazole,

DMAP, DMF, rt or TBDMSOTf, DMAP, DCM, 0 8C; (iv) TIPSOTf,

DMAP, DCM, 0 8C; (v) DIBAL, DCM, 278 8C.

Previous studies from this laboratory have demonstrated

that stable 1⁰-hydroxyalkyloxazolidin-2-ones such as 25-28

may be considered as masked aldehyde equivalents due to

their controlled fragmentation to the corresponding alde-

hyde upon treatment with base.²Although treatment of O-

TBDMS-protected-1⁰-hydroxyalkyloxazolidin-2-one 27

with DBU in THF/H₂O¹⁵resulted in the formation of a

mixture of aldehyde products, presumably due to epimer-

isation and partial O-silyl deprotection upon fragmentation,

treatment of either the O-TES, O-TBDMS- or O-TIPS-

protected 1⁰-hydroxyalkyloxazolidin-2-ones 26-28 with

K₂CO₃in methanol/water gave the corresponding O-silyl

protected aldehydes 30-32 in 75, 72 and 91% yield,

respectively, and in .95% d.e. i₀n each case. Similar

treatment of the O-TMS-protected 1 -h₀ydroxyalkyloxazoli-

din-2-one 25 gave the unprotected C(3 )-hydroxy aldehyde

29 in 75% yield and .95% d.e. (Scheme 6).

In contrast to the selective exocyclic reduction observed

upon treatment of a-benzyloxyaldols 21-24 with DIBAL,

the product distribution upon attempted cleavage of a-

dibenzylaminoaldols 8, 33 and 35 with either DIBAL or

LiOMe indicates that competitive exo- and endocyclic

cleavage pathways are available in this series. This product

distribution is consistent with the exocyclic C(1⁰)-dibenzyl

S. G. Davies et al. / Tetrahedron 60 (2004) 7553–7577

7557

of a-dibenzylaminoaldols 8, 33 and 35, the effect of

systematically changing the stereodirecting group of the

auxiliary and the N- and O-protecting groups upon the

product distribution upon DIBAL reduction was investi-

gated. The effect of altering the size and nature of the O-

protecting group of aldol product 8 upon DIBAL reduction

was ﬁrst attempted, with O-methylation with trimethylox-

onium tetraﬂuoroborate giving O-Me 43 in 71% yield at

83% conversion. Reduction of 43 with DIBAL gave formate

ester 44 as the exclusive reaction product, giving 44 in 85%

isolated yield as a single diastereoisomer (Scheme 9).

Scheme 7. Reagents and conditions: (i) TBDMSOTf, DMAP, DCM, 0 8C;

(ii) TESOTf, DMAP, DCM, 0 8C; (iii) DIBAL (2 equiv.), DCM, 278 8C.

amino group having an enormous steric and conformational

bias, which, when combined with the preferred confor-

mation of the C(4)-alkyl group within the oxazolidinone,¹⁷

effectively shields both faces of the exocyclic carbonyl from

nucleophilic attack. This steric shielding promotes endo-

cyclic cleavage to compete effectively with the exocyclic

cleavage manifold that is encouraged by incorporation of

the gem-dimethyl group within the₀oxazolidinone.¹⁸With

the less sterically encumbered C(1 )-alkoxy group within

21-24, the exocyclic cleavage pathway that is favoured by

the auxiliary predominates, giving the desired C(1⁰)-

hydroxyalkyloxazolidin-2-ones selectively.

Scheme 9. Reagents and conditions: (i) Me₃O^þBF₄², proton sponge, DCM,

rt; (ii) DIBAL (2 equiv.), DCM, 278 8C.

Altering the nature of the N-protecting groups was next

investigated, with N,N-diallyl-oxazolidinone 45 prepared by

standard protocols. Boron mediated aldol reaction with

0

benzaldehyde gave the syn-aldol product 46 (J_{C(2 ) –}

0

¼9.7 Hz) in .95% d.e., giving 46 as a single

C(3 )

diastereoisomer in 66% yield after puriﬁcation (Scheme

10). The syn-relative conﬁguration within 46 was estab-

lished vi₀a single crystal X-ray analysis, with the absolute

(4S,1⁰S,2 R)-conﬁguration determined relative to the known

(S)-conﬁguration of the auxiliary (Fig. 4).

Scheme 10. Reagents and conditions: (i) n-BuLi (1.5 equiv.), THF, 278 8C

then bromoacetyl bromide (1.2 equiv.), 278 8C to rt; (ii) diallylamine

(2.2 equiv.), DCM, rt; (iii) 9-BBNOTf, DCM, 0 8C; ⁱPr₂NEt, 0 8C; PhCHO,

278 8C to rt then MeOH, H₂O_2(aq)

.

TES-protection of the hydroxyl functionality within N,N-

diallyl 46 gave O-TES-aldol 47, with DIBAL reduction

under standard conditions returning predominantly starting

material (40% isolated yield), and giving poor conversion to

the formate ester product of endocyclic cleavage 48 in 20%

isolated yield (Scheme 11).

Scheme 8. Reagents and conditions: (i) LiOMe, THF, rt.

Lastly, the effect of changing the (S)-4-benzyl oxazolidi-

none 4 to the alanine derived (S)-4-methyl oxazolidinone 49

in the aldol and reduction procedure was evaluated, with the

In an attempt to solve the regioselective cleavage problem

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S. G. Davies et al. / Tetrahedron 60 (2004) 7553–7577

Scheme 12. Reagents and conditions: (i) n-BuLi (1.5 equiv.), THF, 278 8C

then bromoacetyl bromide (1.2 equiv.), 278 8C to rt; (ii) dibenzylamine

(2.2 equiv.), DCM, rt; (iii) 9-BBNOTf, DCM, 0 8C; ⁱPr₂NEt, 0 8C; PhCHO,

278 8C to rt then MeOH, H₂O_2(aq); (iv) TBDMSOTf, DMAP, DCM, 0 8C;

(v) DIBAL (2 equiv.), DCM, 278 8C.

excellent yield; no reaction was observed with the C(4⁰)- or

C(5⁰)-branched alkyl aldol products 10 and 11 under these

conditions. O-TES protection of 10 and 11 was achieved via

treatment with TESCl, giving 55 and 56 in good yield

(Scheme 13). Treatment of the O-silyl protected aldols 54-

59 with DIBAL gave, in each case, the corresponding stable

N-1⁰-hydroxyalkyloxazolidin-2-ones 60-65 as single dia-

stereoisomers and in excellent yield in each case. The

C(2⁰)–C(3⁰)-syn- and C(1⁰)–C(2⁰)-anti-relative conﬁgur-

ation within 3⁰-4-nitrophenyl-1⁰-hydroxyalkyloxazolidin-2-

one 64 was established unambiguously by single crystal

Figure 4. Chem 3D representation of the X-ray crystal structure of

(4S,1⁰S,2⁰R)-46 (some H omitted for clarity).

Scheme 11. Reagents and conditions: (i) TESCl (2.5 equiv.), imidazole

(5 equiv.), DMAP (1 equiv.), DMF, rt; (ii) DIBAL (2 equiv.), DCM,

278 8C.

0

syn-aldol product 51 (J_{C(2 )–C(3 )}¼9.6 Hz) being formed in

high yield as a single diastereoisomer after puriﬁcation from

reaction with the oxazolidinone 50. O-Silyl protection to

give 52 and reduction with DIBAL gave formate ester 53 as

the exclusive reaction product in 96% isolated yield

(Scheme 12).

2.3. Diastereoselective preparation of a range of a,b-

dihydroxyaldehydes

Although not applicable to the preparation of a-amino-b-

hydroxyaldehydes, the efﬁciency and generality of this

asymmetric aldol and reduction methodology for the

synthesis of a range of O-protected a,b-dihydroxyaldehydes

was demonstrated. The glycolate syn-aldol products 9 and

12-14 were treated with either TBDMSOTf or TBDMSCl,

giving the corresponding O-TBDMS ethers 54 and 57-59 in

Scheme 13. Reagents and conditions: (i) TBDMSCl, imidazole, DMAP,

DMF, rt; (ii) TBDMSOTf, DMAP, DCM, 0 8C; (iii) TBDMSCl, imidazole,

DMAP, DMF, rt; (iv) DIBAL, DCM, 278 8C.

S. G. Davies et al. / Tetrahedron 60 (2004) 7553–7577

7559

X-ray structural analysis, with the absolute (4S,1⁰S,2⁰S,3⁰S)-

conﬁguration conﬁrmed relative to the known (S)-conﬁgur-

ation of the auxiliary (Fig. 5).¹⁹The conﬁguration at C(1⁰)-

within N-1⁰-hydroxyalkyloxazolidin-2-ones 60-63 and 65

was assigned by analogy to that observed in the crystal

structure of 64 (Scheme 13).²⁰

dimethyloxazolidin-2-one readily undergo highly stereo-

selective boron mediated syn-aldol reactions with a range of

aromatic and aliphatic aldehydes, generating the aldol

products with high diastereoselectivity and in good to

excellent yields. In the a-dibenzylamino series, deprotec-

tion of the functionalised aldol fragments to the correspond-

ing a-amino-b-hydroxy methyl esters or a-amino-b-

hydroxyaldehydes proved problematic, with competitive

exo- and endocyclic cleavage pathways providing a mixture

of products. However, in the a-benzyloxy series, O-silyl

protection of the aldol products, and subsequent DIBAL

reduction gives stereoselectively the corresponding N-1⁰-

hydroxyalkyloxazolidin-2-ones, which undergo base pro-

moted fragmentation to the desired a-alkoxy-b-hydroxyal-

dehydes in good yields and without loss of stereochemical

integrity. These investigation suggest that while the

glycolate aldol reaction, protection and reduction strategy

is efﬁcient for the production of a,b-hydroxyaldehyde

derivatives, the generation of a-amino-b-hydroxycarbonyl

derivatives is limited using this protocol. The application of

this methodology to the asymmetric synthesis of a range of

natural products, including carbohydrate and amino-sugar

derivatives, and alternative strategies for the production of

a-amino carbonyl derivatives are currently under investi-

gation within our laboratory.

3. Experimental

Figure 5. Chem 3D representation of the X-ray crystal structure of

(4S,1⁰S,2⁰S,3⁰S)-64 (some H omitted for clarity).

3.1. General experimental

Treatment of O-TES protected N-1⁰-hydroxyalkyloxazoli-

din-2-ones 61 and 62 with K₂CO₃in MeOH/H₂O returned

the auxiliary (S)-4 and gave the corresponding aldehydes 67

and 68, respectively, as the major reaction products,

although in each case an unidentiﬁed minor product was

apparent in the crude reaction mixture. Chromatographic

puriﬁcation gave homogenous 67 and 68 in 61 and 69%

isolated yield, respectively, as single diastereoisomers. Base

promoted fragmentation of O-TBDMS protected N-1⁰-

hydroxyalkyloxazolidin-2-ones 60 and 63-65 under the

same conditions gave auxiliary (S)-4 and furnished the

corresponding aldehydes 66 and 69-71, respectively, in

good yields and in .95% d.e. after puriﬁcation.²¹In each

case the desired aldehyde was obtained as a single

diastereoisomer, indicating that no epimerisation occurs

during fragmentation or puriﬁcation (Scheme 14).

All reactions were carried out under nitrogen or argon using

standard vacuum line techniques, using glassware that was

ﬂame dried and cooled under nitrogen. THF was distilled

from sodium/benzophenone ketyl; DCM was distilled from

calcium hydride prior to use. n-Butyllithium was used as a

solution in hexanes and was titrated against diphenylacetic

acid prior to use. DIBAL was used as supplied (Aldrich) as a

1 M solution in hexanes. All other reagents were used as

supplied without further puriﬁcation. Flash column chro-

matography was performed on silica gel (Kieselgel 60).

TLC was performed on Merck aluminium sheets coated

with 0.2 mm silica gel 60 F₂₅₄. Plates were visualised either

by UV light (254 nm), iodine, ammonium molybdate (7%

solution in ethanol) or potassium permanganate (1% in 2%

aqueous acetic acid, containing 7% potassium carbonate).

Infra red spectra were recorded as thin ﬁlms or KBr discs

using a Perkin–Elmer PARAGON 1000 FT-IR spec-

trometer with only selected peaks reported. ¹H NMR

spectra were recorded on Varian Gemini 200 (200 MHz),

Bruker DPX-200 (200 MHz), Bruker DPX-400 (400 MHz),

Bruker AV400 (400 MHz) or Bruker AM-500 (500 MHz)

spectrometers. Chemical shifts (d_H) are reported in parts per

million (ppm) and are referenced to the residual solvent

peak and coupling constants (J) are measured in Hertz. ¹³C

spectra were recorded at 50.31 MHz on the Varian Gemini

200 or the Bruker DPX-200 spectrometers, at 100.62 MHz

on the Bruker DQX-400 or the Bruker DPX-400 spec-

trometers and at 125.77 MHz on the Bruker AM-500

spectrometer. Chemical shifts (d_C) are quoted in ppm and

referenced using residual solvent peaks. Low resolution

mass spectra (m/z) were recorded on either a VG Masslab

20-250 instrument (CI, NH₃) or Platform instrument

Scheme 14. Reagents and conditions: (i) K₂CO₃, MeOH, H₂O, rt.

In conclusion, we have demonstrated that a-benzyloxy and

a-dibenzylamino derivatives of N-acetyl-(S)-4-benzyl-5,5-

7560

S. G. Davies et al. / Tetrahedron 60 (2004) 7553–7577

(APCI). MALDI spectra were recorded on a Micromass

MALDI TOF SPEC 2E spectrometer. Major peaks are

listed with intensities quoted as percentages of the base

peak. Accurate mass measurements were recorded on a

VG Autospec and a Waters 2790-Micromass LCT

electrospray ionisation mass spectrometer operating at a

resolution of 5000 full width half height. Positive ion

spectra were calibrated relative to PEG with tetraoctyl-

ammonium bromide as the internal lock mass. Negative

ion spectra were calibrated relative to poly-^DL-alanine

with leucine enkephalin as the internal lock mass. Optical

rotations were recorded on a Perkin–Elmer 241 polari-

meter, using a path length of 10 cm, in spectroscopic

grade solvents (Aldrich), with concentrations (c) given in

g/100 cm³, solvent and temperature as recorded. Elemen-

tal analyses were obtained by Mrs A. Douglas of the

Inorganic Chemistry Analytical Department using an

Elementar Vario EL combustion elemental analyser.

Melting points were recorded on a Gallenkamp Hot

Stage apparatus and are uncorrected.

vacuo. The crude product was puriﬁed by ﬂash column

chromatography on silica gel.

3.5. Representative procedure 4 for the 9-BBNOTf

mediated aldol additions of N-acyl-oxazolidin-2-ones

9-BBNOTf (1.5 equiv.) was added to a stirred solution of

the N-acyl-oxazolidin-2-one (1.0 equiv.) in CH₂Cl₂at 0 8C.

After stirring for 10 min, i-Pr₂NEt (1.4 equiv.) was added

and the reaction mixture was stirred for a further 20 min.

The reaction was then cooled to 278 8C and freshly distilled

aldehyde (1.1 equiv.) was added via syringe. After stirring

for 30 min, the resultant mixture was warmed to 0 8C and

stirred for a further hour. The reaction was quenched with

MeOH/H₂O₂(v:v 1:1), extracted with CH₂Cl₂, washed with

brine, dried and concentrated in vacuo. The crude product

was puriﬁed by ﬂash column chromatography on silica gel.

3.6. Representative procedure 5 for the DIBAL

reduction of N-acyl-oxazoldin-2-ones

3.2. Representative procedure 1 for the N-acylation of

5,5-dimethyl-oxazoldin-2-ones

DIBAL (2.0 equiv.) was added dropwise to a stirred solution

of N-acyl-oxazolidin-2-one (1.0 equiv.) in CH₂Cl₂at

278 8C. The reaction was quenched at 278 8C after

20 min with saturated aqueous NH₄Cl solution, warmed to

rt and stirred for a further 20 min. The resultant mixture was

ﬁltered through Celite^w(eluent: CH₂Cl₂), dried over

MgSO₄and concentrated in vacuo.

n-BuLi (1.1 equiv.) was added to a stirred solution of the

oxazolidin-2-one (1.0 equiv.) in THF at 278 8C. After

15 min, the acid chloride (1.3 equiv.) was added dropwise

via syringe or via cannula as a solution in THF and stirred at

278 8C for 15 min before being warmed to ambient

temperature. After 2 h, the reaction mixture was quenched

with saturated aqueous NH₄Cl solution and acetic acid,

extracted with EtOAc, washed sequentially with saturated

aqueous NaHCO₃and brine, dried over MgSO₄and

concentrated in vacuo. The crude product was puriﬁed by

ﬂash column chromatography on silica gel.

3.7. Representative procedure 6 for the protection of

aldol adducts with TMSCl, TESCl, TBDMSCl or

TBDPSCl

Imidazole (5.0 equiv.), TMSCl, TESCl, TBDMSCl or

TBDPSCl (2.5 equiv.) and DMAP (0.1 equiv.) were added

sequentially to a solution of N-acyl-oxazolidin-2-one

(1.0 equiv.) in DMF at ambient temperature. After stirring

for 18 h, the reaction was quenched with MeOH, diluted

with Et₂O, washed with water, dried and concentrated in

vacuo. The crude product was puriﬁed by ﬂash column

chromatography on silica gel.

3.3. Representative procedure 2 for the preparation of

2⁰-(dialkylamino)acetyl 5,5-dimethyl-oxazolidin-2-ones

Dialkylamine (2.2 equiv.) was added to a stirred solution

of the N-acyl-oxazolidin-2-one (1.0 equiv.) in CH₂Cl₂at

rt and the reaction mixture stirred for 18 h. The resulting

mixture was partitioned between CH₂Cl₂and H₂O, dried

over MgSO₄and concentrated in vacuo. The crude

product was puriﬁed by ﬂash column chromatography

on silica gel.

3.8. Representative procedure 7 for the protection of

aldol adducts with TBDMSOTf or TIPSOTf

DMAP (1.5 equiv.) and TBDMSOTf (2.0 equiv.) were

added sequentially to a solution of N-acyl-oxazolidin-2-

one (1.0 equiv.) in CH₂Cl₂at 0 8C. After stirring for 18 h,

the reaction was quenched with MeOH, extracted with

CH₂Cl₂, washed with brine, dried and concentrated in

vacuo. The crude product was puriﬁed by ﬂash column

chromatography on silica gel.

3.4. Representative procedure 3 for the Et₂BOTf

mediated aldol addition of N-acyl-oxazolidin-2-ones

CF₃SO₃H (1.2 equiv.) was added to Et₃B (1 M in

hexanes; 1.2 equiv.) at rt then warmed to 40 8C. After

stirring for 10 min, the resultant solution was cooled to

0 8C and added to a solution of N-acyl-oxazolidin-2-one

(1.0 equiv.) in CH₂Cl₂via cannula. After stirring for

10 min, i-Pr₂NEt (1.4 equiv.) was added and the

reaction mixture was stirred for a further 20 min. The

reaction was then cooled to 278 8C and freshly distilled

aldehyde (1.1 equiv.) was added via syringe. After

stirring for 30 min, the resultant mixture was warmed

to 0 8C and stirred for a further hour. The reaction was

quenched with MeOH/H₂O₂(v:v 1:1), extracted with

CH₂Cl₂, washed with brine, dried and concentrated in

3.9. Representative procedure 8 for the fragmentation of

N-1⁰-hydroxyalkyloxazolidin-2-ones with K₂CO₃

K₂CO₃(1.4 equiv.) was added to a suspension of the N-

1⁰-hydroxyalkyloxazolidin-2-one

(1.0 equiv.)

in

MeOH/H₂O (v:v 4:1) at ambient temperature. After

stirring for 15 min, the reaction mixture was diluted

with CH₂Cl₂, washed with water and brine and dried.

The crude product was puriﬁed by ﬂash column

chromatography on silica gel.

S. G. Davies et al. / Tetrahedron 60 (2004) 7553–7577

7561

3.10. Representative procedure 9 for the preparation of

esters from N-acyl-oxazolidin-2-ones

sentative procedure 1, 4 (4.00 g, 19.51 mmol), n-BuLi

(8.59 mL, 21.46 mmol) and bromoacetyl bromide (2.21 mL,

25.36 mmol) in THF (80 mL) furnished (S)-4-benzyl-3-(2⁰-

A solution of n-BuLi (5 equiv.) in MeOH prepared at 0 8C

was added via canula to a stirred solution of N-acyl-

oxazolidin-2-one (1 equiv.) in THF at 278 8C and stirred

for 10 min before warming to ambient temperature. After

18 h the reaction mixture was quenched with pH 7 buffer,

extracted with Et₂O, dried over MgSO₄and concentrated in

vacuo. The crude product was puriﬁed by ﬂash column

chromatography on silica gel.

bromo-acetyl)-5,5-dimethyl-oxazolidin-2-one

16.93 mmol, 87%) as an orange oil after ﬂash column

chromatography.

(5.52 g,

R_f0.23 [3:1 30–40 8C petrol/Et₂O]; [a]²_D⁵¼226.7 (c¼1.0,

CHCl₃); d_H(400 MHz, CDCl₃) 1.39 [3H, s, C(CH₃)_A(-

CH₃)_B], 1.40 [3H, s, C(CH₃)_A(CH₃)_B], 2.91 [1H, dd, J¼9.8,

14.5 Hz, CHCH_AH_BPh], 3.19 [1H, dd, J¼3.7, 14.5 Hz,

CHCH_AH_BPh], 4.45 [1H, d, J¼12.4 Hz, CH_AH_BBr], 4.58

[1H, d, J¼12.4 Hz, CH_AH_BBr], 4.51 [1H, dd, J¼3.7,

9.8 Hz, CHCH₂Ph], 7.24–7.34 [5H, m, PhH]; d_C

(100 MHz, CDCl₃) 22.3, 28.6 [C(CH₃)₂], 28.4 [CH₂Br],

34.9 [CHCH₂Ph], 64.0 [CHCH₂Ph], 83.3 [C(CH₃)₂], 127.0,

128.8, 129.0 [p- and m/o-Ph], 136.4 [i-Ph], 152.1 [CvO

endocyclic], 166.2 [CvO exocyclic]; n_max(KBr disc,

cm²¹) 1778 [CvO]; HRMS C₁₄H₁₇NO₃Br [MH^þ] requires

326.0392. Found 326.0391; m/z APCIþ 326 [100%, MH^þ].

3.10.1. Preparation of (S)-4-benzyl-3-(2⁰-benzyloxyace-

tyl)-5,5-dimethyl-oxazolidin-2-one 5. Following represen-

tative procedure 1, n-BuLi (4.30 mL, 10.73 mmol), (S)-4-

benzyl-5,5-dimethyloxazolidin-2-one 4 (2.00 g, 9.76 mmol)

and PhCH₂OCH₂COCl (2.00 mL, 12.69 mmol) in THF

(80 mL) furnished 5 as a pale yellow oil (3.06 g, 8.68 mmol,

89%) after ﬂash column chromatography.

R_f0.1 [3:1 pentane/Et₂O]; [a]²_D²¼233.9 (c¼1.0, CHCl₃); d_H

(400 MHz, CDCl₃) 1.37 [3H, s, C(CH₃)_A(CH₃)_B], 1.41 [3H, s,

C(CH₃)_A(CH₃)_B], 2.90 [1H, dd, J¼14.4, 9.6 Hz, CHCH_AH_B-

Ph], 3.22 [1H, dd, J¼14.4, 3.9 Hz, CHCH_AH_BPh], 4.53 [1H,

dd, J¼9.6, 3.9 Hz, CHCH₂Ph], 4.62 [2H, s, CH₂OCH₂Ph],

4.62–4.76 [2H, ABq, J¼17.9 Hz, CH₂OCH₂Ph], 7.23–7.41

[10H, m, PhH]; d_C(50 MHz, CDCl₃) 22.8, 29.1 [C(CH₃)₂],

35.6[CHCH₂Ph], 63.8[CHCH₂Ph], 70.2[CH₂OCH₂Ph], 73.9

[CH₂OCH₂Ph], 84.1 [C(CH₃)₂], 127.4, 128.4 [p-Ph], 128.5,

129.0, 129.2, 129.6 [m/o-Ph], 137.2, 137.7 [i-Ph], 153.0

Following representative procedure 2, (S)-4-benzyl-3-(2⁰-

bromo-acetyl)-5,5-dimethyl-oxazolidin-2-one (1.64 g,

5.03 mmol) and (PhCH₂)₂NH (2.12 mL, 11.07 mmol) in

CH₂Cl₂(80 mL) furnished 7 (1.87 g, 4.23 mmol, 84%) as an

orange oil after ﬂash column chromatography.

R_f0.21 [3:1 60–80 8C petrol/Et₂O]; [a]²_D⁵¼215.7 (c¼1.0,

CHCl₃); d_H(400 MHz, CDCl₃) 1.35 [3H, s, C(CH₃)_A(-

CH₃)_B], 1.38 [3H, s, C(CH₃)_A(CH₃)_B], 2.89 [1H, dd, J¼4.1,

14.4 Hz, CHCH_AH_BPh], 3.16 [1H, dd, J¼9.3, 14.4 Hz,

CHCH_AH_BPh], 3.87 [4H, s, CH₂N(CH₂Ph)₂], 3.85–3.98

[2H, ABq, J¼18.6 Hz, CH₂N(CH₂Ph)₂], 4.54 [1H, dd,

J¼4.1, 9.3 Hz, CHCH₃], 7.25–7.43 [10H, m, PhH]; d_C

(100 MHz, CDCl₃) 22.3, 28.5 [C(CH₃)₂], 35.3 [CHCH₂Ph],

55.5 [CH₂N(CH₂Ph)₂], 57.5 [CH₂N(CH₂Ph)₂], 63.1

[CHCH₂Ph], 82.8 [C(CH₃)₂], 126.8, 127.1, 128.3, 128.7,

128.8, 129.1 [p-and m/o-Ph], 136.8, 139.2 [i-Ph], 152.5

[CvO endocyclic], 171.7 [CvO exocyclic]; n_max(thin

ﬁlm, cm²¹) 1776 [CvO]; HRMS C₂₈H₃₁N₂O₃[MH^þ]

requires 443.2335. Found 443.2334; m/z ESþ 443 [100%,

MH^þ].

[CvO exocyclic], [CvO endocyclic]; n_max(thin ﬁlm, cm²¹

)

1774, 1716 [CvO]; C₂₁H₂₃NO₄requires C, 71.37; H, 6.56; N,

3.96%. Found C, 71.11; H, 6.54; N, 3.90%; m/z APCIþ 376

[100%, MNa^þ].

3.10.2. Preparation of (2⁰S,3⁰R,4S)-4-benzyl-3-(2⁰-benzyl-

oxy-3⁰-hydroxy-3-phenyl-propionyl)-5,5-dimethyl-oxa-

zolidin-2-one 6. Following representative procedure 3,

CF₃SO₃H (0.90 mL, 10.20 mmol), Et₃B (10.20 mL,

10.20 mmol), 5 (3.00 g, 8.50 mmol), i-Pr₂NEt (1.92 mL,

11.05 mmol) and PhCHO (0.95 mL, 9.35 mmol) in CH₂Cl₂

(50 mL) furnished 6 (3.01 g, 6.56 mmol, 77%) as a white

solid after ﬂash column chromatography.

3.10.4. Preparation of (2⁰S,3⁰R,4S)-4-benzyl-3-(2⁰-diben-

zylamino-3⁰-hydroxy-3-phenyl-propionyl)-5,5-dimethyl-

oxazolidin-2-one 8. Following representative procedure 4,

9-BBNOTf (5.43 mL, 2.71 mmol), 7 (1.00 g, 2.26 mmol), i-

Pr₂NEt (0.55 mL, 3.16 mmol) and PhCHO (0.25 mL,

2.49 mmol) in CH₂Cl₂(50 mL) furnished 8 (1.05 g,

1.92 mmol, 85%) as a white solid after ﬂash column

chromatography.

R_f0.15 [1:1 pentane/Et₂O]; mp 99–101 8C [pentane/Et₂O];

[a]²_D⁴¼þ1.5 (c¼1.0, CHCl₃); d_H(400 MHz, CDCl₃) 0.95

[3H, s, C(CH₃)_A(CH₃)_B], 1.27 [3H, s, C(CH₃)_A(CH₃)_B],

2.73 [1H, dd, J¼14.5, 9.6 Hz, CHCH_AH_BPh], 2.90 [1H, dd,

J¼14.5, 3.7 Hz, CHCH_AH_BPh], 3.08 [1H, d, J¼5.6 Hz,

CH(OH)], 4.28 [1H, dd, J¼9.6, 3.7 Hz, CHCH₂Ph], 4.51

[2H, s, CHOCH₂Ph], 4.98 [1H, t, J¼5.3 Hz, CH(OH)], 5.57

[1H, d, J¼5.3 Hz, CHOCH₂Ph], 7.19–7.44 [15H, m, PhH];

d_C(50 MHz, CDCl₃) 22.1, 27.8 [C(CH₃)₂], 35.1 [CHCH_2-

Ph], 63.7 [CHCH₂Ph], 73.3 [CHOCH₂Ph], 75.1 [CH(OH)],

80.8 [CHOCH₂Ph], 83.0 [C(CH₃)₂], 126.9, 127.1, 128.1 [p-

Ph], 128.2, 128.3, 128.4, 128.7, 129.0 [m/o-Ph], 136.7,

137.0, 138.7 [i-Ph], 152.3 [CvO endocyclic], 170.7 [CvO

exocyclic]; n_max(KBr disc, cm²¹) 1775, 1703 [CvO];

C₂₈H₂₉NO₅requires 73.18, H, 6.36; N, 3.05%. Found C,

73.13; H, 6.38; N, 3.06%; m/z ESþ 482 [100%, MNa^þ].

R_f0.22 [2:1 30–40 8C petrol/Et₂O]; mp 130 8C [hexane/Et_2-

O]; [a]²_D³¼236.5 (c¼0.80, CHCl₃); d_H(400 MHz, CDCl₃)

0.59 [3H, s, C(CH₃)_A(CH₃)_B], 1.28 [3H, s, C(CH₃)_A(CH₃)_B],

2.84 [2H, m, CHCH_AH_BPh], 3.45 [2H, d, J¼14.2 Hz,

N(CH_AH_BPh)(CH_CH_DPh)], 3.87 [1H, s, OH], 4.05 [2H, d,

J¼14.2 Hz, N(CH_AH_BPh)(CH_CH_DPh)], 4.31 [1H, app. t,

J¼7.3 Hz, CHCH₂Ph], 4.78 [1H, d, J¼9.7 Hz, CH(OH)],

5.26 [1H, d, J¼9.7 Hz, CHN(CH₂Ph)₂], 7.18–7.40 [20H, m,

PhH]; d_C(100 MHz, CDCl₃) 21.7, 26.9 [C(CH₃)₂], 36.1

[CHCH₂Ph], 54.6 [CHN(CH₂Ph)₂], 62.6 [CHCH₂Ph], 66.2

[CH(OH)], 71.8 [CHN(CH₂Ph)₂], 81.9 [C(CH₃)₂], 127.0,

3.10.3. Preparation of (S)-4-benzyl-3-(2⁰-dibenzylamino-

acetyl)-5,5-dimethyl-oxazolidin-2-one 7. Following repre-

7562

S. G. Davies et al. / Tetrahedron 60 (2004) 7553–7577

127.3, 128.1, 128.3, 128.4, 128.7, 129.2, 129.4 [p- and

m/o-Ph], 136.5, 138.7, 139.0 [i-Ph], 151.8 [CvO

endocyclic], 169.9 [CvO exocyclic]; n_max(KBr disc,

cm²¹) 1777, 1691 [CvO]; m/z APCIþ 549 [100%,

MH^þ]; HRMS C₃₅H₃₇N₂O₄[MH^þ] requires 549.2753.

Found 549.2778.

3.10.6. Preparation of (2⁰S,3⁰R,4S)-4-benzyl-3-(2⁰-ben-

zyloxy-3⁰-hydroxy-4⁰-methyl-butryryl)-5,5-dimethyl-

oxazolidin-2-one 10. Following representative procedure

3, CF₃SO₃H (0.13 mL, 1.50 mmol), Et₃B (1.5 mL,

1.50 mmol), 5 (440 mg, 1.25 mmol), i-Pr₂NEt (0.30 mL,

1.75 mmol) and Me₂CHCHO (0.13 mL, 1.38 mmol)

in CH₂Cl₂(20 mL) furnished 10 (407 mg, 0.96 mmol,

77%) as a clear colourless oil after ﬂash column

chromatography.

X-ray crystal structure determination for 8. Data were

collected using an Enraf-Nonius k-CCD diffractometer with

graphite monochromated Cu Ka radiation using standard

procedures at 190 K. The structure was solved by direct

methods (SIR92), all non-hydrogen atoms were reﬁned with

anisotropic thermal parameters. Hydrogen atoms were

added at idealised positions. The structure was reﬁned

using CRYSTALS.²²X-ray crystal structure data for 8

[C₃₅H₃₆N₂O₄]: M¼548.68, orthorhombic, space group P21

R_f0.16 [2:1 30–40 8C petrol/Et₂O]; [a]²_D²¼273.4 (c¼2.25,

CHCl₃); d_H(400 MHz, CDCl₃) 0.96 [3H, d, J¼6.8 Hz,

CH(CH₃)_A(CH₃)_B], 1.03 [3H, d, J¼6.8 Hz, CH(CH₃)_A(-

CH₃)_B], 1.40 [3H, s, C(CH₃)_A(CH₃)_B], 1.42 [3H, s,

C(CH₃)_A(CH₃)_B], 1.86–1.98 [1H, m, CH(CH₃)₂], 2.95

[1H, dd, J¼14.4, 9.2 Hz, CHCH_AH_BPh], 3.15 [1H, dd,

J¼14.4, 4.2 Hz, CHCH_AH_BPh], 3.43 [1H, d, J¼8.2 Hz,

CH(OH)], 4.32 [1H, d, J¼11.2 Hz, CHOCH_AH_BPh], 4.52

[1H, dd, J¼9.2, 4.2 Hz, CHCH₂Ph], 4.57 [1H, d,

J¼11.2 Hz, CHOCH_AH_BPh], 5.29 [1H, d, J¼1.8 Hz,

CHOCH₂Ph], 7.16–7.41 [10H, m, PhH]; d_C(100 MHz,

CDCl₃) 18.7, 19.1 [CH(CH₃)₂], 22.0, 28.4 [C(CH₃)₂], 31.8

[CH(CH₃)₂], 35.4 [CHCH₂Ph], 63.9 [CHCH₂Ph], 72.6

[CHOCH₂Ph], 77.8, 78.1 [CH(OH) and CHOCH₂Ph], 83.6

[C(CH₃)₂], 126.9, 128.1 [p-Ph], 128.3, 128.4, 128.7, 129.2

[m/o-Ph], 136.8, 137.2 [i-Ph], 152.7 [CvO endocyclic],

171.1 [CvO exocyclic]; n_max(thin ﬁlm, cm²¹) 1774, 1705

[CvO]; HRMS C₂₅H₃₂NO₅[MH^þ] requires 426.2280.

Found 426.2279; m/z ESþ 426 [60%, MH^þ], 448 [100%,

MNa^þ].

˚

21 21, a¼10.0206(1) A, b¼29.1014(4) A, c¼10.3865(2) A,

V¼3028.8 A , Z¼4, m¼0.078 mm²¹, colourless block,

3

˚

crystal dimensions¼0.4£0.4£0.4 mm³. A total of 3899

unique reﬂections were measured for 1,u,27 and 3012

reﬂections were used in the reﬁnement. The ﬁnal

parameters were wR₂¼0.054 and R₁¼0.057 [I.1s(I)].

Crystallographic data (excluding structure factors) has

been deposited with the Cambridge Crystallographic

Data Centre as supplementary publication number

CCDC234754. Copies of the data can be obtained,

free of charge, on application to CCDC, 12 Union

Road, Cambridge CB2 1EZ, UK [fax: þ44-1223-336033

or e-mail: deposit@ccdc.cam.ac.uk].

3.10.5. Preparation of (2⁰S,3⁰R,4S)-4-benzyl-3-(2⁰-benzyl-

oxy-3⁰-hydroxy-octanoyl)-5,5-dimethyl-oxazolidin-2-one

9. Following representative procedure 3, CF₃SO₃H

(0.22 mL, 2.55 mmol), Et₃B (2.60 mL, 2.60 mmol), 5

(750 mg, 2.12 mmol), i-Pr₂NEt (0.52 mL, 2.97 mmol) and

Me(CH₂)₄CHO (0.28 mL, 2.33 mmol) in CH₂Cl₂(30 mL)

furnished 9 (754 mg, 1.66 mmol, 79%) as a pale yellow oil

after ﬂash column chromatography.

3.10.7. Preparation of (2⁰S,3⁰R,4S)-4-benzyl-3-(2⁰-benzyl-

oxy-3⁰-hydroxy-5⁰-methyl-hexanoyl)-5,5-dimethyl-oxa-

zolidin-2-one 11. Following representative procedure 3,

CF₃SO₃H (0.15 mL, 1.70 mmol), Et₃B (1.70 mL,

1.70 mmol), 5 (500 mg, 1.41 mmol), i-Pr₂NEt (0.34 mL,

1.98 mmol) and Me₂CHCH₂CHO (0.17 mL, 1.55 mmol) in

CH₂Cl₂(30 mL) furnished 11 (593 mg, 1.35 mmol, 96%) as

a cream solid after ﬂash column chromatography.

R_f0.16 [1:1 pentane/Et₂O]; [a]²_D⁵¼253.5 (c¼2.1, CHCl₃);

d_H(400 MHz, CDCl₃) 0.88 [3H, t, J¼6.8 Hz, CH₂CH_2-

CH₂CH₂CH₃], 1.28–1.35 [4H, m, CH₂CH_AH_BCH_AH_BCH_2-

CH₃] 1.39 [3H, s, C(CH₃)_A(CH₃)_B], 1.40 [3H, s,

C(CH₃)_A(CH₃)_B], 1.39–1.42 [1H, m, CH₂CH_AH_BCH_2-

CH₃], 1.45–1.51 [1H, m, CH₂CH_AH_BCH₂CH₂CH₃],

1.55–1.66 [2H, CH₂CH₂CH₂CH₂CH₃], 2.19 [1H, s,

CH(OH)], 2.90 [1H, dd, J¼9.3, 14.5 Hz, CHCH_AH_BPh],

3.10 [1H, dd, J¼4.0, 14.5 Hz, CHCH_AH_BPh], 3.84 [1H,

app. s, CH(OH)], 4.38 [1H, d, J¼11.4 Hz, CHOCH_AH_BPh],

4.53 [1H, dd, J¼4.0, 9.3 Hz, CHCH₂Ph], 4.58 [1H, d,

J¼11.4 Hz, CHOCH_AH_BPh], 5.17 [1H, d, J¼2.6 Hz,

CHOCH₂Ph], 7.22–7.36 [10H, m, PhH]; d_C(100 MHz,

CDCl₃) 14.0 [CH₂CH₂CH₂CH₃], 22.1, 28.4 [C(CH₃)₂],

22.5, 25.2, 31.7, 34.0 [CH₂CH₂CH₂CH₂CH₃], 35.3

[CHCH₂Ph], 63.9 [CHCH₂Ph], 72.7 [CH(OH)], 72.8

[CHOCH₂Ph], 79.4 [CHOCH₂Ph], 83.5 [C(CH₃)₂], 126.9,

128.1 [p-Ph], 128.4, 128.4, 128.7, 129.1 [m/o-Ph], 136.8,

137.2 [i-Ph], 152.8 [CvO endocyclic], 171.0 [CvO

exocyclic]; n_max(thin ﬁlm, cm²¹) 1775, 1709 [CvO];

C₂₇H₃₅NO₅requires C, 71.50; H, 7.78; N, 3.09%. Found C,

71.09; H, 7.78; N, 3.28%; HRMS C₂₇H₃₅NO₅Na [MNa^þ]

requires 476.2413. Found 476.2409; m/z ESþ 454 [20%,

MH^þ], 476 [60%, MNa^þ].

R_f0.18 [1:1 pentane/Et₂O]; mp 91–92 8C [pentane/Et₂O];

[a]²_D⁵¼255.3 (c¼1.25, CHCl₃); d_H(400 MHz, CDCl₃) 0.90

[3H, d, J¼6.7 Hz, CH(CH₃)_A(CH₃)_B], 0.95 [3H, d,

J¼6.7 Hz, CH(CH₃)_A(CH₃)_B], 1.36–1.43 [1H, m, CH_AH_B-

CH(CH₃)₂], 1.38 [3H, s, C(CH₃)_A(CH₃)_B], 1.41 [3H, s,

C(CH₃)_A(CH₃)_B], 1.56–1.64 [1H, m, CH_AH_BCH(CH₃)₂],

1.73–1.82 [1H, m, CH₂CH(CH₃)₂], 2.26 [1H, s, CH(OH)],

2.89 [1H, dd, J¼9.3, 14.4 Hz, CHCH_AH_BPh], 3.10 [1H, dd,

J¼4.1, 14.4 Hz, CHCH_AH_BPh], 3.96 [1H, s, CH(OH)], 4.40

[1H, d, J¼11.4 Hz, CHOCH_AH_BPh], 4.53 [1H, dd, J¼4.1,

9.3 Hz, CHCH₂Ph], 4.57 [1H, d, J¼11.4 Hz, CHOCH_AH_B-

Ph], 5.16 [1H, d, J¼2.9 Hz, CHOCH₂Ph], 7.16–7.41 [10H,

m, PhH]; d_C(100 MHz, CDCl₃) 22.0, 28.3 [C(CH₃)₂], 22.1,

23.3 [CH(CH₃)₂], 24.5 [CH₂CH(CH₃)₂], 35.3 [CHCH₂Ph],

42.7 [CH₂CH(CH₃)₂], 63.9 [CHCH₂Ph], 70.8 [CH(OH)],

72.9 [CHOCH₂Ph], 80.0 [CHOCH₂Ph], 83.4 [C(CH₃)₂],

126.9, 128.0 [p-Ph], 128.3, 128.4, 128.7, 129.1 [m/o-Ph],

136.8, 137.3 [i-Ph], 152.8 [CvO endocyclic], 171.0 [CvO

exocyclic]; n_max(KBr disc, cm²¹) 1754, 1715 [CvO];

C₂₆H₃₃NO₅requires C, 71.05; H, 7.57; N, 3.19%. Found C,

71.06; H, 7.43; N, 3.23%; HRMS C₂₆H₃₃NO₅Na [MNa^þ]

requires 462.2256. Found 462.2249; m/z ESþ 462 [100%,

MNa^þ].

S. G. Davies et al. / Tetrahedron 60 (2004) 7553–7577

7563

3.10.8. Preparation of (2⁰S,3⁰R,4S)-benzyl-3-(2⁰-benzyl-

oxy-3⁰-hydroxy-5⁰-phenyl-pent-4⁰-enoyl)-5,5-dimethyl-

oxazolidin-2one 12. Following representative procedure 3,

CF₃SO₃H (0.09 mL, 1.02 mmol), Et₃B (1.02 mL,

1.02 mmol), 5 (300 mg, 0.85 mmol), i-Pr₂NEt (0.19 mL,

1.11 mmol) and PhCHvCHCHO (0.12 mL, 0.94 mmol) in

CH₂Cl₂(10 mL) furnished 12 (343 mg, 0.71 mmol, 83%) as

a pale yellow oil after ﬂash column chromatography.

(40 mL) furnished 14 (2.59 g, 5.77 mmol, 81%) as a white

solid after ﬂash column chromatography.

R_f0.15 [1:1 pentane/Et₂O]; mp 83–84 8C [pentane/Et₂O];

d_H(400 MHz, CDCl₃) 1.232 [3H, s, C(CH₃)_A(CH₃)_B], 1.33

[3H, s, C(CH₃)_A(CH₃)_B], 2.77 [1H, dd, J¼14.5, 9.6 Hz,

CHCH_AH_BPh], 2.96 [1H, dd, J¼14.5, 3.7 Hz, CHCH_AH_B-

Ph], 3.06–3.10 [1H, m, CH(OH)], 4.41 [1H, dd, J¼9.6,

3.7 Hz, CHCH₂Ph], 4.536–4.59 [2H, ABq, J¼11.7 Hz,

CHOCH₂Ph], 5.04 [1H, dd, J¼6.9, 5.0 Hz, CH(OH)], 5.67

[1H, d, J¼4.9 Hz, CHOCH₂Ph], 6.34–6.39 [2H, m, ArH],

7.21–7.39 [11H, m, ArH]; d_C(100 MHz, CDCl₃) 22.1, 28.1

[C(CH₃)₂], 35.1 [CHCH₂Ph], 63.8 [CHCH₂Ph], 69.06

[CH(OH)], 73.3 [CHOCH₂Ph], 78.7 [CHOCH₂Ph], 83.3

[C(CH₃)₂], 108.0, 110.5 [CH furan], 126.9, 128.1 [p-Ph],

128.3, 128.7, 128.8, 129.0, 129.1 [m/o-Ph and CH furan],

136.7, 137.0 [i-Ph], 152.2 [i-Ar furan], 152.3 [CvO

endocyclic], 170.0 [CvO exocyclic]; n_max(thin ﬁlm,

cm²¹) 1770, 1704 [CvO]; C₂₆H₂₇NO₆requires C, 69.47;

H, 6.05; N, 3.12%. Found C, 69.35; H, 6.05; N, 3.01%;

[a]²_D⁰¼þ31.9 (c¼1.0, CHCl₃); m/z ESþ 432 [30%,

MH^þ2H₂O], 472 [100%, MNa^þ].

R_f0.11 [3:2 40–60 8C petrol/Et₂O]; [a]²_D⁵¼þ40.6 (c¼0.63,

CHCl₃); d_H(400 MHz, CDCl₃) 1.12 [3H, s, C(CH₃)_A(-

CH₃)_B], 1.31 [3H, s, C(CH₃)_A(CH₃)_B], 2.76–2.82 [2H, m,

CHCH_AH_BPh and CH(OH)], 2.966 [1H, dd, J¼14.5, 3.9 Hz,

CHCH_AH_BPh], 4.45 [1H, dd, J¼9.5, 3.9 Hz, CHCH₂Ph],

4.50–4.60 [3H, m, CHOCH₂Ph and CH(OH)], 5.42 [1H, d,

J¼5.0 Hz, CHOCH₂Ph], 6.29 [1H, dd, J¼6.9, 16.0 Hz,

CHvCHPh], 6.66 [1H, d, J¼15.9 Hz, CHvCHPh], 7.19–

7.38 [15H, m, PhH]; d_C(100 MHz, CDCl₃) 22.1, 28.6

[C(CH₃)₂], 35.3 [CHCH₂Ph], 63.7 [CHCH₂Ph], 73.2

[CHOCH₂Ph], 74.1 [CH(OH)], 79.9 [CHOCH₂Ph], 83.3

[C(CH₃)₂], 126.7 [CHvCHPh], 126.9, 126.9, 128.2 [p-Ph],

128.4, 128.5, 128.5, 128.7, 128.8, 129.1 [m/o-Ph], 132.9

[CHvCHPh], 136.1, 136.7, 137.0 [i-Ph], 152.6 [CvO

endocyclic], 170.5 [CvO exocyclic]; n_max(thin ﬁlm, cm²¹

)

3.10.11. Preparation of (2⁰S,3⁰S,4S)-benzyl-3-(2⁰-benzyl

oxy-3⁰-hydroxy-3⁰-pyridin-2⁰⁰-yl)-5,5-dimethyl-oxazoli-

din-2one 15. Following representative procedure 3,

CF₃SO₃H (0.09 mL, 1.02 mmol), Et₃B (1.02 mL,

1.02 mmol), 5 (300 mg, 0.85 mmol), i-Pr₂NEt (0.19 mL,

1.11 mmol) and ArCHO (0.09 mL, 0.94 mmol) in CH₂Cl₂

(10 mL) furnished 15 (251 mg, 0.55 mmol, 64%) as a clear

colourless oil after ﬂash column chromatography.

1769 [CvO endocyclic], 1713 [CvO exocyclic]; HRMS

C₃₀H₃₁NO₅Na [MNa^þ] requires 508.2100. Found

508.2093; m/z ESþ 508 [50%, MNa^þ].

3.10.9. Preparation of (2⁰S,3⁰R,4S)-4-benzyl-3-(2⁰-benzyl-

oxy-3⁰-hydroxy-3⁰-(4⁰⁰-nitro-phenyl)-propionyl)-5,5-

dimethyl-oxazolidin-2one 13. Following representative

procedure 3, CF₃SO₃H (0.09 mL, 1.02 mmol), Et₃B

(1.02 mL, 1.02 mmol), 5 (300 mg, 0.85 mmol), i-Pr₂NEt

(0.19 mL, 1.11 mmol) and ArCHO (141 mg, 0.94 mmol) in

CH₂Cl₂(20 mL) furnished 13 (350 mg, 0.69 mmol, 82%) as

a peach foam after ﬂash column chromatography.

R_f0.1 [3:2 Et₂O/40–60 8C petrol]; d_H(400 MHz, CDCl₃)

1.39 [3H, s, C(CH₃)_A(CH₃)_B], 1.41 [3H, s, C(CH₃)_A(CH₃)_B],

2.91 [1H, dd, J¼14.5, 9.7 Hz, CHCH_AH_BPh], 3.17 [1H, dd,

J¼14.5, 3.5 Hz, CHCH_AH_BPh], 4.24 [1H, d, J¼12.1 Hz,

CHOCH_AH_BPh], 4.53 [1H, d, J¼12.1 Hz, CHOCH_AH_BPh],

4.58 [1H, dd, J¼9.7, 3.5 Hz, CHCH₂Ph], 4.65 [1H, br s,

CH(OH)], 5.17 [1H, d, J¼1.8 Hz, CH(OH)], 5.51 [1H, d,

J¼3.0 Hz, CHOCH₂Ph], 6.94–8.57 [14H, m, ArH]; d_C

(100 MHz, CDCl₃) 22.2, 28.5 [C(CH₃)₂], 35.1 [CHCH₂Ph],

64.0 [CHCH₂Ph], 72.7 [CHOCH₂Ph], 72.8 [CH(OH)], 80.1

[CHOCH₂Ph], 83.6 [C(CH₃)₂], 120.9, 122.6, 126.8 [p-Ph

and p-Ar], 127.9, 128.2, 128.7, 129.1 [m/o-Ph], 127.8,

136.7, 147.8 [m/o-Ar], 136.7, 137.0 [i-Ph], 152.9 [i-Ar],

157.5 [CvO endocyclic], 170.1 [CvO exocyclic]; n_max

(thin ﬁlm, cm²¹) 1772, 1714 [CvO]; HRMS C₂₇H₂₉N₂O₅

[MH^þ] requires 461.2076. Found 461.2072; [a]²_D⁵¼240.0

(c¼0.6, CHCl₃); m/z APCIþ 206 [25%, SQH^þ], 461 [100%,

MH^þ].

R_f0.18 [1:2 30–40 8C petrol/Et₂O]; [a]²_D²¼224.9 (c¼0.55,

CHCl₃); d_H(400 MHz, CDCl₃) 1.30 [3H, s, C(CH₃)_A

(CH₃)_B], 1.40 [3H, s, C(CH₃)_A(CH₃)_B], 2.91 [1H, dd,

J¼14.4, 9.3 Hz, CHCH_AH_BPh], 3.07 [1H, dd, J¼14.4,

4.3 Hz, CHCH_AH_BPh], 3.30 [1H, d, J¼8.0 Hz, CH(OH)],

4.21 [1H, d, J¼11.7 Hz, CHOCH_AH_BPh], 4.456 [1H, d,

J¼11.7 Hz, CHOCH_AH_BPh], 4.52 [1H, dd, J¼9.2, 4.3 Hz,

CHCH₂Ph], 5.13 [1H, d, J¼4.6 Hz, CH(OH)], 5.38 [1H, d,

J¼2.8 Hz, CHOCH₂Ph], 6.99–7.02 [2H, m, ArH], 7.16–

7.35 [8H, m, ArH], 7.604 [2H, m, ArH], 8.15–8.18 [2H, m,

ArH]; d_C(100 MHz, CDCl₃) 22.1, 28.3 [C(CH₃)₂], 35.2

[CHCH₂Ph], 63.8 [CHCH₂Ph], 72.9 [CHOCH₂Ph], 73.4

[CH(OH)], 79.9 [CHOCH₂Ph], 83.9 [C(CH₃)₂], 127.0,

127.2 [p-Ph], 123.3, 128.2, 128.4, 128.8, 129.1 [m/o-Ph

and m/o-Ar], 136.2, 136.4 [i-Ph], 147.4, 147.6 [i-Ar and p-

Ar], 152.8 [CvO endocyclic], 169.7 [CvO exocyclic];

n_max(KBr disc, cm²¹) 1771, 1710 [CvO]; C₂₈H₂₈N₂O₇

requires C, 66.66; H, 5.59; N, 5.55%. Found C, 66.64; H,

5.71; N, 5.44%.

3.10.12. Preparation of (2⁰S,3⁰R,4S)-4-benzyl-3-(2⁰-diben-

zylamino-3⁰-hydroxy-propionyl)-5,5-dimethyl-oxazoli-

din-2-one 16. Following representative procedure 4, 9-

BBNOTf (2.71 mL, 1.36 mmol), 7 (500 mg, 1.13 mmol), i-

Pr₂NEt (0.28 mL, 1.58 mmol) and MeCHO (0.06 mL,

1.24 mmol) in CH₂Cl₂(30 mL) furnished 16 (447 mg,

0.92 mmol, 81%) as a white solid after ﬂash column

chromatography.

3.10.10. Preparation of (2⁰S,3⁰S,4S)-4-benzyl-3-(2⁰-ben-

zyloxy-3-furan-2-yl-3-hydroxy-propionyl)-5,5-dimethyl-

oxazolidin-2-one 14. Following representative procedure 3,

CF₃SO₃H (0.75 mL, 8.50 mmol), Et₃B (8.50 mL,

8.50 mmol), 5 (2.50 g, 7.08 mmol), i-Pr₂NEt (1.73 mL,

9.91 mmol) and ArCHO (0.64 mL, 7.79 mmol) in CH₂Cl₂

R_f0.35 [1:1 petrol/Et₂O]; mp 100 8C [hexane/Et₂O];

[a]²_D³¼294.9 (c¼0.96, CHCl₃); d_H(400 MHz, CDCl₃)

1.13 [3H, d, J¼7.9 Hz, CHCH₃], 1.34 [3H, s, C(CH₃)_A

7564

S. G. Davies et al. / Tetrahedron 60 (2004) 7553–7577

(CH₃)_B], 1.45 [3H, s, C(CH₃)_A(CH₃)_B], 2.88 [1H, dd,

J¼9.1, 14.3 Hz, CHCH_AH_BPh], 3.08 [1H, dd, J¼4.9,

14.3 Hz, CHCH_AH_BPh], 3.38 [1H, s, OH], 3.48 [2H, d,

J¼14.2 Hz, N(CH_AH_BPh)(CH_CH_DPh)], 3.99–4.06 [1H, m,

CH(OH)], 4.01 [2H, d, J¼14.2 Hz, N(CH_AH_BPh)(CH_CH_D-

Ph)], 4.65 [1H, dd, J¼5.0, 9.0 Hz, CHCH₂Ph], 4.90 [1H, d,

J¼9.2 Hz, CHN(CH₂Ph)₂], 7.18–7.40 [15H, m, Ph]; d_C

(100 MHz, CDCl₃) 18.2 [CHCH₃], 22.2, 28.4 [C(CH₃)₂],

35.8 [CHCH₂Ph], 54.6 [CHN(CH₂Ph)₂], 63.4, 64.5, 66.0

[CHCH₂Ph, CH(OH) and CHN(CH₂Ph)₂], 82.0 [C(CH₃)₂],

127.1, 127.3, 128.4, 128.8, 129.1, 129.2 [p- and m/o-Ph],

136.5, 138.8 [i-Ph], 152.3 [CvO endocyclic], 171.6 [CvO

exocyclic]; n_max(KBr disc, cm²¹) 1777, 1678 [CvO];

C₃₀H₃₄N₂O₄requires C, 74.05; H, 7.04; N, 5.76%. Found C,

74.19; H, 7.31; N, 5.68%; m/z APCIþ 487 [100%, MH^þ].

3.10.13. Preparation of (2⁰S,3⁰R,4S)-4-benzyl-3-(2⁰-diben-

zylamino-3⁰-hydroxy-octanoyl)-5,5-dimethyl-oxazolidin-

2-one 17. Following representative procedure 4, 9-BBNOTf

(4.40 mL, 2.20 mmol), 7 (650 mg, 1.46 mmol), i-Pr₂NEt

(0.36 mL, 2.04 mmol) and Me(CH₂)₄CHO (0.22 mL,

1.61 mmol) in CH₂Cl₂(30 mL) furnished 17 (490 mg,

0.90 mmol, 62%) as a white solid after ﬂash column

chromatography.

J¼14.0 Hz, N(CH_AH_BPh)(CH_CH_DPh)], 3.85 [1H, dd,

J¼2.9, 9.4 Hz, CH(OH)], 4.01 [2H, d, J¼14.0 Hz, N(CH_A-

H_BPh)(CH_CH_DPh)], 4.69 [1H, dd, J¼5.0, 8.9 Hz, CHCH_2-

Ph], 4.97 [1H, d, J¼9.4 Hz, CHN(CH₂Ph)₂], 7.18–7.34

[10H, m, PhH], 7.36–7.42 [5H, m, PhH]; d_C(100 MHz,

CDCl₃) 15.6, 20.6 [CH(CH₃)₂], 22.3, 27.4 [C(CH₃)₂], 30.2

[CH(CH₃)₂], 35.9 [CHCH₂Ph], 54.7 [CHN(CH₂Ph)₂], 62.6

[CHN(CH₂Ph)₂], 63.6 [CHCH₂Ph], 72.3 [CH(OH)], 82.2

[C(CH₃)₂], 127.1, 127.2 [p-Ph], 128.4, 128.8, 129.1, 129.3

[m/o-Ph], 136.5, 138.9 [i-Ph], 152.4 [CvO endocyclic],

171.2 [CvO exocyclic]; n_max(thin ﬁlm, cm²¹) 1775, 1690

[CvO]; HRMS C₃₂H₃₉N₂O₄[MH^þ] requires 515.2910.

Found 515.2933; m/z ESþ 515 [100%, MH^þ], 537 [20%,

MNa^þ].

3.10.15. Preparation of (2⁰S,3⁰R,4S)-4-benzyl-3-(2⁰-diben-

zylamino-3⁰-hydroxy-5-methyl-hexanoyl)-5,5-dimethyl-

oxazolidin-2-one 19. Following representative procedure 4,

9-BBNOTf (2.71 mL, 1.36 mmol), 7 (500 mg, 1.13 mmol),

i-Pr₂NEt (0.18 mL, 1.58 mmol) and Me₂CHCH₂CHO

(0.13 mL, 1.24 mmol) in CH₂Cl₂(30 mL) furnished 19

(372 mg, 0.70 mmol, 62%) as a pale yellow oil and returned

7 (99 mg, 0.22 mmol, 20%) as a pale yellow oil after ﬂash

column chromatography.

Mp 86 8C [hexane/Et₂O]; [a]²_D³¼261.3 (c¼0.93, CHCl₃);

d_H(400 MHz, CDCl₃) 0.85 [3H, t, J¼6.9 Hz, CH₂CH_2-

CH₂CH₂CH₃], 1.17–1.57 [8H, m, CH₂CH₂CH₂CH₂CH₃],

1.33 [3H, s, C(CH₃)_A(CH₃)_B], 1.44 [3H, s, C(CH₃)_A(CH₃)_B],

2.88 [1H, dd, J¼9.0, 14.3 Hz, CHCH_AH_BPh], 3.09 [1H, dd,

J¼4.9, 14.3 Hz, CHCH_AH_BPh], 3.38 [1H, s, CH(OH)], 3.44

[2H, d, J¼13.9 Hz, N(CH_AH_BPh)(CH_CH_DPh)], 3.83–3.90

[1H, m, CH(OH)], 4.01 [2H, d, J¼13.9 Hz, N(CH_AH_B-

Ph)(CH_CH_DPh], 4.65 [1H, dd, J¼4.9, 9.0 Hz, CHCH₂Ph],

4.91 [1H, d, J¼9.1 Hz, CHN(CH₂Ph)₂], 7.22–7.40 [15H, m,

PhH]; d_C(100 MHz, CDCl₃) 14.0 [CH₂CH₂CH₂CH₂CH₃],

22.3, 28.3 [C(CH₃)₂], 22.5, 25.5, 31.6, 33.0 [CH₂CH₂CH_2-

CH₂CH₃], 35.7 [CHCH₂Ph], 54.6 [CHN(CH₂Ph)₂], 63.4,

64.8, 68.3, [CHCH₂Ph, CH(OH), CHN(CH₂Ph)₂], 82.0

[C(CH₃)₂], 127.1, 127.3 [p-Ph], 128.4, 128.8, 129.1, 129.2

[m/o-Ph], 136.5, 138.8 [i-Ph], 152.2 [CvO endocyclic],

171.6 [CvO exocyclic]; n_max(KBr disc, cm²¹) 3425 [O–

H] 1775, 1700 [CvO] C₃₄H₄₂N₂O₄requires C, 75.25; H,

7.8; N 5.2%. Found C, 75.5; H, 8.0; N, 5.1%; m/z APCIþ

543 [100%, MH^þ].

R_f0.19 [3:1 30–40 8C petrol/Et₂O]; [a]²_D⁵¼253.5 (c¼1.15,

CHCl₃); d_H(400 MHz, CDCl₃) 0.92–1.34 [7H, m,

CH(CH₃)₂and CH_AH_BCH(CH₃)₂], 1.34 [3H, s, C(CH₃)_A

(CH₃)_B], 1.40–1.50 [1H, m, CH_AH_BCH(CH₃)₂], 1.45 [3H,

s, C(CH₃)_A(CH₃)_B], 1.81–1.90 [1H, m, CH₂CH(CH₃)₂],

2.89 [1H, dd, J¼9.0, 14.3 Hz, CHCH_AH_BPh], 3.10 [1H, dd,

J¼5.0, 14.3 Hz, CHCH_AH_BPh], 3.34 [1H, s, CH(OH)], 3.44

[2H, d, J¼14.0 Hz, N(CH_AH_BPh)(CH_CH_DPh)], 3.89–3.9

[1H, m, CH(OH)], 4.00 [2H, d, J¼14.0 Hz, N(CH_AH_B-

Ph)(CH_CH_DPh)], 4.70 [1H, dd, J¼5.0, 9.0 Hz, CHCH₂Ph],

4.90 [1H, d, J¼9.3 Hz, CHN(CH₂Ph)₂], 7.23–7.51 [15H, m,

PhH]; d_C(100 MHz, CDCl₃) 21.4, 22.3 [CH₂CH(CH₃)₂],

23.8, 24.7 [C(CH₃)₂], 28.4 [CH₂CH(CH₃)₂], 35.8 [CHCH_2-

Ph], 42.1 [CH₂CH(CH₃)₂], 54.7 [CHN(CH₂Ph)₂], 63.4

[CHCH₂Ph], 65.3 [CHN(CH₂Ph)₂], 66.4 [CH(OH)], 82.0

[C(CH₃)₂], 127.1, 127.3 [p-Ph], 128.4, 128.8, 129.1, 129.3

[m/o-Ph], 136.5, 138.9 [i-Ph], 152.3 [CvO endocylic],

171.6 [CvO exocyclic]; n_max(thin ﬁlm, cm²¹) 1775, 1692

[CvO]; C₃₃H₄₀N₂O₄requires C, 74.97; H, 7.63; N, 5.30%.

Found C, 75.09; H, 7.20; N, 5.15%; HRMS C₃₃H₄₁N₂O₄

[MH^þ] requires 529.3066. Found 529.3036; m/z ESþ 529

[100%, MH^þ], 551 [35%, MNa^þ].

3.10.14. Preparation of (2⁰S,3⁰R,4S)-4-benzyl-3-(2⁰-diben-

zylamino-3⁰-hydroxy-4-methyl-pentanoyl)-5,5-dimethyl-

oxazolidin-2-one 18. Following representative procedure 4,

9-BBNOTf (2.71 mL, 1.36 mmol), 7 (500 mg, 1.13 mmol),

i-Pr₂NEt (0.18 mL, 1.58 mmol) and Me₂CHCHO (0.11 mL,

1.24 mmol) in CH₂Cl₂(30 mL) furnished 18 (240 mg,

0.47 mmol, 41%) as a pale yellow oil and returned 7

(168 mg, 0.38 mmol, 34%) as a pale yellow oil after ﬂash

column chromatography.

3.10.16. Preparation of (2⁰S,3⁰R,4S)-4-benzyl-3-(2⁰-diben-

zylamino-3⁰-hydroxy-5⁰-phenyl-pent-4⁰-enoyl)-5,5-

dimethyl-oxazolidin-2-one 20. Following representative

procedure 4, 9-BBNOTf (2.71 mL, 1.36 mmol), 7 (500 mg,

1.13 mmol), i-Pr₂NEt (0.18 mL, 1.58 mmol) and

PhCHvCHCHO (0.13 mL, 1.24 mmol) in CH₂Cl₂

(30 mL) furnished 20 (474 mg, 0.83 mmol, 73%) as a

white solid and returned 7 (124 mg, 0.27 mmol, 24%) as a

pale yellow oil after ﬂash column chromatography.

R_f0.23 [2:1 pentane/Et₂O]; [a]²_D⁵¼288.9 (c¼0.7, CHCl₃);

d_H(400 MHz, CDCl₃) 0.82 [3H, d, J¼6.8 Hz, CH(CH₃)_A

(CH₃)_B], 0.99 [3H, d, J¼6.8 Hz, CH(CH₃)_A(CH₃)_B], 1.34

[3H, s, C(CH₃)_A(CH₃)_B], 1.45 [3H, s, C(CH₃)_A(CH₃)_B],

1.52–1.59 [1H, m, CH(CH₃)₂], 2.97 [1H, dd, J¼9.0,

14.3 Hz, CHCH_AH_BPh], 3.21 [1H, dd, J¼5.0, 14.3 Hz,

CHCH_AH_BPh], 3.31 [1H, s, CH(OH)], 3.44 [2H, d,

R_f0.24 [2:1 30–40 8C petrol/Et₂O]; mp 141–142 8C

[petrol/Et₂O]; [a]_D²⁵¼þ81.3 (c¼0.3, CHCl₃); d_H(400 MHz,

CDCl₃) 0.86 [3H, s, C(CH₃)_A(CH₃)_B], 1.30 [3H, s, C(CH₃)-

_A(CH3)_B], 2.84 [1H, dd, J¼8.4, 14.3 Hz, CHCH_AH_BPh], 2.91

[1H, dd, J¼5.7, 14.3 Hz, CHCH_AH_BPh], 3.51 [2H, d,

S. G. Davies et al. / Tetrahedron 60 (2004) 7553–7577

7565

J¼14.1 Hz, N(CH_AH_BPh)(CH_CH_DPh)], 3.79 [1H, s,

CH(OH)], 4.07 [2H, d, J¼14.1 Hz, N(CH_AH_BPh)(CH_CH_D-

Ph)],4.42–4.54[2H, m,CHCH₂PhandCH(OH)], 5.21[1H,d,

J¼9.6 Hz, CHN(CH₂Ph)₂], 6.13 [1H, dd, J¼8.3, 15.9 Hz,

CHvCHPh], 6.64 [1H, d, J¼15.9 Hz, CHvCHPh], 7.18–

7.59 [20H, m, PhH]; d_C(100 MHz, CDCl₃) 22.0, 27.6

[C(CH₃)₂], 36.0 [CHCH₂Ph], 54.4 [CHN(CH₂Ph)₂], 63.0

[CHCH₂Ph], 64.6 [CHN(CH₂Ph)₂], 71.0 [CH(OH)], 82.0

[C(CH₃)₂], 126.7 [CHvCHPh], 127.3, 127.4, 128.0 [p-Ph],

128.5, 128.7, 129.2, 129.3 [m/o-Ph], 134.2 [CHvCHPh],

136.0, 136.6, 138.7 [i-Ph], 152.2 [CvO endocyclic], 171.0

[CvO exocyclic]; n_max(KBr disc, cm²¹) 1638, 1617 [CvO];

HRMS C₃₇H₃₉N₂O₄[MH^þ] requires 575.2910. Found

575.2901; m/z ESþ 575 [100%, MH^þ].

CDCl₃) 4.7 [Si(CH₂CH₃)₃], 6.6 [Si(CH₂CH₃)₃], 22.1, 27.5

[C(CH₃)₂], 34.9 [CHCH₂Ph], 63.5 [CHCH₂Ph], 73.8

[CHOCH₂Ph], 77.0 [CH(OTES)], 81.5 [CHOCH₂Ph], 82.0

[C(CH₃)₂], 126.7, 127.7, 127.9 [p-Ph], 128.0, 128.1, 128.2,

128.3, 128.6, 128.9 [m/o-Ph], 136.9, 138.0, 139.9 [i-Ph],

151.7 [CvO endocyclic], 171.3 [CvO exocyclic]; n_max

(KBr disc, cm²¹

)

1778, 1700 [CvO]; HRMS

C₃₄H₄₇N₂O₅Si [MNH^þ₄] requires 591.3264. Found

591.3254; m/z ESþ 442 [100%, MH^þ2OTES], 591 [55%,

MNH^þ₄].

3.10.19. Preparation of (2⁰S,3⁰R,4S)-4-benzyl-3-[2⁰-ben-

zyloxy-3⁰-(tert-butyl-dimethyl-silanyloxy)-3⁰⁰-phenyl-

propionyl]-5,5-dimethyl-oxazolidin-2-one 23. Following

representative procedure 6,

6 (210 mg, 0.46 mmol),

3.10.17. Preparation of (2⁰S,3⁰R,4S)-4-benzyl-3-(2⁰-ben-

zyloxy-3⁰-trimethylsilanoxy-3⁰-phenyl-propionyl)-5,5-

dimethyl-oxazolidin-2-one 21. Following representative

procedure 6, 6 (1.24 g, 2.71 mmol), trimethylsilyl chloride

(0.86 mL, 6.78 mmol), imidazole (921 mg, 13.55 mmol)

and DMAP (33 mg, 0.27 mmol) in DMF (5 mL) furnished

21 (1.27 g, 2.38 mmol, 88%) as a white solid after ﬂash

column chromatography.

TBDMSCl (173 mg, 1.14 mmol) imidazole (156 mg,

2.30 mmol) and DMAP (6 mg, 0.05 mmol) in DMF

(3 mL) furnished 23 (258 mg, 0.45 mmol, 98%) as a white

solid after ﬂash column chromatography.

R_f0.15 [10:1 pentane/Et₂O]; mp 85–86 8C [pentane/Et₂O];

[a]²_D⁴¼þ30.4 (c¼1.0, CHCl₃); d_H(400 MHz, CDCl₃)

20.10 [3H, s, Si(CH₃)_A(CH₃)_B], 0.07 [3H, s, Si(CH₃)_A(-

CH₃)_B], 0.57 [3H, s, C(CH₃)_A(CH₃)_B], 0.83 [9H, s,

SiC(CH₃)₃], 1.13 [3H, s, C(CH₃)_A(CH₃)_B], 2.48 [1H, dd,

J¼14.6, 10.0 Hz, CHCH_AH_BPh], 2.67 [1H, dd, J¼14.6,

2.8 Hz, CHCH_AH_BPh], 3.97 [1H, dd, J¼10.0, 3.0 Hz,

CHCH₂Ph], 4.57 [1H, d, J¼12.0 Hz, CHOCH_AH_BPh],

4.81 [1H, d, J¼12.0 Hz, CHOCH_AH_BPh], 4.94 [1H, d,

J¼7.4 Hz, CH(OTBDMS)], 5.67 [1H, d, J¼7.4 Hz,

CHOCH₂Ph], 7.18–7.37 [15H, m, PhH]; d_C(50 MHz,

CDCl₃) 25.0, 24.7 [Si(CH₃)₂], 18.2 [SiC(CH₃)₃], 25.7

[SiC(CH₃)₃], 22.1, 27.4 [C(CH₃)₂], 34.9 [CHCH₂Ph], 63.4

[CHCH₂Ph], 73.9 [CHOCH₂Ph], 77.3 [CH(OTBDMS)],

81.6 [CHOCH₂Ph], 82.0 [C(CH₃)₂], 126.7, 127.7 [p-Ph],

127.9, 128.1, 128.3, 128.3, 128.6, 128.9 [m/o-Ph], 136.9,

137.9, 139.6 [i-Ph], 151.6 [CvO endocyclic], 171.4 [CvO

exocyclic]; n_max(KBr disc, cm²¹) 1778, 1699. [CvO];

C₃₄H₄₃NO₅Si requires C, 71.17; H, 7.55; N 2.44%. Found

C, 71.19; H, 8.01; N, 2.37%; m/z CIþ (NH₃) 442 [87%,

MH^þ2OTBDMS], 530 [20%, MH^þ2CO₂], 591 [3%,

MNH^þ₄].

R_f0.21 [5:1 30–40 8C petrol/Et₂O]; mp 100–101 8C

[pentane/Et₂O]; [a]²_D⁵¼þ14.9 (c¼0.85, CHCl₃); d_H

(400 MHz, CDCl₃) 0.05 [9H, s, Si(CH₃)₃], 0.77 [3H, s,

C(CH₃)_A(CH₃)_B], 1.20 [3H, s, C(CH₃)_A(CH₃)_B], 2.61 [1H,

dd, J¼9.9, 14.6 Hz, CHCH_AH_BPh], 2.80 [1H, dd, J¼3.2,

14.6 Hz, CHCH_AH_BPh], 4.10 [1H, dd, J¼3.2, 9.9 Hz,

CHCH₂Ph], 4.57 [1H, d, J¼12.1 Hz, CHOCH_AH_BPh],

4.71 [1H, d, J¼12.1 Hz, CHOCH_AH_BPh], 5.01 [1H, d,

J¼6.6 Hz, CHOCH₂Ph], 5.63 [1H, d, J¼6.6 Hz,

CH(OTMS)], 7.19–7.30 [13H, m, PhH], 7.38–7.40 [2H,

m, PhH]; d_C(100 MHz, CDCl₃) 0.16 [Si(CH₃)₃], 22.2, 27.7

[C(CH₃)₂], 35.0 [CHCH₂Ph], 63.6 [CHCH₂Ph], 73.6

[CHOCH₂Ph], 76.6 [CH(OTMS)], 81.2 [CHOCH₂Ph],

82.2 [C(CH₃)₂], 126.7, 127.7, 128.0 [p-Ph], 127.7, 128.1,

128.2, 128.6, 129.0 [m/o-Ph], 136.9, 137.9, 139.8 [i-Ph],

151.9 [CvO endocyclic], 171.0 [CvO exocyclic]; n_max

(KBr disc, cm²¹

)

1771, 1694 [CvO]; HRMS

C₃₁H₃₇NO₅Na [MNa^þ] requires 554.2339. Found

554.2349; m/z ESþ 554 [100%, MNa^þ].

3.10.20. Preparation of (2⁰S,3⁰R,4S)-4-benzyl-3-[2⁰-ben-

zyloxy-3⁰-(triisopropylsilanyloxy)-3⁰-phenyl-propionyl]-

5,5-dimethyl-oxazolidin-2-one 24. Following representa-

tive procedure 7, 6 (300 mg, 0.65 mmol), TIPSOTf

(0.35 mL, 1.31 mmol) and DMAP (119 mg, 0.98 mmol) in

CH₂Cl₂(20 mL) furnished 24 (388 mg, 0.63 mmol, 97%) as

a white solid after ﬂash column chromatography.

3.10.18. Preparation of (2⁰S,3⁰R,4S)-4-benzyl-3-[2⁰-ben-

zyloxy-3⁰-(triethyl-silanyloxy)-3⁰-phenyl-propionyl]-5,5-

dimethyl-oxazolidin-2-one 22. Following representative

rrocedure 6, 6 (470 mg, 1.02 mmol), TESCl (0.43 mL,

2.56 mmol), imidazole (348 mg, 5.12 mmol) and DMAP

(12 mg, 0.10 mmol) in DMF (5 mL) furnished 22 (550 mg,

0.96 mmol, 94%) as a white solid after ﬂash column

chromatography.

R_f0.31 [9:1 30–40 8C petrol/Et₂O]; mp 94–95 8C

[petrol/Et₂O]; d_H(400 MHz, CDCl₃) 0.96 [8H, app. d,

J¼4.2 Hz, Si(CH(CH₃)₂], 1.01–1.08 [13H, m,

Si(CH(CH₃)₂], 0.50 [3H, s, C(CH₃)_A(CH₃)_B], 1.22 [3H, s,

C(CH₃)_A(CH₃)_B], 2.14 [1H, dd, J¼14.7, 10.2 Hz, CHCH_A-

H_BPh], 2.60 [1H, dd, J¼14.7, 2.6 Hz, CHCH_AH_BPh], 3.91

[1H, dd, J¼10.2, 2.6 Hz, CHCH₂Ph], 4.59 [1H, d,

J¼12.0 Hz, CHOCH_AH_BPh], 4.87 [1H, d, J¼12.0 Hz,

CHOCH_AH_BPh], 5.07 [1H, d, J¼7.8 Hz, CH(OTIPS)],

5.73 [1H, d, J¼7.8 Hz, CHOCH₂Ph], 7.16–7.31 [9H, m,

PhH], 7.38–7.40 [4H, m, PhH]; d_C(100 MHz, CDCl₃) 12.6

[Si(CH(CH₃)₂)₃], 17.8 [Si(CH(CH₃)₂)₃], 22.1, 27.4

R_f0.15 [9:1 pentane/Et₂O]; mp 70–72 8C [pentane/Et₂O];

[a]²_D⁴¼þ26.8 (c¼1.0, CHCl₃); d_H(400 MHz, CDCl₃) 0.45–

0.58 [6H, m, Si(CH₂CH₃)₃], 0.63 [3H, s, C(CH₃)_A(CH₃)_B],

0.85 [9H, t, J¼7.9 Hz, Si(CH₂CH₃)₃], 1.15 [3H, s, C(CH₃)_A

(CH₃)_B], 2.51 [1H, dd, J¼14.6, 10.0 Hz, CHCH_AH_BPh],

2.70 [1H, dd, J¼14.6, 2.9 Hz, CHCH_AH_BPh], 4.00 [1H, dd,

J¼10.0, 2.9 Hz, CHCH₂Ph], 4.58 [1H, d, J¼12.0 Hz,

CHOCH_AH_BPh], 4.79 [1H, d, J¼12.0 Hz, CHOCH_AH_BPh],

4.97 [1H, d, J¼7.2 Hz, CH(OTES)], 5.66 [1H, d, J¼7.2 Hz,

CHOCH₂Ph], 7.17–7.39 [15H, m, PhH]; d_C(100 MHz,

7566

S. G. Davies et al. / Tetrahedron 60 (2004) 7553–7577

[C(CH₃)₂], 34.8 [CHCH₂Ph], 63.5 [CHCH₂Ph], 73.9

[CHOCH₂Ph], 77.6 [CH(OTIPS)], 81.9 [C(CH₃)₂], 82.2

[CHOCH₂Ph], 126.6, 127.7, [2£p-Ph], 128.1, 128.2, 128.2,

128.3, 128.4, 128.6, 129.9 [1£p-Ph and m/o-Ph], 137.0,

138.0, 140.0 [i-Ph], 151.6 [CvO endocyclic], 171.7 [CvO

exocyclic]; n_max(KBr disc, cm²¹) 1779, 1699 [CvO];

HRMS C₃₇H₄₉NO₅SiNa [MNa^þ] requires 638.3278. Found

638.3295; [a]²_D⁴¼þ26.8 (c¼1.0, CHCl₃); m/z ESIþ 638

[100%, MNa^þ].

3.10.23. Preparation of (1⁰S,2⁰S,3⁰R,4S)-benzyl-3-[2⁰-ben-

zyloxy-3⁰-(tert-butyl-dimethyl-silanyloxy)-1⁰-hydroxy-3⁰-

phenyl-propionyl]-5,5-dimethyl-oxazolidin-2-one

27.

Following representative procedure 5, 23 (3.20 g,

5.58 mmol) and DIBAL (11.2 mL, 11.17 mmol) in

CH₂Cl₂(70 mL) furnished 27 (3.19 g, 5.54 mmol, 99%) as

a white solid.

Mp 115–117 8C [pentane/Et₂O]; [a]²_D³¼235.0 (c¼1.0,

CHCl₃); d_H(400 MHz, CDCl₃) 20.12 [3H, s, Si(CH₃)_A

(CH₃)_B], 0.06 [3H, s, Si(CH₃)_A(CH₃)_B], 0.91 [9H, s,

SiC(CH₃)₃], 1.08 [3H, s, C(CH₃)_A(CH₃)_B], 1.17 [3H, s,

C(CH₃)_A(CH₃)_B], 2.52 [1H, dd, J¼14.8, 10.3 Hz, CHCH_A-

H_BPh], 3.06 [1H, dd, J¼14.8, 4.3 Hz, CHCH_AH_BPh], 4.04

[1H, dd, J¼10.3, 4.3 Hz, CHCH₂Ph], 4.23–4.27 [2H, m,

CH(OH) and CH(OTBDMS)], 4.31 [1H, d, J¼11.4 Hz,

CHOCH_AH_BPh], 4.52 [1H, d, J¼11.4 Hz, CHOCH_AH_BPh],

4.73 [1H, app. t, J¼8.3 Hz, OH], 5.02 [1H, d, J¼3.3 Hz,

CHOCH₂Ph], 6.99–7.01 [2H, m, PhH], 7.18–7.35 [11H, m,

PhH], 7.42–7.43 [2H, m, PhH]; d_C(100 MHz, CDCl₃) 24.7

[Si(CH₃)₂], 18.2 [SiC(CH₃)₃], 22.1, 27.6 [C(CH₃)₂], 25.8

[SiC(CH₃)₃], 35.1 [CHCH₂Ph], 65.9 [CHCH₂Ph], 74.1

[CHOCH₂Ph], 74.2 [CH(OTBDMS)], 79.0 [CHOCH₂Ph],

81.0 [CH(OH)], 81.9 [C(CH₃)₂], 126.6, 127.0, 127.5, 127.6,

127.8, 128.0, 128.3, 128.6, 128.8 [p- and m/o-Ph], 136.8,

138.1, 140.4 [i-Ph], 157.2 [CvO endocyclic]; n_max(KBr

3.10.21. Preparation of (1⁰S,2⁰S,3⁰R,4S)-benzyl-3-[2⁰-ben-

zyloxy-3⁰-(trimethyl-silanyloxy)-1⁰-hydroxy-3⁰-phenyl-

propionyl]-5,5-dimethyl-oxazolidin-2-one 25. Following

representative procedure 5, 21 (500 mg, 0.94 mmol) and

DIBAL (2.85 mL, 1.88 mmol) in CH₂Cl₂(20 mL) furnished

25 (496 mg, 0.93 mmol, 99%) as a white solid.

Mp 103–104 8C [pentane/Et₂O]; [a]²_D⁴¼248.3 (c¼0.6,

CHCl₃); d_H(400 MHz, CDCl₃) 0.08[9H, s, Si(CH₃)₃],

1.14 [3H, s, C(CH₃)_A(CH₃)_B], 1.20 [3H, s, C(CH₃)_A(CH₃)_B],

2.57 [1H, dd, J¼9.7, 14.7 Hz, CHCH_AH_BPh], 3.09 [1H, dd,

J¼4.7, 14.7 Hz, CHCH_AH_BPh], 4.08 [1H, dd, J¼4.7,

9.7 Hz, CHCH₂Ph], 4.12 [1H, s, CH(OH)], 4.15 [1H, d,

J¼11.1 Hz, CHOCH_AH_BPh], 4.22 [1H, dd, J¼3.0, 8.3 Hz,

CHOCH₂Ph], 4.41 [1H, d, J¼11.1 Hz, CHOCH_AH_BPh],

4.76 [1H, app. t, J¼8.3 Hz, CH(OH)], 5.06 [1H, d,

J¼3.0 Hz, CH(OTMS)], 7.05–7.10 [2H, m, PhH], 7.17–

7.44 [13H, m, PhH]; d_C(100 MHz, CDCl₃) 0.0 [Si(CH₃)₃],

22.1, 27.6 [C(CH₃)₂], 35.2 [CHCH₂Ph], 66.0 [CHCH₂Ph],

74.0 [CH(OTMS)], 74.6 [CHOCH₂Ph], 79.1 [CH(OH)],

81.8 [CHOCH₂Ph], 82.0 [C(CH₃)₂], 126.6, 127.4, 127.6 [p-

Ph], 126.8, 128.0, 128.1, 128.2, 128.6, 128.9 [m/o-Ph],

136.8, 138.0, 140.9 [i-Ph], 157.4 [CvO]; n_max(KBr disc,

cm²¹) 1727 [CvO]; HRMS C₃₁H₃₉NO₅SiNa [MNa^þ]

requires 556.2495. Found 556.2491; m/z ESþ 556 [100%,

MNa^þ]

disc, cm²¹

)

3362 [O–H broad], 1726 [CvO];

C₃₄H₄₅NO₅Si requires C, 70.92; H, 7.88; N, 2.43%.

Found C, 70.84; H, 7.86; N, 2.68%; m/z ESþ 598 [40%,

MNa^þ].

3.10.24. Preparation of (1⁰S,2⁰S,3⁰R,4S)-benzyl-3-[2⁰-ben-

zyloxy-3⁰-(trimethyl-silanyloxy)-1⁰-hydroxy-3⁰-phenyl-

propionyl]-5,5-dimethyl-oxazolidin-2-one 28. Following

representative procedure 5, 24 (300 mg, 0.49 mmol) and

DIBAL (0.98 mL, 0.98 mmol) in CH₂Cl₂(10 mL) furnished

24 (41 mg, 0.07 mmol, 14%) as a white solid, 28 (194 mg,

0.31 mmol, 64%) as a white solid and an unidentiﬁed

compound (29 mg) as a white solid after ﬂash column

chromatography.

3.10.22. Preparation of (1⁰S,2⁰S,3⁰R,4S)-benzyl-3-[2⁰-ben-

zyloxy-3⁰-(triethyl-silanyloxy)-1⁰-hydroxy-3⁰-phenyl-pro-

pionyl]-5,5-dimethyl-oxazolidin-2-one 26. Following

representative procedure 5, 22 (200 mg, 0.35 mmol) and

DIBAL (0.70 mL, 0.70 mmol) in CH₂Cl₂(5 mL) furnished

26 (164 mg, 0.29 mmol, 81%) as a white solid.

R_f0.39 [1:1 30–40 8C petrol/Et₂O]; [a]²_D⁵¼þ30.0 (c¼0.24,

CHCl₃); d_H(400 MHz, CDCl₃) 0.97–1.09 [21H, m,

Si(CH(CH₃)₂)₃], 1.12 [3H, s, C(CH₃)_A(CH₃)_B], 1.18 [3H,

s, C(CH₃)_A(CH₃)_B], 2.52 [1H, dd, J¼14.8, 9.9 Hz, CHCH_A-

H_BPh], 2.96 [1H, dd, J¼14.8, 4.6 Hz, CHCH_AH_BPh], 3.98

[1H, dd, J¼9.9, 4.6 Hz, CHCH₂Ph], 4.50–4.57 [2H, m,

CHOCH₂Ph and CH(OH)], 4.63 [1H, s, CH(OH)], 4.65 [1H,

d, J¼11.6 Hz, CHOCH_AH_BPh], 4.72 [1H, d, J¼11.6 Hz,

CHOCH_AH_BPh], 5.08 [1H, app. s, CH(OTIPS)], 6.95 [2H,

m, PhH,], 7.13–7.21 [3H, m, PhH], 7.25–7.45 [10H, m,

PhH]; d_C(100 MHz, CDCl₃) 12.1 [Si(CH(CH₃)₂)₃], 17.8

[Si(CH(CH₃)₂)₃], 22.1, 27.6 [C(CH₃)₂], 35.2 [CHCH₂Ph],

65.7 [CHCH₂Ph], 73.7 [CHOCH₂Ph], 75.0 [CH(OTIPS)],

78.7, 79.2 [CH(OH) and CHOCH₂Ph], 81.4 [C(CH₃)₂],

126.5, 127.3, 127.8, 127.9, 128.0, 128.4, 128.6, 128.7 [p-Ph

and m/o-Ph], 136.9, 138.1, 139.3 [i-Ph], 157.0 [CvO]; n_max

(thin ﬁlm, cm²¹) 1728 [CvO]; HRMS C₃₇H₅₁NO₅SiNa

[MNa^þ] requires 640.3434. Found 640.3422; m/z ESIþ 640

[70%, MNa^þ].

Mp 80–81 8C [pentane/Et₂O]; [a]²_D⁴¼223.5 (c¼1.0,

CHCl₃); d_H(400 MHz, CDCl₃) 0.50–0.57 [6H, m, Si(CH_2-

CH₃)₃], 0.88 [9H, t, J¼7.9 Hz, Si(CH₂CH₃)₃], 1.11 [3H, s,

C(CH₃)_A(CH₃)_B], 1.18 [3H, s, C(CH₃)_A(CH₃)_B], 2.55 [1H,

dd, J¼14.8, 9.9 Hz, CHCH_AH_BPh], 3.06 [1H, dd, J¼14.8,

4.5 Hz, CHCH_AH_BPh], 4.05 [1H, dd, J¼9.9, 4.5 Hz,

CHCH₂Ph], 4.26–4.29 [2H, m, CHOCH₂Ph and

CH(OH)], 4.35 [1H, d, J¼11.3 Hz, CHOCH_AH_BPh], 4.53

[1H, d, J¼11.3 Hz, CHOCH_AH_BPh], 4.71 [1H, app. t,

J¼8.1 Hz, CH(OH)], 5.024 [1H, d, J¼3.5 Hz, CH(OTES)],

7.00–7.43 [15H, m, PhH]; d_C(100 MHz, CDCl₃) 4.6

[Si(CH₂CH₃)₃], 6.7 [Si(CH₂CH₃)₃], 22.1, 27.6 [C(CH₃)₂],

35.2 [CHCH₂Ph], 65.9 [CHCH₂Ph], 74.1 [CHOCH₂Ph],

74.2 [CHOCH₂Ph], 79.0 [CH(OH)], 80.9 [CH(OTES)], 81.8

[C(CH₃)₂], 126.5, 126.9, 127.5 [p-Ph], 127.6, 127.9, 128.0,

128.3, 128.6, 128.8 [m/o-Ph], 136.9, 138.1, 140.4 [i-Ph],

157.22 [CvO endocyclic]; n_max(KBr disc, cm²¹) 1727

[CvO]; HRMS C₃₄H₄₅NO₅NaSi [MNa^þ] requires

598.2965. Found 598.2970; m/z ESþ 598 [55%, MNa^þ].

3.10.25. Preparation of (2S,3R)-2-benzyloxy-3-hydroxy-

3-phenyl-propionaldehyde 29. Following representative

S. G. Davies et al. / Tetrahedron 60 (2004) 7553–7577

7567

procedure 8, 25 (230 mg, 0.43 mmol) and K₂CO₃(83 mg,

0.60 mmol) in MeOH/H₂O (v:v 4:1; 50 mL) furnished 29

(83 mg, 0.32 mmol, 75%) as a clear colourless oil and 4

(87 mg, 0.42 mmol, 99%) as a white solid after ﬂash column

chromatography.

[CvO]; HRMS C₂₂H₃₄NO₃Si [MNH^þ₄] requires 388.2308.

Found 388.2306; m/z GCMS (NH₃) 239 [55%, MH^þ2

OTBDMS], 256 [40%, MNH^þ₄2OTBDMS], 388 [60%,

MNH^þ₄].

3.10.28. Preparation of (2S,3R)-2-benzyloxy-3-(triiso-

propyl-silanyloxy)-3-phenyl-propionaldehyde 32. Fol-

lowing representative procedure 8, 28 (100 mg,

0.16 mmol) and K₂CO₃(32 mg, 0.23 mmol) in MeOH/

H₂O (v:v 4:1; 10 mL) furnished 32 (60 mg, 0.15 mmol,

91%) as a clear colourless oil and 4 (32 mg, 0.15 mmol,

97%) as a white solid after ﬂash column chromatography.

R_f

0.18

[1:1

30–40 8C

petrol/Et₂O];

[a]²_D⁵¼2101.43(c¼0.35, CHCl₃); d_H(400 MHz, CDCl₃)

3.98 [1H, dd, J¼1.5, 4.6 Hz, CHOCH₂Ph], 4.49 [1H, d,

J¼11.7 Hz, CHOCH_AH_BPh], 4.63 [1H, d, J¼11.7 Hz,

CHOCH_AH_BPh], 5.02 [1H, d, J¼4.6 Hz, CH(OH)], 7.18–

7.41 [10H, m, PhH], 9.65 [1H, d, J¼1.5 Hz, CHO]; d_C

(100 MHz, CDCl₃) 73.4 [CH(OH)], 73.5 [CHOCH₂Ph],

86.9 [CHOCH₂Ph], 126.37 [p-Ph], 128.2, 128.3, 128.6

[m/o-Ph], 136.5, 139.3 [i-Ph], 201.96 [CHO]; n_max(thin

ﬁlm, cm²¹) 1732 [CvO]; HRMS C₁₆H₂₀NO₃[MNH^þ₄]

requires 274.1443. Found 274.1439; m/z CIþ 168 [100%,

MNH^þ₄2PhCHO], 274 [15%, MNH^þ₄].

R_f0.44 [9:1 30–40 8C petrol/Et₂O]; [a]²_D⁵¼215.6 (c¼0.85,

CHCl₃); d_H(400 MHz, CDCl₃) 0.95–1.10 [21H, m,

Si(CH(CH₃)₂)₃], 3.98 [1H, dd, J¼1.7, 5.2 Hz, CHOCH₂Ph],

4.50 [1H, d, J¼12.2 Hz, CHOCH_AH_BPh], 4.69 [1H, d,

J¼12.2 Hz, CHOCH_AH_BPh], 5.08 [1H, d, J¼5.2 Hz,

CH(OTIPS)], 7.27–7.38 [10H, m, PhH], 9.63 [1H, d,

J¼1.7 Hz, CHO]; d_C(100 MHz, CDCl₃) 12.2, 17.8

[Si(CH(CH₃)₂)₃], 72.7 [CHOCH₂Ph], 75.3 [CH(OTIPS)],

86.5 [CHOCH₂Ph], 126.9, 127.9 [p-Ph], 127.9, 128.0,

128.1, 128.4 [m/o-Ph], 137.3, 139.9 [i-Ph], 202.0 [CHO];

n_max(thin ﬁlm, cm²¹) 1733 [CvO]; HRMS C₂₅H₄₀NO₃Si

[MNH^þ₄] requires 430.2777. Found 430.2787; m/z

CIþ(NH₃) 430 [5%, MNH^þ₄].

3.10.26. Preparation of (2S,3R)-2-benzyloxy-3-(triethyl-

silanyloxy)-3-phenyl-propionaldehyde 30. Following

representative procedure 8, 26 (345 mg, 0.60 mmol) and

K₂CO₃(116 mg, 0.84 mmol) in MeOH/H₂O (50 mL)

furnished 30 (167 mg, 0.45 mmol, 75%) as a clear colour-

less oil and 4 (112 mg, 0.54 mmol, 90%) as a white solid

after ﬂash column chromatography.

R_f0.18 [12:1 30–40 8C petrol/Et₂O]; [a]²_D⁵¼278.5

(c¼0.35, CHCl₃); d_H(400 MHz, CDCl₃) 0.47–0.57 [6H,

m, Si(CH₂CH₃)₃], 0.84–0.88 [9H, m, Si(CH₂CH₃)₃], 3.85

[1H, dd, J¼4.3, 1.5 Hz, CHOCH₂Ph], 4.459 [1H, d,

J¼12.3 Hz, CHOCH_AH_BPh], 4.56 [1H, d, J¼12.3 Hz,

CHOCH_AH_BPh], 5.05 [1H, d, J¼4.3 Hz, CH(OTES)],

7.13–7.16 [2H, m, PhH], 7.17–7.44 [8H, m, PhH], 9.65

[1H, t, J¼1.5 Hz, CHO]; d_C(100 MHz, CDCl₃) 4.6

[Si(CH₂CH₃)₃], 6.7 [Si(CH₂CH₃)₃], 73.1 [CHOCH₂Ph],

75.2 [CHOTES], 87.0 [CHOCH₂Ph], 126.7, 127.9, 128.1,

128.4 [m/o-Ph], 128.7, 130.4 [p-Ph], 137.1, 140.2 [i-Ph],

203.0 [CHO]; n_max(thin ﬁlm, cm²¹) 1732 [CvO]; HRMS

C₂₂H₃₄NO₃Si [MH^þ] requires 388.2308. Found 388.2317;

m/z CIþ 221 [80%, MNH^þ₄2HOTBDMS], 388 [100%,

MNH^þ₄].

3.10.29. Preparation of (2⁰S,3⁰R,4S)-4-benzyl-3-[2⁰-(N,N-

dibenzylamino)-3⁰-(tert-butyl-dimethyl-silanyloxy)-3⁰-

phenyl-propionyl]-5,5-dimethyl-oxazolidin-2-one

8

33.

Following representative procedure 7, (200 mg,

0.36 mmol), TBDMSOTf (0.17 mL, 0.73 mmol) and

DMAP (66 mg, 0.54 mmol) in CH₂Cl₂(10 mL) furnished

33 (229 mg, 0.35 mmol, 96%) as a white solid after ﬂash

column chromatography.

R_f0.22 [9:1 pentane/Et₂O]; mp 125 8C [petrol/Et₂O];

[a]²_D⁵¼222.7 (c¼1.15, CHCl₃); d_H(400 MHz, CDCl₃)

20.28 [3H, s, Si(CH₃)_A(CH₃)_B], 0.16 [3H, s, Si(CH₃)_A

(CH₃)_B], 0.75 [3H, s, C(CH₃)_A(CH₃)_B], 1.021 [9H, s,

SiC(CH₃)₃], 1.25 [3H, s, C(CH₃)_A(CH₃)_B], 2.84 [1H, dd,

J¼9.6, 14.4 Hz, CHCH_AH_BPh], 3.10 [1H, dd, J¼3.5,

14.4 Hz, CHCH_AH_BPh], 3.95 [2H, d, J¼14.4 Hz, N(CH_A-

H_BPh)(CH_CH_DPh)], 4.26 [2H, d, J¼14.4 Hz, N(CH_AH_B-

Ph)(CH_CH_DPh)], 4.27–4.30 [1H, m, CHCH₂Ph], 5.36 [1H,

d, J¼8.2 Hz, CH(OTBDMS)], 5.45 [1H, d, J¼8.2 Hz,

CHN(CH₂Ph)₂], 7.20–7.41 [20H, m, PhH]; d_C(100 MHz,

CDCl₃) 24.6, 24.2 [Si(CH₃)₂], 18.1 [SiC(CH₃)₃], 22.3,

27.7 [C(CH₃)₂], 26.1 [SiC(CH₃)₃], 35.5 [CHCH₂Ph], 55.6

[CHN(CH₂Ph)₂], 63.0 [CHCH₂Ph], 65.6 [CHN(CH₂Ph)₂],

74.9 [CH(OTBDMS)], 81.3 [C(CH₃)₂], 126.6, 126.8, 127.9

[p-Ph], 128.0, 128.1, 128.3, 128.6, 128.7, 129.2 [m/o-Ph],

137.1, 140.3, 141.3 [i-Ph], 151.3 [CvO endocylic], 171.6

[CvO exocyclic]; n_max(KBr disc, cm²¹) 1772, 1695

[CvO]; HRMS C₄₁H₅₁N₂O₄Si [MH^þ] requires 663.3618.

Found 663.3625; m/z ESþ 663 [100%, MH^þ].

3.10.27. Preparation of (2S,3R)-2-benzyloxy-3-(tert-

butyl-dimethyl-silanyloxy)-3-phenyl-propionaldehyde

31. Following representative procedure 8, 27 (2.3 g,

4.00 mmol) and K₂CO₃(774 mg, 5.60 mmol) in MeOH/

H₂O (v:v 4:1; 50 mL) furnished 31 (1.06 g, 2.88 mmol,

72%) as a clear colourless oil and 4 (824 mg, 4.00 mmol,

100%) as a white solid after ﬂash column chromatography.

R_f0.15 [12:1 30–40 8C petrol/Et₂O]; [a]²_D⁶¼267.0 (c¼0.9,

CHCl₃); d_H(400 MHz, CDCl₃) 20.10 [3H, s, Si(CH₃)_A

(CH₃)_B], 0.01 [3H, s, Si(CH₃)_A(CH₃)_B], 0.88 [9H, s,

SiC(CH₃)₃], 3.86 [1H, dd, J¼4.5, 1.6 Hz, CHOCH₂Ph],

4.45 [1H, d, J¼12.2 Hz, CHOCH_AH_BPh], 4.57 [1H, d,

J¼12.2 Hz, CHOCH_AH_BPh], 5.03 [1H, d, J¼4.5 Hz,

CH(OTBDMS)], 7.16–7.44 [10H, m, PhH], 9.63 [1H, d,

J¼1.6 Hz, CHO]; d_C(50 MHz, CDCl₃) 25.4, 24.8

[Si(CH₃)₂], 18.0 [SiC(CH₃)₃], 25.6 [SiC(CH₃)₃], 73.1

[CHOCH₂Ph], 75.4 [CHOCH₂Ph], 87.2 [CH(OTBDMS)],

127.0, 127.1 [p-Ph], 127.9, 128.3, 128.5 [m/o-Ph], 130.0,

136.6 [i-Ph], 140.2 [CHO]; n_max(thin ﬁlm, cm²¹) 1733

3.10.30. Preparation of (2⁰S,3⁰R,4S)-4-benzyl-3-[2⁰-(N,N-

dibenzylamino)-3⁰-(triethyl-silanyloxy)-3⁰-phenyl-pro-

pionyl]-5,5-dimethyl-oxazolidin-2-one 35. Following

representative procedure 6,

8 (415 mg, 0.76 mmol),

TESCl (0.32 mL, 1.89 mmol), imidazole (257 mg,

3.79 mmol) and DMAP (10 mg, 0.08 mmol) in DMF

7568

S. G. Davies et al. / Tetrahedron 60 (2004) 7553–7577

(2 mL) furnished 35 (411 mg, 0.62 mmol, 82%) as a white

solid after ﬂash column chromatography.

[a]²_D³¼288.0 (c¼0.47, CHCl₃); d_H(40 MHz, CDCl₃) 0.31–

0.46 [6H, m, Si(CH₂CH₃)₃], 0.83 [9H, t, J¼7.9 Hz,

Si(CH₂CH₃)₃], 1.10 [3H, s, C(CH₃)_A(CH₃)_B], 1.51 [3H, s,

C(CH₃)_A(CH₃)_B], 2.44 [1H, dd, J¼11.4, 14.5 Hz, CHCH_A-

H_BPh), 3.12 [1H, dd, J¼3.4, 14.5 Hz, CHCH_AH_BPh], 3.41

[1H, d, J¼5.8 Hz, CH(OTES)], 3.64 [4H, s, CHN(CH_2-

Ph)₂], 4.34 [1H, m, CHCH₂Ph], 5.44 [1H, d, J¼5.8 Hz,

CHN(CH₂Ph)₂], 6.98–7.01 [3H, m, NH and 2£PhH], 7.18–

7.33 [18H, m, PhH], 8.09 [1H, s, OCHO]; d_C(100 MHz,

CDCl₃) 4.7 [Si(CH₂CH₃)₃], 6.9 [Si(CH₂CH₃)₃], 22.9, 24.8

[C(CH₃)₂], 35.7 [CHCH₂Ph], 54.5 [CHN(CH₂Ph)₂], 56.8,

67.2, 74.4 [CHCH₂Ph, CHN(CH₂Ph)₂, CH(OTES)], 85.4

[C(CH₃)₂], 126.4, 126.9, 127.3, 128.0, 128.1, 128.3, 128.4,

129.0 [p- and m/o-Ph], 137.9, 139.8, 143.3 [i-Ph], 160.2

R_f0.17 [9:1 pentane/Et₂O]; mp 92 8C [pentane/EtOAc];

[a]²_D⁴¼219.3 (c¼0.94, CHCl₃); d_H(400 MHz, CDCl₃) 0.50

[6H, m, Si(CH₂CH₃)₃], 0.68 [3H, s, C(CH₃)_A(CH₃)_B], 1.21

[3H, s, C(CH₃)_A(CH₃)_B], 0.90 [9H, t, J¼7.9 Hz, Si(CH_2-

CH₃)₃], 2.79 [1H, dd, J¼9.6, 14.6 Hz, CHCH_AH_BPh], 3.00

[1H, dd, J¼3.7, 14.6 Hz, CHCH_AH_BPh], 3.87 [2H, d,

J¼14.5 Hz, CHN(CH_AH_BPh)(CH_CH_DPh], 4.17 [2H, d,

J¼14.5 Hz, CHN(CH_AH_BPh)(CH_CH_DPh)], 4.21 [1H, m,

CHCH₂Ph], 5.30 [1H, d, J¼8.6 Hz, CH(OTES)], 5.37 [1H,

d, J¼8.6 Hz, CHN(CH₂Ph)₂], 7.16–7.36 [20H, m, PhH]; d_C

(100 MHz, CDCl₃) 5.0 [Si(CH₂CH₃)₃], 6.8 [Si(CH₂CH₃)₃],

22.1, 27.5 [C(CH₃)₂], 35.5 [CHCH₂Ph], 55.4 [CHN(CH_2-

Ph)₂], 62.9, 65.3, 74.7 [CHCH₂Ph, CHN(CH₂Ph)₂,

CH(OTES)], 81.3 [C(CH₃)₂], 126.5, 126.8, 127.9, 128.0,

128.1, 128.6, 128.6, 129.1 [p- and m/o-Ph], 137.0, 140.3,

141.2 [i-Ph], 151.3 [CvO endocyclic], 171.5 [CvO

exocyclic]; n_max(thin ﬁlm, cm²¹) 1779, 1688 [CvO];

HRMS C₄₁H₅₁N₂O₄Si requires 663.3618. Found 663.3639;

m/z APCIþ 663 [MH^þ, 100%].

[CvO amide], 169.9 [CvO ester]; n_max(thin ﬁlm, cm²¹

)

1727, 1669 [CvO]; HRMS C₄₁H₅₃N₂O₄Si requires

665.3775. Found 665.3781; m/z APCIþ 619 [25%,

MH^þ2CO₂], 665 [100%, MH^þ].

3.10.33. Preparation of (2S,3R)-2-dibenzylamino-3-

hydroxy-3-phenyl-propionic acid methyl ester 40 and

(1⁰S,2S,3R)-N-(1⁰-benzyl-2⁰-hydroxy-2⁰-methyl-propyl)-

2-dibenzylamino-3-hydroxy-3-phenyl-propionamide 37.

3.10.31. Preparation of (2S,2⁰S,3⁰R)-formic acid 2-(3⁰-

(tert-butyl-dimethyl-silanoxy)-2⁰-dibenzylamino-3⁰-phe-

nyl-propionylamino)-1,1-dimethyl-2-benzyl-ethyl ester

34. Following representative procedure 5, 33 (175 mg,

0.26 mmol) and DIBAL (0.80 mL, 053 mmol) in CH₂Cl₂

(10 mL) furnished 33 (38 mg, 0.06 mmol, 22%) as a white

solid, 34 (60 mg, 0.09 mmol, 35%) as a pale yellow oil and

unidentiﬁed compounds (63 mg) as a white solid after ﬂash

column chromatography.

Following representative procedure 9,

8

(50 mg,

0.09 mmol), n-BuLi (0.18 mL, 0.46 mmol) in MeOH

(2 mL) and THF (2 mL) furnished 40⁸(15 mg, 0.04 mmol,

44%) as a clear colourless oil, 37 (9 mg, 0.02 mmol, 19%)

as a clear colourless oil and 4 (11 mg, 0.05 mmol, 60%) as a

white solid after ﬂash column chromatography.

Compound 40. R_f0.24 [8:1 30–40 8C petrol/Et₂O];

[a]²_D⁵¼2180.3 (c¼0.35, CHCl₃); d_H(400 MHz, CDCl₃)

3.42 [1H, d, J¼9.9 Hz, CHN(CH₂Ph)₂], 3.46 [2H, d,

J¼13.2 Hz, CHN(CH_AH_BPh)(CH_CH_DPh)], 3.64 [3H, s,

CO₂CH₃], 4.15 [2H, d, J¼13.2 Hz, CHN(CH_AH_BPh)(CH_C-

H_DPh)], 4.95 [1H, d, J¼9.9 Hz, CH(OH)], 7.12–7.42 [15H,

m, PhH].

Compound 34. R_f0.14 [5:1 pentane/Et₂O]; [a]²_D⁵¼276.6

(c¼3.0, CHCl₃); d_H(400 MHz, CDCl₃) 20.37 [3H, s,

Si(CH₃)_A(CH₃)_B], 20.08 [3H, s, Si(CH₃)_A(CH₃)_B], 0.88

[9H, s, SiC(CH₃)₃], 1.02 [3H, s, C(CH₃)_A(CH₃)_B], 1.47 [3H,

s, C(CH₃)_A(CH₃)_B], 2.45 [1H, dd, J¼11.0, 14.7 Hz,

CHCH_AH_BPh], 3.12 [1H, dd, J¼3.4, 14.7 Hz, CHCH_AH_B-

Ph], 3.40 [1H, d, J¼6.1 Hz, CH(OTBDMS)], 3.60 [2H, d,

J¼14.4 Hz, N(CH_AH_BPh)(CH_CH_DPh)], 3.74 [2H, d,

J¼14.4 Hz, N(CH_AH_BPh)(CH_CH_DPh)], 4.32–4.38 [1H, m,

CHCH₂Ph], 5.42 [1H, d, J¼6.1 Hz, CHN(CH₂Ph)₂], 6.81

[1H, d, J¼10.4 Hz, NH], 7.04–7.05 [2H, m, PhH], 7.17–

7.33 [18H, m, PhH], 8.050 [1H, s, CHO]; d_C(100 MHz,

CDCl₃) 24.9, 24.8 [Si(CH₃)₂], 18.1 [SiC(CH₃)₃], 22.9,

24.9 [C(CH₃)₂], 26.1 [SiC(CH₃)₃], 35.8 [CHCH₂Ph], 54.5

[CHN(CH₂Ph)₂], 56.6 [CHCH₂Ph], 67.6 [CH(OTBDMS)],

74.4 [CHN(CH₂Ph)₂], 85.4 [C(CH₃)₂], 126.5, 126.9, 127.4

[p-Ph], 127.7, 128.0, 128.2, 128.3, 128.5, 128.9 [m/o-Ph],

137.9, 139.7, 143.3 [i-Ph], 160.1 [CHO], 169.8 [CvO

amide]; n_max(thin ﬁlm, cm²¹) 1725, 1674 [CvO]; HRMS

C₄₁H₅₃N₂O₄Si [MH^þ] requires 665.3775. Found 665.3774;

m/z ESþ 665 [100%, MH^þ].

Compound 37. R_f0.11 [1:1 30–40 8C petrol/Et₂O];

[a]²_D⁵¼269.9 (c¼1.25, CHCl₃); d_H(400 MHz, CDCl₃)

0.67 [3H, s, C(CH₃)_A(CH₃)_B], 1.11 [3H, s, C(CH₃)_A(CH₃)_B],

2.55 [1H, dd, J¼12.2, 14.7 Hz, CHCH_AH_BPh], 2.69 [2H, d,

J¼14.0 Hz, CHN(CH_AH_BPh)(CH_CH_DPh)], 2.87 [1H, d,

J¼9.2 Hz, CH(OH)], 3.19 [1H, dd, J¼3.7, 14.7 Hz,

CHCH_AH_BPh], 3.81 [2H, d, J¼14.0 Hz, CHN(CH_AH_B-

Ph)(CH_CH_DPh)], 4.07 [1H, s, CH(OH)], 4.30–4.36 [1H, m,

CHCH₂Ph], 4.98 [1H, d, J¼9.2 Hz, CHN(CH₂Ph)₂], 5.27

[1H, d, J¼9.8 Hz, NH], 7.11–7.43 [20H, m, PhH]; d_C

(100 MHz, CDCl₃) 26.8, 27.2 [C(CH₃)₂], 35.6 [CHCH₂Ph],

54.0 [CHN(CH₂Ph)₂], 56.6 [CHCH₂Ph], 69.1 [CH(OH)],

70.3 [CHN(CH₂Ph)₂], 72.4 [C(CH₃)₂], 126.7, 127.4, 127.6,

128.3, 128.7, 129.3 [p- and m/o-Ph], 138.4, 138.6, 140.4 [i-

Ph], 167.7 [CvO]; n_max(thin ﬁlm, cm²¹) 1654 [CvO];

HRMS C₃₄H₃₉N₂O₃[MH^þ] requires 523.2961. Found

523.2970; m/z ESIþ 523 [100%, MH^þ].

3.10.32. Preparation of (2S,2⁰S,3⁰R)-formic acid 2-(2⁰-

dibenzylamino-3⁰-phenyl-3⁰-(triethyl-silanoxy)-propion-

ylamino)-1,1-dimethyl-2-benzyl-ethyl ester 36. Following

representative procedure 5, 35 (114 mg, 0.17 mmol) and

DIBAL (0.34 mL, 0.34 mmol) in CH₂Cl₂(5 mL) furnished

35 (60 mg, 0.09 mmol, 53%) as a white solid and 36 (34 mg,

0.05 mmol, 30%) as a clear colourless oil after ﬂash column

chromatography.

3.10.34. Preparation of (2S,3R)-3-(tert-butyl-dimethyl-

silanoxy)-2-dibenzylamino-3-phenyl-propionic acid

methyl ester 41 and (1⁰S,2S,3R)-N-(1⁰-benzyl-2⁰-

hydroxy-2⁰-methyl-propyl)-3-(tert-butyl-dimethyl-silan-

oxy)-2-dibenzylamino-3-phenyl-propionamide 38. Fol-

lowing representative procedure 9, 35 (150 mg, 0.23 mmol),

n-BuLi (0.45 mL, 1.13 mmol) in MeOH (5 mL) and THF

S. G. Davies et al. / Tetrahedron 60 (2004) 7553–7577

7569

(5 mL) furnished 35 (16 mg, 0.02 mmol, 11%), 41 (24 mg,

0.05 mmol, 33%) as a clear colourless oil, 38 (92 mg,

0.14 mmol, 63%) as a clear colourless oil and 4 (5 mg,

0.02 mmol, 11%) as a white solid after ﬂash column

chromatography.

(400 MHz, CDCl₃) 0.50 [6H, q, J¼8.0 Hz, Si(CH₂CH₃)₃],

0.87 [9H, t, J¼8.0 Hz, Si(CH₂CH₃)₃], 3.64 [1H, d,

J¼5.6 Hz, CHN(CH₂Ph)₂], 3.66 [3H, s, CO₂CH₃], 4.02

[4H, ABq, J¼14.4 Hz, CHN(CH₂Ph)₂], 5.37 [1H, d,

J¼5.6 Hz, CH(OTES)], 7.14–7.30 [15H, m, PhH]; d_C

(100 MHz, CDCl₃) 4.8 [Si(CH₂CH₃)₃], 6.8 [Si(CH₂CH₃)₃],

51.0 [CO₂CH₃], 55.4 [CHN(CH₂Ph)₂], 67.4, 75.7

[CHN(CH₂Ph)₂and CH(OTES)], 126.5, 127.0, 127.3,

127.8, 128.0, 128.4 [p- and m/o-Ph], 140.0, 141.8 [i-Ph],

171.8 [CvO]; n_max(KBr disc, cm²¹) 1733 (CvO); HRMS

C₃₀H₄₀NO₃Si requires 490.2777. Found 490.2768; m/z

APCIþ 490 [MH^þ, 100%].

Compound 41. R_f0.48 [9:1 30–40 8C petrol/Et₂O];

[a]²_D⁵¼234.0 (c¼1.0, CHCl₃); d_H(400 MHz, CDCl₃)

20.26 [3H, s, Si(CH₃)_A(CH₃)_B], 0.03 [3H, s, Si(CH₃)_A

(CH₃)_B], 0.90 [9H, s, SiC(CH₃)₃], 3.64 [1H, d, J¼5.5 Hz,

CHN(CH₂Ph)₂], 3.66 [3H, s, CO₂CH₃], 3.85 [2H, d,

J¼14.5 Hz, CHN(CH_AH_BPh)(CH_CH_DPh)], 4.21 [2H, d,

J¼14.5 Hz, CHN(CH_AH_BPh)(CH_CH_DPh)], 5.33 [1H, d,

J¼5.5 Hz, CH(OTBDMS)], 7.11–7.29 [15H, m, PhH]; d_C

(100 MHz, CDCl₃) 25.4, 24.4 [Si(CH₃)₂], 18.0

[SiC(CH₃)₃], 25.8 [SiC(CH₃)₃], 51.0 [CO₂CH₃], 55.4

Compound 39. R_f0.22 [1:1 30–40 8C petrol/Et₂O];

[a]²_D⁵¼262.2 (c¼1.65, CHCl₃); d_H(400 MHz, CDCl₃)

0.35–0.49 [6H, m, Si(CH₂CH₃)₃], 0.81–0.87 [9H, m,

Si(CH₂CH₃)₃], 0.93 [3H, s, C(CH₃)_A(CH₃)_B], 1.10 [3H, s,

C(CH₃)_A(CH₃)_B], 2.44 [1H, dd, J¼11.2, 14.7 Hz,

CHCH_AH_BPh], 3.08 [1H, dd, J¼3.4, 14.7 Hz, CHCH_A-

H_BPh], 3.40 [1H, d, J¼6.2 Hz, CH(OTES)], 3.65–3.72

[4H, m, CHN(CH₂Ph)₂], 4.08–4.14 [1H, m, CHCH₂Ph],

5.47 [1H, d, J¼6.2 Hz, CHN(CH₂Ph)₂], 6.49 [1H, d,

J¼9.6 Hz, NH], 6.99–7.02 [2H, m, PhH], 7.16–7.37

[18H, m, PhH]; d_C(100 MHz, CDCl₃) 4.8 [Si(CH₂CH₃)₃],

6.9 [Si(CH₂CH₃)₃], 26.3, 27.3 [C(CH₃)₂], 35.8 [CHCH_2-

Ph], 54.6 [CHN(CH₂Ph)₂], 58.1 [CHCH₂Ph], 67.5

[CHN(CH₂Ph)₂], 73.2 [C(CH₃)₂], 74.6 [CH(OTES)],

126.3, 127.4, 127.5 [p-Ph], 126.9, 128.1, 128.2, 128.3,

128.4, 128.8 [m/o-Ph], 138.5, 139.9, 143.2 [i-Ph], 170.9

[CvO]; n_max(thin ﬁlm, cm²¹) 1644 [CvO]; HRMS

C₄₀H₅₃N₂O₃Si [MH^þ] requires 637.3825. Found

637.3821; m/z ESIþ 637 [100%, MH^þ].

3.10.36. Preparation of (2⁰S,3⁰R,4S)-4-benzyl-3-(2⁰-diben-

zylamino-3⁰-methoxy-3-phenyl-propionyl)-5,5-dimethyl-

oxazolidin-2-one 43. Me₃O^þBF₄²(133 mg, 0.90 mmol)

was added to a stirred solution of 8 (100 mg, 0.18 mmol)

and Proton Sponge^w(193 mg, 0.90 mmol) in CH₂Cl₂

(5 mL) at ambient temperature. After stirring for 72 h, the

reaction mixture was ﬁltered through Celite^wand concen-

trated in vacuo. Puriﬁcation by ﬂash column chromato-

graphy furnished 43 (72 mg, 0.13 mmol, 71%) as a pale

yellow oil and returned 8 (14 mg, 0.03 mmol, 14%) as a

white solid.

[CHN(CH₂Ph)₂],

67.5

[CHN(CH₂Ph)₂],

75.9

[CHOTBDMS}, 126.5, 127.7 [m/o-Ph (CHPh)], 127.1 [p-

Ph (CHN(CH₂Ph)₂], 127.3 [p-Ph (CHPh)], 128.0, 128.4 [m/

o-Ph (CHN(CH₂Ph)₂], 140.0 [i-Ph (CHN(CH₂Ph)₂], 141.7

[i-Ph (CHPh)], 171.7 [CvO]; n_max(thin ﬁlm, cm²¹) 1746

[CvO]; HRMS C₃₀H₄₀NO₃Si [MH^þ] requires 490.2777.

Found 490.2768; m/z ESIþ 490 [100%, MH^þ].

Compound 38. R_f0.21 [1:1 30–40 8C petrol/Et₂O];

[a]²_D⁵¼267.8 (c¼2.75, CHCl₃); d_H(400 MHz, CDCl₃)

20.35 [3H, s, Si(CH₃)_A(CH₃)_B], 20.03 [3H, s, Si(CH₃)_A

(CH₃)_B], 0.89 [9H, s, SiC(CH₃)₃], 0.90 [3H, s, C(CH₃)_A

(CH₃)_B], 1.04 [3H, s, C(CH₃)_A(CH₃)_B], 2.45 [1H, dd,

J¼11.0, 14.8 Hz, CHCH_AH_BPh], 3.079[1H, dd, J¼3.3,

14.8 Hz, CHCH_AH_BPh], 3.40 [1H, d, J¼6.2 Hz,

CH(OTBDMS)], 3.65 [2H, d, J¼14.5 Hz, CHN(CH_AH_B-

Ph)(CH_CH_DPh)], 3.75 [2H, d, J¼14.5 Hz, CHN(CH_AH_B-

Ph)(CH_CH_DPh)], 4.08–4.14 [1H, m, CHCH₂Ph], 5.46 [1H,

d, J¼6.2 Hz, CHN(CH₂Ph)₂], 6.38 [1H, d, J¼9.5 Hz, NH],

7.02–7.04 [2H, m, PhH], 7.15–7.35 [18H, m, PhH]; d_C

(100 MHz, CDCl₃) 24.8, 24.7 [Si(CH₃)₂], 18.0

[SiC(CH₃)₃], 26.1 [SiC(CH₃)₃], 26.3, 27.3 [C(CH₃)₂], 35.9

[CHCH₂Ph], 54.5 [CHN(CH₂Ph)₂], 58.1 [CHCH₂Ph], 67.8

[CHN(CH₂Ph)₂], 73.2 [C(CH₃)₂], 74.5 [CH(OTBDMS)],

126.4, 126.9, 127.5 [p-Ph], 127.6, 128.1, 128.3, 128.3,

128.5, 128.8 [m/o-Ph], 138.5, 139.8, 143.2 [i-Ph], 170.8

[CvO]; n_max(thin ﬁlm, cm²¹) 1652 [CvO]; HRMS

C₄₀H₅₃N₂O₃Si [MH^þ] requires 637.3825. Found 637.3827;

m/z ESIþ 637 [100%, MH^þ].

R_f0.33 [3:1 30–40 8C petrol/Et₂O]; [a]²_D⁵¼24.8 (c¼0.38,

CHCl₃); d_H(400 MHz, CDCl₃) 0.76 [3H, s, C(CH₃)_A

(CH₃)_B], 1.24 [3H, s, C(CH₃)_A(CH₃)_B], 2.77 [1H, dd,

J¼9.7, 14.5 Hz, CHCH_AH_BPh], 3.00 [1H, dd, J¼3.7,

14.5 Hz, CHCH_AH_BPh], 3.22 [3H, s, CHO(CH₃)], 3.94

[2H, d, J¼14.5 Hz, N(CH_AH_BPh)(CH_CH_DPh)], 4.12 [2H, d,

J¼14.5 Hz, N(CH_AH_BPh)(CH_CH_DPh)], 4.24 [1H, dd,

J¼3.7, 9.7 Hz, CHCH₂Ph], 4.71 [1H, d, J¼8.5 Hz,

CHN(CH₂Ph)₂], 5.43 [1H, d, J¼8.5 Hz, CH(OCH₃)],

7.16–7.35 [20H, m, PhH]; d_C(100 MHz, CDCl₃) 22.1,

27.6 [C(CH₃)₂], 35.4 [CHCH₂Ph], 55.4 [CHN(CH₂Ph)₂],

56.9 [CH(OCH₃)], 63.1 [CHCH₂Ph], 65.0 [CH(OCH₃)],

81.6 [C(CH₃)₂], 82.9 [CHN(CH₂Ph)₂], 126.6, 126.7 [p-Ph],

128.0, 128.2, 128.3, 128.7, 128.7, 129.1 [m/o-Ph], 137.0,

138.0, 140.2 [i-Ph], 151.5 [CvO endocyclic], 171.5 [CvO

exocyclic]; n_max(thin ﬁlm, cm²¹) 1776, 1689 [CvO];

HRMS C₃₆H₃₉N₂O₄[MH^þ] requires 563.2910. Found

563.2919; m/z ESþ 563 [100%, MH^þ].

3.10.35. Preparation of (2S,3R)-2-dibenzylamino-3-phe-

nyl-3-(triethyl-silanoxy)-propionic acid methyl ester 42,

(1⁰S,2S,3R)-N-(1⁰-benzyl-2⁰-hydroxy-2⁰-methyl-propyl)-

2-dibenzylamino-3-phenyl-3-(triethyl-silanoxy)-propion-

amide 39 and(1⁰S,2S,3R)-N-(1⁰-benzyl-2⁰-hydroxy-2⁰-

methyl-propyl)-2-dibenzylamino-3-hydroxy-3-phenyl-

propionamide 37. Following representative procedure 9,

35 (150 mg, 0.23 mmol), n-BuLi (0.45 mL, 1.13 mmol) in

MeOH (5 mL) and THF (5 mL) furnished 42 (9 mg,

0.02 mmol, 8%) as a white solid, 39 (67 mg, 0.11 mmol,

46%) as a pale yellow oil, 35 (16 mg, 0.02 mmol, 10%) as a

white solid, 37 (13 mg, 0.025 mmol, 11%) as a clear

colourless oil and 4 (6 mg, 0.03 mmol, 13%) as a white solid

after ﬂash column chromatography.

Compound 42. R_f0.48 [9:1 30–40 8C petrol/Et₂O]; mp

61 8C [pentane/Et₂O]; [a]²_D³¼254.4 (c¼0.50, CHCl₃); d_H

7570

S. G. Davies et al. / Tetrahedron 60 (2004) 7553–7577

3.10.37. Preparation of (1⁰S,2S,3R)-N-(1⁰-benzyl-2⁰-

hydroxy-2⁰-methyl-propyl)-2-dibenzylamino-3-meth-

oxy-3-phenyl-propionamide 44. Following representative

procedure 5, 43 (50 mg, 0.09 mmol) and DIBAL (0.18 mL,

0.18 mmol) in CH₂Cl₂(5 mL) furnished 44 (43 mg,

0.08 mmol, 85%) as a pale yellow oil after ﬂash column

chromatography.

d_H(400 MHz, CDCl₃) 0.58 [3H, s, C(CH₃)_A(CH₃)_B], 1.21

[3H, s, C(CH₃)_A(CH₃)_B], 2.80 [1H, dd, J¼9.4, 14.3 Hz,

CHCH_AH_BPh], 2.97 [1H, dd, J¼4.5, 14.3 Hz, CHCH_AH_B-

Ph], 3.17 [2H, dd, J¼7.6, 15.1 Hz, N(CH_AH_BCHvCH₂)₂],

3.61 [2H, dd, J¼5.1, 15.1 Hz, N(CH_AH_BCHvCH₂)₂], 4.05

[1H, s, OH], 4.22 [1H, dd, J¼4.5, 9.4 Hz, CHCH₂Ph], 4.74

[1H, d, J¼9.7 Hz, CH(OH)] 5.17–5.27 [5H, m, CHN(CH_2-

CHvCH₂)₂and CHN(CH₂CHvCH₂)₂), 5.81–5.89 [2H, m,

N(CH₂CHvCH₂)₂] 7.22–7.38 [10H, m, PhH]; d_C

(100 MHz, CDCl₃) 21.8, 26.9 [C(CH₃)₂], 35.5 [CHCH₂Ph],

52.5 [CHN(CH₂CHvCH₂)₂], 63.1 [CHCH₂Ph], 66.3

[CH(OH)], 71.7 [CHN(CH₂CHvCH₂)₂], 81.7 [C(CH₃)₂],

118.0 [CHN(CH₂CHvCH₂)₂], 126.8, 127.9 [p-Ph], 128.3,

128.3, 128.6, 129.0 [m/o-Ph], 135.1 [CHN(CH_2-

CHvCH₂)₂], 136.6, 138.7 [i-Ph], 151.7 [CvO endocyclic],

170.8 [CvO exocyclic]; n_max(KBr disc, cm²¹) 3407 [O–

H], 1770, 1684 [CvO]; C₂₇H₃₂N₂O₄requires C, 72.3; H,

7.2; N, 6.25%. Found C, 72.5; H, 7.5; N, 6.2%; m/z APCIþ

449 [MH^þ, 58%], 343 [100%].

R_f0.28 [1:1 pentane/Et₂O]; [a]²_D⁵¼272.1 (c¼2.1, CHCl₃);

d_H(400 MHz, CDCl₃) 1.18 [3H, s, C(CH₃)_A(CH₃)_B], 1.54

[3H, s, C(CH₃)_A(CH₃)_B], 2.49 [1H, dd, J¼11.6, 14.6 Hz,

CHCH_AH_BPh], 3.13 [3H, s, CH(OCH₃)], 3.13–3.18 [1H, m,

CHCH_AH_BPh], 3.45 [1H, d, J¼6.0 Hz, CH(OCH₃)], 3.51–

3.59 [4H, m, N(CH₂Ph)₂], 4.38–4.45 [1H, m, CHCH₂Ph],

4.82 [1H, d, J¼6.0 Hz, CHN(CH₂Ph)₂], 7.00 [1H, d,

J¼10.1 Hz, NH], 7.05–7.07 [2H, m, PhH], 7.20–7.34

[18H, m, PhH], 8.09 [1H, s, CHO]; d_C(100 MHz, CDCl₃)

23.1, 24.7 [C(CH₃)₂], 35.5 [CHCH₂Ph], 54.7 [CHN(CH_2-

Ph)₂], 56.3 [CHCH₂Ph], 57.5 [CH(OCH₃)], 66.4

[CH(OCH₃)], 82.9 [CHN(CH₂Ph)₂], 85.2 [C(CH₃)₂],

126.3, 126.9 [p-Ph], 127.5, 128.2, 128.3, 129.0 [m/o-Ph],

137.7, 139.8, 140.0 [i-Ph], 160.1 [CHO], 170.0 [CvO

amide]; n_max(thin ﬁlm, cm²¹) 1725, 1674 [CvO]; HRMS

C₃₆H₄₁N₂O₄[MH^þ] requires 565.3066. Found 565.3061;

m/z ESþ 565 [100%, MH^þ].

3.10.38. Preparation of (S)-2⁰-N-(N⁰-N⁰-diallylaminoace-

tyl)-4-benzyl-5,5-dimethyl-oxazolidin-2-one 45. ₀Follow-

ing representative procedure 2, (S)-4-benzyl-3-(2 -bromo-

acetyl)-5,5-dimethyl-oxazolidin-2-one (4.71 g, 14.4 mmol)

and (CH₂vCHCH₂)NH (3.09 g, 3.93 mL) in CH₂Cl₂

(100 mL) furnished 45 as a yellow oil (3.76 g, 11.0 mmol,

76%) after ﬂash column chromatography.

X-ray crystal structure determination for 46. Data were

collected using an Enraf-Nonius k-CCD diffractometer with

graphite monochromated Cu Ka radiation using standard

procedures at 190 K. The structure was solved by direct

methods (SIR92), all non-hydrogen atoms were reﬁned with

anisotropic thermal parameters. Hydrogen atoms were

added at idealised positions. The structure was reﬁned

using CRYSTALS.²²X-ray crystal structure data for 46

[C₂₇H₃₂N₂O₄]: M¼448.56, orthorhombic, space group P 21

˚

21 21, a¼11.0817(3) A, b¼14.9551(4) A, c¼15.1422(5) A,

V¼2509.5 A , Z¼4, m¼0.080 mm²¹, colourless block,

3

˚

crystal dimensions¼0.6£0.6£0.8 mm³. A total of 3092

unique reﬂections were measured for 1,u,27 and 2381

reﬂections were used in the reﬁnement. The ﬁnal parameters

were wR₂¼0.051 and R₁¼0.040 [I.3s(I)]. Crystallo-

graphic data (excluding structure factors) has been depos-

ited with the Cambridge Crystallographic Data Centre as

supplementary publication number CCDC234753. Copies

of the data can be obtained, free of charge, on application to

CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [fax:

þ44-1223-336033 or e-mail: deposit@ccdc.cam.ac.uk].

[a]²_D⁴¼224.6 (c¼0.79, CHCl₃); d_H(400 MHz, CDCl₃) 1.30

[3H, s, C(CH₃)_A(CH₃)_B], 1.33 [3H, s, C(CH₃)_A(CH₃)_B],

2.84 [1H, dd, J¼9.5, 14.4 Hz, CHCH_AH_BPh], 3.11 [1H, dd,

J¼4.0, 14.4 Hz, CHCH_AH_BPh], 3.23 [4H, d, J¼6.8 Hz,

N(CH₂CHvCH₂)₂], 3.87 [2H, ABq, J¼18.6 Hz, CH_2-

N(CH₂CHvCH₂)₂], 4.46 [1H, dd, J¼4.0, 9.5 Hz, CHCH_2-

Ph], 5.08–5.17 [4H, m, N(CH₂CHvCH₂)₂], 5.78–5.88

[2H, m, N(CH₂CHvCH₂)₂], 7.16–7.28 [5H, m, PhH]; d_C

(100 MHz, CDCl₃) 22.2, 28.4 [C(CH₃)₂], 35.2 [CHCH₂Ph],

55.4 [CH₂N(CH₂CHvCH₂)₂], 57.1 [CH₂N(CH_2-

CHvCH₂)₂), 63.2 [CHCH₂Ph], 82.7 [C(CH₃)₂], 117.8

[CH₂N(CH₂CHvCH₂)₂) 126.7 [p-Ph], 128.6, 129.0 [m/o-

Ph], 135.5 [CH₂N(CH₂CHvCH₂)₂), 136.8 [i-Ph], 152.5

[CvO endocyclic], 171.5 [CvO endocyclic]; n_max(thin

ﬁlm, cm²¹) 2978 [C–H], 1777, 1707 [CvO]; HRMS

C₂₀H₂₇N₂O₃requires 343.2022. Found 343.2014; m/z

APCIþ 343 [MH^þ, 100%].

3.10.40. Preparation of (4S,2⁰S,3⁰R)-N-(2⁰-(N⁰-N⁰-diallyl-

amino)-3⁰-triethylsiloxy-3⁰-phenyl-1⁰-oxopropyl)-4-ben-

zyl-5,5-dimethyl-oxazolidin-2-one

47.

Following

representative procedure 6, 46 (342 mg, 1.12 mmol),

TESCl (288 mg, 0.32 mL, 2.80 mmol), imidazole

(260 mg, 5.60 mmol) and DMAP (93 mg, 1.12 mmol) in

DMF (10 mL) furnished 47 (604 mg, 1.073 mmol, 96%) as

a colourless oil after puriﬁcation by ﬂash column

chromatography.

3.10.39. Preparation of (4S,2⁰S,3⁰R)-N-(2⁰-(N⁰-N⁰-diallyl-

amino)-3⁰-hydroxy-3⁰-phenyl-1⁰-oxopropyl)-4-benzyl-

5,5-dimethyl-oxazolidin-2-one 46. Following representa-

tive procedure 4, 45 (200 mg, 0.584 mmol), 9-BBNOTf

(1.75 mL, 0.83 mmol), i-Pr₂NEt (0.14 mL, 0.81 mmol),

PhCHO (0.073 mL,0.64 mmol) and CH₂Cl₂(5 mL) furn-

ished 46 (172 mg, 0.191 mmol, 66%) as a white crystalline

solid after puriﬁcation by ﬂash column chromatography

followed by recrystallisation from hexane/ether solution.

[a]²_D⁴¼þ8.8 (c¼0.99, CHCl₃); d_H(400 MHz, CDCl₃) 0.43–

0.50 [6H, m, Si(CH₂CH₃)₃], 0.66 [3H, s, C(CH₃)_A(CH₃)_B],

1.21 [3H, s, C(CH₃)_A(CH₃)_B], 0.86 [9H, t, J¼7.7 Hz,

Si(CH₂CH₃)₃], 2.80 [1H, dd, J¼9.4, 14.3 Hz, CHCH_AH_B-

Ph], 2.99 [1H, dd, J¼3.6, 14.3 Hz, CHCH_AH_BPh], 3.41 [2H,

dd, J¼6.3, 15.0 Hz, CHN(CH_AH_BCHvCH₂)₂), 3.59 [2H,

dd, J¼5.8, 15.0 Hz, N(CH_AH_BCHvCH₂)₂], 4.15 [1H, dd,

J¼3.6, 9.4 Hz, CHCH_AH_BPh], 5.06–5.23 [5H, m,

CHN(CH₂CHvCH₂)₂), 5.33 [1H, d, J¼8.9 Hz,

CH(OTES)], 5.79–5.89 [2H, m, N(CH₂CHvCH₂)₂],

7.17–7.38 [10H, m, PhH]; d_C(400 MHz, CDCl₃) 4.9

Mp 73 8C [hexane/Et₂O]; [a]²_D³¼þ82.6 (c¼0.94, CHCl₃);

S. G. Davies et al. / Tetrahedron 60 (2004) 7553–7577

7571

[Si(CH₂CH₃)₃], 6.8 [Si(CH₂CH₃)₃], 22.0, 27.4 [C(CH₃)₂],

35.3 [CHCH₂Ph], 53.9 [CHN(CH₂CHvCH₂)₂], 63.0, 66.5,

74.1 [CHCH₂Ph, CHN(CH₂CHvCH₂)₂, CH(OTES)], 81.4

[C(CH₃)₂], 116.0 [CHN(CH₂CHvCH₂)₂], 126.7, 127.8,

128.0, 128.1, 128.6, 129.1 [p-Ph and m/o-Ph], 137.3

[CHN(CH₂CHvCH₂)₂], 137.0, 141.6 [i-Ph], 151.7 [CvO

)

1779, 1689 [CvO]; HRMS C₃₃H₄₇N₂O₄Si requires

563.3305. Found 563.3323; m/z APCIþ 563 [MH^þ, 100%].

3.10.41. Preparation of (2S,2⁰S,3⁰R)-formic acid 2-(2⁰-

diallylamino-3⁰-hydroxy-3⁰-phenyl-propionylamino)-

1,1-dimethyl-(2S)-benzyl-ethyl ester 48. Following repre-

sentative procedure 5, 47 (50 mg, 0.089 mmol) and DIBAL

(0.34 mL, 0.34 mmol) in DCM (3 mL) furnished 47 (20 mg,

0.036 mmol, 40%) as a white solid and 48 (12 mg,

0.018 mmol, 20%) as a colourless oil.

8.46 mmol) and (PhCH₂)₂NH (3.57 mL, 18.61 mmol) in

CH₂Cl₂(100 mL) furnished 50 (2.53 g, 6.91 mmol, 82%) as

an orange oil after ﬂash column chromatography.

R_f0.43 [1:1 30–40 8C petrol/Et₂O]; mp 78–79 8C

[petrol/Et₂O]; [a]²_D⁵¼þ33.2 (c¼0.85, CHCl₃); d_H

(400 MHz, CDCl₃) 1.28 [3H, d, J¼6.5 Hz, CHCH₃], 1.38

[3H, s, C(CH₃)_A(CH₃)_B], 1.402 [3H, s, C(CH₃)_A(CH₃)_B],

3.87 [4H, s, CH₂N(CH₂Ph)₂], 3.91 [2H, s, CH₂N(CH₂Ph)₂],

4.16 [1H, q, J¼6.5 Hz, CHCH₃], 7.22–7.55 [10H, m, PhH];

d_C(100 MHz, CDCl₃) 14.7 [CHCH₃], 21.6, 27.8 [C(CH₃)₂],

55.6 [CH₂N(CH₂Ph)₂], 57.7 [CH₂N(CH₂Ph)₂], 58.7

[CHCH₃], 82.0 [C(CH₃)₂], 127.1 [p-Ph], 128.3, 128.8

[m/o-Ph], 139.1 [i-Ph], 152.6 [CvO endocyclic], 171.9

[CvO exocyclic]; n_max(KBr disc, cm²¹) 1761, 1700

[CvO]; HRMS C₂₂H₂₇N₂O₃[MH^þ] requires 367.2022.

Found 367.2022; m/z ESþ 367 [100%, MH^þ], 389 [100%,

MNa^þ].

endocyclic], 171.3 [CvO exocyclic]; n_max(thin ﬁlm, cm²¹

[a]²_D³¼291.9 (c¼0.14, CHCl₃); d_H(400 MHz, CDCl₃)

0.29–0.42 [6H, m, Si(CH₂CH₃)₃], 0.78 [9H, t, J¼7.9 Hz,

Si(CH₂CH₃)₃], 1.27 [3H, s, C(CH₃)_A(CH₃)_B], 1.56 [3H, s,

C(CH₃)_A(CH₃)_B], 2.49 [1H, dd, J¼11.0, 14.3 Hz, CHCH_A-

H_BPh], 2.92 [2H, m, CHN(CH_AH_BCHvCH₂)₂], 3.07–3.16

[3H, m, CHCH_AH_BPh, CHN(CH_AH_BCHvCH₂)₂], 3.53

[1H, d, J¼4.9 Hz, CH(OTES)], 4.34 [1H, m, CHCH₂Ph],

4.97–5.08 [4H, m, N(CH₂CHvCH₂)₂], 5.40 [1H, d,

J¼4.9 Hz, CHN(CH₂CHvCH₂)₂], 5.60–5.70 [2H, m,

N(CH₂CHvCH₂)₂], 7.18–7.36 [11H, m, NH, PhH], 8.03

[1H, s, OCHO]; d_C(100 MHz, CDCl₃) 4.6 [Si(CH₂CH₃)₃],

6.9 [Si(CH₂CH₃)₃], 23.0, 25.1 [C(CH₃)₂], 35.8 [CHCH₂Ph],

53.5 [CHN(CH₂CHvCH₂)₂], 56.8 [CHCH₂Ph], 67.5

[CH(OTES)], 74.2 [CHN(CH₂CHvCH₂)₂], 85.5

[C(CH₃)₂], 116.6 [CHN(CH₂CHvCH₂)₂], 126.4, 126.9

[p-Ph], 127.1, 127.8, 128.3, 129.1 [m/o-Ph], 137.2

[CHN(CH₂CHvCH₂)₂], 138.1, 143.6 [i-Ph], 160.3

[OCHO], 170.5 [CvO]; n_max(thin ﬁlm, cm²¹) 2922 [C–

H], 1732, 1674 [CvO]; HRMS C₃₃H₄₉N₂O₄Si requires

565.3462. Found 565.3459; m/z APCIþ 565 [MH^þ, 100%].

3.10.43. Preparation of (2⁰S,3⁰R,4S)-4-methyl-3-(2⁰-

dibenzylamino-3⁰-hydroxy-3-phenyl-propionyl)-5,5-

dimethyl-oxazolidin-2-one 51. Following representative

procedure 4, 9-BBNOTf (5.90 mL, 2.95 mmol), 50

(720 mg, 1.97 mmol), i-Pr₂NEt (0.51 mL, 2.95 mmol) and

PhCHO (0.23 mL, 2.17 mmol) in CH₂Cl₂(40 mL) furn-

ished 51 (722 mg, 1.53 mmol, 78%) as a pale yellow solid

after ﬂash column chromatography.

R_f0.3 [1:1 30–40 8C petrol/Et₂O]; mp 89–90 8C

[petrol/Et₂O]; [a]²_D⁵¼þ7.1 (c¼1.25, CHCl₃); d_H

(400 MHz, CDCl₃) 0.71 [3H, s, C(CH₃)_A(CH₃)_B], 1.15

[3H, d, J¼6.6 Hz, CHCH₃], 1.26 [3H, s, C(CH₃)_A(CH₃)_B],

3.76 [2H, d, J¼14.1 Hz, CHN(CH_AH_BPh)(CH_CH_DPh)],

3.83 [1H, q, J¼6.6 Hz, CHCH₃], 3.89 [1H, s, CH(OH)],

4.25 [2H, d, J¼14.1 Hz, CHN(CH_AH_BPh)(CH_CH_DPh)],

4.87 [1H, d, J¼9.6 Hz, CHN(CH₂Ph)₂], 5.33 [1H, d,

J¼9.6 Hz, CH(OH)], 7.19–7.39 [15H, m, PhH]; d_C

(100 MHz, CDCl₃) 15.0 [CHCH₃], 21.3, 26.7 [C(CH₃)₂],

54.8 [CHN(CH₂Ph)₂], 58.7 [CHCH₃], 66.6 [CH(OH)], 72.2

[CHN(CH₂Ph)₂], 80.9 [C(CH₃)₂], 127.3, 128.0 [p-Ph],

128.3, 128.5, 129.1 [m/o-Ph], 138.8, 138.9 [i-Ph], 151.7

[CvO endocyclic], 170.8 [CvO exocyclic]; n_max(KBr

disc, cm²¹) 1771, 1668 [CvO]; HRMS C₂₉H₃₃N₂O₄

[MH^þ] requires 473.2440. Found 473.2455; m/z ESþ 473

[100%, MH^þ], 495 [80%, MNa^þ].

3.10.42. Preparation of (S)-4-methyl-3-(2⁰-dibenzyl-

amino-acetyl)-5,5-dimethyl-oxazolidin-2-one 50. Follow-

ing representative procedure 1, 49 (1.70 g, 13.18 mmol), n-

BuLi (5.8 mL, 14.50 mmol) and bromoacetyl bromide

(1.5 mL, 17.13 mmol) in THF (80 mL) furnished (S)-4-

methyl-3-(2⁰-bromo-acetyl)-5,5-dimethyl-oxazolidin-2-one

(2.57 g, 10.32 mmol, 78%) as an orange solid after ﬂash

column chromatography.

3.10.44. Preparation of (2⁰S,3⁰R,4S)-4-methyl-3-(3⁰-(tert-

butyl-dimethyl-silanoxy)-2⁰-dibenzylamino-3-phenyl-

propionyl)-5,5-dimethyl-oxazolidin-2-one 52. Following

representative procedure 7, 51 (100 mg, 0.21 mmol),

TBDMSOTf (0.10 mL, 0.42 mmol) and DMAP (38 mg,

0.32 mmol) in CH₂Cl₂(5 mL) furnished 52 (124 mg,

0.21 mmol, 99%) as a pale yellow oil after ﬂash column

chromatography.

R_f0.26 [2:1 30–40 8C petrol/Et₂O]; mp 53–54 8C

[petrol/Et₂O]; [a]²_D⁵¼þ33.29 (c¼0.85, CHCl₃); d_H

(400 MHz, CDCl₃) 1.288 [3H, d, J¼6.6 Hz, CHCH₃],

1.410 [3H, s, C(CH₃)_A(CH₃)_B], 1.443 [3H, s, C(CH₃)_A

(CH₃)_B], 4.175 [1H, q, J¼6.6 Hz, CHCH₃], 4.434 [1H, d,

J¼12.5 Hz, CH_AH_BBr], 4.536 [1H, d, J¼12.5 Hz, CH_AH_B-

Br]; d_C(100 MHz, CDCl₃) 14.3 [CHCH₃], 21.5, 27.8

[C(CH₃)₂], 28.5 [CH₂Br], 59.4 [CHCH₃], 82.6 [C(CH₃)₂],

152.2 [CvO endocyclic], 166.3 [CvO exocyclic]; n_max

(KBr disc, cm²¹) 1769, 1706 [CvO]; HRMS C₈H₁₃NO₃Br

[MH^þ] requires 250.0079. Found 250.0067; m/z GCMS 250

[100%, MH^þ].

R_f0.13 [5:1 30–40 8C petrol/Et₂O]; [petrol/Et₂O];

[a]²_D⁵¼þ20.1 (c¼0.6, CHCl₃); d_H(400 MHz, CDCl₃)

20.29 [3H, s, Si(CH₃)_A(CH₃)_B], 0.10 [3H, s, Si(CH₃)_A

(CH₃)_B], 0.95 [3H, s, C(CH₃)_A(CH₃)_B], 0.96 [9H, s,

Si(CH₃)₃], 1.21 [3H, d, J¼6.5 Hz, CHCH₃], 1.28 [3H, s,

C(CH₃)_A(CH₃)_B], 3.89 [1H, q, J¼6.6 Hz, CHCH₃], 4.02

[2H, d, J¼14.3 Hz, CHN(CH_AH_BPh)(CH_CH_DPh)], 4.26

[2H, d, J¼14.3 Hz, CHN(CH_AH_BPh)(CH_CH_DPh)], 5.27

Following representative procedure 2, (S)-4-methyl-3-(2⁰-

bromo-acetyl)-5,5-dimethyl-oxazolidin-2-one (2.10 g,

7572

S. G. Davies et al. / Tetrahedron 60 (2004) 7553–7577

[1H, d, J¼7.4 Hz, CHN(CH₂Ph)₂], 5.34 [1H, d, J¼7.4 Hz,

CH(OTBDMS)], 7.15–7.27 [13H, m, PhH], 7.318–7.342

[2H, m, PhH]; d_C(100 MHz, CDCl₃) 24.8, 24.3

[Si(CH₃)₂], 14.7 [CHCH₃], 18.1 [SiC(CH₃)₃], 21.5, 27.2

[C(CH₃)₂], 26.0 [SiC(CH₃)₃], 55.9 [CHN(CH₂Ph)₂], 58.5

[CHCH₃], 65.5 [CH(OTBDMS)], 75.0 [CHN(CH₂Ph)₂],

80.5 [C(CH₃)₂], 126.6, 127.6 [p-Ph], 127.8, 127.9, 128.5,

128.5 [m/o-Ph], 140.3, 141.2 [i-Ph], 151.4 [CvO endo-

m, PhH]; d_C(100 MHz, CDCl₃) 24.4, 24.1 [Si(CH₃)₂],

14.0 [CH₂CH₂CH₂CH₂CH₃], 18.2 [SiC(CH₃)₃], 22.3, 28.5

[C(CH₃)₂], 22.5, 25.2, 32.0, 33.6 [CH₂CH₂CH₂CH₂CH₃],

26.0 [SiC(CH₃)₃], 34.9 [CHCH₂Ph], 64.2 [CHCH₂Ph], 73.1

[CHOCH₂Ph], 73.9 [CHOTBDMS], 79.9 [CHOCH₂Ph],

82.6 [C(CH₃)₂], 126.8, 127.8 [p-Ph], 128.3, 128.4, 128.7,

129.0 [m/o-Ph], 137.0, 137.8 [i-Ph], 152.2 [CvO endo-

cyclic], 171.8 [CvO exocyclic]; n_max(thin ﬁlm, cm²¹

)

cyclic], 171.9 [CvO exocyclic]; n_max(thin ﬁlm, cm²¹

)

1778, 1703 [CvO]; HRMS C₃₃H₅₀NO₅Si [MH^þ] requires

568.3458. Found 568.3455; m/z ESþ 568 [30%, MH^þ], 585

[100%, MNH^þ₄], 590 [70%, MNa^þ].

1780, 1706 [CvO]; HRMS C₃₅H₄₇N₂O₄Si [MH^þ] requires

587.3305. Found 587.3306; m/z ESþ 587 [100%, MH^þ],

609 [5%, MNa^þ].

3.10.47. Preparation of (2⁰S,3⁰R,4S)-4-benzyl-3-(2-benzyl

oxy-4-methyl-3-triethylsilanoxy-pentanoyl)-5,5-

dimethyl-oxazolidin-2-one 55. Following representative

procedure 6, 10 (360 mg, 0.85 mmol), TESCl (0.36 mL,

2.11 mmol), imidazole (288 mg, 4.23 mmol) and DMAP

(10 mg, 0.09 mmol) in DMF (5 mL) furnished 55 (388 mg,

0.72 mmol, 85%) as a pale yellow oil after ﬂash column

chromatography.

3.10.45. Preparation of (1⁰S,2S,3R)-N-(1⁰-methyl-2⁰-

hydroxy-2⁰-methyl-propyl)-2-dibenzylamino-3-phenyl-

3-(tert-butyl-dimethyl-silanoxy)-propionamide 53. Fol-

lowing representative procedure 5, 52 (120 mg,

0.20 mmol) and DIBAL (0.60 mL, 0.40 mmol) in CH₂Cl₂

(5 mL) furnished 53 (113 mg, 0.19 mmol, 96%) as a pale

yellow oil after ﬂash column chromatography.

R_f0.5 [1:1 30–40 8C petrol/Et₂O]; [a]²_D⁵¼273.3 (c¼1.0,

CHCl₃); d_H(400 MHz, CDCl₃) 20.16 [3H, s, Si(CH₃)_A

(CH₃)_B], 0.14 [3H, s, Si(CH₃)_A(CH₃)_B], 0.96 [9H, s,

Si(CH₃)₃], 1.15 [3H, d, J¼6.8 Hz, CHCH₃], 1.171 [3H, s,

C(CH₃)_A(CH₃)_B], 1.46 [3H, s, C(CH₃)_A(CH₃)_B], 3.53 [1H,

d, J¼5.0 Hz, CHN(CH₂Ph)₂], 3.69 [2H, d, J¼14.0 Hz,

CHN(CH_AH_BPh)(CH_CH_DPh)], 3.95–3.99 [1H, m,

CHCH₃], 4.09 [2H, d, J¼14.0 Hz, CHN(CH_AH_BPh)(CH_C-

H_DPh)], 5.73 [1H, d, J¼5.0 Hz, CH(OTBDMS)], 7.21–7.30

[12H, m, PhHand NH], 7.33–7.37 [2H, m, PhH], 7.45 [2H,

d, J¼7.2 Hz, PhH], 8.04 [1H, s, CHO]; d_C(100 MHz,

CDCl₃) 25.0, 24.4 [Si(CH₃)₂], 15.8 [CHCH₃], 18.2

[SiC(CH₃)₃], 23.1, 24.0 [C(CH₃)₂], 26.1 [SiC(CH₃)₃], 52.1

[CHCH₃], 54.9 [CHN(CH₂Ph)₂], 67.2 [CHN(CH₂Ph)₂],

75.0 [CH(OTBDMS)], 84.8 [C(CH₃)₂], 127.1, 127.2 [p-

Ph], 127.4, 128.1, 128.4, 128.5 [m/o-Ph], 139.7, 143.2 [i-

Ph], 160.0 [OCHO], 170.2 [CvO amide]; n_max(thin ﬁlm,

cm²¹) 1728, 1674 [CvO]; HRMS C₃₅H₄₉N₂O₄Si [MH^þ]

requires 589.3462. Found 589.3437; m/z ESþ 589 [60%,

MH^þ], 611 [100%, MNa^þ].

R_f0.31 [9:1 30–40 8C petrol/Et₂O]; [a]²_D⁵¼25.32(c¼0.7,

CHCl₃); d_H(400 MHz, CDCl₃) 0.64 [6H, q, J¼7.9 Hz,

Si(CH₂CH₃)₃], 0.91 [3H, d, J¼6.7 Hz, CH(CH₃)_A(CH₃)_B],

0.97 [9H, t, J¼7.9 Hz, Si(CH₂CH₃)₃], 0.95–0.99 [3H, m,

CH(CH₃)_A(CH₃)_B], 1.31 [3H, s, C(CH₃)_A(CH₃)_B], 1.34 [3H,

s, C(CH₃)_A(CH₃)_B], 1.62–1.69 [1H, m, CH(CH₃)₂], 2.62

[1H, dd, J¼10.2, 14.6 Hz, CHCH_AH_BPh], 2.86 [1H, dd,

J¼2.6, 14.6 Hz, CHCH_AH_BPh], 3.937 [1H, dd, J¼3.2,

6.5 Hz, CH(OTES)], 4.37 [1H, dd, J¼2.6, 10.2 Hz, CHCH_2-

Ph], 4.56 [1H, d, J¼11.9 Hz, CHOCH_AH_BPh], 4.67 [1H, d,

J¼11.9 Hz, CHOCH_AH_BPh], 5.33 [1H, d, J¼6.5 Hz,

CHOCH₂Ph], 7.19–7.38 [10H, m, PhH]; d_C(100 MHz,

CDCl₃) 5.3 [Si(CH₂CH₃)₃], 7.0 [Si(CH₂CH₃)₃], 16.7, 20.7

[CH(CH₃)₂], 22.3, 28.3 [C(CH₃)₂], 30.7 [CH(CH₃)₂], 34.7

[CHCH₂Ph], 64.3 [CHCH₂Ph], 73.2 [CHOCH₂Ph], 78.3

[CHOTES], 79.8 [CHOCH₂Ph], 82.5 [C(CH₃)₂], 126.7,

127.7 [p-Ph], 128.2, 128.3, 128.7, 129.0 [m/o-Ph], 137.0,

138.0 [i-Ph], 152.2 [CvO endocylic], 172.4 [CvO

exocyclic]; n_max(thin ﬁlm, cm²¹) 1778, 1699 [CvO];

C₃₁H₄₅NO₅Si requires C, 68.98; H, 8.40; N, 2.59%. Found

C, 68.93; H, 8.63; N, 2.58%; HRMS C₃₁H₄₆NO₅Si [MH^þ]

requires 540.3145. Found 540.3149; m/z ESþ 562 [100%,

MNa^þ].

3.10.46. Preparation of (2⁰S,3⁰R,4S)-4-benzyl-3-(2-benzyl

oxy-3-(tert-butyl-dimethyl-silanoxy)-octanoyl)-5,5-

dimethyl-oxazolidin-2-one 54. Following representative

procedure 6, 9 (720 mg, 1.59 mmol), TBDMSCl (600 mg,

3.97 mmol), imidazole (540 mg, 7.94 mmol) and DMAP

(20 mg, 0.16 mmol) in DMF (10 mL) furnished 54 (791 mg,

1.40 mmol, 88%) as a pale yellow oil after ﬂash column

chromatography.

3.10.48. Preparation of (2⁰S,3⁰R,4S)-4-benzyl-3-(2-benzyl

oxy-5-methyl-3-triethylsilanoxy-hexanoyl)-5,5-

dimethyl-oxazolidin-2-one 56. Following representative

procedure 6, 11 (375 mg, 0.85 mmol), TESCl (0.36 mL,

2.13 mmol), imidazole (290 mg, 4.28 mmol) and DMAP

(11 mg, 0.09 mmol) in DMF (6 mL) furnished 56 (400 mg,

0.72 mmol, 85%) as a pale yellow oil after ﬂash column

chromatography.

R_f0.18 [10:1 30–40 8C petrol/Et₂O]; [a]²_D⁵¼24.9 (c¼1.25,

CHCl₃); d_H(400 MHz, CDCl₃) 0.04 [3H, s, Si(CH₃)_A

(CH₃)_B], 0.06 [3H, s, Si(CH₃)_A(CH₃)_B], 0.84–0.88 [3H, m,

CH₂CH₂CH₂CH₂CH₃], 0.88 [9H, s, SiC(CH₃)₃], 1.20–1.29

[4H, m, CH₂CH₂CH₂CH₂CH₃], 1.32 [3H, s, C(CH₃)_A

(CH₃)_B], 1.35 [3H, s, C(CH₃)_A(CH₃)_B], 1.37–1.43 [3H,

m, CH_AH_BCH₂CH₂CH₂CH₃], 1.53–1.57 [1H, m, CH_AH_B-

CH₂CH₂CH₂CH₃], 2.71 [1H, dd, J¼10.0, 14.6 Hz, CHCH_A-

H_BPh], 2.95 [1H, dd, J¼2.9, 14.6 Hz, CHCH_AH_BPh], 3.97–

4.00 [1H, m, CHOTBDMS], 4.39 [1H, dd, J¼2.9, 10.0 Hz,

CHCH₂Ph], 4.58–4.58 [2H, ABq, J¼11.9 Hz, CHOCH_2-

Ph], 5.29 [1H, d, J¼5.1 Hz, CHOCH₂Ph], 7.21–7.37 [10H,

R_f0.23 [9:1pentane/Et₂O]; [a]²_D⁵¼24.6 (c¼0.9, CHCl₃); d_H

(400 MHz, CDCl₃) 0.52 [6H, q, J¼7.9 Hz, Si(CH₂CH₃)₃],

0.86 [3H, d, J¼6.6 Hz, CH(CH₃)_A(CH₃)_B], 0.90 [3H, d,

J¼6.6 Hz, CH(CH₃)_A(CH₃)_B], 0.93 [9H, t, J¼7.9 Hz,

Si(CH₂CH₃)₃], 1.30–1.37 [1H, m, CH_AH_BCH(CH₃)₂],

1.35 [3H, s, C(CH₃)_A(CH₃)_B], 1.39 [3H, s, C(CH₃)_A(CH₃)-

_{B], 1.42–1.48 [1H, m, CHA}H_BCH(CH₃)₂], 1.63–1.69 [1H, m,

CH₂CH(CH₃)₂], 2.75 [1H, dd, J¼9.9, 14.5 Hz, CHCH_AH_B-

Ph], 2.98 [1H, dd, J¼3.2, 14.5 Hz, CHCH_AH_BPh], 4.07–

S. G. Davies et al. / Tetrahedron 60 (2004) 7553–7577

7573

4.11 [1H, m, CH(OTES)], 4.41 [1H, dd, J¼3.2, 9.9 Hz,

CHCH₂Ph], 4.48 [1H, d, J¼11.9 Hz, CHOCH_AH_BPh], 4.56

[1H, d, J¼11.9 Hz, CHOCH_AH_BPh], 5.31 [1H, d, J¼4.8 Hz,

CHOCH₂Ph], 7.19–7.36 [10H, m, PhH]; d_C(100 MHz,

CDCl₃) 5.1 [Si(CH₂CH₃)₃], 7.0 [Si(CH₂CH₃)₃], 22.3, 22.4

[CH(CH₃)₂], 23.3, 28.4 [C(CH₃)₂], 24.0 [CH₂CH(CH₃)₂],

35.1 [CHCH₂Ph], 42.7 [CH₂CH(CH₃)₂], 64.2 [CHCH₂Ph],

71.8 [CH(OTES)], 72.9 [CHOCH₂Ph], 79.9 [CHOCH₂Ph],

82.6 [C(CH₃)₂], 126.7, 127.8 [p-Ph], 128.2, 128.4, 128.6,

129.1 [m/o-Ph], 137.0, 137.7 [i-Ph], 152.3 [CvO endo-

2.9 Hz, CHCH_AH_BPh], 4.17 [1H, dd, J¼10.0, 2.9 Hz,

CHCH₂Ph], 4.51 [1H, d, J¼12.0 Hz, CHOCH_AH_BPh], 4.60

[1H, d, J¼12.0 Hz, CHOCH_AH_BPh], 5.12 [1H, d, J¼7.4 Hz,

CH(OTBDMS)], 5.58 [1H, d, J¼6.0 Hz, CHOCH₂Ph], 7.19–

7.29 [10H, m, PhH], 7.58 [2H, d, J¼8.7 Hz, ArH], 8.15 [2H, d,

J¼8.7 Hz, ArH]; d_C(100 MHz, CDCl₃) 25.0, 24.8

[Si(CH₃)₂], 18.2 [SiC(CH₃)₃], 22.2, 27.8 [C(CH₃)₂], 25.7

[SiC(CH₃)₃], 34.8 [CHCH₂Ph], 63.7 [CHCH₂Ph], 73.7

[CHOCH₂Ph], 75.7 [CH(OTBDMS)], 80.6 [CHOCH₂Ph],

82.5 [C(CH₃)₂], 126.9, 128.0 [p-Ph], 123.2, 128.3, 128.4,

128.6, 128.7, 128.9 [m/o-Ph and m/o-Ar], 136.6, 137.2 [i-Ph],

147.5, 147.6 [p-Ar and i-Ar], 151.9 [CvO endocyclic], 170.4

[CvO exocyclic]; n_max(KBr disc, cm²¹) 1765, 1691 [CvO];

HRMS C₃₄H₄₆N₃O₇Si [MNH₄^þ] requires 636.3105. Found

636.310645; m/z CIþ (NH₃) 487 [80%, MH^þ2OTBDMS],

636 [100%, MNH^þ₄].

cyclic], 171.5 [CvO exocyclic]; n_max(thin ﬁlm, cm²¹

)

1778, 1702 [CvO]; C₃₂H₄₇NO₅Si requires C, 69.40; H,

8.55; N, 2.53%. Found C, 69.43; H, 8.59; N, 2.55%; HRMS

C₃₂H₄₈NO₅Si [MH^þ] requires 554.3302. Found 554.3298;

m/z ESþ 576 [100%, MNa^þ].

3.10.49. Preparation of (2⁰S,3⁰R,4S)-4-benzyl-3-[2-benzyl

oxy-3-(tert-butyl-dimethyl-silanoxy)-5-phenyl-pent-4-

enoyl]-5,5-dimethyl-oxazolidin-2-one 57. Following

representative procedure 6, 12 (300 mg, 0.62 mmol),

TBDMSCl (375 mg, 2.48 mmol), imidazole (337 mg,

4.96 mmol) and DMAP (7 mg, 0.06 mmol) in DMF

(5 mL) furnished 57 (361 mg, 0.60 mmol, 97%) as a pale

yellow oil after ﬂash column chromatography.

3.10.51. Preparation of (2⁰S,3⁰S,4S)-4-benzyl-3-(2⁰-ben-

zyloxy-3⁰-(tert-butyl-dimethyl-silanyloxy)-furan-2⁰⁰-yl-

propionyl)-5,5-dimethyl-oxazolidin-2-one 59. Following

representative procedure 6, 14 (1.78 g, 3.97 mmol),

TBDMSCl (1.5 g, 9.93 mmol), imidazole (1.35 g,

19.85 mmol) and DMAP (52 mg, 0.4 mmol) in DMF

(15 mL) furnished 59 (1.98 g, 3.51 mmol, 88%) as a white

solid after ﬂash column chromatography.

R_f0.17 [9:1 30–40 8C petrol/Et₂O]; [a]²_D⁵¼þ54.8 (c¼0.6,

CHCl₃); d_H(400 MHz, CDCl₃) 0.11 [3H, s, Si(CH₃)_A

(CH₃)_B], 0.14 [3H, s, Si(CH₃)_A(CH₃)_B], 0.94 [9H, s,

SiC(CH₃)₃], 0.95 [3H, s, C(CH₃)_A(CH₃)_B], 1.24 [3H, s,

C(CH₃)_A(CH₃)_B], 2.65 [1H, dd, J¼10.0, 14.6 Hz, CHCH_A-

H_BPh], 2.87 [1H, dd, J¼3.2, 14.6 Hz, CHCH_AH_BPh], 4.32

[1H, dd, J¼3.2, 9.9 Hz, CHCH₂Ph], 4.60 [1H, d,

J¼12.0 Hz, CHOCH_AH_BPh], 4.60–4.63 [1H, m,

CH(OTBDMS)], 4.71 [1H, d, J¼12.0 Hz, CHOCH_AH_BPh],

5.57 [1H, d, J¼6.8 Hz, CHOCH₂Ph], 6.29 [1H, dd, J¼7.5,

16.0 Hz, CHvCHPh], 6.56 [1H, d, J¼16.0 Hz,

CHvCHPh], 7.19–7.42 [15H, m, PhH]; d_C(100 MHz,

CDCl₃) 24.6, 24.5 [Si(CH₃)₂], 15.3 [SiC(CH₃)₃], 18.4,

28.0 [C(CH₃)₂], 25.9 [SiC(CH₃)₃], 35.1 [CHCH₂Ph], 63.7

[CHCH₂Ph], 73.7 [CHOCH₂Ph], 76.0 [CH(OTBDMS)],

80.6 [CHOCH₂Ph], 82.4 [C(CH₃)₂], 126.7 [CHvCHPh],

126.8, 127.8, 128.3, 128.5, 128.6, 128.7, 129.0 [p- and m/o-

Ph], 132.3 [CHvCHPh], 136.4, 137.0, 137.8 [i-Ph], 152.2

[CvO endocyclic], 171.3 [CvO exocyclic]; n_max(thin

ﬁlm, cm²¹) 1776, 1702 [CvO]; HRMS C₃₆H₄₅NO₅SiNa

[MNa^þ] requires 622.2965. Found 622.2986; m/z ESþ 622

[100%, MNa^þ].

R_f0.1 [10:1 pentane/Et₂O]; mp 76–77 8C [pentane/Et₂O];

[a]²_D³¼217.0 (c¼1.2, CHCl₃); d_H(400 MHz, CDCl₃)

20.04 [3H, s, Si(CH₃)_A(CH₃)_B], 0.11 [3H, s, Si(CH₃)_A

(CH₃)_B], 0.84 [9H, s, SiC(CH₃)₃], 1.04 [3H, s, C(CH₃)_A

(CH₃)_B], 1.24 [3H, s, C(CH₃)_A(CH₃)_B], 2.59 [1H, dd,

J¼14.6, 10.0 Hz, CHCH_AH_BPh], 2.81 [1H, dd, J¼14.6,

3.0 Hz, CHCH_AH_BPh], 4.20 [1H, dd, J¼10.0, 3.0 Hz,

CHCH₂Ph], 4.65 [1H, d, J¼11.9 Hz, CHOCH_AH_BPh],

4.84 [1H, d, J¼11.9 Hz, CHOCH_AH_BPh], 5.07 [1H, d,

J¼7.8 Hz, CH(OTBDMS)], 5.75 [1H, J¼7.8 Hz, CHOCH_2-

Ph], 6.28–6.32 [2H, m, ArH], 7.19–7.38 [11H, m, ArH]; d_C

(50 MHz, CDCl₃) 25.2, 24.9 [Si(CH₃)₂], 14.1

[SiC(CH₃)₃], 22.2, 28.0 [C(CH₃)₂], 25.7 [SiC(CH₃)₃], 34.9

[CHCH₂Ph], 63.7 [CHCH₂Ph], 70.5 [CH(OTBDMS)], 74.0

[CHOCH₂Ph], 79.3 [CHOCH₂Ph], 82.3 [C(CH₃)₂], 108.3,

110.4, 142.1 [CH furan], 126.7, 127.7 [p-Ph], 128.2, 128.6,

129.0 [m/o-Ph], 136.9, 137.9 [i-Ph], 157.7 [i-Ar furan],

153.0 [CvO endocyclic], 170.7 [CvO exocyclic]; n_max

(KBr disc, cm²¹) 1777 [CvO endocyclic], 1699 [CvO

exocyclic]; C₃₂H₄₁NO₆Si requires C, 68.18; H, 7.33; N,

2.48%. Found C, 68.11; H, 7.37; N, 2.51%; m/z ESþ 432

[80%, MH^þ2OTBDMS], 586 [100%, MNa^þ].

3.10.50. Preparation of (2⁰S,3⁰R,4S)-4-benzyl-3-[2⁰-ben-

zyloxy-3⁰-(tert-butyl-dimethyl-silanyloxy)-3⁰⁰-(4⁰⁰⁰-nitro-

3.10.52. Preparation of (1⁰S,2⁰S,3⁰R,4S)-4-benzyl-3-[2-

benzyloxy-3-(tert-butyl-dimethyl-silanoxy)-1-hydroxy-

octyl)-5,5-dimethyl-oxazolidin-2-one 60. Following repre-

sentative procedure 5, 54 (775 mg, 1.37 mmol) and DIBAL

(2.75 mL, 2.75 mmol) in CH₂Cl₂(20 mL) furnished 60

(777 mg, 1.37 mmol, 100%) as a pale yellow oil.

phenyl)-propionyl]-5,5-dimethyl-oxazolidin-2-one

58.

Following representative procedure 7, 13 (114 mg,

0.23 mmol), TBDMSOTf (0.31 mL, 1.36 mmol) and

DMAP (134 mg, 1.04 mmol) in CH₂Cl₂(5 mL) furnished

58 (126 mg, 0.20 mmol, 88%) as a white solid after ﬂash

column chromatography.

[a]²_D⁴¼þ11.1 (c¼1.45, CHCl₃); d_H(400 MHz, CDCl₃) 0.01

[3H, s, Si(CH₃)_A(CH₃)_B], 0.10 [3H, s, Si(CH₃)_A(CH₃)_B],

0.83 [9H, s, SiC(CH₃)₃], 0.84–1.03 [3H, m, CH₂CH₂CH_2-

CH₂CH₃], 1.03 [3H, s, C(CH₃)_A(CH₃)_B], 1.16–1.35 [5H, m,

CH₂CH_AH_BCH₂CH₂CH₃], 1.33 [3H, s, C(CH₃)_A(CH₃)_B],

1.40–1.49 [2H, m, CH_AH_BCH_AH_BCH₂CH₂CH₃], 1.68–

1.77 [1H, m, CH_AH_BCH₂CH₂CH₂CH₃], 2.73 [1H, dd,

R_f0.26 [5:1 30–40 8C petrol/Et₂O]; mp 118–119 8C

[petrol/Et₂O]; [a]_D²²¼þ31.4 (c¼0.5, CHCl₃); d_H(400 MHz,

CDCl₃) 20.05 [3H, s, Si(CH₃)_A(CH₃)_B], 0.07 [3H, s,

Si(CH₃)_A(CH₃)_B], 0.91 [9H, s, SiC(CH₃)₃], 0.92 [3H, s,

C(CH₃)_A(CH₃)_B], 1.21 [3H, s, C(CH₃)_A(CH₃)_B], 2.59[1H, dd,

J¼14.6, 10.0 Hz, CHCH_AH_BPh], 2.79 [1H, dd, J¼14.6,

7574

S. G. Davies et al. / Tetrahedron 60 (2004) 7553–7577

J¼9.8, 14.8 Hz, CHCH_AH_BPh], 3.23 [1H, dd, J¼4.8,

14.8 Hz, CHCH_AH_BPh], 3.87–3.91 [1H, m, CHOTBDMS],

4.00 [1H, dd, J¼4.8, 9.8 Hz, CHCH₂Ph], 4.20 [1H, dd,

J¼3.7, 8.8 Hz, CHOCH₂Ph], 4.57 [1H, d, J¼4.2 Hz,

CH(OH)], 4.64–4.73 [2H, ABq, J¼11.9 Hz, CHOCH₂Ph],

5.00 [1H, dd, J¼4.2, 8.8 Hz, CH(OH)], 7.10 [2H, d,

J¼7.1 Hz, PhH], 7.20–7.39 [8H, m, PhH]; d_C(100 MHz,

CDCl₃) 24.9, 24.5 [Si(CH₃)₂], 14.0 [CH₂CH₂CH₂CH_2-

CH₃], 17.9 [SiC(CH₃)₃], 22.2, 25.9 [C(CH₃)₂], 22.5, 25.9,

30.7, 31.8 [CH₂CH₂CH₂CH₃], 25.7 [SiC(CH₃)₃], 35.6

[CHCH₂Ph], 65.1 [CHCH₂Ph], 72.9 [CHOTBDMS], 73.0

[CHOCH₂Ph], 76.6 [CHOCH₂Ph], 79.5 [CH(OH)], 81.1

[C(CH₃)₂], 126.7, 127.9 [p-Ph], 128.0, 128.5, 128.7, 128.9

[m/o-Ph], 137.0, 138.1 [i-Ph], 157.0 [CvO]; n_max(thin

ﬁlm, cm²¹) 1731 [CvO]; HRMS C₃₃H₅₁NO₅SiNa [MNa^þ]

requires 592.3434. Found 592.3434; m/z ESþ 592 [100%,

MNa^þ], 452 [100%].

7.8 Hz, CHOCH₂Ph], 4.55 [1H, s, CH(OH)], 4.62–4.71

[2H, ABq, J¼11.9 Hz, CHOCH₂Ph], 4.93–4.96 [1H, m,

CH(OH)], 7.11–7.38 [10H, m, PhH]; d_C(100 MHz,

CDCl₃) 4.8 [Si(CH₂CH₃)₃], 6.8 [Si(CH₂CH₃)₃], 22.0, 24.1

[C(CH₃)₂], 22.2, 23.8 [CH₂CH(CH₃)₂], 27.5 [CH_2-

CH(CH₃)₂], 35.6 [CHCH₂Ph], 40.2 [CH₂CH(CH₃)₂],

65.2 [CHCH₂Ph], 70.6 [CH(OTES)], 73.0 [CHOCH₂Ph],

77.3 [CHOCH₂Ph], 79.6 [CH(OH)], 81.2 [C(CH₃)₂],

126.7, 127.9 [p-Ph], 128.1, 128.5, 128.7, 128.9 [m/o-

Ph], 137.0, 138.0 [i-Ph], 157.0 [CvO]; n_max(thin ﬁlm,

cm²¹) 1732 [CvO]; HRMS C₃₂H₄₉NO₅Si [MH^þ]

requires 578.3278. Found 578.3278; m/z ESþ 578

[100%, MH^þ].

3.10.55. Preparation of (1⁰S,2⁰S,3⁰R,4S)-4-benzyl-3-[2-

benzyloxy-3-(tert-butyl-dimethyl-silanoxy)-1-hydroxy-5-

phenyl-pent-4-enyl]-5,5-dimethyl-oxazolidin-2-one 63.

Following representative procedure 5, 57 (287 mg,

0.48 mmol) and DIBAL (0.96 mL, 0.96 mmol) in CH₂Cl₂

(10 mL) furnished 63 (280 mg, 0.47 mmol, 97%) as a pale

yellow oil.

3.10.53. Preparation of (1⁰S,2⁰S,3⁰R,4S)-4-benzyl-3-[2⁰-

benzyloxy-3⁰-(triethyl-silanoxy)-1-hydroxy-4⁰-methyl-

pentyl)-5,5-dimethyl-oxazolidin-2-one 61. Following

representative procedure 5, 55 (172 mg, 0.32 mmol) and

DIBAL (0.64 mL, 0.64 mmol) in CH₂Cl₂(10 mL) furnished

61 (168 mg, 0.31 mmol, 97%) as a clear colourless oil.

[a]²_D⁵¼þ5.5 (c¼1.5, CHCl₃); d_H(400 MHz, CDCl₃) 0.06

[3H, s, Si(CH₃)_A(CH₃)_B], 0.11 [3H, s, Si(CH₃)_A(CH₃)_B],

0.93 [9H, s, SiC(CH₃)₃], 1.13 [3H, s, C(CH₃)_A(CH₃)_B], 1.26

[3H, s, C(CH₃)_A(CH₃)_B], 2.69 [1H, dd, J¼9.5, 14.8 Hz,

CHCH_AH_BPh], 3.18 [1H, dd, J¼4.8, 14.8 Hz, CHCH_AH_B-

Ph], 4.04 [1H, dd, J¼4.8, 9.5 Hz, CHCH₂Ph], 4.30 [1H, dd,

J¼3.8, 8.4 Hz, CHOCH₂Ph], 4.31 [1H, s, CH(OH)], 4.59

[1H, app. t, J¼4.6 Hz, CH(OTBDMS)], 4.72–4.79 [2H,

ABq, J¼11.8 Hz, CHOCH₂Ph], 4.93 [1H, d, J¼8.1 Hz,

CH(OH)], 6.30 [1H, dd, J¼6.0, 16.1 Hz, CHvCHPh], 6.60

[1H, d, J¼16.1 Hz, CHvCHPh], 7.07–7.42 [15H, m, PhH];

d_C(100 MHz, CDCl₃) 25.1, 24.6 [Si(CH₃)₂], 18.1

[SiC(CH₃)₃], 22.1, 27.5 [C(CH₃)₂], 25.8 [SiC(CH₃)₃], 35.4

[CHCH₂Ph], 65.6 [CHCH₂Ph], 73.5 [CH(OTBDMS)], 73.7

[CHOCH₂Ph], 79.2 [CHOCH₂Ph], 79.5 [CH(OH)], 81.4

[C(CH₃)₂], 126.6 [CHvCHPh], 126.7, 127.4, 127.7 [p-Ph],

127.9, 128.1, 128.4, 128.5, 128.6, 128.8 [m/o-Ph], 131.8

[CHvCHPh], 136.6, 136.9, 137.1 [i-Ph], 157.1 [CvO];

n_max(thin ﬁlm, cm²¹) 1728 [CvO]; HRMS C₃₆H₄₇NO_5-

SiNa [MNa^þ] requires 624.31215. Found 624.3225; m/z

ESþ 624 [100%, MNa^þ].

[a]²_D⁵¼þ4.75 (c¼0.61, CHCl₃); d_H(400 MHz, CDCl₃)

0.67–0.71 [6H, m, Si(CH₂CH₃)₃], 0.90–1.00 [15H, m,

Si(CH₂CH₃)₃and CH(CH₃)₂], 1.09 [3H, s, C(CH₃)_A

(CH₃)_B], 1.26 [3H, s, C(CH₃)_A(CH₃)_B], 1.94–2.02 [1H,

m, CH(CH₃)₂], 2.69 [1H, dd, J¼10.1, 14.9 Hz, CHCH_AH_B-

Ph], 3.25 [1H, dd, J¼4.5, 14.9 Hz, CHCH_AH_BPh], 3.72 [1H,

dd, J¼3.6, 7.0 Hz, CH(OTES)], 4.06 [1H, dd, J¼4.5,

10.1 Hz, CHCH₂Ph], 4.22 [1H, dd, J¼3.6, 8.5 Hz,

CHOCH₂Ph], 4.34 [1H, d, J¼5.6 Hz, CH(OH)], 4.69–

4.75 [2H, m, CHOCH₂Ph], 5.08 [1H, dd, J¼5.6, 8.5 Hz,

CH(OH)], 7.10 [2H, d, J¼7.1 Hz, PhH], 7.18–7.39 [8H, m,

PhH]; d_C(100 MHz, CDCl₃) 5.0 [Si(CH₂CH₃)₃], 6.9

[Si(CH₂CH₃)₃], 19.5, 20.2 [CH(CH₃)₂], 22.2, 27.6

[C(CH₃)₂], 30.0 [CH(CH₃)₂], 35.5 [CHCH₂Ph], 65.2

[CHCH₂Ph], 73.2 [CHOCH₂Ph], 77.3 [CH(OTES)], 78.3

[CHOCH₂Ph], 79.5 [CH(OH)], 81.3 [C(CH₃)₂], 126.6 [p-

Ph], 127.7, 128.4, 128.6, 128.8 [1£p-Ph and m/o-Ph], 137.0,

138.2 [i-Ph], 157.1 [CvO]; n_max(thin ﬁlm, cm²¹) 1728

[CvO]; HRMS C₃₁H₅₁N₂O₅Si [MNH^þ₄] requires 559.3567.

Found 559.3594; m/z ESþ 564 [100%, MNa^þ].

3.10.56. Preparation of (1⁰S,2⁰S,3⁰R,4S)-benzyl-3-[2⁰-ben-

zyloxy-3⁰-(tert-butyl-dimethyl-silanyloxy)-1⁰-hydroxy-3⁰-

(4⁰⁰-nitro-phenyl)-propionyl]-5,5-dimethyl-oxazolidin-2-

one 64. Following representative procedure 5, 58 (75 mg,

0.12 mmol) and DIBAL (0.24 mL, 0.24 mmol) in CH₂Cl₂

(5 mL) furnished 64 (74 mg, 0.12 mmol, 99%) as a yellow

solid.

3.10.54. Preparation of (1⁰S,2⁰S,3⁰R,4S)-4-benzyl-3-[2⁰-

benzyloxy-3⁰-(triethyl-silanoxy)-1-hydroxy-5⁰-methyl-

hexyl)-5,5-dimethyl-oxazolidin-2-one 62. Following

representative procedure 5, 56 (340 mg, 0.61 mmol) and

DIBAL (1.23 mL, 1.23 mmol) in CH₂Cl₂(10 mL) furnished

62 (338 mg, 0.60 mmol, 99%) as a clear colourless oil.

Mp 82 8C [pentane/CH₂Cl₂]; [a]²_D²¼þ14.8 (c¼0.6, CHCl₃);

d_H(400 MHz, CDCl₃) 20.14 [3H, s, Si(CH₃)_A(CH₃)_B], 0.07

[3H, s, Si(CH₃)_A(CH₃)_B], 0.91 [9H, s, SiC(CH₃)₃], 1.13

[3H, s, C(CH₃)_A(CH₃)_B], 1.26 [3H, s, C(CH₃)_A(CH₃)_B],

2.59 [1H, dd, J¼14.8, 9.4 Hz, CHCH_AH_BPh], 3.00 [1H, dd,

J¼14.8, 5.0 Hz, CHCH_AH_BPh], 4.05 [1H, dd, J¼9.4,

5.1 Hz, CHCH₂Ph], 4.24 [1H, d, J¼11.5 Hz, CHOCH_AH_B-

Ph], 4.28 [1H, d, J¼9.6 Hz, CH(OH)], 4.28–4.30 [1H, m,

CHOCH₂Ph], 4.58 [1H, d, J¼11.5 Hz, CHOCH_AH_BPh],

4.56–4.61 [1H, m, CH(OH)], 5.07 [1H, d, J¼2.8 Hz,

CH(OTBDMS)], 7.01–7.03 [2H, m, ArH], 7.16–7.33 [8H,

[a]²_D⁵¼þ11.0 (c¼1.2, CHCl₃); d_H(400 MHz, CDCl₃)

0.53–0.62 [6H, m, Si(CH₂CH₃)₃], 0.85 [3H, d, J¼6.4 Hz,

CH₂CH(CH₃)_A(CH₃)_B], 0.90–0.96 [12H, m, Si(CH₂CH₃)₃

and CH₂CH(CH₃)_A(CH₃)_B], 1.12 [3H, s, C(CH₃)_A(CH₃)

_B], 1.28 [3H, s, C(CH₃)_A(CH₃)_B], 1.33–1.40 [1H, m,

CH_AH_BCH(CH₃)₂], 1.42–1.52 [1H, m, CH_AH_B-

CH(CH₃)₂], 1.64–1.68 [1H, m, CH₂CH(CH₃)₂], 2.72

[1H, dd, J¼9.3, 14.4 Hz, CHCH_AH_BPh], 3.19 [1H, dd,

J¼4.4, 14.4 Hz, CHCH_AH_BPh], 4.00–4.04 [2H, m,

CH(OTES) and CHCH₂Ph], 4.21 [1H, dd, J¼2.2,

S. G. Davies et al. / Tetrahedron 60 (2004) 7553–7577

7575

m, ArH], 7.54 [2H, d, J¼8.6 Hz, ArH], 8.08–8.12 [2H, m,

ArH]; d_C(100 MHz, CDCl₃) 25.3, 24.8 [Si(CH₃)₂], 18.2

[SiC(CH₃)₃], 22.1, 27.5 [C(CH₃)₂], 25.8 [SiC(CH₃)₃], 35.1

[CHCH₂Ph], 66.0 [CHCH₂Ph], 73.7 [CH(OTBDMS)], 74.1

[CHOCH₂Ph], 79.1 [CH(OH)], 80.4 [CHOCH₂Ph], 82.2

[C(CH₃)₂], 126.8, 127.8 [p-Ph], 123.1, 127.8, 128.4, 128.7

[m/o-Ph], 136.4, 137.4 [i-Ph], 147.3, 148.3 [p-Ar and i-Ar],

157.5 [CvO endocyclic]; n_max(KBr disc, cm²¹) 3362 [O–

H broad], 1718 [CvO].

furan], 7.04–7.38 [11H, m, ArH]; d_C(100 MHz, CDCl₃)

25.0, 25.3 [Si(CH₃)₂], 18.1 [SiC(CH₃)₃], 22.2, 27.7

[C(CH₃)₂], 25.7 [SiC(CH₃)₃], 35.3 [CHCH₂Ph], 35.4

[CHCH₂Ph], 69.2 [CH(OTBDMS)], 74.1 [CHOCH₂Ph],

78.6 [CHOCH₂Ph], 79.8 [CH(OH)], 81.8 [C(CH₃)₂], 108.1,

110.4, 141.8 [CH furan], 126.5, 127.7 [p-Ph], 128.1, 128.3,

128.6, 128.8 [m/o-Ph], 138.1, 137.0 [i-Ph], 153.4 [i-Ar

furan], 157.2 [CvO endocyclic]; n_max(thin ﬁlm, cm²¹

)

3402 [O–H broad], 1702 [CvO]; C₃₂H₄₃NO₆Si requires C,

67.93; H, 7.66; N, 2.48%. Found C, 67.25; H, 7.31; N,

2.67%; m/z ESþ 452 [65%, MH^þ2TBDMS], 583 [100%,

MNH^þ₄].

X-ray crystal structure determination for 64. Data were

collected using an Enraf-Nonius k-CCD diffractometer with

graphite monochromated Cu Ka radiation using standard

procedures at 190 K. The structure was solved by direct

methods (SIR92), all non-hydrogen atoms were reﬁned with

anisotropic thermal parameters. Hydrogen atoms were

added at idealised positions. The structure was reﬁned

using CRYSTALS.²²

3.10.58. Preparation of (2S,3R)-2-benzyloxy-3-(tert-

butyl-dimethyl-silanoxy)-octanal 66. Following represen-

tative procedure 8, 60 (687 mg, 1.21 mmol) and K₂CO₃

(234 mg, 1.70 mmol) in MeOH/H₂O (v:v 4:1; 100 mL)

furnished 66 (390 mg, 1.08 mmol, 89%) as a clear

colourless oil and 4 (242 mg, 1.18 mmol, 98%) as a white

solid after ﬂash column chromatography.

X-ray crystal structure data for 64 [C₃₄H₄₆N₂O₈Si]:

M¼638.83, orthorhombic, space group P 21 21 21,

a¼7.3881(1) A, b¼14.5390(3) A, c¼32.6682(7) A,

R_f0.38 [9:1 pentane/Et₂O]; [a]²_D⁵¼24.4 (c¼1.55, CHCl₃);

d_H(400 MHz, CDCl₃) 0.01 [3H, s, Si(CH₃)_A(CH₃)_B], 0.03

[3H, s, Si(CH₃)_A(CH₃)_B], 0.85–0.88 [3H, m, CH₂CH₂CH_2-

CH₃], 0.87 [9H, s, SiC(CH₃)₃], 1.07–1.16 [1H, m, CH_2-

˚

V¼3509.07(11) A , Z¼4, m¼0.117 mm²¹, colourless

3

˚

plate, crystal dimensions¼0.1£0.2£0.5 mm³. A total of

9588 unique reﬂections were measured for 5,u,30 and

4715 reﬂections were used in the reﬁnement. The ﬁnal

parameters were wR₂¼0.051 and R₁¼0.040 [I.3s(I)],

Flack enantiopole¼0.01(19).

CH₂CH_AH_BCH₂CH₃],

1.20–1.36

[6H,

m,

CH_AH_BCH₂CH_AH_BCH₂CH₃], 1.69–1.77 [1H, m, CH_AH_B-

CH₂CH₂CH₂CH₃], 3.77 [1H, dd, J¼1.3, 4.6 Hz, CHOCH_2-

Ph], 3.90–3.94 [1H, m, CH(OTBDMS)], 4.50 [1H, d,

J¼12.1 Hz, CHOCH_AH_BPh], 4.78 [1H, d, J¼12.1 Hz,

CHOCH_AH_BPh], 7.31–7.37 [5H, m, PhH], 9.78 [1H, d,

J¼1.3 Hz, CHO]; d_C(100 MHz, CDCl₃) 24.7, 24.6

The X-ray crystal structure of 64 showed that disorder was

present within the crystal. The OTBDMS group was best

modelled as disordered over two sites in a ratio of 0.62:0.38.

The O-benzyl and 4-benzyl-5,5-dimethyloxazolidin-2-one

fragments of the structure also contain some disorder which

is reﬂected in the prolated ADPs for the atoms contained

within these fragments.

[Si(CH₃)₂],

14.0

[CH₂CH₂CH₂CH₂CH₃],

18.0

[SiC(CH₃)₃], 22.5, 25.3, 31.7, 33.1 [CH₂CH₂CH₂CH₂CH₃],

25.8 [SiC(CH₃)₃], 72.7 [CHOCH₂Ph], 73.2

[CH(OTBDMS)], 85.0 [CHOCH₂Ph], 128.0, 128.5 [m/o-

Ph], 128.1 [p-Ph], 137.4 [i-Ph], 203.7 [CvO]; n_max(thin

ﬁlm, cm²¹) 1734 [CvO]; m/z ESþ 91 [70%], 215 [100%],

257 [15%].

Crystallographic data (excluding structure factors) has been

deposited with the Cambridge Crystallographic Data Centre

as supplementary publication number CCDC234755.

Copies of the data can be obtained, free of charge, on

application to CCDC, 12 Union Road, Cambridge CB2 1EZ,

UK [fax: þ44-1223-336033 or e-mail: deposit@ccdc.cam.

ac.uk].

3.10.59. Preparation of (2S,3R)-2-benzyloxy-3-(triethyl-

silanoxy)-4-methyl-pentanal 67. Following representative

procedure 8, 61 (168 mg, 0.31 mmol) and K₂CO₃(60 mg,

0.43 mmol) in MeOH/H₂O (v:v 4:1; 20 mL) furnished 67

(64 mg, 0.19 mmol, 61%) as a clear colourless oil and 4

(59 mg, 0.29 mmol, 93%) as a white solid after ﬂash column

chromatography.

3.10.57. Preparation of (1⁰S,2⁰S,3⁰S,4S)-4-benzyl-3-[2⁰-

benzyloxy-3⁰-(tert-butyl-dimethyl-silanyloxy)-1⁰-

hydroxy-3⁰-furan-2-yl-propionyl]-5,5-dimethyl-oxazoli-

din-2-one 65. Following representative procedure 5, 59

(2.00 g, 3.55 mmol) and DIBAL (7.10 mL, 7.10 mmol) in

CH₂Cl₂(50 mL) furnished 65 (1.80 g, 3.18 mmol, 90%) as a

very viscous pale yellow oil.

R_f0.42 [9:1 30–40 8C petrol/Et₂O]; [a]²_D⁵¼228.8 (c¼0.5,

CHCl₃); d_H(400 MHz, CDCl₃) 0.54–0.61 [6H, m, Si(CH_2-

CH₃)₃], 0.88 [3H, d, J¼1.2 Hz, CH(CH₃)_A(CH₃)_B], 0.89

[3H, d, J¼1.2 Hz, CH(CH₃)_A(CH₃)_B], 0.913–0.96 [9H, m,

Si(CH₂CH₃)₃], 1.86–1.91 [1H, m, CH(CH₃)₂], 3.75–3.79

[2H, m, CHOCH₂Ph and CH(OTES)], 4.54 [1H, d,

J¼11.9 Hz, CHOCH_AH_BPh], 4.73 [1H, d, J¼11.9 Hz,

CHOCH_AH_BPh], 7.26–7.36 [5H, m, PhH], 9.77 [1H, d,

J¼1.5 Hz, CHO]; d_C(100 MHz, CDCl₃) 5.0 [Si(CH_2-

CH₃)₃], 6.9 [Si(CH₂CH₃)₃], 17.7, 19.6 [CH(CH₃)₂], 30.9

[CH(CH₃)₂], 72.9, 85.5 [CHOCH₂Ph and CH(OTES)], 77.6

[CHOCH₂Ph], 128.1 [p-Ph], 128.3, 128.4 [m/o-Ph], 137.2

[i-Ph], 204.0 [CHO]; n_max(thin ﬁlm, cm²¹) 1732 [CvO];

HRMS C₁₉H₃₆NO₃Si [MNH₄^þ] requires 354.2464. Found

354.2465; m/z CIþ 354 [15%, MNH^þ₄].

[a]²_D³¼220.8 (c¼0.5, CHCl₃); d_H(400 MHz, CDCl₃)

20.06 [3H, s, Si(CH₃)_A(CH₃)_B], 0.06 [3H, s, Si(CH₃)_A

(CH₃)_B], 0.89 [9H, s, SiC(CH₃)₃], 1.12 [3H, s, C(CH₃)_A

(CH₃)_B], 1.19 [3H, s, C(CH₃)_A(CH₃)_B], 2.62 [1H, dd,

J¼14.9, 10.4 Hz, CHCH_AH_BPh], 3.25 [1H, dd, J¼14.9,

4.1 Hz, CHCH_AH_BPh], 4.10 [1H, dd, J¼10.4, 4.1 Hz,

CHCH₂Ph], 4.20 [1H, d, J¼7.5 Hz, CH(OH)], 4.33 [1H,

dd, J¼7.5, 4.4 Hz, CH(OH)], 4.58–4.68 [2H, ABq,

J¼11.3 Hz, CHOCH₂Ph], 4.98–5.02 [2H, m,

CH(OTBDMS) and CHOCH₂Ph], 6.30–6.35 [2H, m, CH

7576

S. G. Davies et al. / Tetrahedron 60 (2004) 7553–7577

3.10.60. Preparation of (2S,3R)-2-benzyloxy-3-(triethyl-

silanoxy)-5-methyl-hexanal 68. Following representative

procedure 8, 62 (227 mg, 0.50 mmol) and K₂CO₃(97 mg,

0.70 mmol) in MeOH/H₂O (v:v 4:1; 30 mL) furnished 68

(120 mg, 0.34 mmol, 69%) as a clear colourless oil and 4

(87 mg, 0.42 mmol, 85%) as a white solid after ﬂash column

chromatography.

H_BPh], 4.62 [1H, d, J¼12.2 Hz, CHOCH_AH_BPh], 5.13 [1H,

d, J¼4.1 Hz, CH(OTBDMS)], 7.10–7.13 [2H, m, PhH],

7.26–7.27 [3H, m, PhH], 7.53 [2H, d, J¼8.8 Hz, ArH],

8.16–8.19 [2H, m, ArH], 9.701 [1H, d, J¼1.5 Hz, CHO]; d_C

(100 MHz, CDCl₃) 25.3, 24.8 [Si(CH₃)₂], 18.1

[SiC(CH₃)₃], 25.6 [SiC(CH₃)₃], 65.8 [CHOCH₂Ph], 74.6

[CH(OTBDMS)], 85.9 [CHOCH₂Ph], 123.3 [p-Ph], 127.9,

128.2, 128.5, 128.6 [m/o-Ph and m/o-Ar], 136.5, 147.5 [i-Ph

and i-Ar], 202.5 [CHO]; n_max(KBr disc, cm²¹) 1734

[CvO]; HRMS C₂₂H₃₃N₂O₅Si [MNH^þ₄] requires 433.2159.

Found 433.2166; m/z CIþ 433 [12%, MNH^þ₄].

R_f0.23 [12:1 30–40 8C petrol/Et₂O]; [a]²_D⁵¼218.6

(c¼0.75, CHCl₃); d_H(400 MHz, CDCl₃) 0.53–0.59 [6H,

m, Si(CH₂CH₃)₃], 0.85 [3H, d, J¼6.5 Hz, CH₂CH(CH₃)_A

(CH₃)_B], 0.88 [3H, d, J¼6.5 Hz, CH₂CH(CH₃)_A(CH₃)_B],

0.90–0.95 [9H, m, Si(CH₂CH₃)₃], 1.25–1.32 [1H, m,

CH_AH_BCH(CH₃)₂], 1.47–1.54 [1H, m, CH₂CH(CH₃)₂],

1.57–1.64 [1H, m, CH_AH_BCH(CH₃)₂], 3.72 [1H, dd, J¼1.4,

4.1 Hz, CHOCH₂Ph], 4.03–4.07 [1H, m, CH(OTES)], 4.51

[1H, d, J¼12.1 Hz, CHOCH_AH_BPh], 4.79 [1H, d,

J¼12.1 Hz, CHOCH_AH_BPh], 7.26–7.38 [5H, m, PhH],

9.78 [1H, d, J¼1.4 Hz, CHO]; d_C(100 MHz, CDCl₃) 4.9

[Si(CH₂CH₃)₃], 6.8 [Si(CH₂CH₃)₃], 22.1, 23.0 [CH_2-

CH(CH₃)₂], 24.1 [CH₂CH(CH₃)₂], 42.4 [CH₂CH(CH₃)₂],

71.4 [CH(OTES)], 72.8 [CHOCH₂Ph], 84.9 [CHOCH₂Ph],

128.1 [p-Ph], 128.2, 128.5 [m/o-Ph], 137.2 [i-Ph], 204.3

[CHO]; n_max(thin ﬁlm, cm²¹) 1734 [CvO]; m/z CIþ 368

[10%, MNH^þ₄].

3.10.63. Preparation of (2S,3S)-2-benzyloxy-3-(tert-

butyl-dimethyl-silanyloxy)-3-furan-2-yl-propionalde-

hyde 71. Following representative procedure 8, 65 (1.9 g,

3.39 mmol) and K₂CO₃(656 mg, 4.75 mmol) in MeOH/

H₂O (50 mL) furnished 71 (1.04 g, 2.88 mmol, 85%) as a

clear colourless oil and 4 (625 mg, 3.05 mmol, 90%) as a

white solid after ﬂash column chromatography.

[a]²_D⁵¼292.4 (c¼0.45, CHCl₃); d_H(400 MHz, CDCl₃)

20.07 [3H, s, Si(CH₃)_A(CH₃)_B], 0.03 [3H, s, Si(CH₃)_A

(CH₃)_B], 0.87 [9H, s, SiC(CH₃)₃], 4.03 [1H, dd, J¼5.4,

1.5 Hz, CHOCH₂Ph], 4.57–4.70 [2H, ABq, J¼12.1 Hz,

CHOCH₂Ph], 5.02 [1H, d, J¼5.4 Hz, CH(OTBDMS)],

6.31–6.36 [2H, m, ArH], 7.27–7.39 [6H, m, ArH], 9.69

[1H, d, J¼1.5 Hz, CHO]; d_C(100 MHz, CDCl₃) 25.3, 25.1

[Si(CH₃)₂], 18.2 [SiC(CH₃)₃], 25.6 [SiC(CH₃)₃], 69.1

[CHOCH₂Ph], 73.1 [CHOCH₂Ph], 85.3 [CH(OTBDMS)],

108.5, 110.4, 142.2 [CH (furan)], 128.0 [p-Ph], 128.4 [m/o-

Ph], 137.2 [i-Ph], 152.6 [i-Ar furan], 201.4 [CHO]; n_max

(thin ﬁlm, cm²¹) 1735 [CvO]; HRMS C₂₀H₃₂NO₄Si

[MNH^þ₄] requires 378.2101. Found 378.2100; m/z

CIþ(NH₃) 246 [22%, MH^þ2TBDMS,], 378 [100%,

MNH^þ₄].

3.10.61. Preparation of (2S,3R)-2-benzyloxy-3-(tert-

butyl-dimethyl-silanoxy)-5-phenyl-pent-4-enal 69. Fol-

lowing representative procedure 8, 63 (270 mg,

0.45 mmol) and K₂CO₃(87 mg, 0.63 mmol) in MeOH/

H₂O (v:v 4:1; 30 mL) furnished 69 (114 mg, 0.29 mmol,

64%) as a clear colourless oil and 4 (86 mg, 0.42 mmol,

93%) as a white solid after ﬂash column chromatography.

R_f0.19 [12:1 30–40 8C petrol/Et₂O]; [a]²_D⁵¼224.8 (c¼0.6,

CHCl₃); d_H(400 MHz, CDCl₃) 0.07 [6H, s, Si(CH₃)₂], 0.92

[9H, s, SiC(CH₃)₃], 3.84 [1H, dd, J¼1.8, 4.9 Hz, CHOCH_2-

Ph], 4.61 [1H, d, J¼12.3 Hz, CHOCH_AH_BPh], 4.64–4.67

[1H, m, CH(OTBDMS)], 4.80 [1H, d, J¼12.3 Hz,

CHOCH_AH_BPh], 6.33 [1H, dd, J¼6.0, 16.0 Hz,

CHvCHPh], 6.62 [1H, dd, J¼0.9, 16.0 Hz, CHvCHPh],

7.26–7.39 [5H, m, PhH], 9.742 [1H, d, J¼1.7 Hz, CHO]; d_C

(100 MHz, CDCl₃) 25.0, 24.5 [Si(CH₃)₂], 18.2

[SiC(CH₃)₃], 25.8 [SiC(CH₃)₃], 73.1 [CHOCH₂Ph], 73.8

[CH(OTBDMS)], 86.0 [CHOCH₂Ph], 126.6, 127.8, 128.0,

128.5, 128.6 [CHvCHPh, p-and m/o-Ph], 131.5

[CHvCHPh], 136.4, 137.3 [i-Ph], 202.6 [CHO]; n_max

(thin ﬁlm, cm²¹) 1734 [CvO]; m/z CIþ 414 [15%,

MNH^þ₄].

Acknowledgements

The authors wish to acknowledge Astra-Zeneca for funding

(R. L. N.) and New College, Oxford for a Junior Research

Fellowship (A. D. S.).

References and notes

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upon repeated chromatographic puriﬁcation.

0

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Article Doi

N-α-Benzyloxyacetyl derivatives of (S)-4-benzyl-5,5- dimethyloxazolidin-2-one for the asymmetric synthesis of differentially protected α,β-dihydroxyaldehydes

DOI: 10.1016/j.tet.2004.05.123

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Full text of DOI:10.1016/j.tet.2004.05.123

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