Total Synthesis of Quercitols: (+)-allo-, (–)-proto-, (+)-talo-, (–)-gala-, (+)-gala-, neo-, and (–)-epi-Quercitol

Abstract

The cyclohexenenones exo- and endo-2 were converted into the cyclohexenyl acetates exo- and endo-3 and exo- and endo-5 with a diastereoselectivity of >99:1 (2 steps). Ether cleavage with DDQ in ­CH₂Cl₂/H₂O (20:1) and in situ ketal hydrolysis afforded the cyclohexenones 6 and 7 in up to 83% and 87% yield, respectively. Compound 6 was converted into (+)-allo- and (–)-proto-quercitol with a diastereoselectivity of 100:0 (4 steps). Moreover, 6 was carried on to (–)-talo-quercitol whereas 7 furnished the four remaining title quercitols (3–5 steps) including both enantiomers of gala-quercitol.

Key words

cyclohexenones - diastereoselectivity - ether cleavage - α-hydroxy ketone - oxidation - reduction

• References and Notes

• 1 Aucktor J, Anselmi C, Brückner R, Keller M. Synlett 2014; 25: 1312
• 2a Reviews: Hudlicky T, Cebulak M. Cyclitols and their Derivatives: A Handbook of Physical, Spectral, and Synthetic Data. Verlag Chemie; Weinheim: 1993
• 2b Gueltekin MS, Celik M, Balci M. Curr. Org. Chem. 2004; 8: 1159
• 3 Synthesis of (+)-allo-quercitol (8a): Yadav JS, Maiti A, Sankar AR, Kunwar AC. J. Org. Chem. 2001; 66: 8370
• 4 C-3 of this compound represents a chirotopic nonstereogenic center. Because of the latter attribute it suffices to connect C-3 and 3-OH by an ‘ordinary bond’ rather than by a wedge or by hatches.

Syntheses of (–)-proto-quercitol (8b):
• 5a McCasland GE, Naumann MO, Durham LJ. J. Org. Chem. 1968; 33: 4220
• 5b Angyal SJ, Odier L. Carbohydr. Res. 1982; 101: 209
• 5c Gültekin MS, Çelik M, Turkut E, Tanyeli C, Balci M. Tetrahedron: Asymmetry 2004; 15: 453 ; corrigendum: Tetrahedron: Asymmetry 2004, 15, 1959

Syntheses of (+)-talo-quercitol (8c):
• 6a McCasland GE, Furuta S, Johnson LF, Shoolery JN. J. Am. Chem. Soc. 1961; 83: 2335
• 6b Angelaud R, Babot O, Charvat T, Landais Y. J. Org. Chem. 1999; 64: 9613
• 6c Hydloft L, Madsen R. J. Am. Chem. Soc. 2000; 122: 8444
• 6d Ref. 3.

Syntheses of (–)-gala-quercitol (8d):
• 7a Ref. 6a.
• 7b Dubreuil D, Cleophax J, Vieira de Almeida M, Verre-Sebrié C, Liaigre J, Vass G, Gero SD. Tetrahedron 1997; 53: 16747
• 7c Ref. 6b.
• 7d Maezaki N, Nagahashi N, Yoshigami R, Iwata C, Tanaka T. Tetrahedron Lett. 1999; 40: 3781
• 7e Ref. 6c.
• 7f Shih T.-L, Lin Y.-L. Synth. Commun. 2005; 35: 1809
• 7g Murugan A, Yadav AK, Gurjar MK. Tetrahedron Lett. 2005; 46: 6235

Syntheses of (+)-gala-quercitol (ent-8d):
• 8a Ref. 5b.
• 8b Shih T.-L, Lin Y.-L, Kuo W.-S. Tetrahedron 2005; 61: 1919

Syntheses of neo-quercitol (8e):
• 9a Ref. 5b.
• 9b Kühlmeyer R, Keller R, Schwesinger R, Netscher T, Fritz H, Prinzbach H. Chem. Ber. 1984; 117: 1765
• 9c Ref. 8b.
• 9d Murali C, Gurale BP, Shashindhar MS. Eur. J. Org. Chem. 2010; 755
• 9e Aydin G, Savran T, Aktaş F, Baran A, Balci M. Org. Biomol. Chem. 2013; 11: 1511

Syntheses of (–)-epi-quercitol (8f):
• 10a Ref. 7b.
• 10b Biamonte MA, Vasella A. Helv. Chim. Acta 1998; 81: 688
• 10c Horne G, Potter BV. L. Chem. Eur. J. 2001; 7: 80
• 10d Ref. 7f; therein 8f was referred to as dextrorotatory. In accordance therewith, synthetic ent-8f was referred to as levorotatory in ref. 8b. The two findings disagree with our synthetic 8f being levorotatory (Scheme 7).
• 11 DDQ oxidations of primary PMB ethers of primary or secondary alcohols giving p-methoxybenzaldehyde plus these alcohols: Oikawa Y, Yoshioka T, Yonemitsu O. Tetrahedron Lett. 1982; 23: 885
• 12 DDQ oxidations of secondary PMB ethers (specifically: p-methoxybenzhydryl ethers) of primary alcohols giving p-methoxybenzophenone plus these alcohols: Sharma GV. M, Prasad TR, Rakesh SB. Synth. Commun. 2004; 34: 941
• 13 DDQ oxidations of secondary PMB esters of carboxylic acids giving p-methoxyacetophenone plus these carboxylic acids: Yoo S.-E, Kim HR, Yi KY. Tetrahedron Lett. 1990; 31: 5913
• 14 The benzylic C–O bond in the 1,4-dioxane moieties of the tri­cyclic cyclohexanetriol triacetates¹ 41 was cleaved with DDQ in CH₂Cl₂/H₂O (20:1), and the resulting alcohols were benzoylated. This provided the nonhydrolyzable spiro­ketals 9a–e in overall yields around 90% (Scheme 8).
• 15a In the tricyclic cyclohexanetriol triacetate 41b (which now rendered the spiroketal 9b by oxidative cleavage as depicted in Scheme 8) we had been able to cleave¹ the benzylic C–O bond by an ionic hydrogenolysis with Et₃SiH/F₃CCO₂H.^15b We then effected a benzylic bromination, whereupon treatment with Zn induced a reductive elimination; it ring-opened the spiroketal moiety.¹ The scope and limitations of that approach have not yet been investigated.
• 15b Ma Z, Hu H, Xiong W, Zhai H. ­Tetrahedron 2007; 63: 7523
• 16 pK _a1 of DDQ-H₂ (16): Akutagawa T, Saito G. Bull. Chem. Soc. Jpn. 1995; 68: 1753
• 17 Ammonolysis of pentaacetate rac-25: see ref. 22c.
• 18 In the present work we terminated the synthesis of each quercitol by an ammonolysis, the substrate of which was a pentaacetate (Scheme 4: 25 → 8g, 26 → 8a; Scheme 7: 37 → 8f), a triacetate (Scheme 5: 29 → 8c; Scheme 6: 35 → 8d; Scheme 7: 39 → 8e) or a mixed oligocarboxylate (Scheme 6; post-34 → ent-8d). Each ammonolysis was executed under conditions described by Balci et al.^22c for two analogous ammonolyses.
• 19 NMR Data of (–)-proto-Quercitol (8b, Figure 1) ¹H NMR (500 MHz, D₂O): δ = 1.80 (ddd, J _gem = 14.0 Hz, J _6-Hax,₁ = 11.7 Hz, J _6-Hax,₅ = 3.1 Hz, 1 H, 6-H_ax), 1.98 (dddd, J _gem = 14.0 Hz, J _6-Heq,₁ = 4.8 Hz, J _6-Heq,₅ = 3.3 Hz, ⁴ J _6-Heq,₄ = 1.2 Hz, 1 H, 6-H_eq), 3.55 (dd, J ₂,₃ = 9.7 Hz, J ₂,₁ = 9.1 Hz, 1 H, 2-H), 3.70 (dd, J ₃,₂ = 9.7 Hz, J ₃,₄ = 3.3 Hz, 1 H, 3-H), 3.74 (ddd, J ₁,_6-Hax = 11.7 Hz, J ₁,₂ = 9.1 Hz, J ₁,_6-Heq = 4.8 Hz, 1 H, 1-H), 3.92 (ddd, J ₄,₅ = 3.6 Hz, J ₄,₃ = 3.3 Hz, ⁴ J ₄,_6-Heq = 1.2 Hz, 1 H, 4-H), 4.01 (ddd, J ₅,₄ = 3.6 Hz, J ₅,_6-Heq = 3.3 Hz, J ₅,_6-Hax = 3.1 Hz, 1 H, 5-H) ppm.
• 20 Preparation of cyclohexenetriol triacetate 20 from cyclohexa-1,4-diene by an oxidation to endo-peroxide/hydroperoxide and an enzymatic kinetic resolution: see ref. 5c.
• 21 Preparation of cyclohexenetriol triacetate ent-20 from d-(–)-quinic acid: Shih T.-L, Kuo W.-S, Lin Y.-L. Tetrahedron Lett. 2004; 45: 5751

Syntheses of cyclohexenetriol triacetate rac-20 from cyclohexa-1,4-diene:
• 22a Seçen H, Salamci E, Sütbeyaz Y, Balci M. Synlett 1993; 609
• 22b Gültekin MS, Salamci E, Balci M. Carbohydr. Res. 2003; 338: 1615
• 22c Salamci E, Seçen H, Sütbeyaz Y, Balci M. J. Org. Chem. 1997; 62: 2453
• 22d Salamci E, Seçen H, Sütbeyaz Y, Balci M. Synth. Commun. 1997; 27: 2223
• 23 Method: Dupau P, Epple R, Thomas AA, Fokin VV, Sharpless KB. Adv. Synth. Catal. 2002; 344: 421
• 24 Dihydroxylation of cyclohexenetriol triacetate 20 with OsO₄/ N-methylmorpholine-N-oxide: see ref. 5c.
• 25 Dihydroxylations of cyclohexenetriol triacetates ent-20 and rac-20 with KMnO₄: see ref. 21, 22a,c.

OH-Directed triacetoxyborohydride reductions of β-hydroxyketones were studied in depth by
• 26a Evans DA, Chapman KT. Tetrahedron Lett. 1986; 27: 5939
• 26b Evans DA, Chapman KT, Carreira EM. J. Am. Chem. Soc. 1988; 110: 3560

OH-Directed diastereoselective triacetoxyborohydride reduction of an α-hydroxycyclohexenone:
• 26c Bao X, Cao Y.-X, Chu W.-D, Qu H, Du J.-Y, Zhao X.-H, Ma X.-Y, Wang C.-T, Fan C.-A. Angew. Chem. Int. Ed. 2013; 52: 14167

OH-Directed diastereoselective triacetoxyborohydride reduction of an α-hydroxybi-cyclo[2.2.2]octanone:
• 26d Griffith DR, Botta L, St Denis TG, Snyder SA. J. Org. Chem. 2014; 79: 88

OH-Directed diastereoselective triacetoxyborohydride reduction of a 4-hydroxydihydro-2H-pyran-3(4H)-one:
• 26e Shangguan N, Kiren S, Williams LJ. Org. Lett. 2007; 9: 1093
• 27 Example for stereocomplementary diastereoselective α-hydroxy­cyclohexanone reductions with LiBH(s-Bu)₃ vs. triacyloxyborohydride: Breit B, Bigot A. Chem. Commun. 2008; 6498
• 28 The ammonolysis of the pentaacetate ent-26 was described in ref. 8b.
• 29 NMR Data of (+)-allo-Quercitol (8a, Figure 2) ¹H NMR (500 MHz, D₂O; 323 K): δ = 1.59 (ddd, J _gem = 14.1 Hz, J _6-Hax,₅ = 9.4 Hz, J _6-Hax,₁ = 3.3 Hz, 1 H, 6-H_ax), 2.12 (ddd, J _gem = 14.1 Hz, J _6-Heq,₁ = 6.1 Hz, J _6-Heq,₅ = 4.4 Hz, 1 H, 6-H_eq), 3.56 (dd, J ₄,₅ = 8.0 Hz, J ₄,₃ = 3.1 Hz, 1 H, 4-H), 3.79 (dd, J ₂,₃ = 3.1 Hz, J ₂,₁ = 3.1 Hz, 1 H, 2-H), 4.01 (ddd, J ₃,₂ = 3.1 Hz, J ₃,₄ = 3.1 Hz, ⁴ J ₃,₁ = 1.3 Hz, 1 H, 3-H), 4.03 (ddd, J ₅,_6-Hax = 9.4 Hz, J ₅,₄ = 8.0 Hz, J ₅,_6-Heq = 4.4 Hz, 1 H, 5-H), 4.05 (dddd, J ₁,_6-Heq = 6.1 Hz, J ₁,_6-Hax = 3.3 Hz, J ₁,₂ = 3.1 Hz, ⁴ J ₁,₃ = 1.3 Hz, 1 H, 1-H) ppm.
• 30 Method: Fujii H, Oshima K, Utimoto K. Chem. Lett. 1991; 1847
• 31 Still WC, Kahn M, Mitra A. J. Org. Chem. 1978; 43: 2923
• 32 Synthesis of cyclohexenetriol triacetate 30 by an asymmetric eliminative epoxide opening: de Sousa SE, O’Brien P, Pilgram CD. Tetrahedron 2002; 58: 4643
• 33 Dihydroxylations of cyclohexenetriol triacetate ent-30 with KMnO₄ or RuO₄ gave an almost 1:1 ratio of the corresponding glycols ent-28 and ent-29; after peracetylation, the combined overall yield was 74%, see ref. 8b.
• 34 NMR Data of (+)-talo-Quercitol (8c, Figure 3) ¹H NMR (500 MHz, D₂O, 313 K): δ = 1.82–1.92 (m, 2 H, 6-H₂), 3.71 (dd, J ₄,₃ = 9.9 Hz, J ₄,₅ = 3.1 Hz, 1 H, 4-H), 3.75 (dd, J ₃,₄ = 9.9 Hz, J ₃,₂ = 2.7 Hz, 1 H, 3-H), 3.99 (ddd, J ₁,_6-Hax = 10.6 Hz, J ₁,_6-Heq = 5.9 Hz, J ₁,₂ = 2.8 Hz, 1 H, 1-H), 4.03 (ddd, J ₂,₁ = 2.8 Hz, J ₂,₃ = 2.7 Hz, ⁴ J ₂,_6-Heq = 1.2 Hz, 1 H, 2-H), 4.07 (ddd, J ₅,_6-Heq = 3.3 Hz, J ₅,_6-Hax = 3.3 Hz, J ₅,₄ = 3.3 Hz, 1 H, 5-H) ppm.
• 35 For a different synthesis of cyclohexenetriol triacetate 32: see ref. 32.
• 36 Synthesis of cyclohexenetriol triacetate ent-32 from d-(–)-quinic acid: see ref. 8b.
• 37 Synthesis of cyclohexenetriol triacetate rac-32 from cyclohexa-1,4-diene: see ref. 22c.
• 38 Dihydroxylation of cyclohexenetriol triacetate rac-32 with OsO₄/NMO: see ref. 22c.
• 39 Dihydroxylations of cyclohexenetriol triacetate ent-32 with KMnO₄ or RuO₄: see ref. 8b.
• 40 NMR Data of (–)-gala-Quercitol (8d, Figure 4) ¹H NMR (500 MHz, D₂O): δ = 1.72 (ddd, J _gem = 12.3 Hz, J _6-Hax,₅ = 11.4 Hz, J _6-Hax,₁ = 10.6 Hz, 1 H, 6-H_ax), 2.00 (dddd, J _gem = 12.3 Hz, J _6-Heq,₁ = 4.6 Hz, J _6-Heq,₅ = 4.4 Hz, ⁴ J _6-Heq,₄ = 1.3 Hz, 1 H, 6-H_eq), 3.67 (dd, J ₂,₁ = 9.1 Hz, J ₂,₃ = 3.2 Hz, 1 H, 2-H), 3.79 (ddd, J ₁,_6-Hax = 10.6 Hz, J ₁,₂ = 9.1 Hz, J ₁,_6-Heq = 4.6 Hz, 1 H, 1-H), 3.92 (ddd, J ₄,₃ = 4.3 Hz, J ₄,₅ = 3.1 Hz, ⁴ J ₄,_6-Heq = 1.3 Hz, 1 H, 4-H), 4.00 (dd, J ₃,₄ = 4.3 Hz, J ₃,₂ = 3.2 Hz, 1 H, 3-H), 4.01 (ddd, J ₅,_6-Hax = 11.4 Hz, J ₅,_6-Heq = 4.4 Hz, J ₅,₄ = 3.1 Hz, 1 H, 5-H) ppm.

Method:
• 41a Adkins H, Roebuck AK. J. Am. Chem. Soc. 1948; 70: 4041
• 41b Ogawa S, Aoki Y, Takagaki T. Carbohydr. Res. 1987; 164: 499
• 41c Doddi VR, Kumar A, Vankar YD. Tetrahedron 2008; 54: 9117
• 42 In principle, the epoxidation of cyclohexenol 34 may lead to the syn- and/or the anti-epoxide (Scheme 9). If the Fürst–Plattner rule is respected, the ring opening of either epoxide should deliver the respective ‘diaxially substituted dihydroxyformate’ initially, that is, compounds 43 and iso-43, respectively. In the sequel, each of these dihydroxyformates would furnish (+)-gala-quercitol (ent-8d).
• 43 NMR Data of (+)-gala-Quercitol (ent-8d, Figure 5) ¹H NMR (500 MHz, CD₃OD): δ = 1.77 (ddd, J _gem = 12.3 Hz, J _6-Hax,₁ = 10.4 Hz, J _6-Hax,₅ = 10.4 Hz, 1 H, 6-H_ax), 1.90 (dddd, J _gem = 12.3 Hz, J _6-Heq,₁ = 4.4 Hz, J _6-Heq,₅ = 4.4 Hz, ⁴ J _6-Heq,₂ = 1.2 Hz, 1 H, 6-H_eq), 3.64 (dd, J ₄,₅ = 8.5 Hz, J ₄,₃ = 3.2 Hz, 1 H, 4-H), 3.73 (ddd, J ₅,_6-Hax = 10.0 Hz, J ₅,₄ = 8.6 Hz, J ₅,_6-Heq = 4.4 Hz, 1 H, 5-H), 3.81 (dd, J ₂,₃ = 5.0 Hz, J ₂,₁ = 2.9 Hz, 1 H, 2-H), 3.91 (dd, J ₃,₂ = 5.0 Hz, J ₃,₄ = 3.3 Hz, 1 H, 3-H), 3.95 (ddd, J ₁,_6-Hax = 10.6 Hz, J ₁,_6-Heq = 4.4 Hz, J ₁,₂ = 2.9 Hz, 1 H, 1-H) ppm.
• 44 Dihydroxylations of cyclohexenetriol triacetate ent-38 with KMnO₄ or RuO₄ provided the glycols ent-39 and ent-40 with dr = 58:42 in 65% and 77% combined yield, respectively; see ref. 8b.

First descriptions of the AD-mix protocols:
• 45a Sharpless KB, Amberg W, Bennani YL, Crispino GA, Hartung J, Jeong K.-S, Kwong H.-L, Morikawa K, Wang Z.-M, Xu D, Zhang X.-L. J. Org. Chem. 1992; 57: 2768 ; (in the presence of MeSO₂NH₂)
• 45b See footnote 6 in: Jeong K.-S, Sjö P, Sharpless KB. Tetrahedron Lett. 1992; 33: 3833 ; (in the absence of MeSO₂NH₂)

Recent reviews:
• 45c Zaitsev AB, Adolfsson H. Synthesis 2006; 1725
• 45d Noe MC, Letavic MA, Snow SL, McCombie S. Org. React. 2005; 66: 109
• 45e Kolb HC, Sharpless KB In Transition Metals for Organic Synthesis . Vol. 2. Beller M, Bolm C. Wiley-VCH; Weinheim: 2004: 275-298
• 46 The relative amounts of the quercitol pentaacetates 36 and 37 were determined from the integrals over non-overlapping ¹H NMR signals (400 MHz, CDCl₃) of this mixture. Their resonances are printed in boldface in the following enumerations:NMR Data of Pentaacetate 36 ¹H NMR (400 MHz, CDCl₃): δ = 1.53 (dt, J _gem = 12.5 Hz, J _6-Hax,₁ = J _6-Hax,₅ = 11.7 Hz, 1 H, 6-H_ax), 1.99 (s, 6 H, 2 × O₂CCH₃), 2.02 (s, 6 H, 2 × O₂CCH₃), 2.15 (s, 3 H, 3-O₂CCH₃), 2.52 (dt, J _gem = 12.5 Hz, J _6-Heq,1 = J _6-Heq,5 = 5.1 Hz, 1 H, 6-H_eq), 5.03 (dd, J ₂,₁ = 10.2 Hz, J ₂,₃ = 2.9 Hz, 2 H, 2-H and 4-H), 5.24 (ddd, J ₁,_6-Hax = 11.7 Hz, J ₁,₂ = 10.2 Hz, J ₁,_6-Heq = 5.1 Hz, 2 H, 1-H and 5-H), 5.59 (t, J _3,2 = J _3,4 = 2.9 Hz, 1 H, 3-H) ppm.NMR Data of Pentaacetate 37 (Figure 6) ¹H NMR (400 MHz, CDCl₃): δ = 1.99 (s, 3 H, O₂CCH₃), 2.00 (s, 3 H, O₂CCH₃), 2.01 (s, 3 H, O₂CCH₃), 2.03 (s, 3 H, O₂CCH₃), 2.04 (ddd, J _6-Hax,₁ = 12.5 Hz, J _gem = 12.1 Hz, J _6-Hax,₅ = 11.9 Hz, 1 H, 6-H_ax), 2.17 (s, 3 H, O₂CCH₃), 2.22 (dddd, J _gem = 12.1 Hz, J _6-Heq,₅ = 5.2 Hz, J _6-Heq,₁ = 4.7 Hz, ⁴ J _6-Heq,₂ = 1.3 Hz, 1 H, 6-H_ax), 4.95 (ddd, J ₅,_6-Hax = 11.9 Hz, J ₅,₄ = 9.7 Hz, J ₅,_6-Heq = 5.2 Hz, 1 H, 5-H), 4.97 (dd, J ₃,₄ = 10.5 Hz, J ₃,₂ = 2.8 Hz, 1 H, 3-H), 4.98 (ddd, J ₁,_6-Hax = 12.5 Hz, J ₁,_6-Heq = 4.7 Hz, J ₁,₂ = 2.6 Hz, 1 H, 1-H), 5.40 (dd, J _4,3 = 10.5 Hz, J _4,5 = 9.7 Hz, 1 H, 4-H), 5.55 (ddd, J _2,3 = 2.8 Hz, J _2,1 = 2.6 Hz, ⁴ J _2,6-Heq, = 1.3 Hz, 1 H, 2-H) ppm.
• 47 The authors of ref. 8b peracetylated the mixture of glycols ent-39 and ent-40 (mentioned in ref. 44) to obtain the pentaacetates (meso)-36 and ent-37. They separated the latter compounds by flash chromatography on silica gel, which we could not.

Complementary diastereocontrol of cyclohexene dihydroxylations due to the presence of DHQ- vs. DHQD-substituted ligands:
• 48a Chida N, Ohtsuka M, Nakazawa K, Ogawa S. J. Org. Chem. 1991; 56: 2976
• 48b Mahapatra T, Nanda S. Tetrahedron: Asymmetry 2010; 21: 2199
• 49 According to ref. 8b, an ammonolysis of the pentaacetate (meso)-36 (mentioned in ref. 47) rendered the quercitol 8e. Likewise, an ammonolysis of the pentaacetate ent-37 (also mentioned in ref. 47) gave the quercitol ent-8f. Both quercitols were diastereomerically pure.
• 50 NMR Data of neo-Quercitol (8e, Figure 7) ¹H NMR (500 MHz, D₂O): δ = 1.32 (dt, J _gem = 12.3 Hz, J _6-Hax,₁ = J _6-Hax,₅ = 11.8 Hz, 1 H, 6-H_ax), 2.18 (dt, J _gem = 12.3 Hz, J _6-Heq,₁ = J _6-Heq,₅ = 4.8 Hz, 1 H, 6-H_eq), 3.44 (dd, J ₂,₁ = 9.7 Hz, J ₂,₃ = 3.0 Hz, 2 H, 2-H and 4-H), 3.79 (ddd, J ₁,_6-Hax = 11.8 Hz, J ₁,₂ = 9.7 Hz, J ₁,_6-Heq = 4.8 Hz, 2 H, 1-H and 5-H), 4.03 (t, J ₃,₂ = J ₃,₄ = 3.0 Hz, 1 H, 3-H) ppm.
• 51 NMR Data of (–)-epi-Quercitol (8f, Figure 8) ¹H NMR (400 MHz, D₂O): δ = 1.74 (m_c, 1H, 6-H_ax), 1.96 (m_c, 1 H, 6-H_eq), 3.67 - 3.54 (m, 3 H, 3-H, 4-H, 5-H), 3.77 (ddd, J ₁,_6-Hax = 12.3 Hz, J ₁,_6-Heq = 4.5 Hz, J ₁,₂ = 2.7 Hz, 1 H, 1-H), 3.98 (m_c, 1 H, 2-H) ppm.
• 52 We reached five quercitols of the present study via a total of four diastereoisomeric cyclohexenetriol triacetate precursors: 20 [Scheme 4; → (–)-proto-quercitol (8b)], 30 [Scheme 5; → (+)-talo-quercitol (8c)], 32 [Scheme 6; → (–)-gala-quercitol (8d)], and 38 [Scheme 7; → neo-quercitol (8e) and (–)-epi-quercitol (8f)]. The value of the eight stereoisomeric cyclohexenetriol triacetates as precursors of synthetic cyclohexitols was recognized previously by Balci et al.²² and by: Kee A, O’Brien P, Pilgram CD, Watson ST. Chem. Commun. 2000; 1521