Silatropic carbonyl ene cyclizations in the synthesis of pseudosugars and hydroxylated piperidines

Silatropic Carbonyl Ene Cyclizations in the Synthesis of

Pseudosugars and Hydroxylated Piperidines

Jeremy Robertson,* Petra M. Stafford, and Stephen J. Bell

Department of Chemistry, University of Oxford, Chemistry Research Laboratory, Mansfield Road,

Oxford, OX1 3TA, United Kingdom

jeremy.robertson@chem.ox.ac.uk

Received April 1, 2005

We describe two applications of silicon-tethered thermal allyl transfer reactions of R-silyloxyalde-

hydes; formally, these processes can be regarded as silatropic carbonyl ene reactions in which the

silicon tether is transferred to the aldehyde oxygen concurrent with carbonyl allylation. In the

first application, isoserinal substrates, which bear side-chain nitrogen functionality, are elaborated

to dihydroxypiperidines. In the second application, a product of cyclohexadienyl transfer is taken

on to carbocylic analogues of, for example, mannose. In both series, the silatropic ene reactions are

effected thermally, with no added Lewis acid, and are both stereospecific and highly stereoselective.

SCHEME 1. Thermal Allylic Transfer Reactions

via Aldehyde/Silyl Group Precomplexation

Introduction

Arising out of an ongoing investigation of the scope of

silicon-tethered ene cyclizations, we discovered that

substrates of the form 1 (Scheme 1) are converted into

dioxasilolanes 3 upon heating.¹We proposed that these

reactionsswhich showed moderate to excellent stereo-

selectivity and very high stereospecificityscould proceed,

in principle, by cooperative carbonyl and silyl activation

by precomplexation (e.g., via 2). Formally, the allyl

transfer event is an unusual variant of the intramolecular

ene reaction (Scheme 2), in which a silyl group is

transferred rather than a proton; that is, a silatropic

carbonyl ene reaction.²We have described generic reac-

tions in both the R- and â-silyloxyaldehyde series;^1a,3in

this paper we extend the process to include substrates

bearing side-chain amine functionality (leading to hy-

droxylated piperidines) and those bearing a more complex

transferring allylic group (leading to pseudosugars).

Hydroxylated Piperidines. The therapeutic poten-

tial of hydroxylated piperidines, including iminosugars,

SCHEME 2. Formal Silatropic Carbonyl Ene

Cyclization

(1) (a) Robertson, J.; Hall, M. J.; Green, S. P. Org. Biomol. Chem.

2003, 1, 3635-3638. See also: (b) Bashiardes, G.; Chaussebourg, V.;

Laverdan, G.; Pornet, J. Chem. Commun. 2004, 122-123.

(2) For early studies on silatropic processes see: (a) Slutsky, J.;

Kwart, H. J. Am. Chem. Soc. 1973, 95, 8678-8685. (b) Coates, R. M.;

Sandefur, L. O.; Smillie, R. D. J. Am. Chem. Soc. 1975, 97, 1619-

1621. For a recent theoretical treatment supporting the concerted

silatropic ene mechanism in the uncatalysed Mukaiyama aldol reaction

see: (c) Wong, C. T.; Wong, M. W. J. Org. Chem. 2005, 70, 124-131.

See also: (d) Dubac, J.; Laporterie, A. Chem. Rev. 1987, 87, 319-334.

(3) Hall, M. J. D.Phil. Thesis, University of Oxford, Oxford, U.K.,

2003.

derives in large part from the glycosidase inhibitory

properties of the protonated form which is envisaged to

mimic the transition state for acidic glycoside hydrolysis.

Published on Web 08/09/2005

J. Org. Chem. 2005, 70, 7133-7148

7133

Robertson et al.

SCHEME 3. Application to Hydroxylated

Piperidine Synthesis

silolane 14 (Scheme 5) whose stereochemistry was es-

tablished by NOE experiments (Table 1); this compound

could not be purified by chromatography and was taken

on crude into the desilylation which afforded syn-diol 16

in excellent overall yield. Interestingly, di(isopropyl)silyl

substrate 11 cyclized under similar conditions; this time

the dioxasilolane (15) was stable to chromatography and

could be fully characterized. The fact that the reaction

takes place with isopropyl- in place of phenyl-silyl sub-

stituents has implications for the mechanism of the

formal silatropic ene process: the isopropyl substituents

cannot be argued to facilitate a cooperative activation

mechanism of the form implied in Scheme 1; they merely

provide a steric impediment toward O-Si bond forma-

tion, and on the basis of this and other observations, we

favor a mechanism closer to that implied by Scheme 2

in which the importance of carbonyl/silyl precomplexation

is down-played. (E)-Crotyl substrate 12 cyclized to give

apparently only one dioxasilolane (17) which was desi-

lylated to syn,syn-diol 18; in comparison, the cyclization

of the (Z)-analogue (13) produced an 11:1 mixture of

syn,anti-(20) and anti,anti-(21) diastereomers.

SCHEME 4^a

In all cases, the relative stereochemistry of the diols

was confirmed by Corey-Winter elimination as sum-

marized in Scheme 6. Corroboration of the stereochem-

istry at the methyl-bearing carbon was not sought,

assignment being made by analogy to other cases in

which the stereochemistry had been established by a bis-

(allylation)/RCM protocol;^1ahowever, the specific rota-

tions of compounds 23 {[R]²²_D-6.58° (c 0.73, CHCl₃)} and

24 {[R]²²_D+6.22° (c 0.37, CHCl₃)} supported the assign-

ment that diastereomers 18 and 20 differed solely at the

allylic methine center.

As an illustration of the synthetic potential of the

silatropic ene products, the alkene in diol 16 was

subjected to ozonolysis and the polar lactol 26 taken on

directly into the hydrogenolysis step, N-deprotection

being accompanied by amino-acetal reduction. Acetyla-

tion of this material (27), to aid purification (f 28), and

subsequent partial deacylation led to the cyclic dihydroxy-

piperidine 29 in 18% yield over the four steps. This low

yield was attributable largely to the ozonolysis reaction

[step (i) f 26, Scheme 7] that appeared to generate a

number of polar, inseparable byproducts.

^aReagents: (i) Ph₂Si(R)H, B(C₆F₅)₃, CH₂Cl₂; (ii) [(COD)Ir-

-

(PPh₂Me)₂]⁺PF₆cat., CH₂Cl₂; (iii) DIBAL, CH₂Cl₂.

Numerous natural and nonnatural polyhydroxypiperi-

dines have been screened in this capacity, and applica-

tions, in various stages of clinical and preclinical develop-

ment, range from the treatment of diabetes, Gaucher’s

disease, and viral infections including influenza, hepa-

titis, and HIV. The area has been thoroughly reviewed.⁴

Of note is that less highly oxygenated piperidines (di-

and trihydroxylated) can also exhibit activity.⁵

Within this context, we envisaged application of our

methodology to the synthesis of hydroxylated piperidines

by incorporating amine functionality in the R-side-chain

and effecting cyclization onto the internal carbon of the

alkene formed during the silatropic ene reaction (Scheme

3).

This proposal required access to O-[(alk-2-enyl)diphen-

ylsilyl]isoserinal derivatives (4); we had already prepared

the Si-prenyl/N-Cbz derivative 10 (Scheme 4) for separate

silicon-tethered Type I carbonyl ene cyclizations,⁶and for

completeness, (E)- and (Z)-crotyl analogues 12 and 13,

respectively, were prepared using our earlier methodol-

ogy.⁷On heating, prenyl substrate 10 cyclized smoothly,

albeit slowly, generating the trans-substituted dioxa-

A significant improvement in overall yield was ob-

tained simply by altering the order of events to aid

purification at each stage. Diol acetylation (f 30) as the

first step enabled a much cleaner ozonolysis to give an

“anomeric” mixture (31 and 32) that was deprotected and

reduced as before giving, after methanolysis, free dihy-

droxypiperidine 27. The relative stereochemistry in this

3

compound was confirmed by the magnitude of the J_3,4

coupling constant (9.4 Hz) indicative of diequatorial diol

functionality.

Cyclohexadienyl Transfer. The potential of thermal

silatropic ene reactions to offer stereoselective routes to

useful synthetic intermediates and biologically active

molecules would be limited if restricted merely to the

formal transfer of simple allylic groups (allyl, prenyl,

crotyl), and in more recent work we have focused on

extending the methodology to the transfer of more

complex groups (bearing, for example, γ-alkoxy or tri-

alkylsilyl substitution).⁸Projecting a route into carbocy-

clic analogues⁹of higher sugars, our interest focused on

(4) Lillelund, V.; Jensen, H. H.; Liang, X. F.; Bols, M. Chem. Rev.

2002, 102, 515-553 and references therein.

(5) (a) Bernotas, R. C.; Papandreou, G.; Urbach, J.; Ganem, B.

Tetrahedron Lett. 1990, 31, 3393-3396. (b) Ichikawa, Y.; Igarashi, Y.;

Ichikawa, M.; Suhara, Y. J. Am. Chem. Soc. 1998, 120, 3007-3018.

(c) Patil, N. T.; John, S.; Sabharwal, S. G.; Dhavale, D. D. Bioorg. Med.

Chem. 2002, 10, 2155-2160.

(6) Robertson, J.; Hall, M. J.; Stafford, P. M.; Green, S. P. Org.

Biomol. Chem. 2003, 1, 3758-3767.

(7) (a) For the silylation procedure see: (a) Blackwell, J. M.; Foster,

K. L.; Beck, V. H.; Piers, W. E. J. Org. Chem. 1999, 64, 4887-4892.

The alkene isomerisation process was adapted from: (b) Matsuda, I.;

Kato, T.; Sato, S.; Izumi, Y. Tetrahedron Lett. 1986, 27, 5747-5750.

7134 J. Org. Chem., Vol. 70, No. 18, 2005

Silatropic Carbonyl Ene Reactions

SCHEME 5^a

^aReagents: (i) PhCH₃, 120-130 °C, 17-24 h; (ii) KF, H₂O₂, aq. MeOH.

SCHEME 6^a

TABLE 1. NOE Results for Dioxasilolane 14

enhancement/%

irradiate H1′a H1′b

3

4

2′′

H1′a

H1′b

3

23.4 5.5 2.4 0.9

2.8 5.7 0.0

23.0

3.0

1.5

1.7 2.4

6.7

4

3.5

5.1 1.8

2′′

0.0

0.0 3.6 3.8

the possibility of tethered cyclohexadienyl transfer, in

which cyclization via one of the diastereotopic olefins (A

or B) would be expected to be preferred, leading to

stereochemical control at the starred carbon (Scheme 8).

The stereochemical situation is analogous to the pre-

ferred mode of cyclization (chairlike vs boatlike) for the

(Z)-crotyl substrates, and cyclization through olefin A was

predicted to lead to the syn,anti-configured product after

desilylation (see below). Although such tethered variants

are not precedented, the desymmetrization of silylated

cyclohexadienes has been described for the synthesis of

cyclitols and related compounds,¹⁰(()-peduncularine,¹¹

^aReagents: (i) (Im)₂CdS, THF; (ii) P(OEt)₃.

and taxol intermediates.¹²Of particular relevance is

Studer’s recent development of stereoselective intermo-

lecular carbonyl cyclohexadienylations using the corre-

sponding silicon and titanium derivatives.¹³

To test this hypothesis, novel dialkyl(cyclohexadienyl)-

silanes 34 and 35 (Scheme 9) were prepared in excellent

yield using variants of literature procedures.^10g,11These

(8) Robertson, J.; Tyrrell, A. T. Unpublished results, 2004. See also

ref 3.

(9) (a) Rassu, G.; Auzzas, L.; Pinna, L.; Battistini, L.; Curti, C.

Advances in Chemical Synthesis of Carbasugars and Analogues. In

Studies in Natural Products Chemistry, Vol. 29, Part J; Atta-ur-

Rahman, Ed.; Elsevier: Amsterdam, 2003, 449-520. (b) Suami, T.;

Ogawa, S. Adv. Carbohydr. Chem. Biochem. 1990, 48, 21. For a useful

overview see: (c) Wagner, S. H.; Lundt, I. J. Chem. Soc., Perkin Trans.

1 2001, 780-788.

(10) (a) Angelaud, R.; Landais, Y. J. Org. Chem. 1996, 61, 5202-

5203. (b) Angelaud, R.; Landais, Y.; Schenk, K. Tetrahedron Lett. 1997,

38, 1407-1410. (c) Angelaud, R.; Landais, Y. Tetrahedron Lett. 1997,

38, 8841-8844. (d) Angelaud, R.; Landais, Y.; Parra-Rapado, L.

Tetrahedron Lett. 1997, 38, 8845-8848. (e) Angelaud, R.; Babot, O.;

Charvat, T.; Landais, Y. J. Org. Chem. 1999, 64, 9613-9624. (f)

Landais, Y.; Zekri, E. Tetrahedron Lett. 2001, 42, 6547-6551. (g)

Landais, Y.; Zekri, E. Eur. J. Org. Chem. 2002, 4037-4053.

(11) (a) Roberson, C. W.; Woerpel, K. A. Org. Lett. 2000, 2, 621-

623. (b) Roberson, C. W.; Woerpel, K. A. J. Am. Chem. Soc. 2002, 124,

11342-11348.

(12) (a) Ihara, M.; Suzuki, S.; Tokunaga, Y.; Fukumoto, K. J. Chem.

Soc., Perkin Trans. 1 1995, 2811-2812. (b) Fujishima, H.; Takeshita,

H.; Toyota, M.; Ihara, M. Chem. Commun. 1999, 893-894. (c) Majo,

V. J.; Suzuki, S.; Toyota, M.; Ihara, M. J. Chem. Soc., Perkin Trans. 1

2000, 3375-3381.

J. Org. Chem, Vol. 70, No. 18, 2005 7135

Robertson et al.

SCHEME 7^a

^aReagents: (i) O₃, CH₂Cl₂, then PPh₃; (ii) H₂, [Pd/C], EtOH; (iii) Ac₂O, pyridine, (DMAP); (iv) Amberlite IRA(OH) resin, MeOH.

SCHEME 8. Predicted Sense of Stereocontrol during Cyclohexadienyl Transfer Reactions

SCHEME 9^a

SCHEME 10^a

^aReagents: (i) s-BuLi, TMEDA, THF, then Ph₂SiHCl; (ii)

s-BuLi, TMEDA, THF, then i-Pr₂SiHCl; (iii) CuCl₂, CuI, THF;

ethyl mandelate, Et₃N, DMAP, DMF; (iv) PhCH₃, 80-120 °C, 2-4

h.

^aReagents: (i) PhCH₃, 120 °C, 20 h; (ii) KF, H₂O₂, aq. MeOH.

(<20% conversion after 5 h at 120 °C) to offer a potential

window of stability within which to complete the sila-

tropic ene process.

silanes could not be used directly to silylate R-hydroxy-

esters,¹⁴and we were unable to find a way to convert

silane 35 into the corresponding chlorosilane in accept-

able yield. Fortunately, application of Ishikawa’s chlori-

nation protocol¹⁵worked well with silane 34 (to give 36

in situ), and direct silylation of, for example, (()-ethyl

mandelate, under standard conditions, provided ester 37

in excellent yield. In a thermal stability test, heating this

ester (37) resulted in complete conversion to ethyl O-

(triphenylsilyl)mandelate within 2 h in d₈-toluene (NMR

tube); however, degassing the solvent prior to heating

effected a significant reduction in the rate of this process

DIBAL reduction of ester 37 gave the aldehyde (38,

Scheme 10) which was heated in degassed toluene, and

the dioxasilolane 39 (not shown) cleaved to afford a 3:1

mixture of diastereomeric diols (40 and 41) in low overall

yield. The stereochemistry of the major product (40) was

established by X-ray crystallography,¹⁶the stereochem-

istry of the minor product (41) being assigned tentatively

on the basis of the earlier results with (Z)-crotyl sub-

strates. The low yield in this reaction was subsequently

traced to oxidative side-reactions induced by the hydro-

gen peroxide that had been added in the cleavage step

(13) (a) Schleth, F.; Studer, A. Angew. Chem., Int. Ed. 2004, 43, 313-

315. (b) Schleth, F.; Vogler, T.; Harms, K.; Studer, A. Chem. Eur. J.

2004, 10, 4171-4185.

(16) Crystal data for 40:

C₁₄H₁₆O₂, M ) 216.28, colorless plates,

(14) For example, application of Piers’ protocol (ref 7a) to (S)-ethyl

lactate and silane 34 led only to (S)-ethyl O-(phenyl)lactate in low yield.

(15) Kunai, A.; Kawakami, T.; Toyoda, E.; Ishikawa, M. Organo-

metallics 1992, 11, 2708-2711.

orthorhombic, a ) 8.4023(2), b ) 16.1062(4), c ) 17.4221(6) Å, V )

2357.72(11) Å³, T ) 150 K, space group Pnaa, Z ) 8, µ(Mo KR) ) 0.08

mm^-1, 5322 reflections measured (R_int) 0.02), 1655 reflections used,

final wR ) 0.0664.

7136 J. Org. Chem., Vol. 70, No. 18, 2005

Silatropic Carbonyl Ene Reactions

SCHEME 11^a

SCHEME 12^a

^aReagents: (i) 36 (prepared in situ from 34), Et₃N, DMAP,

CH₂Cl₂; (ii) DIBAL, CH₂Cl₂; (iii) PhCH₃, 120 °C, 18 h, then TBAF,

THF.

in order to aid separation of the phenylsilyl residues; in

later work with different substrates the peroxide was

omitted and yields improved.

It was expected that a directing group bulkier than

phenyl would increase the stereoselectivity of the reac-

tion, and a suitable substrate was prepared from pival-

aldehyde cyanohydrin in an optimized procedure derived

from our model studies (Scheme 11); important modifica-

tions included increasing the loading of CuI in the

chlorination step and use of an excess of DMAP in

dichloromethane in place of triethylamine/DMF for the

silylation reaction. DIBAL reduction of silyl cyanohydrin

42 was efficient, paralleling our previous experience, and

the silatropic ene substrate 43 was readily obtained on

a gram scale. It was pleasing to find that this compound

behaved exactly as expected on heating, the peroxide-

free desilylation conditions affording diol 44 as a single

diastereomer in high overall yield.

^aReagents: (i) OsO₄, NMO, THF; (ii) NaH, BnBr, DMF; (iii)

aq. TFA; (iv) NaIO₄, aq. THF, then NaBH₄, MeOH; (v) VO(acac)₂,

t-BuOOH, CH₂Cl₂; (vi) aq. HCl, THF; (vii) Ac₂O, pyridine, DMAP.

FIGURE 1. Diagnostic COSY and HMBC correlations in 51.

This diol was elaborated in two ways which differed

in the nature of the first oxidation step. In the first route

(Scheme 12), acetonide formation (f 45) was followed by

regioselective dihydroxylation (of the alkene remote to

the dioxolane), the low yield in this step (f 46) being

attributed to double dihydroxylation and loss of the

product during aqueous workup. Di-O-benzylation, aceto-

nide hydrolysis, and diol cleavage with a reductive

workup furnished cyclohexene derivative 48. Interest-

ingly, acidic treatment of the directed epoxidation product

49 and acetylation led to chloride 51 with essentially

complete regiocontrol. Support for this structure was

gained from a combination of NMR and MS experi-

ments: ¹H-¹H COSY, coupling constant analysis, and

an HMBC experiment established proton assignment and

configuration around the ring (Figure 1), and HRMS

established incorporation of Cl [found for M(³⁵Cl)Na⁺

478.1994]. This sense of regio- and stereocontrol may be

a result of direct diaxial opening of the epoxide in the

half-chair conformation that gives the chlorohydrin in

conformation 50a (Figure 2) which would relax to pre-

ferred conformation 50b; however, diaxial opening of the

epoxide in the alternative half-chair conformation would

give chlorohydrin 52 which conceivably could rearrange,

possibly during the acetylation, to give the same overall

result.

FIGURE 2. Plausible products from the acidolysis of epoxide

49.

13). Although the cycloaddition step was not usefully

stereoselective, the major isomer (53) could be separated

and elaborated by reduction, di-O-benzylation, dihy-

droxylation, a second di-O-benzylation, and hydrolysis to

give hexa-ol derivative 59. Diol cleavage with a reductive

workup as before led to the mannose analogue 60 in good

yield, in which the stereochemistry could be rigorously

established (and that of the preceding intermediates

inferred).

Conclusion

These silatropic carbonyl ene processes result in the

products of functionalized allylation of R-hydroxyalde-

hydes with high stereospecificity and good, and predict-

able, stereoselectivity in favor of syn-diol products;

furthermore, the reactions proceed thermally, in the

absence of added Lewis acids, are tolerant of side-chain

functionality, and the transferring group need not be a

As an alternative, singlet oxygen cycloaddition across

diene 45 was used to initiate a reasonably efficient

synthesis of tetra-O-benzyl pseudo-mannose (60, Scheme

J. Org. Chem, Vol. 70, No. 18, 2005 7137

Robertson et al.

SCHEME 13^a

^aReagents: (i) O₂, methylene blue, CH₂Cl₂, hν; (ii) LiAlH₄, THF; (iii) NaH, BnBr, DMF; (iv) OsO₄, NMO, THF; (v) NaH, BnBr, DMF;

(vi) aq. TFA; (vii) NaIO₄-SiO₂, THF, then NaBH₄, MeOH.

and the solvents were removed in vacuo. The resulting oil was

purified by flash column chromatography (silica gel, petrol)

to give the title compound as a colorless oil (2.96 g, 65%). R_f

0.36 (petrol). ν_max/cm^-1(thin film): 3087m, 3069s, 3050m,

3017s, 2962m, 2926m, 2858m, 2125s, 1956w, 1883w, 1818w,

1766w, 1649m, 1589m, 1486m, 1428s, 1396m, 1362m, 1330w,

1302w, 1262w, 1152m, 1118s, 1066w, 1028w, 990m, 908s,

808s, 732s, 698s, 647m. δ_H(400 MHz, CDCl₃): 1.57 (3H, d, J

6.0, CH₃), 2.16 (2H, dd, J 8.0, 3.6, SiCH₂), 4.95 (1H, t, J 3.6,

SiH), 5.45-5.65 (2H, m, CHdCH), 7.41-7.50 (6H, m), and

simple allylic unit. In addition to being of mechanistic

interest, this methodology generates intermediates for

elaboration into useful compounds including, as exempli-

fied here, hydroxylated piperidines and carbasugars. We

are currently establishing the scope of the process for

accessing a variety of 1,2-dihydroxy-3-substituted-pent-

4-enes.¹⁷

Experimental Section

7.64-7.68 (4H, m, 2 × Ph). δ_C(100.6 MHz, CDCl₃): 12.7, 13.6,

+

123.4, 124.8, 128.0, 129.7, 134.1, 135.2. m/z (CI⁺): 256 (MNH₄

,

(But-2-ynyl)diphenylsilane. To a stirred solution of 2-bu-

tyne (1.57 mL, 20.0 mmol) and TMEDA (3.0 mL, 20.0 mmol)

in anhydrous tetrahydrofuran (20 mL) cooled to -78 °C was

added t-BuLi (1.7 M in pentane, 12.4 mL, 21.0 mmol) dropwise,

and the solution was stirred for 30 min at -78 °C and then

warmed to RT over 30 min. The reaction mixture was recooled

to -78 °C, and diphenylchlorosilane (3.90 mL, 20.0 mmol) was

added. The resulting solution was stirred for 30 min at -78

°C and at RT for 1 h and then partitioned between water (50

mL) and ether (50 mL). The aqueous layer was extracted with

ether (2 × 50 mL), and the combined organic fractions were

washed with brine (100 mL), dried (MgSO₄), and the solvents

were removed in vacuo. The resulting oil was purified by flash

column chromatography (silica gel, petrol) to give the title

compound as a colorless oil (4.52 g, 96%). R_f0.18 (pentane).

ν_max/cm^-1(thin film): 3069m, 3049m, 3011m, 2916m, 2880w,

2854w, 2134s, 1957w, 1915w, 1820w, 1588w, 1567w, 1486w,

1428s, 1395w, 1331w, 1303w, 1263w, 1179m, 1117s, 1066w,

1028w, 998w, 807s, 733s, 697s, 674s. δ_H(400 MHz, CDCl₃):

1.83 (3H, t, J 2.8, CH₃), 2.15 (2H, dq, J 3.2, 2.8, SiCH₂), 5.08

(1H, t, J 3.2, SiH), 7.39-7.55 (6H, m), and 7.72-7.74 (4H, m,

2 × Ph). δ_C(100.6 MHz, CDCl₃): 3.0, 3.6, 74.9, 75.7, 127.8,

129.9, 133.0, 135.2. m/z (EI⁺): 236 (M⁺, 18%), 221 (23), 183

(100), 158 (15), 105 (60), 53 (21). Accurate mass (EI⁺): found,

236.1022; C₁₆H₁₆Si (M⁺) requires 236.1021. found, C 81.35, H

6.99; C₁₆H₁₆Si requires C 81.30, H 6.82.

(Z-But-2-enyl)diphenylsilane. To a stirred solution of

(but-2-ynyl)diphenylsilane (4.50 g, 19.1 mmol) was added

DIBAL (1.0 M in heptane, 38.0 mL, 38.0 mmol), and the

solution was heated at reflux for 5 h. The mixture was cooled

to RT, poured into a mixture of dilute hydrochloric acid (1.0

M, 50 mL), ice (100 mL), and ether (100 mL), and stirred for

15 min. The layers were separated, and the aqueous phase

was extracted with ether (2 × 100 mL); the combined organic

fractions were washed successively with dilute hydrochloric

acid (1.0 M, 2 × 100 mL), brine (100 mL), then dried (MgSO₄),

44%), 239 (MH⁺, 16), 200 (100), 183 (96), 122 (14), 105 (36).

+

Accurate mass (CI⁺): found, 256.1520; C₁₆H₂₂NSi (MNH₄

requires 256.1522.

)

(S)-Methyl N-(Benzyloxycarbonyl)[(but-3-enyl)diphen-

ylsilanyloxy]isoserinate (7). To a stirred solution of but-3-

enyl(diphenyl)silane¹⁸(934 mg, 3.92 mmol) and methyl (S)-

N-(benzyloxycarbonyl)isoserinate (5)¹⁹(992 mg, 3.92 mmol) in

anhydrous dichloromethane (4.0 mL), was added tris(pen-

tafluorophenyl)borane (100 mg, 0.20 mmol), and the reaction

mixture was heated at reflux for 16 h. The solution was

allowed to cool to RT and then partitioned between water (50

mL) and ether (50 mL); the aqueous layer was separated and

extracted with ether (2 × 25 mL). The combined organic

extracts were washed with brine (50 mL), dried (MgSO₄), and

the solvents were removed in vacuo. The resulting oil was

purified by flash column chromatography (silica gel, 4:1 petrol/

ether) to furnish the title compound (7) as a colorless syrup

(1.34 g, 70%). R_f0.26 (2:1 petrol/ether). [R]²²-16.2° (c 1.03,

D

chloroform). ν_max/cm^-1(thin film): 3355m, 3070m, 3001m,

2951m, 1726s, 1638w, 1589w, 1515m, 1429m, 1244m, 1118s,

996m, 910w, 740m, 700s. δ_H(400 MHz, CDCl₃): 1.26-1.38

(2H, m, SiCH₂), 2.07-2.22 (2H, m, CH₂CHd), 3.54 (2H, app.

t, J 5.6, NHCH₂), 3.58 (3H, s, OCH₃), 4.34 (1H, t, J 5.6, OCH),

4.91 (1H, dd, J 10.4, 1.6), and 5.00 (1H, dd, J 16.8, 1.6, CHd

CH₂), 5.08 (2H, s, CH₂Ph), 5.11 (1H, br t, J 5.6, NH), 5.89 (1H,

ddt, J 16.8, 10.4, 6.4, CHdCH₂), 7.26-7.50 (10H, m), and

7.56-7.60 (5H, m, 3 × Ph). δ_C(100.6 MHz, CDCl₃): 12.8, 26.8,

44.7, 52.0, 66.8, 71.3, 113.2, 128.0, 128.1, 128.5, 130.3, 133.4,

133.7, 134.8, 134.9, 136.4, 140.8, 156.0, 171.5. m/z (ES⁺): 512

(MNa⁺, 100%), 490 (MH⁺, 22), 194 (20). Accurate mass (ES⁺):

found, 490.2050; C₂₈H₃₂NO₅Si (MH⁺) requires 490.2050.

(18) (a) Kahle, K.; Murphy, P. J.; Scott, J.; Tamagni, R. J. Chem.

Soc., Perkin Trans. 1 1997, 997-999. (b) Kim, C.; Choi, S. K.; Park,

E.; Jung, I. J. Korean Chem. Soc. 1997, 41, 88-97.

(19) Stafford, P. M. D.Phil. Thesis, University of Oxford, Oxford,

U.K., 2004.

(17) Robertson, J.; Tyrrell, A. T. Unpublished results, 2005.

7138 J. Org. Chem., Vol. 70, No. 18, 2005

Silatropic Carbonyl Ene Reactions

(S)-MethylN-(Benzyloxycarbonyl)[(E-but-2-enyl)diphen-

ylsilanyloxy]isoserinate (8). (1,5-Cyclooctadiene)bis(meth-

yldiphenylphosphine)iridium(I) hexafluorophosphate (20.3 mg,

0.024 mmol) was dissolved in anhydrous dichloromethane (3.5

mL) and cooled to -78 °C. The Ir(I) catalyst was activated by

passing hydrogen through the solution until the color changed

from blood-red to colorless. The reaction vessel was purged

with argon to remove any remaining hydrogen, and the

solution was warmed to 0 °C. A solution of ester 7 (1.15 g,

2.35 mmol) in anhydrous dichloromethane (12.0 mL) was

cooled to 0 °C and then added via cannula to the solution of

preactivated catalyst. The resulting mixture was stirred at 0

°C, and the reaction progress was monitored by ¹H NMR. After

35 min the solvent was removed in vacuo; the resulting

material was triturated with ether, the extracts filtered though

a short plug of silica gel and Celite, and the solvents were

removed from the filtrate in vacuo. The resulting oil was

purified by flash column chromatography (silica gel, 4:1 petrol/

ether) to furnish the title compound (8) as a colorless oil (1.15

extracts were washed with brine (25 mL), dried (MgSO₄), and

the solvents were removed in vacuo. The crude product was

purified by flash column chromatography (silica gel, 4:1 petrol/

ether) to yield the title compound as a colorless syrup (120

mg, 11%). R_f0.37 (1:1 petrol/ether). [R]²⁰-6.60° (c 1.00,

D

chloroform). ν_max/cm^-1(thin film): 3361m, 3033w, 2946s,

2867s, 1761s, 1729s, 1514m, 1456m, 1376w, 1248m, 1143s,

1097w, 995m, 883m, 844w, 814w, 748s, 697m. δ_H(400 MHz,

CDCl₃): 1.03-1.14 (14H, m, 2 × i-Pr), 1.58 (2H, d, J 8.0,

SiCH₂) overlain by 1.60 and 1.67 (2 × 3H, 2 × s, dC(CH₃)₂),

3.46-3.59 (2H, m, NHCH₂), 3.72 (3H, s, OCH₃), 4.40 (1H, t, J

5.0, OCH), 5.08 and 5.13 (2 × 1H, 2 × d, J 12.4, CH₂Ph)

overlaying 5.11-5.18 (2H, m, CHd and NH), 7.27-7.39 (5H,

m, Ph). δ_C(100.6 MHz, CDCl₃): 12.4, 12.7, 17.3 (two peaks),

17.4, 17.6, 25.8, 45.1, 52.0, 66.8, 71.1, 118.4, 128.1, 128.5, 130.0,

136.4, 156.2, 172.0. m/z (CI⁺): 453 (MNH₄⁺, 100%), 436 (MH⁺,

13). Accurate mass (ES⁺): found, 453.2786; C₂₃H₄₁N₂O₅Si

(MNH₄⁺) requires 453.2785.

(S)-N-(Benzyloxycarbonyl)[(3-methylbut-2-enyl)di(iso-

propyl)silanyloxy]isoserinal (11). To a stirred solution of

(S)-methyl N-(benzyloxycarbonyl)[(3-methylbut-2-enyl)di(iso-

propyl)silanyloxy]isoserinate (83 mg, 0.19 mmol) in anhydrous

dichloromethane (2.0 mL) cooled to -78 °C was added DIBAL

(1.0 M in dichloromethane, 290 µL, 0.29 mmol) dropwise, and

the solution was stirred at -78 °C for 1 h. The reaction was

quenched by the addition of a saturated solution of tartaric

acid in methanol (1 mL). The mixture was warmed to RT and

partitioned between aqueous tartaric acid solution (30% w/v,

15 mL) and ether (15 mL). The aqueous layer was extracted

with ether (3 × 15 mL), and the combined organic extracts

were washed with brine (25 mL), dried (Na₂SO₄), and the

solvents were removed in vacuo. The crude product was

purified by flash column chromatography (silica gel, 8:1 petrol/

ethyl acetate) to furnish aldehyde 11 as a colorless syrup (60

g, 100%). R_f0.44 (1:1 petrol/ether). [R]²²-10.3° (c 1.00,

D

chloroform). ν_max/cm^-1(thin film): 3360m, 3070m, 3048m,

3015m, 2952m, 2884m, 2854w, 1754s, 1727s, 1590w, 1515s,

1429s, 1303m, 1245s, 1119s, 998m, 967m. δ_H(400 MHz,

C₆D₆): 1.61 (3H, dd, J 6.2, 1.0, dCHCH₃), 2.30 (2H, d, J 8.0,

SiCH₂), 3.27 (3H, s, OCH₃), 3.61 (2H, app. t, J 5.6, NHCH₂),

4.52 (1H, t, J 5.6, OCH), 4.98 (1H, t, J 5.6, NH), 5.11 and 5.16

(2 × 1H, 2 × d, J 12.0, CH₂Ph), 5.42-5.52 and 5.59s5.69 (2 ×

1H, 2 × m, CHdCH), 7.25-7.34 (10H, m), and 7.78-7.81 (5H,

m, 3 × Ph). δ_C(100.6 MHz, C₆D₆): 18.4, 20.5, 45.3, 51.6, 66.9,

72.1, 125.2, 126.4, 128.4-128.8 (overlapping), 130.5, 134.7 (two

peaks), 135.6, 135.8, 137.5, 156.5, 171.6. m/z (ES⁺): 512

(MNa⁺, 90%), 507 (MNH₄⁺, 40), 490 (MH⁺, 14), 434 (100), 412

(17). Accurate mass (ES⁺): found, 512.1862; C₂₈H₃₁NO₅Si

(MNa⁺) requires 512.1869.

(S)-MethylN-(Benzyloxycarbonyl)[(Z-but-2-enyl)diphen-

ylsilanyloxy]isoserinate (9). To a stirred solution of ((^Z)-but-

2-enyl)diphenylsilane (1.05 g, 4.41 mmol) and methyl (S)-N-

(benzyloxycarbonyl)isoserinate (5)¹⁹(1.11 g, 4.39 mmol) in

anhydrous dichloromethane (4.5 mL) was added tris(pen-

tafluorophenyl)borane (112 mg, 0.22 mmol), and the reaction

mixture was heated at reflux for 16 h. The solution was

allowed to cool to RT and then partitioned between water (50

mL) and ether (50 mL); the aqueous layer was separated and

extracted with ether (2 × 25 mL). The combined organic

extracts were washed with brine (50 mL), dried (MgSO₄), and

the solvents were removed in vacuo. The resulting oil was

purified by flash column chromatography (silica gel, 4:1 petrol/

ether) to furnish the title compound (9) as a colorless syrup

mg, 78%). R_f0.63 (ether [streaks]). [R]²⁰-1.90° (c 1.00,

D

chloroform). ν_max/cm^-1(thin film): 3349m, 3066w, 3034w,

2944s, 2892m, 2867s, 1732s, 1517m, 1456m, 1403w, 1377w,

1347w, 1328w, 1256s, 1153s, 1128s, 1098m, 1002m, 920w,

883m, 844w, 815w, 775w, 747m, 697m. δ_H(400 MHz, CDCl₃):

0.98-1.14 (14H, m, 2 × i-Pr), 1.59 and 1.67 (2 × 3H, 2 × s,

dC(CH₃)₂) overlays 1.60 (2H, m, SiCH₂), 3.42 (1H, app. dt, J

14.0, 5.0) and 3.58 (1H, ddd, J 14.0, 7.2, 5.0, NHCH₂), 4.18

(1H, t, J 5.0, OCH), 5.08 and 5.12 (2 × 1H, 2 × d, J 12.0, CH₂-

Ph), 5.12-5.19 (2H, m, CHd and NH), 7.30-7.39 (5H, m, Ph),

9.62 (1H, s, CHO). δ_C(100.6 MHz, CDCl₃): 12.4, 12.6 (two

peaks), 17.3, 17.4, 17.7, 25.8, 43.0, 66.9, 76.3, 118.2, 128.1,

128.2, 128.5, 130.4, 136.3, 156.2, 202.2. m/z (CI⁺): 423 (MNH₄

,

+

29%), 406 (MH⁺, 91), 366 (13), 336 (100), 315 (49), 272 (30),

218 (21), 169 (35), 148 (75), 108 (25). Accurate mass (ES⁺):

found, 423.2680; C₂₂H₃₉N₂O₄Si (MNH₄⁺) requires 423.2679.

(1.65 g, 77%). R_f0.35 (1:1 petrol/ether). [R]²²-13.6° (c 1.07,

D

chloroform). ν_max/cm^-1(thin film): 3427m, 3070m, 3049m,

3017m, 2952m, 1725s, 1650w, 1590w, 1515s, 1455m, 1429s,

1396w, 1364w, 1332w, 1215s, 1119s, 991m, 910w, 781m, 737s,

700s, 648m. δ_H(400 MHz, CDCl₃): 1.45 (3H, d, J 5.6,

dCHCH₃), 2.20 (2H, d, J 7.6, SiCH₂), 3.56 (2H, app. t, J 5.6,

NHCH₂), 3.58 (3H, s, CO₂CH₃), 4.39 (1H, t, J 5.6, OCH), 5.08

and 5.11 (2 × 1H, 2 × d, J 13.0, CH₂Ph), 5.15 (1H, br t, J 5.6,

NH), 5.37-5.53 (2H, m, CHdCH), 7.30-7.46 (10H, m), and

7.55-7.63 (5H, m, 3 × Ph). δ_C(100.6 MHz, CDCl₃): 12.6, 15.3,

44.8, 52.0, 66.9, 71.5, 123.4, 124.1, 127.9, 128.1, 128.5, 129.5,

130.2, 133.5, 134.8, 136.4, 156.2, 171.5. m/z (ES⁺): 512 (MNa⁺,

100%), 507 (MNH₄⁺, 27). Accurate mass (ES⁺): found, 507.2322;

C₂₈H₃₅N₂O₅Si (MNH₄⁺) requires 507.2315.

(S)-N-(Benzyloxycarbonyl)[(E-but-2-enyl)diphenylsil-

anyloxy]isoserinal (12). To a stirred solution of silyl iso-

serinate 8 (1.14 g, 2.33 mmol) in anhydrous dichloromethane

(23.0 mL) cooled to -78 °C was added DIBAL (1.0 M in

dichloromethane, 3.50 mL, 3.50 mmol) dropwise, and the

solution was stirred at -78 °C for 2 h. The reaction was

quenched by the addition of a saturated solution of tartaric

acid in methanol (5 mL). The mixture was warmed to RT and

partitioned between aqueous tartaric acid solution (30% w/v,

50 mL) and ether (25 mL). The aqueous layer was extracted

with ether (3 × 25 mL), and the combined organic extracts

were washed with brine (50 mL), dried (Na₂SO₄), and the

solvents were removed in vacuo. The crude product was

purified by flash column chromatography (silica gel, 3:1 petrol/

ether) to furnish aldehyde 12 as a colorless syrup (537 mg,

50%). R_f0.21 (1:1 petrol/ether [streaks]). [R]²²_D+1.27° (c 1.02,

chloroform). ν_max/cm^-1(thin film): 3423m, 3069m, 3049m,

3014m, 2932m, 2854w, 1722s, 1517s, 1454w, 1428m, 1258m,

1153m, 1118s, 998w, 968w, 910w, 739s, 700s. δ_H(500 MHz,

C₆D₆): 1.48 (3H, d, J 6.5, dCHCH₃), 2.06-2.15 (2H, m, SiCH₂),

3.15 and 3.28 (2 × 1H, 2 × app. dt, J 14.0, 5.5, NHCH₂), 3.97

(1H, t, J 5.5, OCH), 4.58 (1H, t, J 5.5, NH), 4.96 and 5.02 (2 ×

(S)-Methyl N-(Benzyloxycarbonyl)[(3-methylbut-2-en-

yl)di(isopropyl)silanyloxy]isoserinate. To a stirred solu-

tion of (3-methylbut-2-enyl)di(isopropyl)silane⁶(500 mg, 2.71

mmol) and methyl (S)-N-(benzyloxycarbonyl)isoserinate (5)¹⁹

(617 mg, 2.44 mmol) in anhydrous toluene (10.0 mL) was

added tris(pentafluorophenyl)borane (123 mg, 0.24 mmol), and

the reaction mixture was heated at reflux for 24 h. The solution

was allowed to cool to RT and then partitioned between water

(50 mL) and ether (50 mL); the aqueous layer was separated

and extracted with ether (2 × 25 mL). The combined organic

J. Org. Chem, Vol. 70, No. 18, 2005 7139

Robertson et al.

1H, 2 × d, J 12.5, CH₂Ph), 5.32 (1H, dq, J 15.8, 6.5, CHd

CHCH₃), 5.46 (1H, dt, J 15.8, 8.0, CHdCHCH₃), 7.16-7.25

(10H, m), and 7.54-7.72 (5H, m, 3 × Ph), 9.27 (1H, s, CHO).

δ_C(125.7 MHz, C₆D₆): 18.5, 20.5, 43.0, 67.2, 77.6, 125.0, 126.8,

128.1-135.5 (overlapping), 134.6, 137.5, 156.6, 200.2. m/z

(ES⁺): 477 (MNH₄⁺, 100%), 460 (MH⁺, 73). Accurate mass

(ES⁺): found, 460.1946; C₂₇H₃₀NO₄Si (MH⁺) requires 460.1944.

3034w, 2946m, 1694s, 1638w, 1538m, 1455m, 1415m, 1271s,

1145m, 1106m, 1012m, 914m, 844w, 824w, 736m, 697s. δ_H(400

MHz, DMSO-d₆): 0.95 and 0.96 (2 × 3H, 2 × s, CMe₂), 2.97

(2H, app. t, J 6.0, NHCH₂), 3.03 (1H, d, J 8.2, CH(OH)CMe₂),

3.60 (1H, app. q, app. J 6.8, CH₂CH(OH)), 4.17 (1H, d, J 8.2,

CH(OH)CMe₂), 4.36 (1H, d, J 7.2, CH₂CH(OH)), 4.90-5.03 (4H,

m, CHdCH₂and CH₂Ph), 5.87 (1H, dd, J 17.6, 10.8, CHdCH₂),

7.20 (1H, br t, J 6.0, NH), 7.29-7.38 (5H, m, Ph). δ_C(100.6

MHz, DMSO-d₆): 22.0, 24.9, 41.2, 45.3, 65.1, 67.6, 75.3, 111.3,

127.7, 127.8, 128.4, 137.3, 146.4, 156.3. m/z (APCI⁺): 294

(MH⁺, 16%), 250 (100), 160 (21), 142 (40), 104 (18). Accurate

mass (ES⁺): found, 294.1708; C₁₆H₂₄NO₄(MH⁺) requires

294.1705.

Alternative Procedure from Aldehyde 10. A stirred

solution of aldehyde 10⁶(743 mg, 1.57 mmol) in anhydrous

toluene (8.0 mL) was heated at 120 °C in a base-washed sealed

tube. After 20 h the reaction mixture was cooled to RT and

the solvent was removed in vacuo to furnish siladioxolane 14

(unstable toward chromatography and taken on directly into

the oxidation reaction). R_f0.83 (ether). δ_H(400 MHz, toluene-

d₈): 1.06 (6H, s, CMe₂), 3.15 (1H, dt, J 14.0, 6.4) and 3.42 (1H,

ddd, J 14.0, 6.4, 3.2, NHCH₂), 3.80 (1H, d, J 6.4, CH(O)CMe₂),

4.20 (1H, td, J 6.4, 3.2, CH₂CHO), 4.90 (1H, t, J 6.4, NH),

4.94-5.12 (4H, m, CHdCH₂and CH₂Ph), 5.90 (1H, dd, J 17.4,

11.0, CHdCH₂), 6.93-7.33 (11H, m), and 7.61-7.72 (4H, m,

Ph). δ_C(100.6 MHz, toluene-d₈): 22.8, 24.1, 41.6, 47.4, 67.1,

77.0, 84.8, 114.0, 128.1, 128.5, 128.7, 128.9, 129.0, 132.4, 133.5,

135.4, 135.6, 135.8, 135.9, 137.9, 144.2, 156.9. m/z (APCI⁺):

474 (MH⁺, 100%), 430 (81), 396 (77), 352 (60), 306 (84), 262

(58), 160 (60), 122 (36). The crude product was dissolved in

methanol (15.0 mL); then, KF (274 mg, 4.72 mmol) and H₂O₂

(35% in water, 1.5 mL) were added, and the reaction mixture

was stirred at RT for 3 h. The solvent was removed in vacuo;

the crude residue was triturated with ether, the combined

extracts were filtered through Celite, and the filtrate was

concentrated in vacuo. Purification by flash column chroma-

tography (silica gel, 1:2 petrol/ether) afforded aminodiol 16

as a colorless glassy solid (447 mg, 95%). Data as above.

(S)-N-(Benzyloxycarbonyl)[(Z-but-2-enyl)diphenylsila-

nyloxy]isoserinal (13). To a stirred solution of silyl isoseri-

nate 9 (1.01 g, 2.07 mmol) in anhydrous dichloromethane (20.0

mL) cooled to -78 °C was added DIBAL (1.0 M in dichlo-

romethane, 3.10 mL, 3.10 mmol) dropwise, and the solution

was stirred at -78 °C for 1.5 h. The reaction was quenched

by the addition of a saturated solution of tartaric acid in

methanol (5 mL). The mixture was warmed to RT and

partitioned between aqueous tartaric acid solution (30% w/v,

50 mL) and ether (25 mL). The aqueous layer was extracted

with ether (3 × 25 mL), and the combined organic extracts

were washed with brine (50 mL), dried (Na₂SO₄), and the

solvents were removed in vacuo. The crude product was

purified by flash column chromatography (silica gel, 3:1 petrol/

ether) to furnish aldehyde 13 as a colorless syrup (720 mg,

76%). R_f0.28 (1:1 petrol/ether [streaks]). [R]²²_D-1.67° (c 1.02,

chloroform). ν_max/cm^-1(thin film): 3425s, 3070m, 3049m,

3017m, 2935m, 2858w, 1704s, 1650w, 1590w, 1515s, 1455m,

1429s, 1394w, 1363w, 1331w, 1257s, 1152s, 1117s, 1027w,

990m, 911m, 857w. δ_H(400 MHz, CDCl₃): 1.46 (3H, d, J 6.0,

dCHCH₃), 2.19-2.29 (2H, m, SiCH₂), 3.45 and 3.59 (2 × 1H,

2 × app. dt, J 14.4, 5.2, NHCH₂), 4.26 (1H, t, J 5.2, OCH),

5.06-5.08 (1H, m, NH) overlaying 5.07 and 5.11 (2 × 1H, 2 ×

d, J 12.4, CH₂Ph), 5.40-5.56 (2H, m, CHdCH), 7.32-7.49

(10H, m), and 7.63-7.69 (5H, m, 3 × Ph), 9.59 (1H, s, CHO).

δ_C(100.6 MHz, CDCl₃): 12.7, 15.3, 42.6, 66.9, 123.2, 124.4,

127.9, 128.1, 128.2, 128.5, 130.5, 133.3, 133.4, 134.8, 136.3,

156.2, 201.0. m/z (APCI⁺): 460 (MH⁺, 35%), 416 (29), 404 (16),

360 (35), 253 (50), 246 (22), 192 (99), 180 (18), 120 (100), 105

(12). Accurate mass (ES⁺): found, 460.1943; C₂₇H₃₀NO₄Si

(MH⁺) requires 460.1944.

(3S,4S)-3-[(Benzyloxycarbonyl)amino]methyl-4-(1,1-

dimethylprop-2-enyl)-2,5-dioxa-1,1-di(isopropyl)-

silolane (15). A solution of aldehyde 11 (49 mg, 0.12 mmol)

in toluene-d₈(600 µL) was heated at 120 °C in a sealed NMR

(2S,3S,4R)-1-(Benzyloxycarbonyl)amino-4-methylhex-

5-en-2,3-diol (18). A stirred solution of aldehyde 12 (419 mg,

0.91 mmol) in anhydrous toluene (4.5 mL) was heated at 130

°C in a base-washed sealed tube. After 17 h the reaction

mixture was cooled to RT, and the solvent was removed in

vacuo. The crude siladioxolane (17) was dissolved in methanol

(9.0 mL); KF (159 mg, 2.74 mmol) and H₂O₂(35% in water,

1.0 mL) were added, and the reaction mixture was stirred at

RT for 4 h. The solvent was removed in vacuo; the crude

residue was triturated with ether, the combined extracts were

filtered through Celite, and the filtrate was concentrated in

vacuo. The crude product was purified by flash column

chromatography (silica gel, 1:1 petrol/ether) to give aminodiol

18 as a colorless crystalline solid (205 mg, 80%). R_f0.27 (ether).

1

tube, and the reaction progress was monitored by H NMR.

After 30 h the mixture was cooled to RT, and the solvent was

removed in vacuo. Purification by flash column chromatogra-

phy (silica gel, 5:1 petrol/ether) gave dioxasilolane 15 as a

colorless oil (45 mg, 91%). R_f0.58 (1:1 petrol/ether). [R]²²

D

-33.1° (c 0.55, chloroform). ν_max/cm^-1(thin film): 3338m,

2946s, 2867s, 1724s, 1513m, 1465m, 1382w, 1248m, 1148w,

1073m, 1041m, 918w, 883w, 849w, 797w, 752w, 696m. δ_H(400

MHz, CDCl₃): 1.00-1.08 (20H, m, 2 × i-Pr and CMe₂), 3.02

(1H, ddd, J 13.0, 8.0, 3.8, NHCHH′), 3.42 (1H, d, J 8.0, CH(O)-

CMe₂), 3.60 (1H, ddd, J 13.0, 8.0, 2.8, NHCHH′), 3.84 (1H, td,

J 8.0, 2.8, CH₂CHO), 5.02-5.14 (4H, m, CHdCH₂and CH₂-

Ph), 5.23-5.30 (1H, m, NH), 5.90 (1H, dd, J 17.6, 10.8, CHd

CH₂), 7.31-7.39 (5H, m, Ph). δ_C(100.6 MHz, CDCl₃): 12.5,

12.7, 16.8 (two peaks), 16.9, 22.6, 24.0, 40.6, 46.7, 66.7, 75.5,

83.8, 113.2, 128.1, 128.5, 136.5, 143.9, 156.3. m/z (APCI⁺): 406

(MH⁺, 46%), 363 (100), 280 (10), 255 (10), 122 (10). Accurate

mass (ES⁺): found, 406.2408; C₂₂H₃₆NO₄Si (MH⁺) requires

406.2413.

M.p. 82-85 °C (ether). [R]²²_D-3.00° (c 1.01, chloroform). ν_max

/

cm^-1(KBr disk): 3456m, 3343m, 2974m, 2951m, 2906m,

1671s, 1552s, 1441m, 1350m, 1277s, 1131s, 1054m, 1036m,

916m, 780w, 750m. δ_H(400 MHz, DMSO-d₆): 1.00 (3H, d, J

6.4, CH₃), 2.31-2.41 (1H, m, CHMe), 3.01-3.10 (3H, m,

NHCH₂and CH(OH)CHMe), 3.52 (1H, ddt, J 13.6, 6.8, 2.0,

CH₂CH(OH)), 4.18 (1H, d, J 8.0, CH(OH)CHMe), 4.37 (1H, d,

J 6.8, CH₂CH(OH)), 4.90-5.09 (4H, m, CHdCH₂and CH₂Ph),

5.71 (1H, ddd, J 17.2, 10.2, 8.0, CHdCH₂), 7.11 (1H, t, J 5.6,

NH), 7.30-7.40 (5H, m, Ph). δ_C(100.6 MHz, DMSO-d₆): 17.3,

41.1, 45.1, 66.0, 70.1, 74.9, 115.1, 128.6, 129.2, 138.1, 142.8,

157.2. m/z (ES⁺): 302 (MNa⁺, 100%), 280 (MH⁺, 37), 236 (81).

Accurate mass (ES⁺): found, 302.1371; C₁₅H₂₁NO₄Na (MNa⁺)

requires 302.1368.

(2S,3S,4S)-1-(Benzyloxycarbonyl)amino-4-methylhex-

5-en-2,3-diol (20). A stirred solution of aldehyde 13 (490 mg,

1.07 mmol) in anhydrous toluene (5.5 mL) was heated at 130

°C in a base-washed sealed tube. After 24 h the reaction

mixture was cooled to RT, and the solvent was removed in

vacuo to furnish the crude siladioxolane (19) which was

(2S,3S)-1-(Benzyloxycarbonyl)amino-4,4-dimethylhex-

5-en-2,3-diol (16). To a stirred solution of dioxasilolane 15

(41 mg, 0.10 mmol) in methanol (1.0 mL) was added KF (17

mg, 0.30 mmol), and the reaction mixture was stirred at RT

for 16 h. The solvent was removed in vacuo; the crude residue

was triturated with ether, and the combined extracts were

filtered through Celite, the solvents were removed in vacuo.

The crude product was purified by flash column chromatog-

raphy (silica gel, 1:2 petrol/ether) to give aminodiol 16 as a

colorless glassy solid (26 mg, 88%). R_f0.49 (ether). [R]²²_D-10.9°

(c 1.01, chloroform). ν_max/cm^-1(KBr disk): 3428s, 3399s, 3084w,

7140 J. Org. Chem., Vol. 70, No. 18, 2005

Silatropic Carbonyl Ene Reactions

dissolved in methanol (10.5 mL); KF (187 mg, 3.22 mmol) and

H₂O₂(35% in water, 1.0 mL) were added, and the reaction

mixture was stirred at RT for 14 h. The solvent was removed

in vacuo; the crude residue was triturated with ether, the

combined extracts were filtered through Celite, and the filtrate

was concentrated in vacuo. The crude product was purified

by flash column chromatography (silica gel, 1:1 petrol/ether)

to give aminodiol 20 as a colorless crystalline solid (233 mg,

MHz, CDCl₃): 1.13 and 1.14 (2 × 3H, 2 × s, CMe₂), 3.44-3.56

(2H, m, NHCH₂), 4.41 (1H, d, J 6.0, CH(OR)CMe₂), 4.64 (1H,

td, J 6.0, 4.4, CH₂CHO), 5.10 and 5.16 (2 × 1H, 2 × d, J 12.4,

CH₂Ph), 5.20 (1H, d, J 17.6) and 5.25 (1H, d, J 10.4, CHd

CH₂) overlaying 5.21 (1H, t, J 6.4, NH), 5.74 (1H, dd, J 17.6,

10.4, CHdCH₂), 7.31-7.40 (5H, m, Ph). δ_C(100.6 MHz,

CDCl₃): 21.5, 22.6, 39.9, 43.4, 67.4, 81.9, 89.7, 116.7, 128.1,

128.4, 128.6, 135.8, 139.6, 153.2, 156.7. m/z (ES⁺): 358 (MNa⁺,

29%), 336 (MH⁺, 100), 209 (28). Accurate mass (ES⁺): found,

336.1270; C₁₇H₂₂NO₄S (MH⁺) requires 336.1270.

78%). R_f0.24 (ether). M.p. 77-79 °C (ether). [R]²²-19.4° (c

D

1.08, chloroform). ν_max/cm^-1(KBr disk): 3481m, 3348m, 3066m,

3034m, 2980m, 2932m, 2884m, 1672s, 1643m, 1548s, 1440m,

1276s, 1109m, 1034m, 906m, 752m. δ_H(400 MHz, DMSO-d₆):

0.92 (3H, d, J 7.2, CH₃), 2.33 (1H, app. sextet, app. J 7.0,

CHMe), 2.98-3.14 (3H, m, NHCH₂and CH(OH)CHMe), 3.49

(1H, ddt, J 10.8, 6.4, 3.6, CH₂CH(OH)), 4.22 (1H, d, J 6.8, CH-

(OH)CHMe), 4.49 (1H, d, J 6.4, CH₂CH(OH)), 4.90-5.05 (4H,

m, CHdCH₂and CH₂Ph), 5.89 (1H, ddd, J 17.6, 10.0, 7.2, CHd

CH₂), 7.11 (1H, t, J 5.6, NH), 7.29-7.38 (5H, m, Ph). δ_C(100.6

MHz, DMSO-d₆): 17.5, 40.6, 44.7, 66.0, 70.4, 75.2, 114.6, 128.5,

129.2, 138.1, 142.9, 157.2. m/z (ES⁺): 302 (MNa⁺, 100%), 280

(MH⁺, 33), 236 (82). Accurate mass (ES⁺): found, 302.1363;

C₁₅H₂₁NO₄Na (MNa⁺) requires 302.1368. Also obtained was

(2S,3R,4R)-1-(benzyloxycarbonyl)amino-4-methylhex-5-en-2,3-

diol (21) as a colorless semisolid (22 mg, 7%). R_f0.33 (ether).

R]²²_D+17.5° (c 0.49, chloroform). ν_max/cm^-1(KBr disk): 3400s,

3338s, 3069m, 3037m, 3000m, 2958m, 2928m, 2869m, 1667s,

1547s, 1440m, 1367w, 1282m, 1149w, 1071m, 1011w, 971w,

919w. δ_H(400 MHz, DMSO-d₆): 0.99 (3H, d, J 7.2, CH₃), 2.48-

2.55 (1H, m, CHMe), 2.92 (1H, ddd, J 13.2, 8.2, 5.6, NHCHH′)

3.11 (1H, ddd, J 8.2, 6.0, 2.8, CH(OH)CHMe), 3.30 (1H, ddt, J

8.2, 6.4, 2.8, CH₂CH(OH)), 3.37 (1H, ddd, J 13.2, 5.6, 2.8,

NHCHH′), 4.58 (1H, d, J 6.4, CH₂CH(OH)), 4.63 (1H, d, J 6.0,

CH(OH)CHMe), 4.93-5.05 (4H, m, CHdCH₂and CH₂Ph), 5.80

(1H, ddd, J 17.2, 10.4, 8.4, CHdCH₂), 6.95 (1H, t, J 5.6, NH),

7.30-7.37 (5H, m, Ph). δ_C(100.6 MHz, DMSO-d₆): 18.5, 39.6,

45.4, 66.1, 71.5, 76.4, 115.6, 128.6, 129.2, 138.5, 141.2, 157.3.

m/z (ES⁺): 302 (MNa⁺, 100%), 280 (MH⁺, 25), 236 (60).

Accurate mass (ES⁺): found, 302.1371; C₁₅H₂₁NO₄Na (MNa⁺)

requires 302.1368.

General Procedure for Corey-Winter Diene Synthe-

sis. To a stirred solution of the diol (0.10 mmol) in anhydrous

tetrahydrofuran (2.0 mL) was added 1,1-thiocarbonyldiimida-

zole (0.20 mmol), and the mixture was heated at reflux. After

20 h the reaction mixture was cooled to RT, and the solvent

was removed in vacuo. The crude thiocarbonate was purified

by flash column chromatography (silica gel, 3:2 petrol/ether)

and was then dissolved in triethyl phosphite (2.0 mL) and

heated at reflux. After 2.5 h the reaction mixture was cooled

to RT, and the solvent was removed in vacuo. The residual oil

was azeotroped with toluene (3 × 5 mL), and the diene was

purified by flash column chromatography (silica gel, 9:1 petrol/

ether).

(4R)-1-(Benzyloxycarbonyl)amino-4-methylhex-2(E),5-

diene (23). With the use of the general procedure, diene 23

was obtained as a colorless oil (91% from diol 18). R_f0.62 (1:1

petrol/ether). [R]²²_D-6.58° (c 0.73, chloroform). ν_max/cm^-1(thin

film): 3336m, 3033w, 2964m, 2922m, 1703s, 1530m, 1455m,

1363w, 1250s, 1134w, 1046w, 972m. δ_H(400 MHz, CDCl₃):

1.09 (3H, d, J 7.2, CH₃), 2.80-2.91 (1H, m, CHMe), 3.80 (2H,

t, J 5.6, NHCH₂), 4.77 (1H, br s, NH), 4.95-4.99 (2H, m, CHd

CH₂), 5.12 (2H, s, CH₂Ph), 5.46 (1H, dt, J 15.5, 5.6, CH₂-

CHd), 5.58 (1H, dd, J 15.5, 6.4, dCHCHMe), 5.76 (1H, ddd, J

17.2, 10.4, 6.8, CHdCH₂), 7.31-7.38 (5H, m, Ph). δ_C(100.6

MHz, CDCl₃): 19.6, 39.9, 42.9, 66.7, 113.2, 124.9, 128.1 (two

peaks), 128.5, 136.6, 136.8, 142.2, 156.1. m/z (ES⁺): 268

(MNa⁺, 100%), 263 (MNH₄⁺, 30), 255 (14), 246 (MH⁺, 84), 241

(10), 236 (20). Accurate mass (ES⁺): found, 246.1488; C₁₅H₂₀-

NO₂(MH⁺) requires 246.1494. Data for the intermediate

thiocarbonate, (4S,5S,1′R)-5-[(benzyloxycarbonyl)amino]methyl-

4-(1-methylprop-2-enyl)-1,3-dioxolane-2-thione, a colorless oil,

are as follows. R_f0.58 (ether). [R]²²_D+22.0° (c 1.17, chloroform).

ν_max/cm^-1(thin film): 3412s, 2968m, 1705s, 1623m, 1455w,

1292s, 1164m, 1045w, 975w, 738w, 697m. δ_H(400 MHz,

CDCl₃): 1.18 (3H, d, J 6.8, CH₃), 2.54-2.65 (1H, m, CHMe),

3.52-3.56 (2H, m, NHCH₂), 4.49 (1H, t, J 7.0, CH(OR)CHMe),

4.66 (1H, dt, J 7.0, 4.0, CH₂CHOR), 5.10 and 5.16 (2 × 1H, 2

× d, J 12.2, CH₂Ph), 5.20-5.29 (3H, m, CHdCH₂and NH),

5.66 (1H, ddd, J 17.6, 9.6, 8.0, CHdCH₂), 7.32-7.41 (5H, m,

Ph). δ_C(100.6 MHz, CDCl₃): 15.5, 41.4, 42.7, 67.4, 83.5, 86.4,

119.2, 128.1, 128.4, 128.6, 135.4, 135.8, 153.1, 156.7. m/z

(ES⁺): 344 (MNa⁺, 12%), 322 (MH⁺, 100), 301 (13), 195 (11).

Accurate mass (ES⁺): found, 322.1112; C₁₆H₂₀NO₄S (MH⁺)

requires 322.1113.

(4S)-1-(Benzyloxycarbonyl)amino-4-methylhex-2(E),5-

diene (24). With the use of the general procedure, diene 24

was obtained as a colorless oil (82% from diol 20). R_f0.62 (1:1

petrol/ether). [R]²²_D+6.22° (c 0.37, chloroform). ν_max/cm^-1(thin

film): 3420s, 3094m, 3028m, 2963m, 2920w, 1695s, 1638m,

1529m, 1454w, 1247s, 1132w, 1045w, 970w, 912w. δ_H(500

MHz, CDCl₃): 1.09 (3H, d, J 6.5, CH₃), 2.86 (1H, app. sextet,

app. J 6.5, CHMe), 3.80 (2H, br t, J 5.5, NHCH₂), 4.78 (1H, br

s, NH), 4.97 (1H, dt, J 10.0, 1.5) and 5.00 (1H, dt, J 17.0, 1.5,

CHdCH₂), 5.12 (2H, s, CH₂Ph), 5.46 (1H, dt, J 15.5, 5.5,

CH₂CHd), 5.59 (1H, dd, J 15.5, 6.5, dCHCHMe), 5.76 (1H,

ddd, J 17.0, 10.0, 6.5, CHdCH₂), 7.30-7.39 (5H, m, Ph). δ_C

(125.7 MHz, CDCl₃): 19.5, 39.8, 42.8, 66.6, 113.1, 124.8, 128.0,

128.4 (two peaks), 136.4, 136.6, 142.1, 156.1. m/z (ES⁺): 268

(MNa⁺, 100%), 246 (MH⁺, 13), 152 (8). Accurate mass (ES⁺):

found, 246.1493; C₁₅H₂₀NO₂(MH⁺) requires 246.1494. Data

for the intermediate thiocarbonate, (4S,5S,1′S)-5-[(benzyloxy-

carbonyl)amino]methyl-4-(1-methylprop-2-enyl)-1,3-dioxolane-

1-(Benzyloxycarbonyl)amino-4,4-dimethylhexa-2(E),5-

diene (22). With the use of the general procedure, diene 22

was obtained as a colorless oil (76% from diol 16). R_f0.55 (1:1

petrol/ether). ν_max/cm^-1(thin film): 3336m, 3066w, 3034w,

2963m, 2869w, 1702s, 1529m, 1456w, 1360w, 1246s, 1135m,

975m, 914m. δ_H(400 MHz, CDCl₃): 1.10 (6H, s, CMe₂), 3.80

(2H, br t, J 6.0, NHCH₂), 4.76 (1H, br s, NH), 4.94 (1H, dd, J

10.8, 1.2) and 4.95 (1H, dd, J 17.2, 1.2, CHdCH₂), 5.12 (2H, s,

CH₂Ph), 5.41 (1H, dt, J 15.8, 6.0, CH₂CHd), 5.61 (1H, dt, J

15.8, 1.2, dCHCMe₂), 5.80 (1H, dd, J 17.2, 10.8, CHdCH₂),

7.30-7.39 (5H, m, Ph). δ_C(100.6 MHz, CDCl₃): 26.8, 39.0, 43.1,

66.7, 110.9, 122.6, 128.1, 128.5, 136.6, 141.4, 146.7, 156.8. m/z

(APCI⁺): 260 (MH⁺, 29%), 215 (44), 199 (100), 156 (27), 151

(87). Accurate mass (CI⁺): found, 260.1649; C₁₆H₂₂NO₂(MH⁺)

requires 260.1651. Data for the intermediate thiocarbonate,

(4S,5S)-5-[(benzyloxycarbonyl)amino]methyl-4-(1,1-dimethylprop-

2-enyl)-1,3-dioxolane-2-thione, a colorless oil, are as follows.

2-thione, a colorless oil, are as follows. R_f0.54 (ether). [R]²²

D

+10.3° (c 1.31, chloroform). ν_max/cm^-1(thin film): 3326m,

3066w, 3033w, 2969m, 1801w, 1710s, 1521m, 1455w, 1336s,

1290s, 1170m, 1045m, 999m, 928m, 735m, 698m. δ_H(400 MHz,

CDCl₃): 1.16 (3H, d, J 6.8, CH₃), 2.60-2.70 (1H, m, CHMe),

3.51-3.57 (2H, m, NHCH₂), 4.64 (1H, dd, J 6.8, 4.4, CH(OR)-

CHMe), 4.67 (1H, td, J 6.0, 4.4, CH₂CHO), 5.10 and 5.15 (2 ×

1H, 2 × d, J 12.2, CH₂Ph), 5.19-5.28 (3H, m, CHdCH₂and

NH), 5.71 (1H, ddd, J 17.6, 10.4, 7.6, CHdCH₂), 7.31-7.43

(5H, m, Ph). δ_C(100.6 MHz, CDCl₃): 14.6, 40.2, 42.7, 67.4,

82.7, 86.6, 119.0, 128.1, 128.4, 128.6, 135.1, 135.8, 154.1, 156.8.

m/z (APCI⁺): 322 (MH⁺, 48%), 236 (27), 182 (44), 171 (51),

R_f0.62 (ether). [R]²²+15.4° (c 1.51, chloroform). ν_max/cm^-1

D

(thin film): 3337s, 3088w, 3034w, 2971m, 1704s, 1520s,

1455m, 1282s, 1166s, 1092w, 1049m, 978s, 929m. δ_H(400

J. Org. Chem, Vol. 70, No. 18, 2005 7141

Robertson et al.

153 (100). Accurate mass (ES⁺): found, 322.1109; C₁₆H₂₀NO₄S

(MH⁺) requires 322.1113.

a 60:40 ratio of amide rotamers; asterisks denote resonances

attributable to the minor rotamer]: 0.83,* 0.86,* 0.89 and 0.92

(6H, 4 × s, CMe₂), 1.97, 1.99, 2.02 and 2.05 (9H, 4 × s, 2 ×

OAc and NAc), 2.66 (0.6H, dd, J 12.5, 10.5, H-2_ax), 2.70* (0.4H,

d, J 13.5, H-6_ax), 3.12 (0.6H, d, J 13.5, H-6_ax), 3.14* (1H, dd, J

13.5, 10.0, H-2_ax), 3.52 (0.6H, dd, J 13.5, 2.0, H-6_eq), 3.95*

(0.4H, ddd, J 13.5, 5.0, 2.0, H-2_eq), 3.98* (0.4H, dd, J 13.5, 2.0,

H-6_eq), 4.52 (0.6H, ddd, J 12.5, 5.5, 2.0, H-2_eq), 4.65 (0.6H, ddd,

J 10.5, 9.5, 5.5, H-3), 4.78* (0.4H, ddd, J 10.0, 9.0, 5.0, H-3),

4.84* (0.4H, d, J 9.0, H-4), 4.85 (0.6H, d, J 9.5, H-4). δ_C(125.7

MHz, DMSO-d₆) [asterisks denote resonances attributable to

the minor rotamer where such assignment could be made]:

19.1, 19.8, 21.4, 21.5, 21.9, 22.1, 24.5, 24.8, 37.1, 37.7, 43.2,

48.2,* 50.8,* 55.5, 68.3, 68.9,* 77.5 (two peaks), 169.4, 169.6,

170.5 (two peaks), 170.8. m/z (APCI⁺): 272 (MH⁺, 100%), 230

(10), 212 (11). Accurate mass (ES⁺): found, 272.1497; C₁₃H₂₂-

NO₅(MH⁺) requires 272.1498.

(3S,4S)-1-N-Acetyl-5,5-dimethyl-3,4-dihydroxypiperi-

dine (29). [In the following procedure, the Amberlite IRA 400

(OH) resin was activated by washing successively with 5%

aqueous NaOH solution (6 × 3 mL) and then water until the

washings were neutral. The activated resin was then washed

with methanol (5 × 5 mL) before use.] To a stirred solution of

acetylated piperidine 28 (74 mg, 0.27 mmol) in anhydrous

methanol (5.5 mL) was added freshly activated Amberlite IRA

400 (OH) resin (2.7 mL), and the suspension was stirred

vigorously at 50 °C for 12 h. The reaction mixture was cooled

to RT, and the resin was removed by filtration through a glass

sinter and washed with methanol (3 × 15 mL), and the filtrate

was concentrated in vacuo to give piperidine 29 as a colorless

syrup (48 mg, 94%). R_f0.05 (ethyl acetate). ν_max/cm^-1(thin

film): 3400s, 2963m, 2872m, 1624s, 1451s, 1365m, 1292w,

1251w, 1219w, 1101m, 1066m, 1042s, 1002m, 909w, 875w. δ_H

(400 MHz, DMSO-d₆) [the spectrum indicates a 60:40 ratio of

amide rotamers; asterisks denote resonances attributable to

the minor rotamer]: 0.69,* 0.76, 0.88* and 0.94 (6H, 4 × s,

CMe₂), 1.95 and 2.01* (3H, 2 × s, NAc), 2.23 (0.6H, dd, J 12.4,

10.8, H-2_ax), 2.35* (0.4H, d, J 12.8, H-6_ax), 2.76* (0.4H, dd, J

13.2, 10.0, H-2_ax), 2.81 (0.6H, d, J 13.2, H-6_ax), 2.91 (0.6H, d,

J 9.0, H-4), 2.93* (0.4H, d, J 8.4, H-4), 3.18 (0.6H, ddd, J 10.8,

9.0, 5.6, H-3), 3.33* (0.4H, ddd, J 10.0, 8.4, 5.2, H-3), 3.39

(0.6H, dd, J 13.2, 2.4, H-6_eq), 3.73* (0.4H, ddd, J 13.2, 5.2, 2.4,

H-2_eq), 3.94* (0.4H, dd, J 12.8, 2.4, H-6_eq), 4.40 (0.6H, ddd, J

12.4, 5.6, 2.4, H-2_eq), 4.80 and 4.90 (2H, 2 × br s, 2 × OH). δ_C

(100.6 MHz, DMSO-d₆) [asterisks denote resonances attribut-

able to the minor rotamer where such assignment could be

made]: 18.5, 19.2, 22.0, 22.1, 25.6, 25.8, 37.2, 37.9, 47.2, 51.7,*

51.9,* 56.7, 68.0, 68.7,* 80.1, 80.2, 169.0. m/z (ES⁺): 188 (MH⁺,

100%), 160 (18). Accurate mass (ES⁺): found, 188.1293; C₉H₁₈-

NO₃(MH⁺) requires 188.1287.

(4R)-1-(Benzyloxycarbonyl)amino-4-methylhex-2(Z),5-

diene (25). With the use of the general procedure, diene 25

was obtained as a colorless oil (48% from diol 21). R_f0.60 (1:1

petrol/ether). [R]²²_D+51.9° (c 0.27, chloroform). ν_max/cm^-1(thin

film): 3335m, 3066w, 3014w, 2963m, 2927m, 1702s, 1524m,

1455w, 1260s, 1096m, 1028m, 914w, 799m, 697m. δ_H(500

MHz, CDCl₃): 1.09 (3H, d, J 6.5, CH₃), 3.15-3.26 (1H, m,

CHMe), 3.83 and 3.90 (2 × 1H, 2 × dt, J 15.0, 5.0, NHCH₂),

4.72 (1H, br s, NH), 4.95 (1H, dt, J 10.5, 1.0) and 5.00 (1H, d,

J 17.0, CHdCH₂), 5.12 (2H, s, CH₂Ph), 5.38-5.46 (2H, m, CHd

CH), 5.76 (1H, ddd, J 17.0, 10.5, 6.5, CHdCH₂), 7.31-7.37 (5H,

m, Ph). δ_C(125.7 MHz, CDCl₃): 20.5, 35.7, 38.1, 66.6, 112.9,

124.7, 128.0, 128.4 (two peaks), 136.4, 136.7, 142.1, 156.1. m/z

(ES⁺): 268 (MNa⁺, 100%), 155 (16). Accurate mass (ES⁺):

found, 268.1314; C₁₅H₁₉NO₂Na (MNa⁺) requires 268.1313.

Data for the intermediate thiocarbonate, (4R,5S,1′R)-5-[(ben-

zyloxycarbonyl)amino]methyl-4-(1-methylprop-2-enyl)-1,3-diox-

olane-2-thione, a colorless oil, are as follows. R_f0.58 (ether).

[R]²²_D-101.8° (c 0.57, chloroform). ν_max/cm^-1(thin film): 3124s,

2965m, 1701s, 1519m, 1451w, 1298s, 1160m, 975m. δ_H(400

MHz, CDCl₃): 1.20 (3H, d, J 7.2, CH₃), 2.58-2.69 (1H, m,

CHMe), 3.39 (1H, ddd, J 14.8, 9.6, 4.4) and 3.85 (1H, ddd, J

14.8, 8.2, 2.6, NHCH₂), 4.71 (1H, t, J 7.4, CH(OR)CHMe), 4.97

(1H, ddd, J 9.6, 7.4, 2.6, CH₂CHO), 5.11 and 5.14 (2 × 1H, 2

× d, J 12.4, CH₂Ph), 5.19-5.26 (3H, m, CHdCH₂and NH),

5.82 (1H, ddd, J 17.6, 10.4, 7.6, CHdCH₂), 7.32-7.41 (5H, m,

Ph). δ_C(100.6 MHz, CDCl₃): 17.4, 37.1, 39.6, 67.3, 82.8, 86.5,

118.0, 128.1, 128.3, 128.6, 136.6, 136.7, 154.5, 157.1. m/z

(ES⁺): 322 (MH⁺, 74%), 304 (19), 183 (41), 154 (100). Accurate

mass (ES⁺): found, 322.1115; C₁₆H₂₀NO₄S (MH⁺) requires

322.1113.

(3S,4S)-1-N-Acetyl-3,4-diacetoxy-5,5-dimethylpiperi-

dine (28). A stirred solution of aminodiol 16 (470 mg, 1.60

mmol) and Sudan red 7B indicator (10.0 µL, 0.05% w/v in

dichloromethane) in anhydrous dichloromethane (32.0 mL)

was cooled to -45 °C. Ozone was passed through the solution

until the magenta color dispersed; excess ozone was purged

from the system with argon. Triphenylphosphine resin (3.0

mmol/g, 600 mg, 2.00 mmol) was added, and the reaction

mixture was stirred at -45 °C for 30 min and then warmed

to RT over 1.5 h. The resin was removed by filtration through

a short plug of silica gel and Celite, and the solvents were

removed from the filtrate in vacuo. The crude product was

dissolved in absolute ethanol (15.0 mL), palladium on carbon

(10 wt %, 55.0 mg, 0.05 mmol) was added, and the flask was

purged with argon and then with hydrogen. The reaction

mixture was stirred vigorously at RT under a positive pressure

of hydrogen for 12 h. The flask was purged with argon and

the mixture filtered through Celite to remove the palladium

catalyst; the residue was washed with ethanol (3 × 5 mL),

and the filtrate was concentrated in vacuo. The residual yellow

foam was taken up in anhydrous dichloromethane (5.0 mL),

and the solution was cooled to 0 °C; pyridine (650 µL, 8.04

mmol), DMAP (5 mg, 0.04 mmol), and acetic anhydride (1.5

mL, 16.0 mmol) were added, and the reaction mixture was

warmed to RT. After 3.5 h the solution was cooled to 0 °C,

and the reaction was quenched by the dropwise addition of

saturated aqueous NaHCO₃solution (20 mL). The mixture was

partitioned between water (25 mL) and ether (25 mL); the

aqueous layer was separated and extracted with ether (3 ×

25 mL). The combined organic fractions were washed with

brine (50 mL), dried (MgSO₄), and the solvents were removed

in vacuo. The residual oil was azeotroped with toluene (2 ×

15 mL) to remove traces of pyridine, and the crude product

was purified by flash column chromatography (silica gel, ethyl

acetate) to furnish the title compound (28) as a colorless syrup

(2S,3S)-1-(Benzyloxycarbonyl)amino-2,3-diacetoxy-4,4-

dimethylhex-5-ene (30). To a stirred solution of aminodiol

16 (320 mg, 1.10 mmol) in anhydrous dichloromethane (11.0

mL) cooled to 0 °C was added pyridine (222 µL, 2.75 mmol)

and acetic anhydride (520 µL, 5.51 mmol), and the reaction

mixture was warmed slowly to RT. After 16 h the solution was

cooled to 0 °C, and the reaction was quenched by the dropwise

addition of saturated aqueous NaHCO₃solution (20 mL). The

mixture was partitioned between water (50 mL) and ether (50

mL); the aqueous layer was separated and extracted with ether

(3 × 25 mL). The combined organic fractions were washed with

brine (50 mL), dried (MgSO₄), and the solvents were removed

in vacuo. The residual oil was azeotroped with toluene (2 ×

25 mL) to remove traces of pyridine, and the crude product

was purified by flash column chromatography (silica gel, 1:1

petrol/ether) to furnish the diacetate 30 as a colorless oil (401

mg, 97%). R_f0.63 (ether). [R]²⁰-26.4° (c 3.06, chloroform).

D

ν_max/cm^-1(thin film): 3359m, 3066w, 3034w, 2972s, 1743s,

1638w, 1527m, 1456w, 1418w, 1373m, 1223s, 1148w, 1112w,

1035m, 971w, 915w, 776w, 737w, 698w. δ_H(400 MHz,

CDCl₃): 1.00 and 1.06 (2 × 3H, 2 × s, CMe₂), 1.98 and 2.16 (2

× 3H, 2 × s, 2 × OAc), 3.08 (1H, dt, J 14.4, 5.6) and 3.35 (1H,

(77 mg, 18%). R_f0.29 (ethyl acetate). [R]²²+8.62° (c 0.55,

D

chloroform). ν_max/cm^-1(thin film): 2965m, 1743s, 1653s,

1439m, 1395w, 1370m, 1294w, 1242s, 1044s, 940w, 904w,

880w, 799m. δ_H(500 MHz, DMSO-d₆) [the spectrum indicates

7142 J. Org. Chem., Vol. 70, No. 18, 2005

Silatropic Carbonyl Ene Reactions

dt, J 14.4, 7.2, NHCH₂), 4.85 (1H, d, J 2.0, CH(OAc)CMe₂),

4.97 (1H, d, J 17.6) and 4.99 (1H, d, J 10.8, CHdCH₂), 5.07

and 5.11 (2 × 1H, 2 × d, J 12.4, CH₂Ph), 5.13 (1H, br t, J 5.6,

NH), 5.26 (1H, ddd, J 7.2, 5.6, 2.0, CH₂CH(OAc)), 5.91 (1H,

dd, J 17.6, 10.8, CHdCH₂), 7.27-7.37 (5H, m, Ph). δ_C(100.6

MHz, CDCl₃): 20.7, 21.0, 23.1, 24.7, 40.2, 42.4, 66.8, 69.4, 77.1,

112.1, 128.1, 128.2, 128.5, 136.5, 143.3, 156.2, 170.1, 171.2.

m/z (ES⁺): 400 (MNa⁺, 100%), 395 (MNH₄⁺, 27), 378 (MH⁺,

47), 334 (23). Accurate mass (ES⁺): found, 400.1734; C₂₀H₂₇-

NO₆Na (MNa⁺) requires 400.1736.

(1H, dd, J 13.6, 3.6, H-2_eq), 4.87 (1H, d, J 6.0, H-4), 5.05 (1H,

td, J 6.0, 3.6, H-3), 9.99 (1H, br s, NH). δ_C(100.6 MHz,

CDCl₃): 20.6, 21.0, 22.3, 24.3, 33.9, 43.3, 50.9, 65.6, 72.9, 169.5

(two peaks). m/z (ES⁺): 230 (MH⁺, 100%). Accurate mass

(ES⁺): found, 230.1393; C₁₁H₂₀NO₄(MH⁺) requires 230.1392.

(3S,4S)-5,5-Dimethyl-3,4-dihydroxypiperidine (27). To

a stirred solution of acetylated piperidine 33 (41 mg, 0.18

mmol) in anhydrous methanol (3.6 mL) was added freshly

activated [see the procedure for 29] Amberlite IRA 400 (OH)

resin (1.8 mL), and the suspension was stirred vigorously at

RT for 12 h. The resin was removed by filtration through a

glass sinter and washed with methanol (3 × 5 mL), and the

filtrate was concentrated in vacuo to give the crude product

as a white solid. Recrystallization from methanol/ether fur-

nished piperidine 27 as colorless needles (26 mg, 98%). R_f0.10

(2:1 ethyl acetate/methanol). M.p. 43-45 °C (from methanol/

(3S,4S,6RS)-1-N-(Benzyloxycarbonyl)-3,4-diacetoxy-

5,5-dimethyl-6-hydroxypiperidine (31) and (32). A stirred

solution of diacetate 30 (400 mg, 1.06 mmol) in anhydrous

dichloromethane and methanol (5:1 v/v, 24.0 mL) was cooled

to -45 °C. Ozone was passed through the solution until a blue

coloration persisted; excess ozone was purged from the system

with argon. Triphenylphosphine (695 mg, 2.65 mmol) was

added, and the reaction mixture was stirred at -45 °C for 1 h

and then warmed to RT. After 4.5 h the solvents were removed

in vacuo, and the crude hemiaminal was purified by flash

column chromatography (silica gel, 1:1 petrol/ether) to furnish

the major diastereomer (31) as a colorless foam (243 mg, 60%)

and the minor diastereomer (32) as a colorless syrup (120 mg,

30%). Data for 31 are as follows. R_f0.52 (ether). [R]²²_D+8.24°

(c 2.15, chloroform). ν_max/cm^-1(thin film): 3443m, 3033w,

2970m, 2007m, 1746s, 1709s, 1498w, 1429m, 1370m, 1326m,

1227s, 1168w, 1130m, 1106w, 1040s, 993w, 969w, 921w, 897w,

846w, 815w, 755w, 699w, 646w, 600m. δ_H(400 MHz, CDCl₃):

0.98 and 1.04 (2 × 3H, 2 × s, CMe₂), 2.01 and 2.06 (2 × 3H, 2

× s, 2 × OAc), 3.19 (1H, dd, J 12.0, 10.0, H-2_ax), 4.15-4.30

(1H, m, H-2_eq), 5.02 (1H, td, J 10.0, 6.4, H-3), 5.10 and 5.15 (2

× 1H, 2 × d, J 12.0, CH₂Ph), 5.35 (1H, d, J 10.0, H-4), 5.40

(1H, br s, H-6), 7.31-7.39 (5H, m, Ph). δ_C(100.6 MHz,

CDCl₃): 19.3, 20.8, 20.9, 23.1, 40.4 (two peaks), 67.8, 68.2, 73.9,

83.0, 128.0, 128.3, 128.6, 135.9, 156.3, 170.4, 170.5. m/z

(ES⁺): 402 (MNa⁺, 100%), 397 (MNH₄⁺, 26), 362 (72), 318 (24).

Accurate mass (ES⁺): found, 402.1530; C₁₉H₂₅NO₇Na (MNa⁺)

requires 402.1529. Data for 32 are as follows. R_f0.45 (ether).

[R]²²_D+1.87° (c 2.68, chloroform). ν_max/cm^-1(thin film): 3450m,

3033w, 2963m, 1745s, 1704s, 1498w, 1429m, 1372m, 1329m,

1244s, 1188m, 1164m, 1121m, 1036s, 1001m, 966w, 933w,

913w, 834w, 739w, 699m, 603m. δ_H(400 MHz, CDCl₃): 1.05

and 1.11 (2 × 3H, 2 × s, CMe₂), 1.95 and 2.12 (2 × 3H, 2 × s,

2 × OAc), 3.59 and 4.02 (2 × 1H, 2 × br d, J 14.6, H-2_axand

H-2_eq), 4.78-4.83 (1H, m, H-3) overlays 4.82 (1H, s, H-6), 5.12

and 5.21 (2 × 1H, 2 × d, J 12.0, CH₂Ph), 5.34 (1H, d, J 6.8,

H-4), 7.30-7.38 (5H, m, Ph). δ_C(100.6 MHz, CDCl₃): 20.9 (two

peaks), 24.4 (two peaks), 37.9, 40.7, 67.4, 68.3, 74.0, 82.2, 127.9,

128.2, 128.6, 136.2, 155.7, 169.3, 169.5. m/z (ES⁺): 402 (MNa⁺,

100%), 397 (MNH₄⁺, 11), 362 (62), 318 (30). Accurate mass

(ES⁺): found,402.1522;C₁₉H₂₅NO₇Na(MNa⁺)requires402.1529.

ether). [R]²⁰+63.1° (c 0.70, methanol). ν_max/cm^-1(KBr disk):

D

3276s, 2927s, 2859s, 2824s, 1654w, 1541w, 1468m, 1454m,

1421m, 1362m, 1273w, 1169w, 1110m, 1082m, 1048m, 994w,

932m, 913m, 901m, 783w, 635m. δ_H(400 MHz, D₂O) 0.78 and

0.79 (2 × 3H, 2 × s, CMe₂), 2.18 (1H, dd, J 12.8, 10.8, H-2_ax),

2.24 (1H, d, J 13.2, H-6_ax), 2.44 (1H, dd, J 13.2, 1.6, H-6_eq),

2.96 (1H, ddd, J 12.8, 5.4, 1.6, H-2_eq), 3.02 (1H, d, J 9.4, H-4),

3.46 (1H, ddd, J 10.8, 9.4, 5.4, H-3). δ_C(100.6 MHz, D₂O) 17.8,

25.1, 36.9, 50.6, 56.3, 69.1, 80.7. m/z (ES⁺): 146 (MH⁺, 100%).

Accurate mass (ES⁺): found, 146.1187; C₇H₁₆NO₂(MH⁺)

requires 146.1181.

General Procedure for Cyclohexadienyl Silane Syn-

thesis. To a stirred solution of 1,4-cyclohexadiene (2.60 mL,

27.5 mmol) in anhydrous tetrahydrofuran (37.5 mL) cooled to

-78 °C was added TMEDA (3.77 mL, 25.0 mmol) and s-BuLi

(1.0 M in cyclohexanes, 25.0 mL, 25.0 mmol) dropwise over

10 min. The yellow solution was warmed to -45 °C and stirred

for 3 h. The chlorosilane (25.0 mmol) in anhydrous tetrahy-

drofuran (12.5 mL) was added, and the mixture was stirred

at -45 °C for a further 30 min. The solution was warmed to

RT, and the reaction was quenched by the addition of

saturated aqueous NH₄Cl solution (100 mL). The mixture was

extracted with ether (3 × 50 mL), the combined organic phases

were washed with brine (100 mL), dried (MgSO₄), and the

solvent was removed in vacuo. The resulting oil was purified

by flash column chromatography (silica gel, 40-60 petrol) to

furnish the cyclohexadienyl silane.

(Cyclohexa-2,5-dienyl)diphenylsilane (34). Colorless oil

(6.56 g, 100% from diphenylchlorosilane). R_f0.35 (petrol). ν_max

/

cm^-1(thin film): 3068m, 3048m, 3025m, 2885w, 2854w,

2820m, 2125s, 1956w, 1884w, 1819w, 1667w, 1622w, 1588w,

1486w, 1428s, 1331w, 1293w, 1190w, 1158w, 1115s, 1066w,

1052w, 998w, 931w, 893m, 803s, 726s, 698s. δ_H(400 MHz,

CDCl₃): 2.36-2.46 and 2.61-2.72 (2 × 1H, 2 × m, CH₂), 2.95-

3.03 (1H, m, SiCH), 4.83 (1H, d, J 3.2, SiH), 5.57-5.63 (2H,

m) and 5.76-5.82 (2H, m, 2 × CHdCH), 7.37-7.47 (6H, m)

and 7.64-7.68 (4H, m, 2 × Ph). δ_C(100.6 MHz, CDCl₃): 26.2,

28.4, 123.2, 125.2, 127.9, 129.7, 132.9, 135.5. m/z (CI⁺): 280

(MNH₄⁺, 38%), 263 (MH⁺, 53), 200 (100), 183 (58), 139 (12),

123 (39), 105 (19). Accurate mass (CI⁺): found, 280.1511;

C₁₈H₂₂NSi (MNH₄⁺) requires 280.1522.

(3S,4S)-3,4-Diacetoxy-5,5-dimethylpiperidine (33). To

a stirred solution of hemiaminals 31 and 32 (188 mg, 0.50

mmol) in absolute ethanol (5.0 mL) was added palladium on

carbon (10 wt %, 26 mg, 0.025 mmol), and the flask was purged

with argon and then with hydrogen. The reaction mixture was

stirred vigorously at RT under a positive pressure of hydrogen

for 16 h. The flask was purged with argon, and the mixture

was filtered through Celite to remove the palladium catalyst;

the residue was washed with ethanol (3 × 10 mL), and the

filtrate was concentrated in vacuo to give the crude product

as a white solid. Recrystallization from chloroform/ether

furnished piperidine 33 as colorless needles (68 mg, 60%). R_f

0.11 (ethyl acetate). M.p. 189-190 °C (from chloroform/ether).

(Cyclohexa-2,5-dienyl)di(isopropyl)silane (35). Color-

less oil (4.69 g, 96% from di(isopropyl)chlorosilane). R_f0.61

(petrol). ν_max/cm^-1(thin film): 3025m, 2941s, 2890s, 2864s,

2821m, 2093s, 1624w, 1462m, 1384w, 1366w, 1291w, 1244w,

1108m, 1053w, 1004m, 897m, 883m, 824m, 801s, 732s, 653m,

625m. δ_H(400 MHz, CDCl₃): 1.08-1.11 (14H, m, 2 × i-Pr),

2.54-2.62 (1H, m, SiCH), 2.70-2.78 (2H, m, CH₂), 3.45 (1H,

d, J 1.7, SiH), 5.52-5.58 (2H, m), and 5.70-5.76 (2H, m, 2 ×

CHdCH). δ_C(100.6 MHz, CDCl₃): 10.4, 19.1, 19.2, 26.1, 26.4,

121.6, 126.6. m/z (CI⁺): 212 (MNH₄⁺, 72%), 195 (MH⁺, 100),

147 (20), 132 (51), 130 (34), 104 (13), 90 (45), 76 (15). Accurate

mass (CI⁺): found, 195.1564; C₁₂H₂₃Si (MH⁺) requires 195.1569.

[R]²²+14.5° (c 0.62, chloroform). ν_max/cm-¹(KBr disk):

D

3465m, 3065m, 2982m, 2889m, 2822w, 2786m, 2746, 2698m,

2659m, 2565w, 2511w, 2438w, 1743s, 1568w, 1462w, 1430w,

1373m, 1289w, 1236s, 1192w, 1135w, 1101w, 1050m, 1024w,

1011w, 949w, 935w, 893w, 869w, 642w, 603w, 594w. δ_H(400

MHz, CDCl₃): 1.13 and 1.23 (2 × 3H, 2 × s, CMe₂), 2.11 and

2.14 (2 × 3H, 2 × s, 2 × OAc), 2.94 and 3.04 (2 × 1H, 2 × d,

J 13.0, H-6_axand H-6_eq), 3.18 (1H, dd, J 13.6, 6.0, H-2_ax), 3.44

Ethyl [(cyclohexa-2,5-dienyl)diphenylsilanyloxy]phen-

ylacetate (37). A flame-dried two-necked flask (50 mL) was

charged with anhydrous CuCl₂(0.51 g, 3.82 mmol) and

J. Org. Chem, Vol. 70, No. 18, 2005 7143

Robertson et al.

anhydrous CuI (10 mg, 0.05 mmol). The flask was equipped

with a flame-dried Schlenk filter attached to a second round-

bottomed flask (50 mL). All joints were sealed with PTFE tape,

and the apparatus was purged several times with argon.

Anhydrous tetrahydrofuran (10.0 mL) was added followed by

the cyclohexadienylsilane 34 (0.5 g, 1.91 mmol), and the orange

suspension was stirred for 27 h at RT. The apparatus was

inverted, and the inorganics were filtered off by suction under

argon. The solution of crude chlorosilane (36) in tetrahydro-

furan was added via cannula to a stirred solution of (()-ethyl

mandelate (0.31 mL, 1.90 mmol), DMAP (6 mg, 0.05 mmol),

and triethylamine (0.8 mL, 5.70 mmol) in anhydrous DMF (38

mL). The reaction mixture was warmed to 40 °C for 5 h, then

cooled to RT and partitioned between water (100 mL) and

ether (25 mL). The aqueous phase was extracted with ether

(3 × 50 mL), and the combined organic fractions were washed

with brine (100 mL), dried (MgSO₄), and the solvents were

removed in vacuo. The resulting yellow oil was purified by

flash column chromatography (silica gel, 20:1 petrol/ether) to

furnish the title compound (37) as a colorless oil (737 mg, 88%).

R_f0.53 (2:1 petrol/ether). ν_max/cm^-1(thin film): 3069w, 3028m,

3000w, 2980w, 2936w, 2889w, 2856w, 2821w, 1960w, 1892w,

1824w, 1752s, 1590w, 1494w, 1454w, 1429m, 1264m, 1206m,

1178m, 1120s, 1072m, 1028m, 948w, 892m, 836m. δ_H(400

MHz, CDCl₃): 1.11 (3H, t, J 7.2, CH₃), 2.06-2.17 and 2.50-

2.61 (2 × 1H, 2 × m, CH₂), 3.12-3.19 (1H, m, SiCH), 4.00 (2H,

2 × dq, J 10.8, 7.2, OCH₂), 5.29 (1H, s, OCHPh), 5.50-5.55

(2H, m) and 5.78-5.86 (2H, m, 2 × CHdCH), 7.30-7.74 (15H,

m, 3 × Ph). δ_C(100.6 MHz, CDCl₃): 13.9, 26.0, 30.1, 61.0, 74.8,

was taken up in ether (25 mL) and washed with water (25

mL). The aqueous phase was extracted with ether (2 × 15 mL),

and the combined organic fractions were washed with brine

(50 mL), dried (MgSO₄), and the solvents were removed in

vacuo. The residual oil was purified by flash column chroma-

tography (silica gel, 5:1 petrol/ether) to furnish the title

compound (40) (21 mg, 19% from ester 37) and a diastereomer,

tentatively assigned as the (1R*,2S*,1′R*)-isomer 41 (7 mg,

6% from ester 37), both as colorless crystalline solids. Data

for 40 are as follows. R_f0.54 (ether). M.p. 100-103 °C

(chloroform). ν_max/cm^-1(KBr disk): 3392s, 3036m, 2921w,

1951w, 1891w, 1818w, 1691w, 1600w, 1494w, 1452w, 1429w,

1409w, 1198w, 1116m, 1064m, 1026m, 971w, 919w, 842w,

761m, 700s. δ_H(500 MHz, CDCl₃): 2.24-2.29 (2H, m, CH₂),

2.31 (1H, d, J 5.0, CH(OH)CH), 2.43 (1H, dddd, J 10.5, 4.5,

4.0, 2.5, CH(OH)CH), 2.78 (1H, d, J 3.9, CH(OH)Ph), 3.64 (1H,

dt, J 10.5, 5.0, CH(OH)CH), 4.73 (1H, dd, J 5.0, 3.9, CH(OH)-

Ph), 5.81 (1H, dt, J 9.5, 4.5, dCHCH₂), 5.86 (1H, dd, J 9.5,

4.5, CHdCHCH₂), 5.87-5.91 (1H, m) and 6.06 (1H, dd, J 9.5,

4.5, CHCHdCH), 7.29-7.40 (5H, m, Ph). δ_C(125.7 MHz,

CDCl₃): 26.5, 34.5, 74.2, 79.1, 123.7, 125.0, 126.2, 126.3, 126.5,

127.9, 128.5, 141.0. m/z (CI⁺): 234 (MNH₄⁺, 100%), 217 (MH⁺,

18), 199 (22), 154 (12), 137 (16), 121 (30), 105 (15), 91 (17).

+

Accurate mass (CI⁺): found, 234.1493; C₁₄H₂₀NO₂(MNH₄

)

requires 234.1494. Data for 41 are as follows. R_f0.58 (ether).

M.p. 75-77 °C (from chloroform). ν_max/cm^-1(KBr disk): 3428s,

3015s, 2925m, 2873m, 1954w, 1885w, 1813w, 1719w, 1604w,

1494m, 1454m, 1429m, 1410m, 1392m, 1216s, 1078m, 1060m,

1023s, 973w, 924w, 843w, 755s, 702s. δ_H(500 MHz, CDCl₃):

1.97 (1H, d, J 5.0, CH(OH)CH), 2.24-2.33 (3H, m, CH₂and

CH(OH)Ph), 2.54-2.61 (1H, m, CH(OH)CH), 3.80 (1H, dt, J

9.5, 5.0, CH(OH)CH), 4.79 (1H, d, J 5.0, CH(OH)Ph), 5.80 (1H,

dt, J 9.5, 4.0, dCHCH₂), 5.87-5.90 (1H, m, CHdCH), 5.91 (1H,

dd, J 9.5, 4.0, CHdCHCH₂), 6.03 (1H, dd, J 9.5, 5.0, CHdCH),

7.31-7.44 (5H, m, Ph). δ_C(125.7 MHz, CDCl₃): 26.4, 34.3, 75.1,

78.1, 123.9, 125.6, 125.7, 126.0, 126.9, 127.8, 128.4, 140.5. m/z

(CI⁺): 234 (MNH₄⁺, 52%), 217 (MH⁺, 40), 199 (74), 183 (24),

154 (29), 136 (43), 121 (50), 105 (100), 94 (69), 78 (73). Accurate

mass (CI⁺): found, 234.1471; C₁₄H₂₀NO₂(MNH₄⁺) requires

234.1494.

123.5, 123.6, 124.2, 124.3, 126.6-135.5 (series of overlapping

+

peaks), 132.5, 132.6, 138.7, 171.6. m/z (CI⁺): 458 (MNH₄

,

17%), 361 (100), 207 (13), 199 (22), 182 (55). Accurate mass

(CI⁺): found, 361.1257; C₂₂H₂₁O₃Si (M⁺-C₆H₇) requires

361.1260.

[(Cyclohexa-2,5-dienyl)diphenylsilanyloxy]phenyl-

acetaldehyde (38). To a stirred solution of ester 37 (220 mg,

0.5 mmol) in anhydrous dichloromethane (5.0 mL), cooled to

-78 °C, was added DIBAL (0.75 mL, 1.0 M in dichlo-

romethane, 0.75 mmol) dropwise, and the solution was stirred

at -78 °C for 45 min. The reaction was quenched by the

addition of a saturated solution of tartaric acid in methanol

(2 mL). The mixture was warmed to RT and partitioned

between aqueous tartaric acid solution (30% w/v, 25 mL) and

ether (25 mL). The aqueous layer was extracted with ether (3

× 25 mL), and the combined organic extracts were washed

with brine (50 mL), dried (Na₂SO₄), and the solvents were

removed in vacuo. The crude product was purified by flash

column chromatography (silica gel, 20:1 petrol/ether) to furnish

the aldehyde (38) as a colorless oil (61 mg, 31%). [Aldehyde

38 is unstable toward chromatography and was generally used

crude.] R_f0.49 (2:1 petrol/ether [streaks]). ν_max/cm^-1(thin

film): 3069m, 3049w, 3028m, 2955w, 2924w, 2889w, 2854w,

2820w, 1960w, 1891w, 1825w, 1736s, 1590w, 1489w, 1453w,

1429s, 1191m, 1118s, 1073m, 1051m, 1028m, 924w, 895w,

853w, 741m, 711s, 699s. δ_H(400 MHz, CDCl₃): 2.10-2.21 and

2.55-2.65 (2 × 1H, 2 × m, CH₂), 3.14-3.22 (1H, m, SiCH),

5.20 (1H, d, J 1.6, CHPh), 5.53-5.60 and 5.78-5.86 (2 × 2H,

2 × m, 2 × CHdCH), 7.30-7.75 (15H, m, 3 × Ph), 9.59 (1H,

d, J 1.6, CHO). δ_C(100.6 MHz, CDCl₃): 26.1, 30.0, 80.6, 123.4,

123.5, 124.2, 124.4, 126.5-136.0 (series of overlapping peaks),

132.4 (two peaks), 136.1, 198.9. m/z (CI⁺): 397 (MH⁺, 20%),

224 (100), 197 (47), 180 (33), 163 (14). Accurate mass (CI⁺):

found, 397.1602; C₂₆H₂₅O₂Si (MH⁺) requires 397.1624.

2-[(Cyclohexa-2,5-dienyl)diphenylsilanyloxy]-3,3-di-

methylbutyronitrile (42). A flame-dried two-necked flask (50

mL) was charged with anhydrous CuCl₂(1.03 g, 7.66 mmol)

and anhydrous CuI (73 mg, 0.38 mmol). The flask was

equipped with a flame-dried Schlenk filter attached to a second

round-bottomed flask (50 mL). All joints were sealed with

PTFE tape, and the apparatus was purged several times with

argon. Anhydrous tetrahydrofuran (15 mL) was added, fol-

lowed by the cyclohexadienylsilane (34) (1.0 g, 3.81 mmol), and

the orange suspension was stirred for 12 h at RT. The

apparatus was inverted, and the inorganics were filtered off

by suction under argon. The solution of crude chlorosilane (36)

in tetrahydrofuran was added via cannula to a stirred solution

of pivalaldehyde cyanohydrin²⁰(216 mg, 1.91 mmol), DMAP

(584 mg, 4.78 mmol), and triethylamine (531 µL, 3.81 mmol)

in anhydrous dichloromethane (20 mL). The reaction mixture

was stirred at RT for 22 h, then partitioned between saturated

aqueous NaHCO₃solution (100 mL) and ether (50 mL). The

aqueous phase was extracted with ether (3 × 50 mL), the

combined organic layers were washed with brine (100 mL),

dried (MgSO₄), and the solvents were removed in vacuo. The

resulting oil was purified by flash column chromatography

(silica gel, petrol f 50:1 petrol/ether) to furnish silylcyanohy-

drin 42 as a colorless oil (700 mg, 98%). R_f0.58 (2:1 petrol/

ether). ν_max/cm^-1(thin film): 3071w, 3050w, 3028m, 2966m,

2873w, 2821w, 2245w, 1961w, 1892w, 1824w, 1591w, 1477m,

1465w, 1429s, 1398w, 1368m, 1335w, 1193w, 1119s, 1035s,

1014s, 994s, 894w, 827m, 778w, 740s, 699s, 625s, 614s. δ_H(400

MHz, CDCl₃): 1.05 (9H, s, t-Bu), 2.07 (1H, dtt, J 13.6, 5.2,

2.8) and 2.53-2.63 (1H, m, CH₂), 3.26-3.34 (1H, m, SiCH),

(1S*,2S*,1′S*)-1-(Cyclohexa-2,4-dienyl)-2-phenylethan-

1,2-diol (40). A degassed solution of crude aldehyde 38

(assumed 0.5 mmol) in anhydrous toluene (5.0 mL) was heated

at 120 °C in a base-washed sealed tube. After 20 h the reaction

mixture was cooled to RT and the solvent was removed in

vacuo. The crude dioxasilolane (39) was dissolved in methanol

(5.0 mL). KF (90 mg, 1.55 mmol) and H₂O₂(35% in water, 500

µL) were added, and the reaction mixture was stirred at RT

for 2 h. The solvent was removed in vacuo, and the residue

(20) Meerpoel, L.; Hoornaert, G. Synthesis 1990, 905-908 and

references therein.

7144 J. Org. Chem., Vol. 70, No. 18, 2005

Silatropic Carbonyl Ene Reactions

4.04 (1H, s, CHCN), 5.56-5.62 and 5.83-5.93 (2 × 2H, 2 ×

m, 2 × CHdCH), 7.41-7.75 (10H, m, 2 × Ph). δ_C(100.6 MHz,

CDCl₃): 25.1, 26.1, 29.6, 36.3, 71.6, 118.7, 123.8, 123.9 (two

peaks), 124.2, 127.9, 128.1, 130.5, 130.6, 131.2, 131.3, 134.6,

135.6. m/z (CI⁺): 391 (MNH₄⁺, 100%), 374 (MH⁺, 10), 311 (37),

294 (26), 267 (14), 215 (13), 198 (10). Accurate mass (CI⁺):

found, 294.1302; C₁₈H₂₀NOSi (M^+-C₆H₇) requires 294.1314.

added CSA (21 mg, 0.09 mmol), and the reaction mixture was

stirred at RT for 1.5 h. The reaction mixture was partitioned

between saturated aqueous NaHCO₃solution (50 mL) and

ether (50 mL); the aqueous phase was separated and extracted

with ether (3 × 25 mL). The combined organic fractions were

washed with brine (50 mL), dried (MgSO₄), and the solvents

were removed in vacuo. The residual oil was purified by flash

column chromatography (silica gel, 20:1 petrol/ether) to furnish

acetonide 45 as a colorless oil (337 mg, 80%). R_f0.74 (5:1 petrol/

ether). ν_max/cm^-1(thin film): 3041w, 2983m, 2957m, 2871m,

1480w, 1468w, 1430w, 1395w, 1378m, 1368s, 1249s, 1208m,

1162m, 1115w, 1077m, 1053m, 1027m, 994w, 973w, 928w,

872w, 700m, 681m, 659w. δ_H(400 MHz, CDCl₃): 0.93 (9H, s,

t-Bu), 1.41 (6H, s, CMe₂), 2.13-2.19 (2H, m, CH₂), 2.51-2.61

(1H, m, CH(OR)CH), 3.67 (1H, d, J 6.0, t-BuCH), 3.87 (1H, t,

J 6.0, CH(OR)CH), 5.76-5.83 (1H, m), 5.91-5.96 (2H, m) and

5.98-6.04 (1H, m, 2 × CHdCH). δ_C(100.6 MHz, CDCl₃): 26.2,

27.1, 27.5, 28.4, 33.4, 37.8, 79.6, 86.7, 108.6, 124.7, 125.0, 125.6,

127.0. m/z (CI⁺): 237 (MH⁺, 100%), 179 (78), 157 (94), 148 (51),

126 (13). Accurate mass (CI⁺): found, 237.1854; C₁₅H₂₅O₂

(MH⁺) requires 237.1855.

(4S*,5S*,1′S*,4′R*,5′S*)-5-(tert-Butyl)-4-(4,5-dibenzyl-

oxycyclohex-2-enyl)-2,2-dimethyl-1,3-dioxolane (47). To

a stirred solution of dioxolane 45 (172 mg, 0.73 mol) in

tetrahydrofuran (7.0 mL) was added NMO (171 mg, 1.46

mmol) and OsO₄(10 mg, 0.04 mmol; the mixture was stirred

at RT for 3 h, then the reaction was quenched by the addition

of dilute aqueous Na₂SO₃solution (10% w/v, 10 mL). The

mixture was partitioned between water (50 mL) and ethyl

acetate (50 mL), and the aqueous phase was separated and

extracted with ethyl acetate (3 × 25 mL). The combined

organic fractions were washed with brine (100 mL), dried

(MgSO₄), and the solvents were removed in vacuo. The residue

was azeotroped with toluene (3 × 10 mL) and then dissolved

in anhydrous DMF (7.0 mL), and the solution was cooled to 0

°C. Benzyl bromide (695 µL, 5.84 mmol) was added, followed

by NaH (233 mg of a 60% dispersion in mineral oil, 5.83 mmol).

The reaction mixture was allowed to warm slowly to RT over

16 h. The solution was cooled to 0 °C, and the reaction was

quenched by the dropwise addition of methanol (2 mL); the

resulting mixture was partitioned between water (50 mL) and

ether (50 mL). The aqueous phase was separated and extracted

with ether (2 × 50 mL); the combined organic fractions were

washed with brine (100 mL), dried (MgSO₄), and the solvents

were removed in vacuo. The residual oil was azeotroped with

toluene (2 × 15 mL) to remove traces of DMF. Purification by

flash column chromatography (silica gel, 10:1 petrol/ether)

gave the title compound (47) as a colorless oil (107 mg, 33%).

R_f0.48 (2:1 petrol/ether). ν_max/cm^-1(thin film): 3087w, 3063w,

3030w, 2981m, 2955m, 2926m, 2870m, 1949w, 1871w, 1809w,

1725w, 1651w, 1606w, 1496w, 1479w, 1454m, 1378m, 1368m,

1332w, 1247m, 1214m, 1167w, 1114s, 1074s, 1028s, 933w,

908w, 902w, 871w, 816w, 735s, 698s. δ_H(400 MHz, CDCl₃):

0.94 (9H, s, t-Bu), 1.35 and 1.38 (2 × 3H, 2 × s, CMe₂), 1.57

(1H, ddd, J 13.6, 9.0, 2.0) and 2.04 (1H, ddd, J 13.6, 6.8, 5.4,

CH₂CH), 2.61-2.68 (1H, m, CH(OR)CH), 3.65 (1H, d, J 7.0,

t-BuCH), 3.70 (1H, dd, J 7.0, 4.4, CH(OR)CH), 3.00-4.05 and

4.05-4.09 (2 × 1H, 2 × m, 2 × CH(OBn)), 4.61 and 4.68 (2 ×

1H, 2 × d, J 12.4, CH₂Ph), 4.66 and 4.72 (2 × 1H, 2 × d, J

12.6, CH₂Ph), 5.85 (1H, br d, J 10.6) and 5.99 (1H, br d, J

10.6, CHdCH), 7.27-7.42 (10H, m, 2 × Ph). δ_C(100.6 MHz,

CDCl₃): 26.2, 27.5, 28.1, 30.0, 33.0, 36.2, 70.5, 71.4, 72.7, 74.1,

80.5, 85.9, 108.3, 127.4, 127.5, 127.6, 127.7, 127.9, 128.3 (two

peaks), 129.4, 138.8, 139.0. m/z (ES⁺): 473 (MNa⁺, 89%), 468

(MNH₄⁺, 100), 343 (62), 279 (20). Accurate mass (ES⁺): found,

451.2856; C₂₉H₃₉O₄(MH⁺) requires 451.2848.

2-[(Cyclohexa-2,5-dienyl)diphenylsilanyloxy]-3,3-di-

methylbutyraldehyde (43). To a stirred solution of silylcy-

anohydrin 42 (920 mg, 2.47 mmol) in anhydrous dichlo-

romethane (25 mL) cooled to -78 °C was added DIBAL (1.0

M in dichloromethane, 3.70 mL, 3.70 mmol) dropwise, and the

solution was stirred at -78 °C for 3 h and then warmed to

-45 °C and stirred for a further 2 h. The reaction was

quenched by the addition of a saturated solution of tartaric

acid in methanol (5 mL). The mixture was warmed to RT and

partitioned between aqueous tartaric acid solution (20% w/v,

50 mL) and ether (50 mL). The aqueous layer was extracted

with ether (3 × 25 mL), and the combined organic extracts

were washed with brine (50 mL), dried (MgSO₄), and the

solvents were removed in vacuo. The crude product was

purified by flash column chromatography (silica gel, 50:1

petrol/ether) to furnish aldehyde 43 as a colorless syrup (842

mg, 91%). R_f0.60 (2:1 petrol/ether). ν_max/cm^-1(thin film):

3070w, 3028w, 2962m, 2871w, 2820w, 1734s, 1590w, 1478w,

1429s, 1396w, 1366m, 1190w, 1119s, 1035s, 1014s, 994m,

935w, 894m, 841m, 740s, 699s, 624s, 614s. δ_H(400 MHz,

CDCl₃): 0.98 (9H, s, t-Bu), 2.03 (1H, dtt, J 13.6, 5.2, 2.8) and

2.49-2.60 (1H, m, CH₂), 3.15-3.22 (1H, m, SiCH), 3.67 (1H,

d, J 2.6, OCH), 5.48-5.58 and 5.76-5.89 (2 × 2H, 2 × m, 2 ×

CHdCH), 7.35-7.77 (10H, m, 2 × Ph), 9.58 (1H, d, J 2.6,

CHO). δ_C(100.6 MHz, CDCl₃): 25.9, 26.0, 29.9, 36.1, 85.1,

123.6, 123.7, 124.1, 124.2, 127.8, 127.9, 130.3, 130.4, 132.5,

134.0, 134.3, 135.6, 203.5. m/z (CI⁺): 377 (MH⁺, 49%), 315 (26),

311 (28), 297 (100), 216 (17), 198 (20), 181 (28), 179 (24), 163

(42). Accurate mass (CI⁺): found, 297.1304; C₁₈H₂₁O₂Si (M⁺-

C₆H₇) requires 297.1311.

(1S*,2S*,1′S*)-1-(Cyclohexa-2,4-dienyl)-3,3-dimethyl-

butan-1,2-diol (44). A degassed solution of aldehyde 43 (842

mg, 2.24 mmol) in anhydrous toluene (12 mL) was heated at

130 °C in a base-washed sealed tube. After 18 h the reaction

mixture was cooled to RT, and the solvent was removed in

vacuo. The crude dioxasilolane was dissolved in tetrahydro-

furan (22 mL), cooled to 0 °C, and TBAF (1.0 M in tetrahy-

drofuran, 5.60 mL, 5.60 mmol) was added dropwise. The

reaction mixture was stirred for 30 min at 0 °C and then

warmed to RT and stirred for a further 1.5 h. The reaction

was quenched by the addition of saturated aqueous NH₄Cl

solution (50 mL). The mixture was extracted with ether (3 ×

50 mL), and the combined organic phases were washed with

brine (100 mL), dried (MgSO₄), and the solvent was removed

in vacuo. The crude product was purified by flash column

chromatography (silica gel, 10:1 petrol/ether) to furnish diol

44 as a colorless crystalline solid (376 mg, 86%). R_f0.39 (1:1

petrol/ether). M.p. 86-88 °C (ether). ν_max/cm^-1(KBr disk):

3445s and 3338s, 3040m, 2957s, 2868m, 2821w, 1480w, 1428w,

1392w, 1361w, 1307w, 1102m, 1050m, 1016m, 986w, 932w,

872w, 852w, 830w, 772w, 740w, 689s. δ_H(400 MHz, CDCl₃):

0.93 (9H, s, t-Bu), 2.16 (1H, dddd, J 13.2, 11.2, 4.4, 2.0) and

2.31 (1H, dddd, J 13.2, 9.2, 4.4, 2.0, CH₂), 2.32 (1H, d, J 6.8,

CH(OH)CH), 2.43-2.52 (1H, m, CH(OH)CH), 2.48 (1H, d, J

6.8, t-BuCH(OH)), 3.25 (1H, d, J 6.8, t-BuCH), 3.73 (1H, t, J

6.8, CH(OH)CH), 5.78 (1H, dt, J 9.6, 4.4, dCHCH₂), 5.86-

5.94 (2H, m, CHdCHCH₂and CHdCH), 6.00-6.06 (1H, m,

CHdCH). δ_C(100.6 MHz, CDCl₃): 25.4, 26.0, 35.1, 38.0, 70.7,

77.2, 124.3, 125.6, 125.7, 126.9. m/z (CI⁺): 214 (MNH₄⁺, 43%),

197 (MH⁺, 100), 179 (94), 163 (18), 134 (45), 126 (17), 114 (34),

109 (43), 98 (30), 94 (41), 85 (26), 78 (70), 58 (35). Accurate

mass (CI⁺): found, 197.1536; C₁₂H₂₁O₂(MH⁺) requires 197.1541.

(1S*,2S*,1′S*,4′R*,5′S*)-1-(4,5-Dibenzyloxycyclohexa-2-

enyl)-3,3-dimethyl butan-1,2-diol. To a stirred solution of

dioxolane 47 (80 mg, 0.18 mmol) in water (3.0 mL) was added

TFA (6.0 mL), and the mixture was stirred at RT for 2 h. The

solution was concentrated in vacuo employing toluene (3 ×

10 mL) to remove water azeotropically. The residual yellow

(4S*,5S*,1′S*)-5-(tert-Butyl)-4-(cyclohexa-2,4-dienyl)-

2,2-dimethyl-1,3-dioxolane (45). To a stirred solution of diol

44 (350 mg, 1.79 mol) in 2,2-dimethoxypropane (5.0 mL) was

J. Org. Chem, Vol. 70, No. 18, 2005 7145

Robertson et al.

oil was purified by flash column chromatography (silica gel,

1:1 petrol/ether) to furnish the title compound as a colorless

oil (72 mg, 99%). R_f0.23 (1:1 petrol/ether). ν_max/cm^-1(thin

film): 3429m, 3088w, 3064w, 3031w, 2954s, 2868m, 1951w,

1875w, 1812w, 1648w, 1606w, 1496w, 1478w, 1454m, 1395m,

1363m, 1306w, 1254w, 1206w, 1090s, 1075s, 1028m, 1014m,

957w, 910m, 855w, 805w, 735s, 698s. δ_H(400 MHz, CDCl₃):

0.92 (9H, s, t-Bu), 1.50 (1H, ddd, J 13.8, 8.6, 1.6) and 2.12 (1H,

ddd, J 13.8, 7.0, 5.6, CH₂), 2.25 and 2.31 (2 × 1H, 2 × br s, 2

× OH), 2.50-2.60 (1H, m, CH(OH)CH), 3.17 (1H, br s,

t-BuCH), 3.61 (1H, d, J 5.6, CH(OH)CH), 3.94-3.99 and 4.02-

4.05 (2 × 1H, 2 × m, 2 × CH(OBn)), 4.59 and 4.67 (2 × 1H, 2

× d, J 12.4, CH₂Ph), 4.69 (2H, s, CH₂Ph), 5.85 and 5.92 (2 ×

1H, 2 × br d, J 10.4, CHdCH), 7.26-7.43 (10H, m, 2 × Ph).

δ_C(100.6 MHz, CDCl₃): 25.9, 27.3, 35.0, 39.0, 70.6, 71.1, 71.2,

72.4, 74.0, 77.1, 127.4, 127.5, 127.6, 127.9, 128.2, 128.3 (two

peaks), 130.1, 138.7, 139.0. m/z (ES⁺): 433 (MNa⁺, 100%), 428

(MNH₄⁺, 34), 303 (17), 279 (71). Accurate mass (ES⁺): found,

428.2809; C₂₆H₃₈NO₄(MNH₄⁺) requires 428.2801.

(1S*,2R*,5S*)-1,2-Dibenzyloxy-5-(hydroxymethyl)cyclo-

hex-3-ene (48). To a stirred solution of (1S*,2S*,1′S*,4′R*,5′S*)-

1-(4,5-dibenzyloxycyclohexa-2-enyl)-3,3-dimethylbutan-1,2-

diol (71 mg, 0.17 mmol) in tetrahydrofuran (3.0 mL) and water

(1.0 mL) was added NaIO₄(167 mg, 0.78 mmol). The reaction

mixture was stirred vigorously at RT for 2.5 h, and then the

reaction was quenched by the addition of brine (25 mL). The

resulting mixture was extracted with ethyl acetate (3 × 15

mL); the combined organic fractions were dried (MgSO₄), and

the solvents were removed in vacuo. The residue was dissolved

in methanol (4.0 mL), and the resulting solution was cooled

to 0 °C; NaBH₄(33 mg, 0.87 mmol) was added, and the reaction

mixture was stirred for 30 min. The reaction was quenched

by the addition of saturated aqueous NH₄Cl solution (15 mL);

the aqueous phase was extracted with ethyl acetate (3 × 15

mL), and the combined organic fractions were washed with

brine (25 mL), dried (MgSO₄), and the solvents were removed

in vacuo. The resulting pale yellow oil was purified by flash

column chromatography (silica gel, 1:1 petrol/ether) to furnish

the title compound (48) as a colorless oil (45 mg, 80%). R_f0.40

(ether). ν_max/cm^-1(thin film): 3434m, 3062w, 3029w, 2923m,

2869s, 1955w, 1876w, 1817w, 1724w, 1654w, 1604w, 1496w,

1454m, 1390w, 1359w, 1336w, 1306w, 1206w, 1098s, 1071s,

1038s, 1028s, 910w, 803w, 736s, 697s. δ_H(400 MHz, CDCl₃):

1.54 (1H, ddd, J 13.6, 8.0, 2.0, CHH′), 1.57 (1H, br s, 6-OH),

2.18 (1H, dt, J 13.6, 6.8, CHH′), 2.55-2.63 (1H, m, CHCH₂),

3.55 (1H, dd, J 10.6, 5.4) and 3.59 (1H, dd, J 10.6, 6.0, CH₂-

OH), 3.92-3.97 and 4.02-4.05 (2 × 1H, 2 × m, 2 × CH(OBn)),

4.60 and 4.67 (2 × 1H, 2 × d, J 12.4, CH₂Ph), 4.69 and 4.72 (2

× 1H, 2 × d, J 12.8, CH₂Ph), 5.79 and 5.85 (2 × 1H, 2 × br d,

J 10.4, HCdCH), 7.26-7.43 (10H, m, 2 × Ph). δ_C(100.6 MHz,

CDCl₃): 27.0, 36.2, 66.2, 70.7, 70.9, 72.4, 73.7, 127.4, 127.5,

127.6, 127.8, 128.0, 128.3 (two peaks), 130.8, 138.8, 138.9. m/z

(ES⁺): 347 (MNa⁺, 65%), 342 (MNH₄⁺, 100), 325 (MH⁺, 14),

217 (19). Accurate mass (ES⁺): found, 347.1626; C₂₁H₂₄O₃Na

(MNa⁺) requires 347.1623.

1312w, 1261w, 1206w, 1112s, 1095s, 1072s, 1027m, 800w,

734m, 698s. δ_H(400 MHz, CDCl₃): 1.12 (1H, ddd, J 14.2, 10.2,

1.6) and 1.83 (1H, dt, J 14.2, 6.4, CHCH₂), 2.38-2.47 (1H, m,

CHCH₂), 3.28 (1H, br d, J 3.8, CH(OBn)CHO), 3.38-3.42 (1H,

m, CH(OR)CHCH₂), 3.62 (1H, d, J 3.8, CH(OBn)CHO), 3.71-

3.76 (2H, m, CH₂OH), 3.77-3.82 (1H, m, CH₂CH(OBn)), 4.63

and 4.68 (2 × 1H, 2 × d, J 12.2, CH₂Ph), 4.67 and 4.71 (2 ×

1H, 2 × d, J 12.0, CH₂Ph), 7.30-7.44 (10H, m, 2 × Ph). δ_C

(100.6 MHz, CDCl₃): 22.8, 32.7, 53.9, 54.6, 64.9, 71.2, 71.4,

71.6, 75.1, 127.6, 127.7, 128.3, 128.4, 138.8, 138.9. m/z (ES⁺):

363 (MNa⁺, 100%), 358 (MNH₄⁺, 12), 255 (13). Accurate mass

(ES⁺): found, 363.1569; C₂₁H₂₄O₄Na (MNa⁺) requires 363.1572.

(1S*,2S*,3R*,4R*,5R*)-3-Acetoxy-5-(acetoxymethyl)-

1,2-dibenzyloxy-4-chlorocyclohexane (51). To a stirred

solution of epoxide 49 (6.0 mg, 0.018 mmol) in tetrahydrofuran

(1.5 mL) and water (300 µL) was added hydrochloric acid (1.0

M, 50 µL). The reaction mixture was stirred at RT for 16 h

and then concentrated in vacuo employing toluene (3 × 2.5

mL) to remove water azeotropically. The residue was dissolved

in anhydrous dichloromethane (1.0 mL); pyridine (15 µL, 0.19

mmol), DMAP (cat.), and acetic anhydride (34 µL, 0.36 mmol)

were added, and the reaction mixture was stirred at RT for

1.5 h. The solution was cooled to 0 °C, and the reaction was

quenched by the dropwise addition of saturated aqueous

NaHCO₃solution (1.0 mL). The mixture was partitioned

between water (5 mL) and ether (5 mL); the aqueous layer

was separated and extracted with ether (3 × 5 mL). The

combined organic fractions were washed with brine (15 mL),

dried (MgSO₄), and the solvents were removed in vacuo. The

residue was purified by flash column chromatography (silica

gel, 1:1 petrol/ether) to furnish the title compound (51) as a

colorless oil (7.7 mg, 95%). R_f0.28 (1:1 petrol/ether). ν_max/cm^-1

(thin film): 3065w, 3031w, 2959m, 2930m, 2873m, 1743s,

1497w, 1454w, 1371m, 1229s, 1072m, 1038m, 906w, 768w,

738w, 698m, 672w. δ_H(400 MHz, CDCl₃): 1.31 (1H, ddd, J

14.4, 12.8, 2.0) and 2.00 (1H, dt, J 14.4, 3.8, CH₂), 2.06 and

2.10 (2 × 3H, 2 × s, 2 × OAc), 2.40-2.50 (1H, m, CHCH₂-

OAc), 3.32 (1H, dd, J 10.0, 2.6, CH(OBn)CHOAc), 3.76 (1H,

dd, J 11.2, 10.0, CHCl), 3.93-3.96 (1H, m, CH(OBn)CH₂), 4.20

(1H, dd, J 11.2, 2.2) and 4.31 (1H, dd, J 11.2, 4.4, CH₂OAc),

4.50 and 4.61 (2 × 1H, 2 × d, J 12.4, CH₂Ph), 4.64 and 4.77 (2

× 1H, 2 × d, J 12.0, CH₂Ph), 5.63 (1H, t, J 10.0, CHOAc),

7.28-7.38 (10H, m, 2 × Ph). δ_C(100.6 MHz, CDCl₃): 20.6, 20.8,

30.4, 37.5, 60.6, 64.5, 71.8, 72.0, 72.1, 74.6, 80.9, 127.3, 127.5,

127.6, 128.2, 128.3 (two peaks), 137.9, 138.3, 169.6, 170.6. m/z

+

(ES⁺): 483 (MNa⁺, ³⁵Cl, 67%), 478 (MNH₄

,

³⁵Cl, 100), 454 (17),

279 (15), 153 (13). Accurate mass (ES⁺): found, 478.1994;

C₂₅H₃₃NO₆Cl (MNH₄

,

³⁵Cl) requires 478.1996.

+

(1S*,4S*,7R*,4′S*,5′S*)- and (1R*,4R*,7R*,4′S*,5′S*)-7-

[5-(tert-Butyl)-2,2-dimethyl-1,3-dioxolan-4-yl]-2,3-dioxa-

bicyclo[2.2.2]-oct-5-ene (53) and (54). A stirred solution of

dioxolane 45 (261 mg, 1.11 mol) and methylene blue indicator

(20 µL, 0.05% w/v in dichloromethane) in anhydrous dichlo-

romethane (165 mL) was cooled to -78 °C. The resulting

mixture was irradiated with a tungsten filament lamp (300

W) while oxygen was passed through the solution; after 4.5 h

the solution was warmed to RT and filtered through a short

plug of silica gel and Celite; the residue was washed with

dichloromethane (3 × 20 mL), and the filtrate was concen-

trated in vacuo. The resulting material was purified by flash

column chromatography (silica gel, 5:1 petrol/ether) to furnish

a mixture of the diastereomeric endoperoxides 53 and 54 as a

colorless crystalline solid (225 mg, 53:54 ) 2:1, 76%). Data for

53 (which could be partially separated from 54) are as follows.

R_f0.44 (1:1 petrol/ether). ν_max/cm^-1(KBr disk): 2961s, 2871m,

1480w, 1469w, 1441w, 1396w, 1380m, 1370s, 1335w, 1301w,

1247s, 1216s, 1175w, 1157m, 1094w, 1073m, 1053m, 1028m,

996w, 960w, 948w, 881w, 867w, 756s, 711w, 667m. δ_H(400

MHz, CDCl₃): 0.89 (9H, s, t-Bu), 1.18 (1H, ddd, J 13.2, 4.8,

1.6, CHH′), 1.41 and 1.47 (2 × 3H, 2 × s, CMe₂), 2.35 (1H,

ddd, J 13.2, 9.2, 4.4, CHH′), 2.75 (1H, tdd, J 9.2, 4.8, 3.2, CH-

(OCMe₂)CH), 3.40 (1H, dd, J 9.2, 4.8, CH(OCMe₂)CH), 3.67

(1S*,2S*,3S*,4S*,5R*)-1,2-Dibenzyloxy-3,4-epoxy-5-(hy-

droxymethyl)cyclohexane (49). To a blue-green suspension

of VO(acac)₂(1.6 mg, 0.006 mmol) in anhydrous dichlo-

romethane (1.5 mL) cooled to 0 °C was added cyclohexene

derivative 48 (36 mg, 0.11 mmol) in anhydrous dichlo-

romethane (1.0 mL). After 10 min tert-butylhydroperoxide (5.0

M in decane, 34.0 µL, 0.17 mmol) was added, and the dark-

red solution was stirred vigorously for 1 h at 0 °C and then

warmed to RT. After 6 h the reaction was quenched by the

addition of dilute aqueous Na₂SO₃solution (10% w/v, 10 mL),

and the mixture was extracted with ether (3 × 15 mL). The

combined organic fractions were washed with brine (25 mL),

dried (MgSO₄), and the solvents were removed in vacuo. The

residue was purified by flash column chromatography (silica

gel, 2:1 petrol/ether) to furnish epoxide 49 as a colorless oil

(20.5 mg, 54%). R_f0.29 (ether). ν_max/cm^-1(thin film): 3436m,

3058w, 3023w, 2928m, 2870m, 1496w, 1453m, 1355w, 1325w,

7146 J. Org. Chem., Vol. 70, No. 18, 2005

Silatropic Carbonyl Ene Reactions

(1H, d, J 4.8, t-BuCH), 4.64-4.68 and 4.87-4.91 (2 × 1H, 2 ×

m, CHO-OCH), 6.68-6.71 (2H, m, CHdCH). δ_C(100.6 MHz,

CDCl₃): 26.1, 27.0, 27.5, 28.6, 33.4, 38.8, 70.2, 72.2, 80.1, 88.8,

109.6, 131.3, 132.4. m/z (CI⁺): 286 (MNH₄⁺, 7%), 269 (MH⁺,

45), 253 (64), 211 (100), 194 (37), 185 (90), 177 (51), 169 (33),

157 (33).. Accurate mass (CI⁺): found, 286.2014; C₁₅H₂₈NO₄

(MNH₄⁺) requires 286.2018. Data for 54 (obtained in admix-

olane (58). To a stirred solution of alkene 56 (24.1 mg, 0.053

mmol) in tetrahydrofuran (2.5 mL) was added NMO (7 mg,

0.06 mmol) and OsO₄(cat.); the reaction mixture was stirred

at RT for 1 h. The reaction was quenched by the addition of

dilute aqueous Na₂SO₃solution (10% w/v, 2.5 mL), and the

mixture was partitioned between water (10 mL) and ethyl

acetate (10 mL); the aqueous phase was separated and

extracted with ethyl acetate (3 × 10 mL). The combined

organic fractions were washed with brine (25 mL), dried

(MgSO₄), and the solvents were removed in vacuo. The residue

(crude diol 57) was azeotroped with toluene (3 × 5 mL) and

then dissolved in anhydrous DMF (2.5 mL), and the solution

was cooled to 0 °C. Benzyl bromide (26 µL, 0.22 mmol) was

added, followed by NaH (9 mg, 0.23 mmol). The reaction

mixture was allowed to warm to RT over 12 h. The solution

was cooled to 0 °C, and the reaction was quenched by the

dropwise addition of methanol (500 µL); the resulting mixture

was partitioned between water (10 mL) and ether (10 mL).

The aqueous phase was separated and extracted with ether

(3 × 10 mL); the combined organic fractions were washed with

brine (25 mL), dried (MgSO₄), and the solvents were removed

in vacuo. The residual oil was azeotroped with toluene (2 ×

10 mL) to remove traces of DMF. Purification by flash column

chromatography (silica gel, 7:1 petrol/ether) gave benzylated

tetraol 58 as a colorless oil (27.4 mg, 77%). R_f0.30 (7:1 petrol/

ether). ν_max/cm^-1(thin film): 3056w, 3030w, 2978w, 2952m,

2932m, 2869m, 1496w, 1453m, 1367m, 1247w, 1208w, 1072s,

1027m, 734m, 697s. δ_H(400 MHz, CDCl₃): 0.89 (9H, s, t-Bu),

1.39 and 1.47 (2 × 3H, 2 × s, CMe₂), 1.74 (1H, dt, J 14.2, 4.0)

and 2.04 (1H, ddd, J 14.2, 11.2, 4.0, CH₂), 2.20-2.30 (1H, m,

CH(OCMe₂)CH), 3.73 (1H, td, J 4.0, 3.6, CH₂CHOBn), 3.81

(1H, dd, J 4.0, 3.6, CH(OBn)CHOBn), 3.84-3.87 (1H, m,

CH(OCMe₂)CH), 3.89 (1H, dd, J 8.2, 3.6, CH(OBn)CHOBn),

4.09 (1H, d, J 7.2, t-BuCH), 4.18 (1H, t, J 8.2, CH(OBn)CH),

4.43 and 4.49 (2 × 1H, 2 × d, J 11.6, CH₂Ph), 4.57 and 4.66 (2

× 1H, 2 × d, J 11.6, CH₂Ph), 4.64 and 4.72 (2 × 1H, 2 × d, J

12.2, CH₂Ph), 4.70 (2H, s, CH₂Ph), 7.23-7.38 (20H, m, 4 ×

Ph). δ_C(100.6 MHz, CDCl₃): 26.4, 27.4, 28.5, 30.8, 32.8, 33.2,

71.2, 72.5, 72.6, 72.7, 74.9, 76.5, 77.0, 80.0, 82.1, 86.9, 107.8,

127.3-128.3 (overlapping), 138.7, 138.8, 138.9, 139.0. m/z

(ES⁺): 687 (MNa⁺, 45%), 682 (MNH₄⁺, 30), 665 (MH⁺, 100),

515 (12), 454 (14), 413 (12), 391 (18), 342 (19), 301 (15), 279

(19), 226 (20). Accurate mass (ES⁺): found, 665.3836; C₄₃H₅₃O₆

(MH⁺) requires 665.3842.

(1S*,2S*,1′R*,2′R*,3′S*,4′R*,5′S*)-1-[2,3,4,5-Tetra(benzyl-

oxy)cyclohexyl]-3,3-dimethylbutan-1,2-diol (59). To a

stirred solution of dioxolane 58 (23.3 mg, 0.035 mmol) in

tetrahydrofuran (2.0 mL) and water (1.0 mL) was added TFA

(2.0 mL), and the mixture was stirred at RT for 1.5 h. The

solution was concentrated in vacuo employing toluene (3 ×

10 mL) to remove water azeotropically. The residue was

purified by flash column chromatography (silica gel, 5:1 petrol/

ether) to furnish diol 59 as a colorless oil (20.3 mg, 93%). R_f

0.35 (2:1 petrol/ether). ν_max/cm^-1(thin film): 3435m, 3064w,

3030w, 2949m, 2927m, 2865w, 1496w, 1454m, 1390w, 1363w,

1309w, 1207w, 1097s, 1066s, 1028m, 734s, 697s. δ_H(400 MHz,

CDCl₃): 0.91 (9H, s, t-Bu), 1.52 (1H, ddd, J 14.2, 12.0, 2.8)

and 1.92 (1H, ddd, J 14.2, 4.0, 3.6, CH₂), 2.09 (1H, dddd, J

12.0, 9.2, 7.6 and 4.0, CH(OH)CH), 3.13 (1H, s, t-BuCH), 3.69

(1H, td, J 3.6, 2.8, CH(OBn)CH₂), 3.78 (1H, d, J 7.6, CH(OH)-

CH), 3.83 (1H, dd, J 3.6, 2.8, CH(OBn)CHOBn), 3.93 (1H, dd,

J 9.2, 2.8, CH(OBn)CH(OBn)), 4.00 (1H, t, J 9.2, CH(OBn)-

CH), 4.34 and 4.54 (2 × 1H, 2 × d, J 12.0, CH₂Ph), 4.59 (2H,

s, CH₂Ph), 4.61 and 4.73 (2 × 1H, 2 × d, J 12.0, CH₂Ph), 4.71

and 5.08 (2 × 1H, 2 × d, J 10.8, CH₂Ph), 7.23-7.36 (20H, m,

4 × Ph). δ_C(125.7 MHz, CDCl₃): 26.3, 26.8, 34.9, 39.7, 70.8,

72.5, 72.9, 73.0, 74.0, 74.1, 76.1, 77.1, 81.1, 81.7, 127.4-128.3

(overlapping), 137.7, 138.2, 138.3, 138.5. m/z (ES⁺): 647

(MNa⁺, 66%), 625 (MH⁺, 100). Accurate mass (ES⁺): found,

625.3526; C₄₀H₄₉O₆(MH⁺) requires 625.3529.

ture with 53) are as follows. R_f0.42 (1:1 petrol/ether). ν_max

/

cm^-1(KBr disk): 3066w, 3017m, 2983m, 2960s, 2871m, 1480w,

1468w, 1458w, 1441w, 1396w, 1380m, 1370s, 1335w, 1301w,

1247s, 1216s, 1179w, 1157m, 1087m, 1068m, 1053m, 1027m,

994w, 960w, 926w, 908w, 867w, 757s, 711w, 668m. δ_H(400

MHz, CDCl₃): 0.99 (9H, s, t-Bu), 1.39 and 1.47 (2 × 3H, 2 ×

s, CMe₂), 1.60 (1H, ddd, J 13.2, 10.8, 2.0) and 1.80 (1H, ddd,

J 13.2, 4.8, 4.0, CH₂), 1.91 (1H, tdd, J 10.8, 4.8, 1.6, CH-

(OCMe₂)CH), 3.68 (1H, d, J 3.4, t-BuCH), 4.28 (1H, dd, J 10.8,

3.4, CH(OCMe₂)CH), 4.61-4.66 and 4.89-4.93 (2 × 1H, 2 ×

m, CHO-OCH), 6.66-6.69 (1H, m) and 6.77 (1H, ddd, J 8.4,

6.4, 2.0, CHdCH). δ_C(100.6 MHz, CDCl₃): 25.2, 26.3, 27.9,

29.3, 34.0, 39.2, 70.3, 71.6, 78.7, 89.7, 109.8, 132.4, 132.8. m/z

(CI⁺): 269 (MH⁺, 46%), 253 (20), 211 (25), 195 (20), 185 (100),

175 (21).. Accurate mass (CI⁺): found, 269.1756; C₁₅H₂₅O₄

(MH⁺) requires 269.1753.

(4S*,5S*,1′S*,2′S*,5′S*)-5-(tert-Butyl)-4-(2,5-dibenzyloxy-

cyclohexa-3-enyl)-2,2-dimethyl-1,3-dioxolane (56). To a

stirred solution of endoperoxide 53 (20 mg, 0.075 mol) in

anhydrous tetrahydrofuran (1.5 mL) cooled to 0 °C was added

LiAlH₄(7.2 mg, 0.19 mmol), and the reaction mixture was

stirred at 0 °C for 30 min and then at RT for 15 min. The

reaction mixture was recooled to 0 °C, quenched by the

dropwise addition of saturated aqueous potassium sodium

tartrate solution (1.5 mL), and stirred for 15 min. The mixture

was partitioned between water (15 mL) and ethyl acetate (15

mL); the aqueous phase was separated and extracted with

ethyl acetate (3 × 15 mL). The combined organic fractions were

washed with brine (25 mL), dried (MgSO₄), and the solvents

were removed in vacuo to furnish the crude diol (55) as a pale

yellow solid. After azeotropic removal of residual moisture with

toluene (3 × 5 mL), the diol was dissolved in anhydrous DMF

(3.0 mL), and the solution was cooled to 0 °C. Benzyl bromide

(36 µL, 0.30 mmol) was added, followed by NaH (12 mg of a

60% dispersion in mineral oil, 0.30 mmol), and the reaction

mixture was warmed slowly to RT over 16 h. The solution was

cooled to 0 °C, and the reaction was quenched by the dropwise

addition of methanol (500 µL); the resulting mixture was

partitioned between water (25 mL) and ether (15 mL). The

aqueous phase was separated and extracted with ether (3 ×

15 mL); the combined organic fractions were washed with

brine (25 mL), dried (MgSO₄), and the solvents were removed

in vacuo. The residual oil was azeotroped with toluene (2 ×

10 mL) to remove traces of DMF. Purification by flash column

chromatography (silica gel, 5:1 petrol/ether) gave the title

compound (56) as a colorless oil (27.2 mg, 81%). R_f0.40 (5:1

petrol/ether). ν_max/cm^-1(thin film): 3030w, 2952m, 2869m,

1497w, 1480w, 1454w, 1377w, 1367m, 1240m, 1216w, 1170w,

1065s, 1028m, 914w, 733m, 697s. δ_H(400 MHz, CDCl₃): 0.91

(9H, s, t-Bu), 1.37 and 1.40 (2 × 3H, 2 × s, CMe₂), 1.82 (1H,

ddd, J 14.0, 11.6, 4.0) and 1.95 (1H, ddt, J 14.0, 3.6, 1.0, CH₂),

2.37 (1H, dddd, J 11.6, 8.0, 3.6, 2.0, CH(OCMe₂)CH), 3.71 (1H,

dd, J 8.8, 2.0, CH(OCMe₂)CH), 3.96 (1H, td, J 4.0, 3.6,

CH₂CHOBn), 4.13 (1H, d, J 8.8, t-BuCH), 4.35 (1H, ddt, J 8.0,

2.6, 1.0, CH(OBn)CHd), 4.54 and 4.70 (2 × 1H, 2 × d, J 11.4,

CH₂Ph), 4.60 (2H, s, CH₂Ph), 5.98 (1H, ddt, J 10.2, 4.0, 1.0)

and 6.06 (1H, dd, J 10.2, 2.6, CHdCH), 7.26-7.40 (10H, m, 2

× Ph). δ_C(100.6 MHz, CDCl₃): 26.3, 27.4, 27.8, 32.2, 32.5, 36.2,

69.6, 70.4, 70.7, 73.5, 80.5, 84.8, 107.1, 127.5, 127.6, 127.7,

127.8, 128.2, 128.3, 128.4, 131.4, 138.5, 140.0. m/z (ES⁺): 473

(MNa⁺, 100%), 468 (MNH₄⁺, 57), 451 (MH⁺, 12), 343 (98), 285

(23). Accurate mass (ES⁺): found, 473.2668; C₂₉H₃₈O₄Na

(MNa⁺) requires 473.2668.

(4S*,5S*,1′S*,2′R*,3′S*,4′R*,5′S*)-5-(tert-Butyl)-4-[2,3,4,5-

tetra(benzyloxy)cyclohexyl]-2,2-dimethyl-1,3-diox-

(1S*,2R*,3S*,4R*,5R*)-1,2,3,4-Tetra(benzyloxy)-5-(hy-

droxymethyl)cyclohexane (60). To a stirred suspension of

J. Org. Chem, Vol. 70, No. 18, 2005 7147

Robertson et al.

NaIO₄on silica gel (25 wt %, 86 mg, 0.10 mmol) in tetrahy-

drofuran (1.0 mL) was added a solution of diol 59 (11.6 mg,

0.019 mmol) in tetrahydrofuran (1.0 mL). The reaction mixture

was stirred vigorously at RT for 3 h and then filtered through

Celite and washed with tetrahydrofuran (2 × 2 mL). The

filtrate was added dropwise to a stirred solution of NaBH₄(4

mg, 0.11 mmol) in tetrahydrofuran (1.0 mL) and methanol (500

µL) and stirred at RT for 25 min. The reaction was quenched

by the addition of saturated aqueous NH₄Cl solution (5 mL);

the aqueous phase was extracted with ether (3 × 5 mL), and

the combined organic fractions were washed with brine (15

mL), dried (MgSO₄), and the solvents were removed in vacuo.

The residual oil was purified by flash column chromatography

(silica gel, 1:1 petrol/ether) to furnish the title compound (60)

as a colorless oil (7.7 mg, 77%). R_f0.57 (ether). ν_max/cm^-1(thin

film): 3469m, 3090w, 3063w, 3030m, 2923m, 2861m, 1953w,

1877w, 1813w, 1724w, 1605w, 1513w, 1496m, 1453m, 1391w,

1362w, 1323w, 1306w, 1251w, 1234w, 1207w, 1154w, 1091s,

1073s, 1028m, 911w, 734s, 697s. δ_H(500 MHz, CDCl₃): 1.64

(1H, ddd, J 14.0, 12.5, 3.0) and 1.73 (1H, dt, J 14.0, 3.5, CH₂),

2.00-2.10 (1H, m, CHCH₂OH), 2.23 (1H, br s, CH₂OH), 3.60-

3.65 (2H, m, CH₂OH), 3.68 (1H, dt, J 3.5, 3.0, CH₂CHOBn),

3.80 (1H, t, J 3.0, CH₂CH(OBn)CH), 3.84 (1H, t, J 9.5,

CH(OBn)CHCH₂OH), 3.89 (1H, dd, J 9.5, 3.0, CH(OBn)CH-

(OBn)CH), 4.32 and 4.48 (2 × 1H, 2 × d, J 12.0, CH₂Ph), 4.59

and 4.76 (2 × 1H, 2 × d, J 12.0, CH₂Ph), 4.60 and 4.67 (2 ×

1H, 2 × d, J 11.0, CH₂Ph), 4.69 and 5.03 (2 × 1H, 2 × d, J

11.0, CH₂Ph), 7.26-7.39 (20H, m, 4 × Ph). δ_C(125.7 MHz,

CDCl₃): 26.8, 39.0, 65.9, 70.7, 72.5, 72.9, 74.6, 74.9, 76.0, 80.5,

82.2, 127.2-128.4 (overlapping), 138.3, 138.4, 138.6 (two

peaks). m/z (ES⁺): 561 (MNa⁺, 100%), 539 (MH⁺, 69), 454 (26),

391 (33), 342 (18), 326 (22). Accurate mass (ES⁺): found,

539.2792; C₃₅H₃₉O₅(MH⁺) requires 539.2797.

Acknowledgment. We gratefully acknowledge the

EPSRC for a studentship (to P.M.S.).

Supporting Information Available: Copies of ¹³C NMR

spectra for new compounds, 2D NMR spectra for 51, and

crystallographic data for 40. This material is available free of

charge via the Internet at http://pubs.acs.org.

JO050644V

7148 J. Org. Chem., Vol. 70, No. 18, 2005

Article Doi

Silatropic carbonyl ene cyclizations in the synthesis of pseudosugars and hydroxylated piperidines

DOI: 10.1021/jo050644v

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Article abstract of DOI:10.1021/jo050644v

Full text of DOI:10.1021/jo050644v

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